Drug Labelling

  • 0 ::
      • Package_label_principal_display_panel ::
          • 0 : PRINCIPAL DISPLAY PANEL Principal Display Panel-Digoxin Tablets, USP 125 mcg (0.125mg)
        • Effective_time : 20130708
          • Description ::
              • 0 : DESCRIPTION: Digoxin is one of the cardiac (or digitalis) glycosides, a closely related group of drugs having in common specific effects on the myocardium. These drugs are found in a number of plants. Digoxin is extracted from the leaves of Digitalis lanata. The term "digitalis" is used to designate the whole group of glycosides. The glycosides are composed of two portIons: a sugar and a cardenolide (hence "glycosides"). Digoxin is described chemically as (3β,5β,12β)-3-[(O-2,6-dideoxy-β-D-ribo-hexopyranosyl-(1→4)-O-2,6-dideoxy-β-D-ribo-hexopyranosyl-(1→4)-2,6-dideoxy-β-D-ribo-hexopyranosyl)oxy]-12,14-dihydroxy-card-20(22)-enolide. lts molecular formula is C41H64O14, Its molecular weight is 780.95, and its structural formula is: Digoxin exists as odorless white crystals that melt with decomposition above 230°C. The drug is practically insoluble in water and in ether; slightly soluble in diluted (50%) alcohol and in chloroform; and freely soluble in pyridine. Digoxin Tablets, USP are supplied as 125 mcg (0.125 mg) or 250 mcg (0.25 mg) tablets for oral administration. Each tablet contains the labeled amount of digoxin USP and the following inactive ingredients: 125 mcg (0.125 mg): anhydrous lactose, colloidal silicon dioxide, corn starch, D&C yellow #10 aluminum lake, FD&C yellow #6 aluminum lake, lactose monohydrate, magnesium stearate and starch 1500. 250 mcg (0.25 mg): anhydrous lactose, colloidal silicon dioxide, corn starch, lactose monohydrate, magnesium stearate and starch 1500. Chemical Structure
            • Warnings ::
                • 0 : WARNINGS: Sinus Node Disease and AV Block: Because digoxin slows sinoatrial and AV conduction, the drug commonly prolongs the PR interval. The drug may cause severe sinus bradycardia or sinoatrial block in patients with preexisting sinus node disease and may cause advanced or complete heart block in patients with preexisting incomplete AV block. In such patients consideration should be given to the insertion of a pacemaker before treatment with digoxin. Accessory AV Pathway (Wolff-Parkinson-White Syndrome): After intravenous digoxin therapy, some patients with paroxysmal atrial fibrillation or flutter and a coexisting accessory AV pathway have developed increased antegrade conduction across the accessory pathway bypassing the AV node, leading to a very rapid ventricular response or ventricular fibrillation. Unless conduction down the accessory pathway has been blocked (either pharmacologically or by surgery), digoxin should not be used in such patients. The treatment of paroxysmal supraventricular tachycardia in such patients is usually direct-current cardioversion. Use in Patients with Preserved Left Ventricular Systolic Function: Patients with certain disorders involving heart failure associated with preserved left ventricular ejection fraction may be particularly susceptible to toxicity of the drug. Such disorders include restrictive cardiomyopathy, constrictive pericarditis, amyloid heart disease, and acute cor pulmonale. Patients with idiopathic hypertrophic subaortic stenosis may have worsening of the outflow obstruction due to the inotropic effects of digoxin. Digoxin should generally be avoided in these patients, although it has been used for ventricular rate control in the subgroup of patients with atrial fibrillation.
              • Clinical_pharmacology_table ::
                  • 0 :
Table 1: Comparisons of the Systemic Availability and Equivalent Doses for Oral Preparations of Digoxin Tablets
* For example, 125 mcg Digoxin Tablets equivalent to 100 mcg Digoxin Injection/IV.
Product Absolute Equivalent Doses (mcg)*
Bioavailability Among Dosage Forms
Digoxin Tablets 60 - 80% 62.5 125 250 500
Digoxin Injection/IV 100% 50 100 200 400
  • 1 :
    Table 2: Times to Onset of Pharmacologic Effect and to Peak Effect of Preparations of Digoxin Tablets
    * Documented for ventricular response rate in atrial fibrillation, inotropic effects and electrocardiographic changes.
    † Depending upon rate of infusion.
    Product Time to Time to
    Onset of Effect* Peak Effect*
    Digoxin Tablets 0.5 - 2 hours 2 - 6 hours
    Digoxin Injection/IV 5-30 minutes† 1 - 4 hours
    • 2 :
      Table 3: Subgroup Analyses of Mortality and Hospitalization During the First Two Years Following Randomization
      * Number of patients with an event during the first 2 years per 1000 randomized patients.
      † Relative-risk (95% confidence interval).
      ‡ DIG Ancillary Study.
      Risk of All-Cause Mortality or
      All-Cause Hospitalization*
      n Placebo Digoxin Tablets Relative risk†
      All patients 0.94
      (EF ≤0.45) 6801 604 593 (0.88-1.00)
      0.96
      NYHA I/II 4571 549 541 (0.89-1.04)
      0.99
      EF 0.25-0.45 4543 568 571 (0.91-1.07)
      0.98
      CTR ≤0.55 4455 561 563 (0.91-1.06)
      0.88
      NYHA III/IV 2224 719 696 (0.80-0.97)
      0.84
      EF <0.25 2258 677 637 (0.76-0.93)
      0.85
      CTR >0.55 2346 687 650 (0.77-0.94)
      1.04
      EF >0.45‡ 987 571 585 (0.88-1.23)
      Risk of HF-Related Mortality or
      HF-Related Hospitalization*
      n Placebo Digoxin Tablets Relative risk†
      All patients 0.69
      (EF ≤0.45) 6801 294 217 (0.63-0.76)
      0.70
      NYHA I/II 4571 242 178 (0.62-0.80)
      0.74
      EF 0.25-0.45 4543 244 190 (0.66-0.84)
      0.71
      CTR ≤0.55 4455 239 180 (0.63-0.81)
      0.65
      NYHA III/IV 2224 402 295 (0.57-0.75)
      0.61
      EF <0.25 2258 394 270 (0.53-0.71)
      0.65
      CTR >0.55 2346 398 287 (0.57-0.75)
      0.72
      EF >0.45‡ 987 179 136 (0.53-0.99)
  • Dosage_and_administration ::
      • 0 : DOSAGE AND ADMINISTRATION: General: Recommended dosages of digoxin may require considerable modification because of individual sensitivity of the patient to the drug, the presence of associated conditions, or the use of concurrent medications. In selecting a dose of digoxin, the following factors must be considered: The body weight of the patient. Doses should be calculated based upon lean (i.e., ideal) body weight. The patient"s renal function, preferably evaluated on the basis of estimated creatinine clearance. The patient"s age. Infants and children require different doses of digoxin than adults. Also, advanced age may be indicative of diminished renal function even in patients with normal serum creatinine concentration (i.e., below 1.5 mg/dL). Concomitant disease states, concurrent medications, or other factors likely to alter the pharmacokinetic or pharmacodynamic profile of digoxin (see PRECAUTIONS). Serum Digoxin Concentrations: In general, the dose of digoxin used should be determined on clinical grounds. However, measurement of serum digoxin concentrations can be helpful to the clinician in determining the adequacy of digoxin therapy and in assigning certain probabilities to the likelihood of digoxin intoxication. About two-thirds of adults considered adequately digitalized (without evidence of toxicity) have serum digoxin concentrations ranging from 0.8 to 2 ng/mL (lower serum trough concentrations of 0.5 to 1 ng/mL may be appropriate in some adult patients, see Maintenance Dosing.) However, digoxin may produce clinical benefits even at serum concentrations below this range. About two-thirds of adult patients with clinical toxicity have serum digoxin concentrations greater than 2 ng/mL. However, since one-third of patients with clinical toxicity have concentrations less than 2 ng/mL, values below 2 ng/mL do not rule out the possibility that a certain sign or symptom is related to digoxin therapy. Rarely, there are patients who are unable to tolerate digoxin at serum concentrations below 0.8 ng/mL. Consequently, the serum concentration of digoxin should always be interpreted in the overall clinical context, and an isolated measurement should not be used alone as the basis for increasing or decreasing the dose of the drug. To allow adequate time for equilibration of digoxin between serum and tissue, sampling of serum concentrations should be done just before the next scheduled dose of the drug. If this is not possible, sampling should be done at least 6 to 8 hours after the last dose, regardless of the route of administration or the formulation used. On a once-daily dosing schedule, the concentration of digoxin will be 10% to 25% lower when sampled at 24 versus 8 hours, depending upon the patient"s renal function. On a twice-daily dosing schedule, there will be only minor differences in serum digoxin concentrations whether sampling is done at 8 or 12 hours after a dose. If a discrepancy exists between the reported serum concentration and the observed clinical response, the clinician should consider the following possibilities: Analytical problems in the assay procedure. Inappropriate serum sampling time. Administration of a digitalis glycoside other than digoxin. Conditions (described in WARNINGS and PRECAUTIONS) causing an alteration in the sensitivity of the patient to digoxin. Serum digoxin concentration may decrease acutely during periods of exercise without any associated change in clinical efficacy due to increased binding of digoxin to skeletal muscle. Heart Failure: Adults: Digitalization may be accomplished by either of two general approaches that vary in dosage and frequency of administration, but reach the same endpoint in terms of total amount of digoxin accumulated in the body. If rapid digitalization is considered medically appropriate, it may be achieved by administering a loading dose based upon projected peak digoxin body stores. Maintenance dose can be calculated as a percentage of the loading dose. More gradual digitalization may be obtained by beginning an appropriate maintenance dose, thus allowing digoxin body stores to accumulate slowly. Steady-state serum digoxin concentrations will be achieved in approximately five half-lives of the drug for the individual patient. Depending upon the patient"s renal function, this will take between 1 and 3 weeks. Rapid Digitalization with a Loading Dose: Peak digoxin body stores of 8 to 12 mcg/kg should provide therapeutic effect with minimum risk of toxicity in most patients with heart failure and normal sinus rhythm. Because of altered digoxin distribution and elimination, projected peak body stores for patients with renal insufficiency should be conservative (i.e., 6 to 10 mcg/kg) (see PRECAUTIONS). The loading dose should be administered in several portions, with roughly half the total given as the first dose. Additional fractions of this planned total dose may be given at 6- to 8-hour intervals, with careful assessment of clinical response before each additional dose. If the patient's clinical response necessitates a change from the calculated loading dose of digoxin, then calculation of the maintenance dose should be based upon the amount actually given. A single initial dose of 500 to 750 mcg (0.5 to 0.75 mg) of Digoxin Tablets usually produces a detectable effect in 0.5 to 2 hours that becomes maximal in 2 to 6 hours. Additional doses of 125 to 375 mcg (0.125 to 0.375 mg) may be given cautiously at 6- to 8-hour intervals until clinical evidence of an adequate effect is noted. The usual amount of Digoxin Tablets that a 70 kg patient requires to achieve 8 to 12 mcg/kg peak body stores is 750 to 1250 mcg (0.75 to 1.25 mg). Digoxin Injection is frequently used to achieve rapid digitalization, with conversion to Digoxin Tablets for maintenance therapy. If patients are switched from intravenous to oral digoxin formulations, allowances must be made for differences in bioavailability when calculating maintenance dosages (see Table 1, CLINICAL PHARMACOLOGY). Maintenance Dosing: The doses of digoxin used in controlled trials in patients with heart failure have ranged from 125 to 500 mcg (0.125 to 0.5 mg) once daily. In these studies, the digoxin dose has been generally titrated according to the patient"s age, lean body weight, and renal function. Therapy is generally initiated at a dose of 250 mcg (0.25 mg) once daily in patients under age 70 with good renal function, at a dose of 125 mcg (0.125 mg) once daily in patients over age 70 or with impaired renal function, and at a dose of 62.5 mcg (0.0625 mg) in patients with marked renal impairment. Doses may be increased every 2 weeks according to clinical response. In a subset of approximately 1800 patients enrolled in the DIG trial (wherein dosing was based on an algorithm similar to that in Table 5) the mean (± SD) serum digoxin concentrations at 1 month and 12 months were 1.01 ± 0.47 ng/mL and 0.97 ± 0.43 ng/mL, respectively. There are no rigid guidelines as to the range of serum concentrations that are most efficacious. Several post hoc analyses of heart failure patients in the DIG trial suggest that the optimal trough digoxin serum level may be 0.5 ng/mL to 1 ng/mL. The maintenance dose should be based upon the percentage of the peak body stores lost each day through elimination. The following formula has had wide clinical use: Maintenance Dose = Peak Body Stores (i.e., Loading Dose) x % Daily Loss 100 Where: % Daily Loss = 14 + Ccr/5 (Ccr is creatinine clearance, corrected to 70 kg body weight or 1.73 m2 body surface area.) Table 5 provides average daily maintenance dose requirements of Digoxin Tablets for patients with heart failure based upon lean body weight and renal function: Table 5: Usual Daily Maintenance Dose Requirements (mcg) of Digoxin Tablets for Estimated Peak Body Stores of 10 mcg/kg * Ccr is creatinine clearance, corrected to 70 kg body weight or 1.73 m2 body surface area. For adults, if only serum creatinine concentrations (Scr) are available, a Ccr (corrected to 70 kg body weight) may be estimated in men as (140 - Age)/Scr. For women, this result should be multiplied by 0.85. Note: This equation cannot be used for estimating creatinine clearance in infants or children. † lf no loading dose administered. ‡ 62.5 mcg = 0.0625 mg Corrected Ccr Lean Body Weight Number of (mL/min kg 50 60 70 80 90 100 Days Before per 70 kg)* lb 110 132 154 176 198 220 Steady State Achieved† 0 62.5‡ 125 125 125 187.5 187.5 22 10 125 125 125 187.5 187.5 187.5 19 20 125 125 187.5 187.5 187.5 250 16 30 125 187.5 187.5 187.5 250 250 14 40 125 187.5 187.5 250 250 250 13 50 187.5 187.5 250 250 250 250 12 60 187.5 187.5 250 250 250 375 11 70 187.5 250 250 250 250 375 10 80 187.5 250 250 250 375 375 9 90 187.5 250 250 250 375 500 8 100 250 250 250 375 375 500 7 Example: Based on Table 5, a patient in heart failure with an estimated lean body weight of 70 kg and a Ccr of 60 mL/min should be given a dose of 250 mcg (0.25 mg) daily of Digoxin Tablets, usually taken after the morning meal. If no loading dose is administered, steady-state serum concentrations in this patient should be anticipated at approximately 11 days. Infants and Children: In general, divided daily dosing is recommended for infants and young children (under age 10). In the newborn period, renal clearance of digoxin is diminished and suitable dosage adjustments must be observed. This is especially pronounced in the premature infant. Beyond the immediate newborn period, children generally require proportionally larger doses than adults on the basis of body weight or body surface area. Children over 10 years of age require adult dosages in proportion to their body weight. Some researchers have suggested that infants and young children tolerate slightly higher serum concentrations than do adults. Daily maintenance doses for each age group are given in Table 6 and should provide therapeutic effects with minimum risk of toxicity in most patients with heart failure and normal sinus rhythm. These recommendations assume the presence of normal renal function: Table 6: Daily Maintenance Doses in Children with Normal Renal Function Age Daily Maintenance Dose (mcg/kg) 2 to 5 Years 10 to 15 5 to 10 Years 7 to 10 Over 10 Years 3 to 5 In children with renal disease, digoxin must be carefully titrated, based upon clinical response. It cannot be overemphasized that both the adult and pediatric dosage guidelines provided are based upon average patient response and substantial individual variation can be expected. Accordingly, ultimate dosage selection must be based upon clinical assessment of the patient. Atrial Fibrillation: Peak digoxin body stores larger than the 8 to 12 mcg/kg required for most patients with heart failure and normal sinus rhythm have been used for control of ventricular rate in patients with atrial fibrillation. Doses of digoxin used for the treatment of chronic atrial fibrillation should be titrated to the minimum dose that achieves the desired ventricular rate control without causing undesirable side effects. Data are not available to establish the appropriate resting or exercise target rates that should be achieved. Dosage Adjustment When Changing Preparations: The difference in bioavailability between Digoxin Injection or Digoxin Tablets must be considered when changing patients from one dosage form to the other.
    • Openfda ::
        • Manufacturer_name ::
            • 0 : NCS HealthCare of KY, Inc dba Vangard Labs
          • Unii ::
              • 0 : 73K4184T59
            • Product_type ::
                • 0 : HUMAN PRESCRIPTION DRUG
              • Rxcui ::
                  • 0 : 197604
                • Spl_set_id ::
                    • 0 : 2e75d6fc-9c0c-4520-9e52-3f668ccd815a
                  • Route ::
                      • 0 : ORAL
                    • Generic_name ::
                        • 0 : DIGOXIN
                      • Brand_name ::
                          • 0 : Digoxin
                        • Pharm_class_cs ::
                            • 0 : Cardiac Glycosides [Chemical/Ingredient]
                          • Product_ndc ::
                              • 0 : 0615-0547
                            • Original_packager_product_ndc ::
                                • 0 : 0143-1240
                              • Substance_name ::
                                  • 0 : DIGOXIN
                                • Spl_id ::
                                    • 0 : f002a62a-bf93-4ec8-b88a-91683b3e19ce
                                  • Application_number ::
                                      • 0 : ANDA077002
                                    • Nui ::
                                        • 0 : N0000175568
                                          • 1 : N0000008157
                                        • Pharm_class_epc ::
                                            • 0 : Cardiac Glycoside [EPC]
                                          • Package_ndc ::
                                              • 0 : 0615-0547-39
                                                • 1 : 0615-0547-05
                                                  • 2 : 0615-0547-31
                                            • Spl_product_data_elements ::
                                                • 0 : Digoxin Digoxin DIGOXIN DIGOXIN ANHYDROUS LACTOSE SILICON DIOXIDE STARCH, CORN LACTOSE MONOHYDRATE MAGNESIUM STEARATE W;40
                                              • Contraindications ::
                                                  • 0 : CONTRAINDICATIONS: Digitalis glycosides are contraindicated in patients with ventricular fibrillation or in patients with a known hypersensitivity to digoxin. A hypersensitivity reaction to other digitalis preparations usually constitutes a contraindication to digoxin.
                                                • Clinical_pharmacology ::
                                                    • 0 : CLINICAL PHARMACOLOGY: Mechanism of Action: Digoxin inhibits sodium-potassium ATPase, an enzyme that regulates the quantity of sodium and potassium inside cells. Inhibition of the enzyme leads to an increase in the intracellular concentration of sodium and thus (by stimulation of sodium-calcium exchange) an increase in the intracellular concentration of calcium. The beneficial effects of digoxin result from direct actions on cardiac muscle, as well as indirect actions on the cardiovascular system mediated by effects on the autonomic nervous system. The autonomic effects include: (1) a vagomimetic action, which is responsible for the effects of digoxin on the sinoatrial and atrioventricular (AV) nodes; and (2) baroreceptor sensitization, which results in increased afferent inhibitory activity and reduced activity of the sympathetic nervous system and renin-angiotensin system for any given increment in mean arterial pressure. The pharmacologic consequences of these direct and indirect effects are: (1) an increase in the force and velocity of myocardial systolic contraction (positive inotropic action); (2) a decrease in the degree of activation of the sympathetic nervous system and renin-angiotensin system (neurohormonal deactivating effect); and (3) slowing of the heart rate and decreased conduction velocity through the AV node (vagomimetic effect). The effects of digoxin in heart failure are mediated by its positive inotropic and neurohormonal deactivating effects, whereas the effects of the drug in atrial arrhythmias are related to its vagomimetic actions. In high doses, digoxin increases sympathetic outflow from the central nervous system (CNS). This increase in sympathetic activity may be an important factor in digitalis toxicity. Pharmacokinetics: Absorption: Following oral administration, peak serum concentrations of digoxin occur at 1 to 3 hours. Absorption of digoxin from digoxin tablets has been demonstrated to be 60% to 80% complete compared to an identical intravenous dose of digoxin (absolute bioavailability). When digoxin tablets are taken after meals, the rate of absorption is slowed, but the total amount of digoxin absorbed is usually unchanged. When taken with meals high in bran fiber, however, the amount absorbed from an oral dose may be reduced. Comparisons of the systemic availability and equivalent doses for oral preparations of digoxin tablets are shown in Table 1. Table 1: Comparisons of the Systemic Availability and Equivalent Doses for Oral Preparations of Digoxin Tablets * For example, 125 mcg Digoxin Tablets equivalent to 100 mcg Digoxin Injection/IV. Product Absolute Equivalent Doses (mcg)* Bioavailability Among Dosage Forms Digoxin Tablets 60 - 80% 62.5 125 250 500 Digoxin Injection/IV 100% 50 100 200 400 In some patients, orally administered digoxin is converted to inactive reduction products (e.g., dihydrodigoxin) by colonic bacteria in the gut. Data suggest that one in ten patients treated with digoxin tablets will degrade 40% or more of the ingested dose. As a result, certain antibiotics may increase the absorption of digoxin in such patients. Although inactivation of these bacteria by antibiotics is rapid, the serum digoxin concentration will rise at a rate consistent with the elimination half-life of digoxin. The magnitude of rise in serum digoxin concentration relates to the extent of bacterial inactivation, and may be as much as two-fold in some cases. Distribution: Following drug administration, a 6- to 8-hour tissue distribution phase is observed. This is followed by a much more gradual decline in the serum concentration of the drug, which is dependent on the elimination of digoxin from the body. The peak height and slope of the early portion (absorption/distribution phases) of the serum concentration-time curve are dependent upon the route of administration and the absorption characteristics of the formulation. Clinical evidence indicates that the early high serum concentrations do not reflect the concentration of digoxin at its site of action, but that with chronic use, the steady-state post-distribution serum concentrations are in equilibrium with tissue concentrations and correlate with pharmacologic effects. In individual patients, these post-distribution serum concentrations may be useful in evaluating therapeutic and toxic effects (see DOSAGE AND ADMINISTRATION: Serum Digoxin Concentrations). Digoxin is concentrated in tissues and therefore has a large apparent volume of distribution. Digoxin crosses both the blood-brain barrier and the placenta. At delivery, the serum digoxin concentration in the newborn is similar to the serum concentration in the mother. Approximately 25% of digoxin in the plasma is bound to protein. Serum digoxin concentrations are not significantly altered by large changes in fat tissue weight, so that its distribution space correlates best with lean (i.e., ideal) body weight, not total body weight. Metabolism: Only a small percentage (16%) of a dose of digoxin is metabolized. The end metabolites, which include 3β-digoxigenin, 3-keto-digoxigenin, and their glucuronide and sulfate conjugates, are polar in nature and are postulated to be formed via hydrolysis, oxidation, and conjugation. The metabolism of digoxin is not dependent upon the cytochrome P-450 system, and digoxin is not known to induce or inhibit the cytochrome P-450 system. Excretion: Elimination of digoxin follows first-order kinetics (that is, the quantity of digoxin eliminated at any time is proportional to the total body content). Following intravenous administration to healthy volunteers, 50% to 70% of a digoxin dose is excreted unchanged in the urine. Renal excretion of digoxin is proportional to glomerular filtration rate and is largely independent of urine flow. In healthy volunteers with normal renal function, digoxin has a half-life of 1.5 to 2.0 days. The half-life in anuric patients is prolonged to 3.5 to 5 days. Digoxin is not effectively removed from the body by dialysis, exchange transfusion, or during cardiopulmonary bypass because most of the drug is bound to tissue and does not circulate in the blood. Special Populations: Race differences in digoxin pharmacokinetics have not been formally studied. Because digoxin is primarily eliminated as unchanged drug via the kidney and because there are no important differences in creatinine clearance among races, pharmacokinetic differences due to race are not expected. The clearance of digoxin can be primarily correlated with renal function as indicated by creatinine clearance. The Cockcroft and Gault formula for estimation of creatinine clearance includes age, body weight, and gender. Table 5 that provides the usual daily maintenance dose requirements of digoxin tablets based on creatinine clearance (per 70 kg) is presented in the DOSAGE AND ADMINISTRATION section. Plasma digoxin concentration profiles in patients with acute hepatitis generally fell within the range of profiles in a group of healthy subjects. Pharmacodynamic and Clinical Effects: The times to onset of pharmacologic effect and to peak effect of preparations of digoxin tablets are shown in Table 2. Table 2: Times to Onset of Pharmacologic Effect and to Peak Effect of Preparations of Digoxin Tablets * Documented for ventricular response rate in atrial fibrillation, inotropic effects and electrocardiographic changes. † Depending upon rate of infusion. Product Time to Time to Onset of Effect* Peak Effect* Digoxin Tablets 0.5 - 2 hours 2 - 6 hours Digoxin Injection/IV 5-30 minutes† 1 - 4 hours Hemodynamic Effects: Digoxin produces hemodynamic improvement in patients with heart failure. Short- and long-term therapy with the drug increases cardiac output and lowers pulmonary artery pressure, pulmonary capillary wedge pressure, and systemic vascular resistance. These hemodynamic effects are accompanied by an increase in the left ventricular ejection fraction and a decrease in end-systolic and end-diastolic dimensions. Chronic Heart Failure: Two 12-week, double-blind placebo-controlled studies enrolled 178 (RADIANCE trial) and 88 (PROVED trial) patients with NYHA class II or III heart failure previously treated with digoxin, a diuretic, and an ACE inhibitor (RADIANCE only) and randomized them to placebo or treatment with digoxin tablets. Both trials demonstrated better preservation of exercise capacity in patients randomized to digoxin tablets. Continued treatment with digoxin tablets reduced the risk of developing worsening heart failure, as evidenced by heart failure-related hospitalizations and emergency care and the need for concomitant heart failure therapy. The larger study also showed treatment-related benefits in NYHA class and patients' global assessment. In the smaller trial, these trended in favor of a treatment benefit. The Digitalis Investigation Group (DIG) main trial was a multicenter, randomized, double-blind, placebo-controlled mortality study of 6801 patients with heart failure and left ventricular ejection fraction ≤0.45. At randomization, 67% were NYHA class I or II, 71% had heart failure of ischemic etiology, 44% had been receiving digoxin, and most were receiving concomitant ACE inhibitor (94%) and diuretic (82%). Patients were randomized to placebo or digoxin tablets, the dose of which was adjusted for the patient"s age, sex, lean body weight, and serum creatinine (see DOSAGE AND ADMINISTRATION), and followed for up to 58 months (median 37 months). The median daily dose prescribed was 0.25 mg. Overall all-cause mortality was 35% with no difference between groups (95% confidence limits for relative risk of 0.91 to 1.07). Digoxin was associated with a 25% reduction in the number of hospitalizations for heart failure, a 28% reduction in the risk of a patient having at least one hospitalization for heart failure, and a 6.5% reduction in total hospitalizations (for any cause). Use of digoxin tablets was associated with a trend to increase in time to all-cause death or hospitalization. The trend was evident in subgroups of patients with mild heart failure as well as more severe disease, as shown in Table 3. Although the effect on all-cause death or hospitalization was not statistically significant, much of the apparent benefit derived from effects on mortality and hospitalization attributed to heart failure. Table 3: Subgroup Analyses of Mortality and Hospitalization During the First Two Years Following Randomization * Number of patients with an event during the first 2 years per 1000 randomized patients. † Relative-risk (95% confidence interval). ‡ DIG Ancillary Study. Risk of All-Cause Mortality or All-Cause Hospitalization* n Placebo Digoxin Tablets Relative risk† All patients 0.94 (EF ≤0.45) 6801 604 593 (0.88-1.00) 0.96 NYHA I/II 4571 549 541 (0.89-1.04) 0.99 EF 0.25-0.45 4543 568 571 (0.91-1.07) 0.98 CTR ≤0.55 4455 561 563 (0.91-1.06) 0.88 NYHA III/IV 2224 719 696 (0.80-0.97) 0.84 EF <0.25 2258 677 637 (0.76-0.93) 0.85 CTR >0.55 2346 687 650 (0.77-0.94) 1.04 EF >0.45‡ 987 571 585 (0.88-1.23) Risk of HF-Related Mortality or HF-Related Hospitalization* n Placebo Digoxin Tablets Relative risk† All patients 0.69 (EF ≤0.45) 6801 294 217 (0.63-0.76) 0.70 NYHA I/II 4571 242 178 (0.62-0.80) 0.74 EF 0.25-0.45 4543 244 190 (0.66-0.84) 0.71 CTR ≤0.55 4455 239 180 (0.63-0.81) 0.65 NYHA III/IV 2224 402 295 (0.57-0.75) 0.61 EF <0.25 2258 394 270 (0.53-0.71) 0.65 CTR >0.55 2346 398 287 (0.57-0.75) 0.72 EF >0.45‡ 987 179 136 (0.53-0.99) In situations where there is no statistically significant benefit of treatment evident from a trial"s primary endpoint, results pertaining to a secondary endpoint should be interpreted cautiously. Chronic Atrial Fibrillation: In patients with chronic atrial fibrillation, digoxin slows rapid ventricular response rate in a linear dose-response fashion from 0.25 to 0.75 mg/day: Digoxin should not be used for the treatment of mufti-focal atrial tachycardia.
                                                  • Version : 11
                                                    • References ::
                                                        • 0 : REFERENCES Digibind® is a registered trademark of GlaxoSmithKline. DigiFab® is a registered trademark of Prostherics Inc. Manufactured By: West-ward Pharmaceutical Corp. Eatontown, NJ 07724 Revised July 2010
                                                      • Set_id : 2e75d6fc-9c0c-4520-9e52-3f668ccd815a
                                                        • Adverse_reactions ::
                                                            • 0 : ADVERSE REACTIONS: In general, the adverse reactions of digoxin are dose-dependent and occur at doses higher than those needed to achieve a therapeutic effect. Hence, adverse reactions are less common when digoxin is used within the recommended dose range or therapeutic serum concentration range and when there is careful attention to concurrent medications and conditions. Because some patients may be particularly susceptible to side effects with digoxin, the dosage of the drug should always be selected carefully and adjusted as the clinical condition of the patient warrants. In the past, when high doses of digoxin were used and little attention was paid to clinical status or concurrent medications, adverse reactions to digoxin were more frequent and severe. Cardiac adverse reactions accounted for about one-half, gastrointestinal disturbances for about one-fourth, and CNS and other toxicity for about one-fourth of these adverse reactions. However, available evidence suggests that the incidence and severity of digoxin toxicity has decreased substantially in recent years. In recent controlled clinical trials, in patients with predominantly mild to moderate heart failure, the incidence of adverse experiences was comparable in patients taking digoxin and in those taking placebo. In a large mortality trial, the incidence of hospitalization for suspected digoxin toxicity was 2% in patients taking Digoxin Tablets compared to 0.9% in patients taking placebo. In this trial, the most common manifestations of digoxin toxicity included gastrointestinal and cardiac disturbances; CNS manifestations were less common. Adults: Cardiac: Therapeutic doses of digoxin may cause heart block in patients with pre-existing sinoatrial or AV conduction disorders; heart block can be avoided by adjusting the dose of digoxin. Prophylactic use of a cardiac pacemaker may be considered if the risk of heart block is considered unacceptable. High doses of digoxin may produce a variety of rhythm disturbances, such as first-degree, second-degree (Wenckebach), or third-degree heart block (including asystole); atrial tachycardia with block; AV dissociation; accelerated junctional (nodal) rhythm; unifocal or multiform ventricular premature contractions (especially bigeminy or trigeminy); ventricular tachycardia; and ventricular fibrillation. Digoxin produces PR prolongation and ST segment depression which should not by themselves be considered digoxin toxicity. Cardiac toxicity can also occur at therapeutic doses in patients who have conditions which may alter their sensitivity to digoxin (see WARNINGS and PRECAUTIONS). Gastrointestinal: Digoxin may cause anorexia, nausea, vomiting, and diarrhea. Rarely, the use of digoxin has been associated with abdominal pain, intestinal ischemia, and hemorrhagic necrosis of the intestines. CNS: Digoxin can produce visual disturbances (blurred or yellow vision), headache, weakness, dizziness, apathy, confusion, and mental disturbances (such as anxiety, depression, delirium; and hallucination). Other: Gynecomastia has been occasionally observed following the prolonged use of digoxin. Thrombocytopenia and maculopapular rash and other skin reactions have been rarely observed. Table 4 summarizes the incidence of those adverse experiences listed above for patients treated with Digoxin Tablets or placebo from two randomized, double-blind, placebo-controlled withdrawal trials. Patients in these trials were also receiving diuretics with or without angiotensin-converting enzyme inhibitors. These patients had been stable on digoxin, and were randomized to digoxin or placebo. The results shown in Table 4 reflect the experience in patients following dosage titration with the use of serum digoxin concentrations and careful follow-up. These adverse experiences are consistent with results from a large, placebo-controlled mortality trial (DIG trial) wherein over half the patients were not receiving digoxin prior to enrollment. Table 4: Adverse Experiences in Two Parallel, Double-Blind, Placebo-Controlled Withdrawal Trials (Number of Patients Reporting) Adverse Experience Digoxin Patients Placebo Patients (n=123) (n=125) Cardiac Palpitation 1 4 Ventricular extrasystole 1 1 Tachycardia 2 1 Heart arrest 1 1 Gastrointestinal Anorexia 1 4 Nausea 4 2 Vomiting 2 1 Diarrhea 4 1 Abdominal pain 0 6 CNS Headache 4 4 Dizziness 6 5 Mental disturbances 5 1 Other Rash 2 1 Death 4 3 Infants and Children: The side effects of digoxin in infants and children differ from those seen in adults in several respects. Although digoxin may produce anorexia, nausea, vomiting, diarrhea, and CNS disturbances in young patients, these are rarely the initial symptoms of overdosage. Rather, the earliest and most frequent manifestation of excessive dosing with digoxin in infants and children is the appearance of cardiac arrhythmias, including sinus bradycardia. In children, the use of digoxin may produce any arrhythmia. The most common are conduction disturbances or supraventricular tachyarrhythmias, such as atrial tachycardia (with or without block) and junctional (nodal) tachycardia. Ventricular arrhythmias are less common. Sinus bradycardia may be a sign of impending digoxin intoxication, especially in infants, even in the absence of first-degree heart block. Any arrhythmia or alteration in cardiac conduction that develops in a child taking digoxin should be assumed to be caused by digoxin, until further evaluation proves otherwise. To report SUSPECTED ADVERSE REACTIONS, contact West-ward Pharmaceutical Corp. at 1-877-233-2001, or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
                                                          • How_supplied ::
                                                              • 0 : HOW SUPPLIED Digoxin Tablets USP, 0.125 mg are Yellow, Round, Scored Tablets, Debossed "W 40" on Scored Side Blistercards of 30 tablets. Blistercards of 31 tablets. Blistercards of 15 tablets. Digoxin Tablets USP, 0.25 mg are White, Round, Scored Tablets, Debossed "W 41" on Scored Side. Store at 20-25ºC (68-77ºF) [See USP Controlled Room Temperature] in a dry place. Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.
                                                            • Dosage_and_administration_table ::
                                                                • 0 :
                                                                  Maintenance Dose = Peak Body Stores (i.e., Loading Dose) x % Daily Loss
                                                                  100
                                                                  Where: % Daily Loss = 14 + Ccr/5
                                                                  (Ccr is creatinine clearance, corrected to 70 kg body weight or 1.73 m2 body surface area.)
                                                                  • 1 :
                                                                    Table 5: Usual Daily Maintenance Dose Requirements (mcg) of Digoxin Tablets for Estimated Peak Body Stores of 10 mcg/kg
                                                                    * Ccr is creatinine clearance, corrected to 70 kg body weight or 1.73 m2 body surface area. For adults, if only serum creatinine concentrations (Scr) are available, a Ccr (corrected to 70 kg body weight) may be estimated in men as (140 - Age)/Scr. For women, this result should be multiplied by 0.85. Note: This equation cannot be used for estimating creatinine clearance in infants or children.
                                                                    † lf no loading dose administered.
                                                                    ‡ 62.5 mcg = 0.0625 mg
                                                                    Corrected Ccr Lean Body Weight Number of
                                                                    (mL/min kg 50 60 70 80 90 100 Days Before
                                                                    per 70 kg)* lb 110 132 154 176 198 220 Steady State Achieved†
                                                                    0 62.5‡ 125 125 125 187.5 187.5 22
                                                                    10 125 125 125 187.5 187.5 187.5 19
                                                                    20 125 125 187.5 187.5 187.5 250 16
                                                                    30 125 187.5 187.5 187.5 250 250 14
                                                                    40 125 187.5 187.5 250 250 250 13
                                                                    50 187.5 187.5 250 250 250 250 12
                                                                    60 187.5 187.5 250 250 250 375 11
                                                                    70 187.5 250 250 250 250 375 10
                                                                    80 187.5 250 250 250 375 375 9
                                                                    90 187.5 250 250 250 375 500 8
                                                                    100 250 250 250 375 375 500 7
                                                                    • 2 :
                                                                      Table 6: Daily Maintenance Doses in Children with Normal Renal Function
                                                                      Age Daily Maintenance Dose
                                                                      (mcg/kg)
                                                                      2 to 5 Years 10 to 15
                                                                      5 to 10 Years 7 to 10
                                                                      Over 10 Years 3 to 5
                                                                  • Precautions ::
                                                                      • 0 : PRECAUTIONS: Use in Patients with Impaired Renal Function: Digoxin is primarily excreted by the kidneys; therefore, patients with impaired renal function require smaller than usual maintenance doses of digoxin (see DOSAGE AND ADMINISTRATION). Because of the prolonged elimination half-life, a longer period of time is required to achieve an initial or new steady-state serum concentration in patients with renal impairment than in patients with normal renal function. If appropriate care is not taken to reduce the dose of digoxin, such patients are at high risk for toxicity, and toxic effects will last longer in such patients than in patients with normal renal function. Use in Patients with Electrolyte Disorders: In patients with hypokalemia or hypomagnesemia, toxicity may occur despite serum digoxin concentrations below 2 ng/mL, because potassium or magnesium depletion sensitizes the myocardium to digoxin. Therefore, it is desirable to maintain normal serum potassium and magnesium concentrations in patients being treated with digoxin. Deficiencies of these electrolytes may result from malnutrition, diarrhea, or prolonged vomiting, as well as the use of the following drugs or procedures: diuretics, amphotericin B, corticosteroids, antacids, dialysis, and mechanical suction of gastrointestinal secretions. Hypercalcemia from any cause predisposes the patient to digitalis toxicity. Calcium, particularly when administered rapidly by the intravenous route, may produce serious arrhythmias in digitalized patients. On the other hand, hypocalcemia can nullity the effects of digoxin in humans; thus, digoxin may be ineffective until serum calcium is restored to normal. These interactions are related to the fact that digoxin affects contractility and excitability of the heart in a manner similar to that of calcium. Use in Thyroid Disorders and Hypermetabolic States: Hypothyroidism may reduce the requirements for digoxin. Heart failure and/or atrial arrhythmias resulting from hypermetabolic or hyperdynamic states (e.g., hyperthyroidism, hypoxia or arteriovenous shunt) are best, treated by addressing the underlying condition. Atrial arrhythmias associated with hypermetabolic states are particularly resistant to digoxin treatment. Care must be taken to avoid toxicity if digoxin is used. Use in Patients with Acute Myocardial Infarction: Digoxin should be used with caution in patients with acute myocardial infarction. The use of inotropic drugs in some patients in this setting may result in undesirable increases in myocardial oxygen demand and ischemia. Use During Electrical Cardioversion: It may be desirable to reduce the dose of digoxin for 1 to 2 days prior to electrical cardioversion of atrial fibrillation to avoid the induction of ventricular arrhythmias, but physicians must consider the consequences of increasing the ventricular response if digoxin is withdrawn. If digitalis toxicity is suspected, elective cardioversion should be delayed. If it is not prudent to delay cardioversion, the lowest possible energy level should be selected to avoid provoking ventricular arrhythmias. Use in Patients with Myocarditis: Digoxin can rarely precipitate vasoconstriction and therefore should be avoided in patients with myocarditis. Use in Patients with Beri Beri Heart Disease: Patients with beri beri heart disease may fail to respond adequately to digoxin if the underlying thiamine deficiency is not treated concomitantly. Laboratory Test Monitoring: Patients receiving digoxin should have their serum electrolytes and renal function (serum creatinine concentrations) assessed periodically; the frequency of assessments will depend on the clinical setting. For discussion of serum digoxin concentrations; see DOSAGE AND ADMINISTRATION section. Drug Interactions: Potassium-depleting diuretics are a major contributing factor to digitalis toxicity. Calcium, particularly if administered rapidly by the intravenous route, may produce serious arrhythmias in digitalized patients. Quinidine, verapamil, amiodarone, propafenone, indomethacin, itraconazole, alprazolam, and spironolactone raise the serum digoxin concentration due to a reduction in clearance and/or in volume of distribution of the drug, with the implication that digitalis intoxication may result. Erythromycin and clarithromycin (and possibly other macrolide antibiotics) and tetracycline may increase digoxin absorption in patients who inactivate digoxin by bacterial metabolism in the lower intestine, so that digitalis intoxication may result (see CLINICAL PHARMACOLOGY: Absorption). Propantheline and diphenoxylate, by decreasing gut motility, may increase digoxin absorption. Antacids, kaolin-pectin, sulfasalazine, neomycin, cholestyramine; certain anticancer drugs, and metoclopramide may interfere with intestinal digoxin absorption, resulting in unexpectedly low serum concentrations. Rifampin may decrease serum digoxin concentration, especially in patients with renal dysfunction, by increasing the non-renal clearance of digoxin. There have been inconsistent reports regarding the effects of other drugs [e.g., quinine, penicillamine] on serum digoxin concentration. Thyroid administration to a digitalized, hypothyroid patient may increase the dose requirement of digoxin. Concomitant use of digoxin and sympathomimetics increases the risk of cardiac arrhythmias. Succinylcholine may cause a sudden extrusion of potassium from muscle cells, and may thereby cause arrhythmias in digitalized patients. Although calcium channel blockers and digoxin may be useful in combination to control atrial fibrillation, their additive effects on AV node conduction can result in advanced or complete heart block. Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia. Digoxin concentrations are increased by about 15% when digoxin and cervedilol are administered concomitantly. Therefore, increased monitoring of digoxin is recommended when initiating, adjusting, or discontinuing carvedilol. Due to the considerable variability of these interactions; the dosage of digoxin should be individualized when patients receive these medications concurrently. Furthermore, caution should be exercised when combining digoxin with any drug that may cause a significant deterioration in renal function, since a decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Drug/Laboratory Test Interactions: The use of therapeutic doses of digoxin may cause prolongation of the PR interval and depression of the ST segment on the electrocardiogram. Digoxin may produce false positive ST-T changes on the electrocardiogram during exercise testing. These electrophysiologic effects reflect an expected effect of the drug and are not indicative of toxicity. Carcinogenesis, Mutagenesis, Impairment of Fertility: There have been no long-term studies performed in animals to evaluate carcinogenic potential, nor have studies been conducted to assess the mutagenic potential of digoxin or its potential to affect fertility. Pregnancy: Teratogenic Effects: Pregnancy Category C: Animal reproduction studies have not been conducted with digoxin. It is also not known whether digoxin can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Digoxin should be given to a pregnant woman only if clearly needed. Nursing Mothers: Studies have shown that digoxin concentrations in the mother's serum and milk are similar. However, the estimated exposure of a nursing infant to digoxin via breastfeeding will be far below the usual infant maintenance dose. Therefore, this amount should have no pharmacologic effect upon the infant. Nevertheless, caution should be exercised when digoxin is administered to a nursing woman. Pediatric Use: Newborn infants display considerable variability in their tolerance to digoxin. Premature and immature infants are particularly sensitive to the effects of digoxin, and the dosage of the drug must not only be reduced but must be individualized according to their degree of maturity. Digitalis glycosides can cause poisoning in children due to accidental ingestion. Geriatric Use: The majority of clinical experience gained with digoxin has been in the elderly population. This experience has not identified differences in response or adverse effects between the elderly and younger patients. However, this drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, which should be based on renal function, and it may be useful to monitor renal function (see DOSAGE AND ADMINISTRATION).
                                                                    • Overdosage ::
                                                                        • 0 : OVERDOSAGE: Signs and Symptoms: The signs and symptoms of toxicity are generally similar to those described in the ADVERSE REACTIONS section but may be more frequent and can be more severe. Signs and symptoms of digoxin toxicity become more frequent with levels above 2 ng/mL. However, in deciding whether a patient"s symptoms are due to digoxin, the clinical state together with serum electrolyte levels and thyroid function are important factors (see DOSAGE AND ADMINISTRATION). Adults: In adults without heart disease, clinical observation suggests that an overdose of digoxin of 10 to 15 mg was the dose resulting in death of half of the patients. If more than 25 mg of digoxin was ingested by an adult without heart disease, death or progressive toxicity responsive only to digoxin-binding Fab antibody fragments resulted. Cardiac manifestations are the most frequent and serious sign of both acute and chronic toxicity. Peak cardiac effects generally occur 3 to 6 hours following overdosage and may persist for the ensuing 24 hours or longer. Digoxin toxicity may result in almost any type of arrhythmia (see ADVERSE REACTIONS). Multiple rhythm disturbances in the same patient are common. Cardiac arrest from asystole or ventricular fibrillation due to digoxin toxicity is usually fatal. Among the extra-cardiac manifestations, gastrointestinal symptoms (e.g., nausea, vomiting, anorexia) are very common (up to 80% incidence) and precede cardiac manifestations in approximately half of the patients in most literature reports. Neurologic manifestations (e.g., dizziness, various CNS disturbances), fatigue, and malaise are very common. Visual manifestations may also occur with aberration in color vision (predominance of yellow green) the most frequent. Neurological and visual symptoms may persist after other signs of toxicity have resolved. In chronic toxicity, non-specific extra-cardiac symptoms, such as malaise and weakness, may predominate. Children: In children aged 1 to 3 years without heart disease, clinical observation suggests that an overdose of digoxin of 6 to 10 mg was the dose resulting in death in half of the patients. If more than 10 mg of digoxin was ingested by a child aged 1 to 3 years without heart disease, the outcome was uniformly fatal when Fab fragment treatment was not given. Most manifestations of toxicity in children occur during or shortly after the loading phase with digoxin. The same arrhythmias or combination of arrhythmias that occur in adults can occur in pediatrics. Sinus tachycardia, supraventricular tachycardia, and rapid atrial fibrillation are seen less frequently in the pediatric population. Pediatric patients are more likely to present with an AV conduction disturbance or a sinus bradycardia. Any arrhythmia or alteration in cardiac conduction that develops in a child taking digoxin should be assumed to be caused by digoxin, until further evaluation proves otherwise. The frequent extracardiac manifestations similar to those seen in adults are gastrointestinal, CNS, and visual. However, nausea and vomiting are not frequent in infants and small children. In addition to the undesirable effects seen with recommended doses, weight loss in older age groups and failure to thrive in infants, abdominal pain due to mesenteric artery ischemia, drowsiness, and behavioral disturbances including psychotic manifestations have been reported in overdose. Treatment: In addition to cardiac monitoring, digoxin should be temporarily discontinued until the adverse reaction resolves and may be all that is required to treat the adverse reaction such as in asymptomatic bradycardia or digoxin-related heart block. Every effort should also be made to correct factors that may contribute to the adverse reaction (such as electrolyte disturbances, thyroid function, or concurrent medications) (see WARNINGS and PRECAUTIONS: Drug Interactions). Once the adverse reaction has resolved, therapy with digoxin may be reinstituted, following a careful reassessment of dose. When the primary manifestation of digoxin overdosage is a cardiac arrhythmia, additional therapy may be needed. If the rhythm disturbance is a symptomatic bradyarrhythmia or heart block, consideration should be given to the reversal of toxicity with Digoxin Immune Fab (Ovine) [DIGIBIND® or DigiFab®] (see Massive Digitalis Overdosage subsection), the use of atropine, or the insertion of a temporary cardiac pacemaker. Digoxin Immune Fab (Ovine) is a specific antidote for digoxin and may be used to reverse potentially life-threatening ventricular arrhythmias due to digoxin overdosage. If the rhythm disturbance is a ventricular arrhythmia, consideration should be given to the correction of electrolyte disorders, particularly if hypokalemia (see Administration of Potassium subsection) or hypomagnesemia is present. Ventricular arrhythmias may respond to lidocaine or phenytoin. Administration of Potassium: Before administering potassium in digoxin overdose for hypokalemia, the serum potassium must be known and every effort should be made to maintain the serum potassium concentration between 5 and 5.5 mmol/L. Potassium salts should be avoided as they may be dangerous in patients who manifest bradycardia or heart block due to digoxin (unless primarily related to supraventricular tachycardia) and in the setting of massive digitalis overdosage. Potassium is usually administered orally, but when correction of the arrhythmia is urgent and the serum potassium concentration is low, potassium may be administered cautiously by the intravenous route. The electrocardiogram should be monitored for any evidence of potassium toxicity (e.g., peaking of T waves) and to observe the effect on the arrhythmia. Massive Digitalis Overdosage: Manifestations of life-threatening toxicity include ventricular tachycardia or ventricular fibrillation, or progressive bradyarrhythmias, or heart block. Digoxin Immune Fab (Ovine) should be used to reverse the toxic effects of ingestion of a massive overdose. The decision to administer Digoxin Immune Fab (Ovine) to a patient who has ingested a massive dose of digoxin but who has not yet manifested life-threatening toxicity should depend on the likelihood that life-threatening toxicity will occur (see above). Digoxin is not effectively removed from the body by dialysis due to its large extravascular volume of distribution. Patients with massive digitalis ingestion should receive large doses of activated charcoal to prevent absorption and bind digoxin in the gut during enteroenteric recirculation. Emesis may be indicated especially if ingestion has occurred within 30 minutes of the patient"s presentation at the hospital. Emesis should not be induced in patients who are obtunded. If a patient presents more than 2 hours after ingestion or already has toxic manifestations, it may be unsafe to induce vomiting because such maneuvers may induce an acute vagal episode that can worsen digitalis-related arrhythmias. In cases where a large amount of digoxin has been ingested, hyperkalemia may be present due to release of potassium from skeletal muscle. Hyperkalemia caused by massive digitalis toxicity is best treated with Digoxin Immune Fab (Ovine); initial treatment with glucose and insulin may also be required if hyperkalemia itself is acutely life-threatening.
                                                                      • Id : f002a62a-bf93-4ec8-b88a-91683b3e19ce
                                                                        • Indications_and_usage ::
                                                                            • 0 : INDICATIONS AND USAGE: Heart Failure: Digoxin Tablets are indicated for the treatment of mild to moderate heart failure. Digoxin Tablets increase left ventricular ejection fraction and improve heart failure symptoms as evidenced by exercise capacity and heart failure-related hospitalizations and emergency care, while having no effect on mortality. Where possible, Digoxin Tablets should be used with a diuretic and an angiotensin-converting enzyme inhibitor, but an optimal order for starting these three drugs cannot be specified. Atrial Fibrillation: Digoxin Tablets are indicated for the control of ventricular response rate in patients with chronic atrial fibrillation.
                                                                          • Adverse_reactions_table ::
                                                                              • 0 :
                                                                                Table 4: Adverse Experiences in Two Parallel, Double-Blind, Placebo-Controlled Withdrawal Trials (Number of Patients Reporting)
                                                                                Adverse Experience Digoxin Patients Placebo Patients
                                                                                (n=123) (n=125)
                                                                                Cardiac
                                                                                Palpitation 1 4
                                                                                Ventricular extrasystole 1 1
                                                                                Tachycardia 2 1
                                                                                Heart arrest 1 1
                                                                                Gastrointestinal
                                                                                Anorexia 1 4
                                                                                Nausea 4 2
                                                                                Vomiting 2 1
                                                                                Diarrhea 4 1
                                                                                Abdominal pain 0 6
                                                                                CNS
                                                                                Headache 4 4
                                                                                Dizziness 6 5
                                                                                Mental disturbances 5 1
                                                                                Other
                                                                                Rash 2 1
                                                                                Death 4 3

Drug Labelling

  • 1 ::
      • Package_label_principal_display_panel ::
          • 0 : PRINCIPAL DISPLAY PANEL - Kit Carton NDC# 62032-524-04 OBAGI® MEDICAL OBAGI-C® RX SYSTEM NORMAL DRY Skin Intervention Kit PRINCIPAL DISPLAY PANEL - Kit Carton
        • Active_ingredient ::
            • 0 : Active Ingredient Hydroquinone USP, 4% (40 mg/g)
              • 1 : Active Ingredient Hydroquinone USP, 4% (40 mg/g)
                • 2 : Active ingredients Purpose Octinoxate 7.5% Sunscreen Zinc Oxide 10.5% Sunscreen
              • Purpose_table ::
                  • 0 :
Active ingredients Purpose
Octinoxate 7.5% Sunscreen
Zinc Oxide 10.5% Sunscreen
  • Stop_use ::
      • 0 : Stop use and ask a doctor if rash occurs
    • Questions ::
        • 0 : Questions or comments? 1.800.636.7546 Monday–Friday 9 a.m.–4 p.m. Pacific Time
      • When_using ::
          • 0 : When using this product keep out of eyes. Rinse with water to remove.
        • Id : 392f9428-6f3f-44ba-8719-fdf26aca7800
          • Indications_and_usage ::
              • 0 : Indications and usage The gradual bleaching of hyperpigmented skin conditions such as chloasma, melasma, freckles, senile lentigines, and other unwanted areas of melanin hyperpigmentation.
                • 1 : Indications and usage The gradual bleaching of hyperpigmented skin conditions such as chloasma, melasma, freckles, senile lentigines, and other unwanted areas of melanin hyperpigmentation.
                  • 2 : Uses helps prevent sunburn if used as directed with other sun protection measures (see Directions ), decreases the risk of skin cancer and early skin aging caused by the sun
                • Spl_unclassified_section ::
                    • 0 : C-Cleansing Gel 6 fl. oz. (177 mL.) AM+PM A gel-based facial cleanser that clarifies and prepares your skin for absorption of the system's product ingredients. This concentrated cleanser gently removes excess oil, makeup, and other everyday impurities, and rinses clean, leaving your skin feeling fresh and clear.
                      • 1 : C-Clarifying Serum Normal to Dry (Skin Lightening Serum) NDC 62032-106-10 1 fl. oz. (30 mL.) Hydroquinone USP, 4% Rx Only AM Antioxidant serum containing Vitamin C and prescription-strength hydroquinone. This patented formulation for normal to dry skin reduces the appearance of dark spots for a lighter, brighter complexion.
                        • 2 : See enclosed Package Insert for full prescribing information. Rx ONLY. FOR EXTERNAL USE ONLY.
                          • 3 : C-Exfoliating Day Lotion Net wt. 2 oz. (57 g.) AM A smooth, lightweight moisturizer that not only hydrates, but also gently exfoliates the skin, revealing a brighter, healthier-looking complexion.
                            • 4 : C-Therapy Night Cream (Skin Lightener) NDC 62032-105-36 Net wt. 2 oz. (57 g.) Hydroquinone USP, 4% Rx Only PM A rich moisturizer that works while you sleep to renew and rejuvenate your skin. The C-Therapy Night Cream is uniquely formulated with prescription-strength hydroquinone to gradually diminish the appearance of dark spots and delivers Vitamins C and E during the skin's nightly renewal process.
                              • 5 : Contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people. Each gram of Obagi-C Rx C-Therapy Night Cream contains:
                                • 6 : See enclosed Package Insert for full prescribing information. Rx ONLY. FOR EXTERNAL USE ONLY.
                                  • 7 : Travel Bag and Patient Instruction Guide
                                    • 8 : Sun Shield Broad Spectrum SPF 50 Matte Net wt. 3 oz. (85 g) This sunscreen combines UVB absorption and UVA protection in an elegant matte finish that is non-comedogenic, hypoallergenic, non-acnegenic, and dermatologist tested. Sheer, PABA free, and fragrance free for all skin types. Drug Facts
                                      • 9 : Obagi-C and the Obagi logo are registered trademarks of OMP, Inc. Distributed by OMP, Inc., Long Beach, CA 90806 ©2012 Obagi Medical Products, Inc. All rights reserved. obagi.com Made in USA 41502211Z 5022
                                    • Inactive_ingredient ::
                                        • 0 : Ingredients water (aqua), sodium laureth sulfate, sodium lauroyl oat amino acids, cocamidopropyl betaine, aloe barbadensis leaf juice (aloe barbadensis), ascorbic acid, glycerin, medicago sativa (alfalfa) extract, borago officinalis extract, chamomilla recutita (matricaria) flower extract (chamomilla recutita extract), sodium chloride, saponins, xanthan gum, phenoxyethanol, methylparaben, ethylparaben, butylparaben, propylparaben, isobutylparaben, fragrance (parfum), red 33 (CI 17200), yellow 5 (CI 19140)
                                          • 1 : Inactive Ingredients propylene glycol, water, ascorbic acid, propylene carbonate, sodium lauryl sulfate.
                                            • 2 : Ingredients water (aqua), ethylhexyl palmitate, ethylhexyl stearate, glycolic acid, caprylic/capric triglyceride, hydroxyethyl acrylate/sodium acryloyldimethyl taurate copolymer, isopropyl palmitate, sodium hyaluronate, squalane, PEG-8 dimethicone, glyceryl stearate, PEG-100 stearate, glycerin, sodium hydroxide, PEG-8 ricinoleate, ascorbyl glucoside, tocopheryl acetate, dimethicone, arginine, cetearyl alcohol, ceteareth-20, steareth-2, bisabolol, tetrasodium EDTA, polysorbate 60, phenoxyethanol, methylparaben, ethylparaben, butylparaben, propylparaben, isobutylparaben, fragrance (parfum)
                                              • 3 : Inactive Ingredients water, glycerin, cetyl alcohol, PPG-2 myristyl ether propionate, sodium lauryl sulfate, TEA-salicylate, lactic acid, phenyl trimethicone, tocopheryl acetate, sodium metabisulfite, ascorbic acid, methylparaben, disodium EDTA, propylparaben, saponins, BHT
                                                • 4 : Inactive ingredients 1,2-hexanediol, caprylyl glycol, ceteareth-20, cetearyl alcohol, chlorphenesin, citric acid, cyclopentasiloxane, dimethicone, dimethicone crosspolymer-3, disodium EDTA, glycerin, hydrogenated palm glycerides, hydroxyethyl acrylate/sodium acryloyldimethyl taurate copolymer, methylisothiazolinone, PEG-40 stearate, pentylene glycol, phenoxyethanol, phenyl trimethicone, polysilicone-11, polysorbate 60, potassium sorbate, sodium benzoate, sodium dihydroxycetyl phosphate, sodium polyacrylate, squalane, stearyl alcohol, tetrahexyldecyl ascorbate, tropolone, water, xanthan gum
                                              • Do_not_use ::
                                                  • 0 : Avoid getting into eyes. For external use only.
                                                    • 1 : Avoid contact with eyes, nose, mouth, or lips. In case of accidental contact, patient should rinse eyes thoroughly with water and contact physician. Sunscreen use is an essential aspect of hydroquinone therapy because even minimal sunlight exposure sustains melanocytic activity. Each gram of Obagi-C Rx C-Clarifying Serum Normal to Dry contains:
                                                      • 2 : Avoid getting into eyes. For external use only.
                                                        • 3 : Avoid contact with eyes, nose, mouth, or lips. In case of accidental contact, patient should rinse eyes thoroughly with water and contact physician. Sunscreen use is an essential aspect of hydroquinone therapy because even minimal sunlight exposure sustains melanocytic activity.
                                                          • 4 : Do not use on damaged or broken skin
                                                        • Openfda ::
                                                            • Manufacturer_name ::
                                                                • 0 : OMP, INC.
                                                              • Product_type ::
                                                                  • 0 : HUMAN PRESCRIPTION DRUG
                                                                • Rxcui ::
                                                                    • 0 : 197795
                                                                  • Spl_set_id ::
                                                                      • 0 : d3b35a0e-cce3-4601-b18f-3e615e3bcd25
                                                                    • Generic_name ::
                                                                        • 0 : HYDROQUINONE, OCTINOXATE AND ZINC OXIDE
                                                                      • Brand_name ::
                                                                          • 0 : OBAGI-C RX SYSTEM NORMAL-DRY SKIN INTERVENTION
                                                                        • Product_ndc ::
                                                                            • 0 : 62032-524
                                                                          • Spl_id ::
                                                                              • 0 : 392f9428-6f3f-44ba-8719-fdf26aca7800
                                                                            • Is_original_packager ::
                                                                                • 0 : 1
                                                                              • Package_ndc ::
                                                                                  • 0 : 62032-524-04
                                                                                    • 1 : 62032-121-90
                                                                                      • 2 : 62032-106-10
                                                                                        • 3 : 62032-105-36
                                                                                  • Version : 1
                                                                                    • Dosage_and_administration ::
                                                                                        • 0 : Directions Use twice daily, morning and evening. Massage a small amount of cleanser and lukewarm water onto skin, rubbing gently in a circular motion. Rinse completely with lukewarm water and gently pat dry.
                                                                                          • 1 : Dosage and administration Use once daily in the morning. Apply 5-7 drops to the entire face, or as directed by your skin care physician. Massage in gently. If no improvement is seen after three (3) months of treatment, use of this product should be discontinued. Sun exposure should be limited by using a sunscreen agent, a sun blocking agent, or protective clothing to cover bleached skin when using and after using this product in order to prevent darkening from reoccurring.
                                                                                            • 2 : Directions Use once daily in the morning. Squeeze a small amount (approximately 1-2 pea-sized drops) onto your hands. Using your fingertips, apply evenly to the entire face. Massage gently until completely absorbed.
                                                                                              • 3 : Dosage and administration Use daily in the evening. Dispense a small amount (approximately 1-2 pea-sized drops) and apply to the entire face. Massage in gently. If no improvement is seen after three (3) months of treatment, use of this product should be discontinued. Sun exposure should be limited by using a sunscreen agent, a sun blocking agent, or protective clothing to cover bleached skin when using and after using this product in order to prevent darkening from reoccurring.
                                                                                                • 4 : Directions apply liberally 15 minutes before sun exposure use a water resistant sunscreen if swimming or sweating reapply at least every 2 hours children under 6 months: Ask a doctor Sun Protection Measures. Spending time in the sun increases your risk of skin cancer and early skin aging. To decrease this risk, regularly use a sunscreen with a Broad Spectrum SPF value of 15 or higher and other sun protection measures including: limit time in the sun, especially from 10 a.m.–2 p.m. wear long-sleeved shirts, pants, hats, and sunglasses
                                                                                              • Effective_time : 20130812
                                                                                                • Spl_product_data_elements ::
                                                                                                    • 0 : OBAGI-C RX SYSTEM NORMAL-DRY SKIN INTERVENTION HYDROQUINONE, OCTINOXATE AND ZINC OXIDE OBAGI-C RX SYSTEM C-CLARIFYING SERUM Skin Lightening Serum with Vitamin C HYDROQUINONE HYDROQUINONE HYDROQUINONE PROPYLENE GLYCOL WATER ASCORBIC ACID SODIUM LAURYL SULFATE PROPYLENE CARBONATE OBAGI-C RX SYSTEM C-THERAPY Skin Lightening with Vitamins C and E HYDROQUINONE HYDROQUINONE HYDROQUINONE EDETATE DISODIUM PPG-2 MYRISTYL ETHER PROPIONATE TROLAMINE SALICYLATE SODIUM LAURYL SULFATE CETYL ALCOHOL GLYCERIN LACTIC ACID .ALPHA.-TOCOPHEROL ACETATE ASCORBIC ACID SODIUM METABISULFITE WATER METHYLPARABEN PROPYLPARABEN BUTYLATED HYDROXYTOLUENE PHENYL TRIMETHICONE OBAGI-C RX SYSTEM SUN SHIELD BROAD SPECTRUM SPF 50MATTE SUNSCREEN OCTINOXATE AND ZINC OXIDE OCTINOXATE OCTINOXATE ZINC OXIDE ZINC OXIDE GLYCERIN PHENOXYETHANOL CYCLOMETHICONE 5 WATER PEG-10 DIMETHICONE (600 CST) PENTYLENE GLYCOL STEARYL ALCOHOL POLYOXYL 20 CETOSTEARYL ETHER PHENYL TRIMETHICONE PEG-40 STEARATE DIMETHICONE SODIUM DIHYDROXYCETYL PHOSPHATE HYDROGENATED PALM GLYCERIDES CITRIC ACID MONOHYDRATE CETOSTEARYL ALCOHOL .ALPHA.-TOCOPHEROL ACETATE 1,2-HEXANEDIOL CAPRYLYL GLYCOL TROPOLONE CHLORPHENESIN XANTHAN GUM POTASSIUM SORBATE SODIUM BENZOATE TETRAHEXYLDECYL ASCORBATE UBIDECARENONE EDETATE DISODIUM METHYLISOTHIAZOLINONE HYDROXYETHYL ACRYLATE/SODIUM ACRYLOYLDIMETHYL TAURATE COPOLYMER (45000 MPA.S AT 1%) SQUALANE POLYSORBATE 60 SODIUM POLYACRYLATE (2500000 MW) OBAGI-C RX SYSTEM C-CLEANSINGWITH VITAMIN C inert WATER GLYCERIN PHENOXYETHANOL ETHYLPARABEN ISOBUTYLPARABEN BUTYLPARABEN PROPYLPARABEN METHYLPARABEN ASCORBIC ACID SODIUM LAUROYL OAT AMINO ACIDS COCAMIDOPROPYL BETAINE SODIUM LAURETH-3 SULFATE ALOE VERA LEAF SODIUM CHLORIDE ALFALFA CHAMOMILE XANTHAN GUM D&C RED NO. 33 FD&C YELLOW NO. 5 OBAGI-C RX SYSTEM C-EXFOLIATING DAYWITH VITAMIN C inert WATER GLYCERIN PHENOXYETHANOL ETHYLPARABEN ISOBUTYLPARABEN BUTYLPARABEN PROPYLPARABEN METHYLPARABEN POLYSORBATE 60 GLYCERYL MONOSTEARATE PEG-100 STEARATE ETHYLHEXYL PALMITATE SQUALANE HYDROXYETHYL ACRYLATE/SODIUM ACRYLOYLDIMETHYL TAURATE COPOLYMER (45000 MPA.S AT 1%) PEG-8 DIMETHICONE PEG-8 RICINOLEATE GLYCOLIC ACID ARGININE ETHYLHEXYL STEARATE MEDIUM-CHAIN TRIGLYCERIDES ISOPROPYL PALMITATE HYALURONATE SODIUM SODIUM HYDROXIDE CETOSTEARYL ALCOHOL POLYOXYL 20 CETOSTEARYL ETHER DIMETHICONE STEARETH-2 ASCORBYL GLUCOSIDE LEVOMENOL EDETATE SODIUM .ALPHA.-TOCOPHEROL ACETATE
                                                                                                  • Purpose ::
                                                                                                      • 0 : Active ingredients Purpose Octinoxate 7.5% Sunscreen Zinc Oxide 10.5% Sunscreen
                                                                                                    • Storage_and_handling ::
                                                                                                        • 0 : Other information store at controlled room temperature: 15°C–25°C (59°F–77°F) protect this product from excessive heat and direct sun
                                                                                                          • 1 : Store at controlled room temperature 15°C–25°C (59°F–77°F).
                                                                                                        • Keep_out_of_reach_of_children ::
                                                                                                            • 0 : Keep out of reach of children.
                                                                                                              • 1 : Keep out of reach of children.
                                                                                                                • 2 : Keep out of reach of children. If swallowed, get medical help or contact a Poison Control Center right away.
                                                                                                              • Warnings ::
                                                                                                                  • 0 : Warnings Avoid getting into eyes. For external use only. Keep out of reach of children.
                                                                                                                    • 1 : Warnings Avoid contact with eyes, nose, mouth, or lips. In case of accidental contact, patient should rinse eyes thoroughly with water and contact physician. Sunscreen use is an essential aspect of hydroquinone therapy because even minimal sunlight exposure sustains melanocytic activity. Each gram of Obagi-C Rx C-Clarifying Serum Normal to Dry contains:
                                                                                                                      • 2 : Warnings Avoid getting into eyes. For external use only. Keep out of reach of children. Sunburn Alert This product contains an alpha hydroxy acid (AHA) that may increase your skin's sensitivity to the sun and particularly the possibility of sunburn. Use a sunscreen, wear protective clothing, and limit sun exposure while using this product and for a week afterwards.
                                                                                                                        • 3 : Warnings Avoid contact with eyes, nose, mouth, or lips. In case of accidental contact, patient should rinse eyes thoroughly with water and contact physician. Sunscreen use is an essential aspect of hydroquinone therapy because even minimal sunlight exposure sustains melanocytic activity.
                                                                                                                          • 4 : Warnings For external use only Do not use on damaged or broken skin Stop use and ask a doctor if rash occurs When using this product keep out of eyes. Rinse with water to remove. Keep out of reach of children. If swallowed, get medical help or contact a Poison Control Center right away.
                                                                                                                        • Active_ingredient_table ::
                                                                                                                            • 0 :
                                                                                                                              Active ingredients Purpose
                                                                                                                              Octinoxate 7.5% Sunscreen
                                                                                                                              Zinc Oxide 10.5% Sunscreen
                                                                                                                          • Set_id : d3b35a0e-cce3-4601-b18f-3e615e3bcd25

Drug Labelling

  • 2 ::
      • Active_ingredient ::
          • 0 : Active ingredients Purpose Octinoxate 7.5% Sunscreen Zinc Oxide 10.5% Sunscreen
        • Package_label_principal_display_panel ::
            • 0 : PRINCIPAL DISPLAY PANEL - Kit Carton NDC # 62032-523-04 OBAGI® MEDICAL OBAGI-C® RX SYSTEM NORMAL OILY Skin Intervention Kit Principal Display Panel - Kit Carton
          • Purpose_table ::
              • 0 :
Active ingredients Purpose
Octinoxate 7.5% Sunscreen
Zinc Oxide 10.5% Sunscreen
  • Stop_use ::
      • 0 : Stop use and ask a doctor if rash occurs
    • Questions ::
        • 0 : Questions or comments? 1.800.636.7546 Monday–Friday 9 a.m.–4 p.m. Pacific Time
      • When_using ::
          • 0 : When using this product keep out of eyes. Rinse with water to remove.
        • Id : eef1e733-50fb-43cc-9579-0d55175e32ec
          • Indications_and_usage ::
              • 0 : Indications and usage The gradual bleaching of hyperpigmented skin conditions such as chloasma, melasma, freckles, senile lentigines, and other unwanted areas of melanin hyperpigmentation.
                • 1 : Indications and usage The gradual bleaching of hyperpigmented skin conditions such as chloasma, melasma, freckles, senile lentigines, and other unwanted areas of melanin hyperpigmentation.
                  • 2 : Uses helps prevent sunburn if used as directed with other sun protection measures (see Directions ), decreases the risk of skin cancer and early skin aging caused by the sun
                • Spl_unclassified_section ::
                    • 0 : C-Cleansing Gel 6 fl. oz. (177 mL.) AM+PM A gel-based facial cleanser that clarifies and prepares your skin for absorption of the system's product ingredients. This concentrated cleanser gently removes excess oil, makeup, and other everyday impurities, and rinses clean, leaving your skin feeling fresh and clear.
                      • 1 : C-Balancing Toner 6.7 fl. oz. (198 mL.) AM+PM Specifically formulated for normal to oily skin, the C-Balancing Toner adjusts your skin's pH balance. As an essential step after cleansing, this alcohol-free, non-drying toner thoroughly removes impurities and dead skin cells to prepare the skin for the next step in your skin care regimen. s.
                        • 2 : C-Clarifying Serum Normal to Oily (Skin Lightening Serum) NDC 62032-122-10 1 fl. oz. (30 mL.) Hydroquinone USP, 4% Rx Only AM Antioxidant serum containing Vitamin C and prescription-strength hydroquinone. This patented formulation for normal to oily skin reduces the appearance of dark spots for a lighter, brighter complexion.
                          • 3 : See enclosed Package Insert for full prescribing information. Rx ONLY. FOR EXTERNAL USE ONLY.
                            • 4 : C-Therapy Night Cream (Skin Lightener) NDC 62032-105-36 Net wt. 2 oz. (57 g.) Hydroquinone USP, 4% Rx Only PM A rich moisturizer that works while you sleep to renew and rejuvenate your skin. The C-Therapy Night Cream is uniquely formulated with prescription-strength hydroquinone to gradually diminish the appearance of dark spots and delivers Vitamins C and E during the skin's nightly renewal process.
                              • 5 : See enclosed Package Insert for full prescribing information. Rx ONLY. FOR EXTERNAL USE ONLY.
                                • 6 : Travel Bag and Patient Instruction Guide
                                  • 7 : Sun Shield Broad Spectrum SPF 50 Matte Net wt. 3 oz. (85 g) This sunscreen combines UVB absorption and UVA protection in an elegant matte finish that is non-comedogenic, hypoallergenic, non-acnegenic, and dermatologist tested. Sheer, PABA free, and fragrance free for all skin types. Drug Facts
                                    • 8 : Store at controlled room temperature 15°C–25°C (59°F–77°F). Obagi-C and the Obagi logo are registered trademarks of OMP, Inc. Distributed by OMP, Inc., Long Beach, CA 90806 ©2012 Obagi Medical Products, Inc. All rights reserved. obagi.com Made in USA 41502111Z 5021
                                  • Inactive_ingredient ::
                                      • 0 : Ingredients water (aqua), sodium laureth sulfate, sodium lauroyl oat amino acids, cocamidopropyl betaine, aloe barbadensis leaf juice (aloe barbadensis), ascorbic acid, glycerin, medicago sativa (alfalfa) extract, borago officinalis extract, chamomilla recutita (matricaria) flower extract (chamomilla recutita extract), sodium chloride, saponins, xanthan gum, phenoxyethanol, methylparaben, ethylparaben, butylparaben, propylparaben, isobutylparaben, fragrance (parfum), red 33 (CI 17200), yellow 5 (CI 19140)
                                        • 1 : Ingredients water (aqua), hamamelis virginiana (witch hazel) water, propylene glycol, sodium pca, benzalkonium chloride, aloe barbadensis leaf juice (aloe barbadensis), panthenol, polyquaternium-10, phenoxyethanol, methylparaben
                                          • 2 : Inactive ingredients 1,2 hexanediol, caprylyl glycol, ceteareth-20, cetearyl alcohol, chlorphenesin, citric acid, cyclopentasiloxane, dimethicone, dimethicone crosspolymer-3, disodium EDTA, glycerin, hydrogenated palm glycerides, hydroxyethyl acrylate/sodium acryloyldimethyl taurate copolymer, methylisothiazolinone, PEG-40 stearate, pentylene glycol, phenoxyethanol, phenyl trimethicone, polysilicone-11, polysorbate 60, potassium sorbate, sodium benzoate, sodium dihydroxycetyl phosphate, sodium polyacrylate, squalane, stearyl alcohol, tetrahexyldecyl ascorbate, tropolone, water, xanthan gum
                                        • Do_not_use ::
                                            • 0 : Do not use on damaged or broken skin
                                          • Openfda ::
                                              • Manufacturer_name ::
                                                  • 0 : OMP, INC.
                                                • Product_type ::
                                                    • 0 : HUMAN PRESCRIPTION DRUG
                                                  • Rxcui ::
                                                      • 0 : 197795
                                                    • Spl_set_id ::
                                                        • 0 : 36b030cc-024d-43f1-89b4-8d121f62aeff
                                                      • Generic_name ::
                                                          • 0 : HYDROQUINONE, OCTINOXATE AND ZINC OXIDE
                                                        • Brand_name ::
                                                            • 0 : OBAGI-C RX SYSTEM NORMAL-OILY SKIN INTERVENTION
                                                          • Product_ndc ::
                                                              • 0 : 62032-523
                                                            • Spl_id ::
                                                                • 0 : eef1e733-50fb-43cc-9579-0d55175e32ec
                                                              • Is_original_packager ::
                                                                  • 0 : 1
                                                                • Package_ndc ::
                                                                    • 0 : 62032-121-90
                                                                      • 1 : 62032-122-10
                                                                        • 2 : 62032-523-04
                                                                          • 3 : 62032-105-36
                                                                    • Version : 1
                                                                      • Description ::
                                                                          • 0 : Each gram of Obagi-C Rx C-Clarifying Serum Normal to Oily contains: Active Ingredient Hydroquinone USP, 4% (40 mg/g) Inactive Ingredients water, propylene glycol, alcohol denat., dipropylene glycol, ascorbic acid, propylene carbonate, sodium lauryl sulfate, fragrance
                                                                            • 1 : Each gram of Obagi-C Rx C-Therapy Night Cream contains: Active Ingredient Hydroquinone USP, 4% (40 mg/g) Inactive Ingredients water, glycerin, cetyl alcohol, PPG-2 myristyl ether propionate, sodium lauryl sulfate, TEA-salicylate, lactic acid, phenyl trimethicone, tocopheryl acetate, sodium metabisulfite, ascorbic acid, methylparaben, disodium EDTA, propylparaben, saponins, BHT
                                                                          • Dosage_and_administration ::
                                                                              • 0 : Directions Use twice daily, morning and evening. Massage a small amount of cleanser and lukewarm water onto skin, rubbing gently in a circular motion. Rinse completely with lukewarm water and gently pat dry.
                                                                                • 1 : Directions Use twice daily, in the morning and evening after cleansing. Pump a small amount (3-4 pumps) onto a cotton pad and gently wipe over entire face. Let air dry. Do not rinse.
                                                                                  • 2 : Dosage and administration Use once daily in the morning. Apply 5-7 drops to the entire face, or as directed by your skin care physician. Massage in gently. If no improvement is seen after three (3) months of treatment, use of this product should be discontinued. Sun exposure should be limited by using a sunscreen agent, a sun blocking agent, or protective clothing to cover bleached skin when using and after using this product in order to prevent darkening from reoccurring.
                                                                                    • 3 : Dosage and Administration Use daily in the evening. Dispense a small amount (approximately 1-2 pea-sized drops) and apply to the entire face. Massage in gently. If no improvement is seen after three (3) months of treatment, use of this product should be discontinued. Sun exposure should be limited by using a sunscreen agent, a sun blocking agent, or protective clothing to cover bleached skin when using and after using this product in order to prevent darkening from reoccurring.
                                                                                      • 4 : Directions apply liberally 15 minutes before sun exposure use a water resistant sunscreen if swimming or sweating reapply at least every 2 hours children under 6 months: Ask a doctor Sun Protection Measures. Spending time in the sun increases your risk of skin cancer and early skin aging. To decrease this risk, regularly use a sunscreen with a Broad Spectrum SPF value of 15 or higher and other sun protection measures including: limit time in the sun, especially from 10 a.m.–2 p.m. wear long-sleeved shirts, pants, hats, and sunglasses
                                                                                    • Effective_time : 20130812
                                                                                      • Spl_product_data_elements ::
                                                                                          • 0 : OBAGI-C RX SYSTEM NORMAL-OILY SKIN INTERVENTION HYDROQUINONE, OCTINOXATE AND ZINC OXIDE OBAGI C RX SYSTEM C CLARIFYING SERUM HYDROQUINONE HYDROQUINONE HYDROQUINONE PROPYLENE GLYCOL WATER ASCORBIC ACID SODIUM LAURYL SULFATE PROPYLENE CARBONATE ALCOHOL DIPROPYLENE GLYCOL OBAGI-C RX SYSTEM C-THERAPY Skin Lightening with Vitamins C and E HYDROQUINONE HYDROQUINONE HYDROQUINONE EDETATE DISODIUM PPG-2 MYRISTYL ETHER PROPIONATE TROLAMINE SALICYLATE SODIUM LAURYL SULFATE CETYL ALCOHOL GLYCERIN LACTIC ACID .ALPHA.-TOCOPHEROL ACETATE ASCORBIC ACID SODIUM METABISULFITE WATER METHYLPARABEN PROPYLPARABEN BUTYLATED HYDROXYTOLUENE PHENYL TRIMETHICONE OBAGI-C RX SYSTEM SUN SHIELD BROAD SPECTRUM SPF 50MATTE SUNSCREEN OCTINOXATE AND ZINC OXIDE OCTINOXATE OCTINOXATE ZINC OXIDE ZINC OXIDE CYCLOMETHICONE 5 WATER GLYCERIN PHENOXYETHANOL PEG-10 DIMETHICONE (600 CST) PENTYLENE GLYCOL STEARYL ALCOHOL POLYOXYL 20 CETOSTEARYL ETHER PHENYL TRIMETHICONE PEG-40 STEARATE DIMETHICONE SODIUM DIHYDROXYCETYL PHOSPHATE HYDROGENATED PALM GLYCERIDES CITRIC ACID MONOHYDRATE CETOSTEARYL ALCOHOL .ALPHA.-TOCOPHEROL ACETATE 1,2-HEXANEDIOL CAPRYLYL GLYCOL TROPOLONE CHLORPHENESIN XANTHAN GUM POTASSIUM SORBATE SODIUM BENZOATE TETRAHEXYLDECYL ASCORBATE UBIDECARENONE EDETATE DISODIUM METHYLISOTHIAZOLINONE HYDROXYETHYL ACRYLATE/SODIUM ACRYLOYLDIMETHYL TAURATE COPOLYMER (45000 MPA.S AT 1%) SQUALANE POLYSORBATE 60 SODIUM POLYACRYLATE (2500000 MW) OBAGI-C RX SYSTEM C-CLEANSINGWITH VITAMIN C inert WATER GLYCERIN PHENOXYETHANOL ETHYLPARABEN ISOBUTYLPARABEN BUTYLPARABEN PROPYLPARABEN METHYLPARABEN ASCORBIC ACID SODIUM LAUROYL OAT AMINO ACIDS COCAMIDOPROPYL BETAINE SODIUM LAURETH-3 SULFATE ALOE VERA LEAF SODIUM CHLORIDE ALFALFA CHAMOMILE XANTHAN GUM D&C RED NO. 33 FD&C YELLOW NO. 5 OBAGI-C RX SYSTEM C-BALANCING TONERFOR NORMAL TO OILY SKIN inert WATER METHYLPARABEN PHENOXYETHANOL PROPYLENE GLYCOL ALOE VERA LEAF HAMAMELIS VIRGINIANA TOP WATER BENZALKONIUM CHLORIDE SODIUM PYRROLIDONE CARBOXYLATE POLYQUATERNIUM-10 (400 MPA.S At 2%)
                                                                                        • Purpose ::
                                                                                            • 0 : Active ingredients Purpose Octinoxate 7.5% Sunscreen Zinc Oxide 10.5% Sunscreen
                                                                                          • Storage_and_handling ::
                                                                                              • 0 : Other information store at controlled room temperature: 15°C–25°C (59°F–77°F) protect this product from excessive heat and direct sun
                                                                                            • Keep_out_of_reach_of_children ::
                                                                                                • 0 : Keep out of reach of children.
                                                                                                  • 1 : Keep out of reach of children.
                                                                                                    • 2 : Keep out of reach of children. If swallowed, get medical help or contact a Poison Control Center right away.
                                                                                                  • Warnings ::
                                                                                                      • 0 : Warnings Avoid getting into eyes. For external use only. Keep out of reach of children.
                                                                                                        • 1 : Warnings Avoid getting into eyes. For external use only. Keep out of reach of children.
                                                                                                          • 2 : Warnings Avoid contact with eyes, nose, mouth, or lips. In case of accidental contact, patient should rinse eyes thoroughly with water and contact physician. Sunscreen use is an essential aspect of hydroquinone therapy because even minimal sunlight exposure sustains melanocytic activity.
                                                                                                            • 3 : Warnings Avoid contact with eyes, nose, mouth, or lips. In case of accidental contact, patient should rinse eyes thoroughly with water and contact physician. Sunscreen use is an essential aspect of hydroquinone therapy because even minimal sunlight exposure sustains melanocytic activity. Contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.
                                                                                                              • 4 : Warnings For external use only Do not use on damaged or broken skin Stop use and ask a doctor if rash occurs When using this product keep out of eyes. Rinse with water to remove. Keep out of reach of children. If swallowed, get medical help or contact a Poison Control Center right away.
                                                                                                            • Active_ingredient_table ::
                                                                                                                • 0 :
                                                                                                                  Active ingredients Purpose
                                                                                                                  Octinoxate 7.5% Sunscreen
                                                                                                                  Zinc Oxide 10.5% Sunscreen
                                                                                                              • Set_id : 36b030cc-024d-43f1-89b4-8d121f62aeff

Drug Labelling

  • 3 ::
      • Package_label_principal_display_panel ::
          • 0 : package label
        • Active_ingredient ::
            • 0 : glycerin
          • Warnings ::
              • 0 : ・Stop using the product when you have skin problems or the product disagrees with your skin ・Stop using the product immediately and consult a dermatologist if you have redness, swelling, itching or irritation on the skin while or after using the product. ・If the product gets into the eyes, don't rub but rinse with water. ・Don't place the product in any place where it will be subjected to extremely high or low temperatures or direct sunlight.
            • Inactive_ingredient ::
                • 0 : water, ethanol, sodium citrate, aminolevulinic acid hcl
              • Effective_time : 20141208
                • Openfda ::
                    • Manufacturer_name ::
                        • 0 : General Bio Co., Ltd.
                      • Unii ::
                          • 0 : PDC6A3C0OX
                        • Product_type ::
                            • 0 : HUMAN OTC DRUG
                          • Spl_set_id ::
                              • 0 : c5fe26fe-2a2d-4b8a-b7aa-d279c56ce5fa
                            • Route ::
                                • 0 : TOPICAL
                              • Generic_name ::
                                  • 0 : GLYCERIN
                                • Brand_name ::
                                    • 0 : P9 PHOTO CLEANSER
                                  • Pharm_class_cs ::
                                      • 0 : Glycerol [Chemical/Ingredient]
                                        • 1 : Allergens [Chemical/Ingredient]
                                      • Pharm_class_pe ::
                                          • 0 : Cell-mediated Immunity [PE]
                                            • 1 : Increased IgG Production [PE]
                                              • 2 : Increased Histamine Release [PE]
                                            • Product_ndc ::
                                                • 0 : 69422-4001
                                              • Pharm_class_epc ::
                                                  • 0 : Non-Standardized Chemical Allergen [EPC]
                                                • Substance_name ::
                                                    • 0 : GLYCERIN
                                                  • Spl_id ::
                                                      • 0 : f610c1d9-3e70-47cb-93f5-fd3b40b62246
                                                    • Application_number ::
                                                        • 0 : part347
                                                      • Is_original_packager ::
                                                          • 0 : 1
                                                        • Nui ::
                                                            • 0 : N0000185001
                                                              • 1 : N0000175629
                                                                • 2 : N0000171131
                                                                  • 3 : N0000185370
                                                                    • 4 : N0000006566
                                                                      • 5 : N0000184306
                                                                    • Package_ndc ::
                                                                        • 0 : 69422-4001-1
                                                                  • Keep_out_of_reach_of_children ::
                                                                      • 0 : keep out of reach of the children
                                                                    • Spl_product_data_elements ::
                                                                        • 0 : P9 PHOTO CLEANSER GLYCERIN GLYCERIN GLYCERIN WATER SODIUM CITRATE AMINOLEVULINIC ACID HYDROCHLORIDE
                                                                      • Set_id : c5fe26fe-2a2d-4b8a-b7aa-d279c56ce5fa
                                                                        • Dosage_and_administration ::
                                                                            • 0 : for external use only
                                                                          • Version : 1
                                                                            • Purpose ::
                                                                                • 0 : skin protectant
                                                                              • Id : f610c1d9-3e70-47cb-93f5-fd3b40b62246
                                                                                • Indications_and_usage ::
                                                                                    • 0 : apply proper amount to the skin and massage and wash away with warm water

Drug Labelling

  • 4 ::
      • Package_label_principal_display_panel ::
          • 0 : PACKAGE LABEL Label Image for 53808-1006 0.125mg Label Image for 0.125mg
        • Openfda ::
            • Manufacturer_name ::
                • 0 : State of Florida DOH Central Pharmacy
              • Unii ::
                  • 0 : 73K4184T59
                • Product_type ::
                    • 0 : HUMAN PRESCRIPTION DRUG
                  • Rxcui ::
                      • 0 : 197604
                    • Spl_set_id ::
                        • 0 : b69e2d2b-725c-4f2c-912d-d068da5c0f31
                      • Route ::
                          • 0 : ORAL
                        • Generic_name ::
                            • 0 : DIGOXIN
                          • Brand_name ::
                              • 0 : DIGOXIN
                            • Pharm_class_cs ::
                                • 0 : Cardiac Glycosides [Chemical/Ingredient]
                              • Product_ndc ::
                                  • 0 : 53808-1006
                                • Original_packager_product_ndc ::
                                    • 0 : 49884-514
                                  • Substance_name ::
                                      • 0 : DIGOXIN
                                    • Spl_id ::
                                        • 0 : fa8c4fad-1802-44b5-9edc-4f45659dee69
                                      • Application_number ::
                                          • 0 : NDA020405
                                        • Nui ::
                                            • 0 : N0000175568
                                              • 1 : N0000008157
                                            • Pharm_class_epc ::
                                                • 0 : Cardiac Glycoside [EPC]
                                              • Package_ndc ::
                                                  • 0 : 53808-1006-1
                                            • Carcinogenesis_and_mutagenesis_and_impairment_of_fertility ::
                                                • 0 : 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Digoxin showed no genotoxic potential in in vitro studies (Ames test and mouse lymphoma). No data are available on the carcinogenic potential of digoxin, nor have studies been conducted to assess its potential to affect fertility.
                                              • Pregnancy ::
                                                  • 0 : 8.1 Pregnancy
                                                • Pharmacokinetics ::
                                                    • 0 : 12.3 Pharmacokinetics Note: The following data are from studies performed in adults, unless otherwise stated. Absorption: Following oral administration, peak serum concentrations of digoxin occur at 1 to 3 hours. Absorption of digoxin from DIGOXIN Tablets has been demonstrated to be 60-80% complete compared to an identical intravenous dose of digoxin (absolute bioavailability). When DIGOXIN Tablets are taken after meals, the rate of absorption is slowed, but the total amount of digoxin absorbed is usually unchanged. When taken with meals high in bran fiber, however, the amount absorbed from an oral dose may be reduced. Comparisons of the systemic availability and equivalent doses for oral preparations of DIGOXIN are shown in Dosage and Administration (2.6). Digoxin is a substrate for P-glycoprotein. As an efflux protein on the apical membrane of enterocytes, P-glycoprotein may limit the absorption of digoxin. In some patients, orally administered digoxin is converted to inactive reduction products (e.g., dihydrodigoxin) by colonic bacteria in the gut. Data suggest that 1 in 10 patients treated with digoxin tablets, colonic bacteria will degrade 40% or more of the ingested dose. As a result, certain antibiotics may increase the absorption of digoxin in such patients. Although inactivation of these bacteria by antibiotics is rapid, the serum digoxin concentration will rise at a rate consistent with the elimination half-life of digoxin. Serum digoxin concentration relates to the extent of bacterial inactivation, and may be as much as doubled in some cases [see Drug Interactions (7.2)]. Patients with malabsorption syndromes (e.g., short bowel syndrome, celiac sprue, jejunoileal bypass) may have a reduced ability to absorb orally administered digoxin. Distribution: Following drug administration, a 6-8 hour tissue distribution phase is observed. This is followed by a much more gradual decline in the serum concentration of the drug, which is dependent on the elimination of digoxin from the body. The peak height and slope of the early portion (absorption/distribution phases) of the serum concentration-time curve are dependent upon the route of administration and the absorption characteristics of the formulation. Clinical evidence indicates that the early high serum concentrations do not reflect the concentration of digoxin at its site of action, but that with chronic use, the steady-state post-distribution serum concentrations are in equilibrium with tissue concentrations and correlate with pharmacologic effects. In individual patients, these post-distribution serum concentrations may be useful in evaluating therapeutic and toxic effects [see Dosage and Administration (2.1)]. Digoxin is concentrated in tissues and therefore has a large apparent volume of distribution (approximately 475-500 L). Digoxin crosses both the blood-brain barrier and the placenta. At delivery, the serum digoxin concentration in the newborn is similar to the serum concentration in the mother. Approximately 25% of digoxin in the plasma is bound to protein. Serum digoxin concentrations are not significantly altered by large changes in fat tissue weight, so that its distribution space correlates best with lean (i.e., ideal) body weight, not total body weight. Metabolism: Only a small percentage (13%) of a dose of digoxin is metabolized in healthy volunteers. The urinary metabolites, which include dihydrodigoxin, digoxigenin bisdigitoxoside, and their glucuronide and sulfate conjugates, are polar in nature and are postulated to be formed via hydrolysis, oxidation, and conjugation. The metabolism of digoxin is not dependent upon the cytochrome P-450 system, and digoxin is not known to induce or inhibit the cytochrome P-450 system. Excretion: Elimination of digoxin follows first-order kinetics (that is, the quantity of digoxin eliminated at any time is proportional to the total body content). Following intravenous administration to healthy volunteers, 50-70% of a digoxin dose is excreted unchanged in the urine. Renal excretion of digoxin is proportional to creatinine clearance and is largely independent of urine flow. In healthy volunteers with normal renal function, digoxin has a half-life of 1.5-2 days. The half-life in anuric patients is prolonged to 3.5-5 days. Digoxin is not effectively removed from the body by dialysis, exchange transfusion, or during cardiopulmonary bypass because most of the drug is bound to extravascular tissues. Special Populations: Geriatrics: Because of age-related declines in renal function, elderly patients would be expected to eliminate digoxin more slowly than younger subjects. Elderly patients may also exhibit a lower volume of distribution of digoxin due to age-related loss of lean muscle mass. Thus, the dosage of digoxin should be carefully selected and monitored in elderly patients [see Use in Specific Populations (8.5)]. Gender: In a study of 184 patients, the clearance of digoxin was 12% lower in female than in male patients. This difference is not likely to be clinically important. Hepatic Impairment: Because only a small percentage (approximately 13%) of a dose of digoxin undergoes metabolism, hepatic impairment would not be expected to significantly alter the pharmacokinetics of digoxin. In a small study, plasma digoxin concentration profiles in patients with acute hepatitis generally fell within the range of profiles in a group of healthy subjects. No dosage adjustments are recommended for patients with hepatic impairment; however, serum digoxin concentrations should be used as appropriate to help guide dosing in these patients. Renal Impairment: Since the clearance of digoxin correlates with creatinine clearance, patients with renal impairment generally demonstrate prolonged digoxin elimination half-lives and greater exposures to digoxin. Therefore, titrate carefully in these patients based on clinical response, and based on monitoring of serum digoxin concentrations, as appropriate. Race: The impact of race differences on digoxin pharmacokinetics have not been formally studied. Because digoxin is primarily eliminated as unchanged drug via the kidney and because there are no important differences in creatinine clearance among races, pharmacokinetic differences due to race are not expected. Drug-drug Interactions Based on literature reports no significant changes in digoxin exposure were reported when digoxin was co-administered with the following drugs: alfuzosin, aliskiren, amlodipine, aprepitant, argatroban, aspirin, atorvastatin, benazepril, bisoprolol, black cohosh, bosentan, candesartan, citalopram, clopidogrel, colesevelam, dipyridamole, disopyramide, donepezil, doxazosin, dutasteride, echinacea, enalapril, eprosartan, ertapenem, escitalopram, esmolol, ezetimibe, famciclovir, felodipine, finasteride, flecainide, fluvastatin, fondaparinux, galantamine, gemifloxacin, grapefruit juice, irbesartan, isradipine, ketorlac, levetiracetam, levofloxacin, lisinopril, losartan, lovastatin, meloxicam, mexilitine, midazolam, milk thistle, moexipril, montelukast, moxifloxacin, mycophenolate, nateglinide, nesiritide, nicardipine, nisoldipine, olmesartan, orlistat, pantoprazole, paroxetine, perindopril, pioglitazone, pravastatin, prazosin, procainamide, quinapril, raloxifene, ramipril, repaglinide, rivastigmine, rofecoxib, ropinirole, rosiglitazone, rosuvastatin, sertraline, sevelamer, simvastatin, sirolimus, solifenacin, tamsulosin, tegaserod, terbinafine, tiagabine, ticlopidine, tigecycline, topiramate, torsemide, tramadol, trandolapril, triamterene, trospium, trovafloxacin, valacyclovir, valsartan, varenicline, voriconazole, zaleplon, zolpidem
                                                  • Drug_interactions ::
                                                      • 0 : 7 DRUG INTERACTIONS Digoxin has a narrow therapeutic index, increased monitoring of serum digoxin concentrations and for potential signs and symptoms of clinical toxicity is necessary when initiating, adjusting, or discontinuing drugs that may interact with digoxin. Prescribers should consult the prescribing information of any drug which is co-prescribed with digoxin for potential drug interaction information. •PGP Inducers/Inhibitors: Drugs that induce or inhibit PGP have the potential to alter digoxin pharmacokinetics. (7.1) •Many drug interactions. The potential for drug-drug interactions must be considered prior to and during drug therapy. See full prescribing information. (7.3, 12.3) 7.1 P-Glycoprotein (PGP) Inducers/Inhibitors Digoxin is a substrate of P-glycoprotein. Drugs that induce or inhibit P-glycoprotein in intestine or kidney have the potential to alter digoxin pharmacokinetics. 7.2 Pharmacokinetic Drug Interactions NA – Not available/reported Digoxin concentrations increased greater than 50% Digoxin Serum Concentration Increase Digoxin AUC Increase Recommendations Amiodarone 70% NA Measure serum digoxin concentrations before initiating concomitant drugs. Reduce digoxin concentrations by decreasing dose by approximately 30-50% or by modifying the dosing frequency and continue monitoring. Captopril 58% 39% Clarithromycin NA 70% Dronedarone NA 150% Gentamicin 129-212% NA Erythromycin 100% NA Itraconazole 80% NA Nitrendipine 57% 15% Propafenone NA 60-270% Quinidine 100% NA Ranolazine 50% NA Ritonavir NA 86% Tetracycline 100% NA Verapamil 50-75% NA Digoxin concentrations increased less than 50% Atorvastatin 22% 15% Measure serum digoxin concentrations before initiating concomitant drugs. Reduce digoxin concentrations by decreasing the dose by approximately 15-30% or by modifying the dosing frequency and continue monitoring. Carvedilol 16% 14% Diltiazem 20% NA Indomethacin 40% NA Nefazodone 27% 15% Nifedipine 45% NA Propantheline 24% 24% Quinine NA 33% Saquinavir 27% 49% Spironolactone 25% NA Telmisartan 20-49% NA Tolvaptan 30% NA Trimethoprim 22-28% NA Digoxin concentrations increased, but magnitude is unclear Alprazolam, azithromycin, cyclosporine, diclofenac, diphenoxylate, epoprostenol, esomeprazole, ibuprofen, ketoconazole, lansoprazole, metformin, omeprazole, rabeprazole, Measure serum digoxin concentrations before initiating concomitant drugs. Continue monitoring and reduce digoxin dose as necessary. Digoxin concentrations decreased Acarbose, activated charcoal, albuterol, antacids, certain cancer chemotherapy or radiation therapy, cholestyramine, colestipol, extenatide, kaolin-pectin, meals high in bran, metoclopramide, miglitol, neomycin, penicillamine, phenytoin, rifampin, St. John’s Wort, sucralfate, sulfasalazine Measure serum digoxin concentrations before initiating concomitant drugs. Continue monitoring and increase digoxin dose by approximately 20-40% as necessary. No significant Digoxin exposure changes Please refer to section 12 for a complete list of drugs which were studied but reported no significant changes on digoxin exposure. No additional actions are required. 7.3 Potentially Significant Pharmacodynamic Drug Interactions Because of considerable variability of pharmacodynamic interactions, the dosage of digoxin should be individualized when patients receive these medications concurrently. Drugs that Affect Renal Function A decline in GFR or tubular secretion, as from ACE inhibitors, angiotensin receptor blockers, nonsteroidal anti-inflammatory drugs [NSAIDS], COX-2 inhibitors may impair the excretion of digoxin. Antiarrthymics Dofetilide Concomitant administration with digoxin was associated with a higher rate of torsades de pointes Sotalol Proarrhythmic events were more common in patients receiving sotalol and digoxin than on either alone; it is not clear whether this represents an interaction or is related to the presence of CHF, a known risk factor for proarrhythmia, in patients receiving digoxin. Dronedarone Sudden death was more common in patients receiving digoxin with dronedarone than on either alone; it is not clear whether this represents an interaction or is related to the presence of advanced heart disease, a known risk factor for sudden death in patients receiving digoxin. Parathyroid Hormone Analog Teriparatide Sporadic case reports have suggested that hypercalcemia may predispose patients to digitalis toxicity. Teriparatide transiently increases serum calcium. Thyroid supplement Thyroid Treatment of hypothyroidism in patients taking digoxin may increase the dose requirements of digoxin. Sympathomimetics Epinephrine Norepinephrine Dopamine Can increase the risk of cardiac arrhythmias Neuromuscular Blocking Agents Succinylcholine May cause sudden extrusion of potassium from muscle cells causing arrhythmias in patients taking digoxin. Supplements Calcium If administered rapidly by intravenous route, can produce serious arrhythmias in digitalized patients. Beta-adrenergic blockers and calcium channel blockers Additive effects on AV node conduction can result in bradycardia and advanced or complete heart block. 7.4 Drug/Laboratory Test Interactions Endogenous substances of unknown composition (digoxin-like immunoreactive substances, [DLIS]) can interfere with standard radioimmunoassays for digoxin. The interference most often causes results to be falsely positive or falsely elevated, but sometimes it causes results to be falsely reduced. Some assays are more subject to these failings than others. Several LC/MS/MS methods are available that may provide less susceptibility to DLIS interference. DLIS are present in up to half of all neonates and in varying percentages of pregnant women, patients with hypertrophic cardiomyopathy, patients with renal or hepatic dysfunction, and other patients who are volume-expanded for any reason. The measured levels of DLIS (as digoxin equivalents) are usually low (0.2-0.4 ng/mL), but sometimes they reach levels that would be considered therapeutic or even toxic. In some assays, spironolactone, canrenone, and potassium canrenoate may be falsely detected as digoxin, at levels up to 0.5 ng/mL. Some traditional Chinese and Ayurvedic medicine substances like Chan Su, Siberian Ginseng, Asian Ginseng, Ashwagandha or Dashen, can cause similar interference. Spironolactone and DLIS are much more extensively protein-bound than digoxin. As a result, assays of free digoxin levels in protein-free ultrafiltrate (which tend to be about 25% less than total levels, consistent with the usual extent of protein binding) are less affected by spironolactone or DLIS. It should be noted that ultrafiltration does not solve all interference problems with alternative medicines. The use of an LC/MS/MS method may be the better option according to the good results it provides, especially in terms of specificity and limit of quantization.
                                                    • Id : fa8c4fad-1802-44b5-9edc-4f45659dee69
                                                      • Indications_and_usage ::
                                                          • 0 : DIGOXIN is a cardiac glycoside indicated for: •Treatment of mild to moderate heart failure in adults. (1.1) •Increasing myocardial contractility in pediatric patients with heart failure. (1.2) •Control of resting ventricular rate in patients with chronic atrial fibrillation in adults. (1.3) 1.1 Heart Failure in Adults DIGOXIN is indicated for the treatment of mild to moderate heart failure in adults. DIGOXIN increases left ventricular ejection fraction and improves heart failure symptoms as evidenced by improved exercise capacity and decreased heart failure-related hospitalizations and emergency care, while having no effect on mortality. Where possible, DIGOXIN should be used in combination with a diuretic and an angiotensin-converting enzyme (ACE) inhibitor. 1.2 Heart Failure in Pediatric Patients Digoxin increases myocardial contractility in pediatric patients with heart failure. 1.3 Atrial Fibrillation in Adults DIGOXIN is indicated for the control of ventricular response rate in adult patients with chronic atrial fibrillation.
                                                        • Description ::
                                                            • 0 : 11 DESCRIPTION DIGOXIN (digoxin) is one of the cardiac (or digitalis) glycosides, a closely related group of drugs having in common specific effects on the myocardium. These drugs are found in a number of plants. Digoxin is extracted from the leaves of Digitalis lanata. The term “digitalis” is used to designate the whole group of glycosides. The glycosides are composed of 2 portions: a sugar and a cardenolide (hence “glycosides”). Digoxin is described chemically as (3β,5β,12β)-3-[(O-2,6-dideoxy-β-D-ribo-hexopyranosyl-(1→4)-O-2,6-dideoxy-β-D-ribo-hexopyranosyl-(1→4)-2,6-dideoxy-β-D-ribo-hexopyranosyl)oxy]-12,14-dihydroxy-card-20(22)-enolide. Its molecular formula is C41H64O14, its molecular weight is 780.95, and its structural formula is: Digoxin exists as odorless white crystals that melt with decomposition above 230°C. The drug is practically insoluble in water and in ether; slightly soluble in diluted (50%) alcohol and in chloroform; and freely soluble in pyridine. DIGOXIN is supplied as 125 mcg (scored) and 250 mcg (scored) tablets for oral administration. Each tablet contains the labeled amount of digoxin USP and the following inactive ingredients: corn and potato starches, lactose and magnesium stearate. The 125 mcg tablets contain D&C Yellow No. 10 and FD&C Yellow No. 6. Structural Formula
                                                          • Spl_unclassified_section ::
                                                              • 0 : LANOXIN is a registered trademark of GlaxoSmithKline Distributed By Par Pharmaceutical Companies, Inc. Spring Valley, NY 10977 Manufactured by DSM Pharmaceuticals, Inc. Greenville, NC 27834 This Product was Repackaged By: State of Florida DOH Central Pharmacy 104-2 Hamilton Park Drive Tallahassee, FL 32304 USA
                                                            • Labor_and_delivery ::
                                                                • 0 : 8.2 Labor and Delivery There are not enough data from clinical trials to determine the safety and efficacy of digoxin during labor and delivery.
                                                              • How_supplied_table ::
                                                                  • 0 :
NDC Strength Quantity/Form Color Source Prod. Code
53808-1006-1 0.125 MG 30 Tablets in a Blister Pack YELLOW 49884-514
  • Pharmacodynamics_table ::
      • 0 :
        Table 7. Times to Onset of Pharmacologic Effect and to Peak Effect of Preparations of DIGOXIN
        a Documented for ventricular response rate in atrial fibrillation, inotropic effects and electrocardiographic changes. b Depending upon rate of infusion.
        Product Time to Onset of Effecta Time to Peak Effecta
        DIGOXIN Tablets 0.5-2 hours 2-6 hours
        DIGOXIN Injection/IV 5-30 minutesb 1-4 hours
    • Contraindications ::
        • 0 : 4 CONTRAINDICATIONS DIGOXIN is contraindicated in patients with: •Ventricular fibrillation [see Warnings and Precautions (5.1)] •Known hypersensitivity to digoxin (reactions seen include unexplained rash, swelling of the mouth, lips or throat or a difficulty in breathing). A hypersensitivity reaction to other digitalis preparations usually constitutes a contraindication to digoxin. •Ventricular fibrillation. (4) •Known hypersensitivity to digoxin or other forms of digitalis. (4)
      • Version : 1
        • Adverse_reactions ::
            • 0 : 6 ADVERSE REACTIONS The following adverse reactions are included in more detail in the Warnings and Precautions section of the label: •Cardiac arrhythmias [see Warnings and Precautions (5.1, 5.2)] •Digoxin Toxicity [see Warnings and Precautions (5.3)] The overall incidence of adverse reactions with digoxin has been reported as 5-20%, with 15-20% of adverse events considered serious. Cardiac toxicity accounts for about one-half, gastrointestinal disturbances for about one-fourth, and CNS and other toxicity for about one-fourth of these adverse events. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact PAR Pharmaceutical, Inc at 1-800-828-9393 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. In general, the adverse reactions of DIGOXIN are dose-dependent and occur at doses higher than those needed to achieve a therapeutic effect. Hence, adverse reactions are less common when DIGOXIN is used within the recommended dose range, is maintained within the therapeutic serum concentration range, and when there is careful attention to concurrent medications and conditions. In the DIG trial (a trial investigating the effect of digoxin on mortality and morbidity in patients with heart failure), the incidence of hospitalization for suspected digoxin toxicity was 2% in patients taking DIGOXIN compared to 0.9% in patients taking placebo [see Clinical Studies (14.1)]. The overall incidence of adverse reactions with digoxin has been reported as 5-20%, with 15-20% of adverse events considered serious. Cardiac toxicity accounts for about one-half, gastrointestinal disturbances for about one-fourth, and CNS and other toxicity for about one-fourth of these adverse events. Gastrointestinal: In addition to nausea and vomiting, the use of digoxin has been associated with abdominal pain, intestinal ischemia, and hemorrhagic necrosis of the intestines. CNS: Digoxin can cause headache, weakness, dizziness, apathy, confusion, and mental disturbances (such as anxiety, depression, delirium, and hallucination). Other: Gynecomastia has been occasionally observed following the prolonged use of digoxin. Thrombocytopenia and maculopapular rash and other skin reactions have been rarely observed.
          • Information_for_patients ::
              • 0 : 17 PATIENT COUNSELING INFORMATION •Advise patients that digoxin is a cardiac glycoside used to treat heart failure and heart arrhythmias. •Instruct patients to take this medication as directed by their physician. •Advise patients that many drugs can interact with DIGOXIN. Instruct patients to inform their doctor and pharmacist if they are taking any over the counter medications, including herbal medication, or are started on a new prescription. •Advise patient that blood tests will be necessary to ensure that their DIGOXIN dose is appropriate for them. •Advise patients to contact their doctor or a health care professional if they experience nausea, vomiting, persistent diarrhea, confusion, weakness, or visual disturbances (including blurred vision, green-yellow color disturbances, halo effect) as these could be signs that the dose of DIGOXIN may be too high. •Advise parents or caregivers that the symptoms of having too high DIGOXIN doses may be difficult to recognize in infants and pediatric patients. Symptoms such as weight loss, failure to thrive in infants, abdominal pain, and behavioral disturbances may be indications of digoxin toxicity. •Suggest to the patient to monitor and record their heart rate and blood pressure daily. •Instruct women of childbearing potential who become or are planning to become pregnant to consult a physician prior to initiation or continuing therapy with DIGOXIN.
            • Dosage_forms_and_strengths ::
                • 0 : 3 DOSAGE FORMS AND STRENGTHS Scored Tablets: 125 mcg are yellow, round, scored tablets with “Y3B” imprinted on one side.. Scored Tablets: 250 mcg are white, round, scored tablets with “X3A” imprinted on one side. Scored Tablets: 62.5 and 187.5 mcg. Scored Tablets 125 and 250 mcg (3)
              • Drug_interactions_table ::
                  • 0 :
                    NA – Not available/reported
                    Digoxin concentrations increased greater than 50%
                    Digoxin Serum Concentration Increase Digoxin AUC Increase Recommendations
                    Amiodarone 70% NA Measure serum digoxin concentrations before initiating concomitant drugs. Reduce digoxin concentrations by decreasing dose by approximately 30-50% or by modifying the dosing frequency and continue monitoring.
                    Captopril 58% 39%
                    Clarithromycin NA 70%
                    Dronedarone NA 150%
                    Gentamicin 129-212% NA
                    Erythromycin 100% NA
                    Itraconazole 80% NA
                    Nitrendipine 57% 15%
                    Propafenone NA 60-270%
                    Quinidine 100% NA
                    Ranolazine 50% NA
                    Ritonavir NA 86%
                    Tetracycline 100% NA
                    Verapamil 50-75% NA
                    Digoxin concentrations increased less than 50%
                    Atorvastatin 22% 15% Measure serum digoxin concentrations before initiating concomitant drugs. Reduce digoxin concentrations by decreasing the dose by approximately 15-30% or by modifying the dosing frequency and continue monitoring.
                    Carvedilol 16% 14%
                    Diltiazem 20% NA
                    Indomethacin 40% NA
                    Nefazodone 27% 15%
                    Nifedipine 45% NA
                    Propantheline 24% 24%
                    Quinine NA 33%
                    Saquinavir 27% 49%
                    Spironolactone 25% NA
                    Telmisartan 20-49% NA
                    Tolvaptan 30% NA
                    Trimethoprim 22-28% NA
                    Digoxin concentrations increased, but magnitude is unclear
                    Alprazolam, azithromycin, cyclosporine, diclofenac, diphenoxylate, epoprostenol, esomeprazole, ibuprofen, ketoconazole, lansoprazole, metformin, omeprazole, rabeprazole, Measure serum digoxin concentrations before initiating concomitant drugs. Continue monitoring and reduce digoxin dose as necessary.
                    Digoxin concentrations decreased
                    Acarbose, activated charcoal, albuterol, antacids, certain cancer chemotherapy or radiation therapy, cholestyramine, colestipol, extenatide, kaolin-pectin, meals high in bran, metoclopramide, miglitol, neomycin, penicillamine, phenytoin, rifampin, St. John’s Wort, sucralfate, sulfasalazine Measure serum digoxin concentrations before initiating concomitant drugs. Continue monitoring and increase digoxin dose by approximately 20-40% as necessary.
                    No significant Digoxin exposure changes
                    Please refer to section 12 for a complete list of drugs which were studied but reported no significant changes on digoxin exposure. No additional actions are required.
                    • 1 :
                      Drugs that Affect Renal Function A decline in GFR or tubular secretion, as from ACE inhibitors, angiotensin receptor blockers, nonsteroidal anti-inflammatory drugs [NSAIDS], COX-2 inhibitors may impair the excretion of digoxin.
                      Antiarrthymics Dofetilide Concomitant administration with digoxin was associated with a higher rate of torsades de pointes
                      Sotalol Proarrhythmic events were more common in patients receiving sotalol and digoxin than on either alone; it is not clear whether this represents an interaction or is related to the presence of CHF, a known risk factor for proarrhythmia, in patients receiving digoxin.
                      Dronedarone Sudden death was more common in patients receiving digoxin with dronedarone than on either alone; it is not clear whether this represents an interaction or is related to the presence of advanced heart disease, a known risk factor for sudden death in patients receiving digoxin.
                      Parathyroid Hormone Analog Teriparatide Sporadic case reports have suggested that hypercalcemia may predispose patients to digitalis toxicity. Teriparatide transiently increases serum calcium.
                      Thyroid supplement Thyroid Treatment of hypothyroidism in patients taking digoxin may increase the dose requirements of digoxin.
                      Sympathomimetics Epinephrine Norepinephrine Dopamine Can increase the risk of cardiac arrhythmias
                      Neuromuscular Blocking Agents Succinylcholine May cause sudden extrusion of potassium from muscle cells causing arrhythmias in patients taking digoxin.
                      Supplements Calcium If administered rapidly by intravenous route, can produce serious arrhythmias in digitalized patients.
                      Beta-adrenergic blockers and calcium channel blockers Additive effects on AV node conduction can result in bradycardia and advanced or complete heart block.
                  • Pediatric_use ::
                      • 0 : 8.4 Pediatric Use The safety and effectiveness of DIGOXIN in the control of ventricular rate in children with atrial fibrillation have not been established. The safety and effectiveness of DIGOXIN in the treatment of heart failure in children have not been established in adequate and well-controlled studies. However, in published literature of children with heart failure of various etiologies (e.g., ventricular septal defects, anthracycline toxicity, patent ductus arteriosus), treatment with digoxin has been associated with improvements in hemodynamic parameters and in clinical signs and symptoms. Newborn infants display considerable variability in their tolerance to digoxin. Premature and immature infants are particularly sensitive to the effects of digoxin, and the dosage of the drug must not only be reduced but must be individualized according to their degree of maturity.
                    • Dosage_and_administration ::
                        • 0 : DIGOXIN dose is based on patient-specific factors (age, lean body weight, renal function, etc.). See full prescribing information. Monitor for toxicity and therapeutic effect. (2) 2.1 Important Dosing and Administration Information In selecting a DIGOXIN dosing regimen, it is important to consider factors that affect digoxin blood levels (e.g., body weight, age, renal function, concomitant drugs) since toxic levels of digoxin are only slightly higher than therapeutic levels. Dosing can be either initiated with a loading dose followed by maintenance dosing if rapid titration is desired or initiated with maintenance dosing without a loading dose. Consider interruption or reduction in DIGOXIN digoxin dose prior to electrical cardioversion [see Warnings and Precautions (5.4)]. Use digoxin solution to obtain the appropriate dose in infants, young pediatric patients, or patients with very low body weight. 2.2 Loading Dosing Regimen in Adults and Pediatric Patients For adults and pediatric patients if a loading dosage is to be given, administer half the total loading dose initially, then ¼ the loading dose every 6-8 hours twice, with careful assessment of clinical response and toxicity before each dose. The recommended loading dose is displayed in Table 1. Table 1. Recommended DIGOXIN Oral Loading Dose mcg = microgram Age Total Oral Loading Dose (mcg/kg) Administer half the total loading dose initially, then ¼ the loading dose every 6 to 8 hours twice 5 to 10 years 20-45 Adults and pediatric patients over 10 years 10-15 2.3 Maintenance Dosing in Adults and Pediatric Patients Over 10 Years Old The maintenance dose is based on lean body weight, renal function, age, and concomitant products [see Clinical Pharmacology (12.3)]. The recommended starting maintenance dose in adults and pediatric patients over 10 years old with normal renal function is given in Table 2. Doses may be increased every 2 weeks according to clinical response, serum drug levels, and toxicity. Table 2. Recommended Starting DIGOXIN Maintenance Dosage in Adults and Pediatric Patients Over 10 Years Old mcg = microgram Age Total Oral Maintenance Dose, mcg/kg/day (given once daily) Adults and pediatric patients over 10 years 3.4-5.1 Table 3 provides the recommended (once daily) maintenance dose for adults and pediatric patients over 10 years old (to be given once daily) according to lean body weight and renal function. The doses are based on studies in adult patients with heart failure. Alternatively, the maintenance dose may be estimated by the following formula (peak body stores lost each day through elimination): Total Maintenance Dose = Loading Dose (i.e., Peak Body Stores) x % Daily Loss/100 (% Daily Loss = 14 + Creatinine clearance/5) Reduce the dose of DIGOXIN in patients whose lean weight is an abnormally small fraction of their total body mass because of obesity or edema. Table 3. Recommended Maintenance Dose (in micrograms given once daily) of DIGOXIN in Pediatric Patients Over 10 Years Old and Adults by Lean Body Weight and by Renal Functiona a Doses are rounded to the nearest dose possible using whole DIGOXIN tablets. Recommended doses approximately 30 percent lower than the calculated dose are designated with an *. Monitor digoxin levels in patients receiving these initial doses and increase dose if needed. b For adults, creatinine clearance was corrected to 70-kg body weight or 1.73 m2 body surface area. If only serum creatinine concentrations (Scr) are available, a corrected Ccr may be estimated in men as (140 – Age)/Scr. For women, this result should be multiplied by 0.85. For pediatric patients, the modified Schwartz equation may be used. The formula is based on height in cm and Scr in mg/dL where k is a constant. Ccr is corrected to 1.73 m2 body surface area. During the first year of life, the value of k is 0.33 for pre-term babies and 0.45 for term infants. The k is 0.55 for pediatric patients and adolescent girls and 0.7 for adolescent boys. GFR (mL/min/1.73 m2) = (k x Height)/Scr c If no loading dose administered. d The doses listed assume average body composition. Corrected Creatinine Clearanceb Lean Body Weightd Number of Days Before Steady State Achievedc kg 40 50 60 70 80 90 100 10 mL/min 62.5* 125 125 187.5 187.5 187.5 250 19 20 mL/min 125 125 125 187.5 187.5 250 250 16 30 mL/min 125 125 187.5 187.5 250 250 312.5 14 40 mL/min 125 187.5 187.5 250 250 312.5 312.5 13 50 mL/min 125 187.5 187.5 250 250 312.5 312.5 12 60 mL/min 125 187.5 250 250 312.5 312.5 375 11 70 mL/min 187.5 187.5 250 250 312.5 375 375 10 80 mL/min 187.5 187.5 250 312.5 312.5 375 437.5 9 90 mL/min 187.5 250 250 312.5 375 437.5 437.5 8 100 mL/min 187.5 250 312.5 312.5 375 437.5 500 7 2.4 Maintenance Dosing in Pediatric Patients Less Than 10 Years Old The starting maintenance dose for heart failure in pediatric patients less than 10 years old is based on lean body weight, renal function, age, and concomitant products [see Clinical Pharmacology (12.3)]. The recommended starting maintenance dose for pediatric patients between 5 years and 10 years old is given in Table 4. These recommendations assume the presence of normal renal function. Table 4. Recommended Starting DIGOXIN Oral Maintenance Dosage in Pediatric Patients between 5 and 10 Years Old Age Oral Maintenance Dose, mcg/kg/dose 5 years to 10 years 3.2-6.4 Twice daily Table 5 provides average daily maintenance dose requirements for pediatric patients between 5 and 10 years old (to be given twice daily) with heart failure based on age, lean body weight, and renal function. Table 5. Recommended Maintenance Dose (in micrograms given TWICE daily) of DIGOXIN in Pediatric Patients between 5 and 10 Years of Agea Based upon Lean Body Weight and Renal Functiona,b a Recommended are doses to be given twice daily. b The doses are rounded to the nearest dose possible using whole DIGOXIN tablets. Recommended doses approximately 30 percent lower than the calculated dose are designated with an *. Monitor digoxin levels in patients receiving these initial doses and increase dose if needed. c The modified Schwartz equation may be used to estimate creatinine clearance. See footnote b under Table 3. d If no loading dose administered. Corrected Creatinine Clearancec Lean Body Weight Number of Days Before Steady State Achievedd kg 20 30 40 50 60 10 mL/min - 62.5 62.5* 125 125 19 20 mL/min 62.5 62.5 125 125 125 16 30 mL/min 62.5 62.5* 125 125 187.5 14 40 mL/min 62.5 62.5* 125 187.5 187.5 13 50 mL/min 62.5 125 125 187.5 187.5 12 60 mL/min 62.5 125 125 187.5 250 11 70 mL/min 62.5 125 187.5 187.5 250 10 80 mL/min 62.5* 125 187.5 187.5 250 9 90 mL/min 62.5* 125 187.5 250 250 8 100 mL/min 62.5* 125 187.5 250 312.5 7 2.5 Monitoring to Assess Safety, Efficacy, and Therapeutic Blood Levels Monitor for signs and symptoms of digoxin toxicity and clinical response. Adjust dose based on toxicity, efficacy, and blood levels. Serum digoxin levels less than 0.5 ng/mL have been associated with diminished efficacy, while levels above 2 ng/mL have been associated with increased toxicity without increased benefit. Interpret the serum digoxin concentration in the overall clinical context, and do not use an isolated measurement of serum digoxin concentration as the basis for increasing or decreasing the DIGOXIN dose. Serum digoxin concentrations may be falsely elevated by endogenous digoxin-like substances [see Drug Interactions (7.4)]. If the assay is sensitive to these substances, consider obtaining a baseline digoxin level before starting DIGOXIN and correct post-treatment values by the reported baseline level. Obtain serum digoxin concentrations just before the next scheduled DIGOXIN dose or at least 6 hours after the last dose. The digoxin concentration is likely to be 10-25% lower when sampled right before the next dose (24 hours after dosing) compared to sampling 8 hours after dosing (using once-daily dosing). However, there will be only minor differences in digoxin concentrations using twice daily dosing whether sampling is done at 8 or 12 hours after a dose. 2.6 Switching from Intravenous Digoxin to Oral Digoxin When switching from intravenous to oral digoxin formulations, make allowances for differences in bioavailability when calculating maintenance dosages (see Table 6). Table 6. Comparison of the Systemic Availability and Equivalent Doses of Oral and Intravenous DIGOXIN Absolute Bioavailability Equivalent Doses (mcg) DIGOXIN Tablets 60-80% 62.5 125 250 500 DIGOXIN Intravenous Injection 100% 50 100 200 400
                      • Clinical_pharmacology_table ::
                          • 0 :
                            Table 7. Times to Onset of Pharmacologic Effect and to Peak Effect of Preparations of DIGOXIN
                            a Documented for ventricular response rate in atrial fibrillation, inotropic effects and electrocardiographic changes. b Depending upon rate of infusion.
                            Product Time to Onset of Effecta Time to Peak Effecta
                            DIGOXIN Tablets 0.5-2 hours 2-6 hours
                            DIGOXIN Injection/IV 5-30 minutesb 1-4 hours
                        • Effective_time : 20150103
                          • Mechanism_of_action ::
                              • 0 : 12.1 Mechanism of Action All of digoxin’s actions are mediated through its effects on Na-K ATPase. This enzyme, the “sodium pump,” is responsible for maintaining the intracellular milieu throughout the body by moving sodium ions out of and potassium ions into cells. By inhibiting Na-K ATPase, digoxin •causes increased availability of intracellular calcium in the myocardium and conduction system, with consequent increased inotropy, increased automaticity, and reduced conduction velocity •indirectly causes parasympathetic stimulation of the autonomic nervous system, with consequent effects on the sino-atrial (SA) and atrioventricular (AV) nodes •reduces catecholamine reuptake at nerve terminals, rendering blood vessels more sensitive to endogenous or exogenous catecholamines •increases baroreceptor sensitization, with consequent increased carotid sinus nerve activity and enhanced sympathetic withdrawal for any given increment in mean arterial pressure •increases (at higher concentrations) sympathetic outflow from the central nervous system (CNS) to both cardiac and peripheral sympathetic nerves •allows (at higher concentrations) progressive efflux of intracellular potassium, with consequent increase in serum potassium levels. The cardiologic consequences of these direct and indirect effects are an increase in the force and velocity of myocardial systolic contraction (positive inotropic action), a slowing of the heart rate (negative chronotropic effect), decreased conduction velocity through the AV node, and a decrease in the degree of activation of the sympathetic nervous system and renin-angiotensin system (neurohormonal deactivating effect).
                            • Geriatric_use ::
                                • 0 : 8.5 Geriatric Use The majority of clinical experience gained with digoxin has been in the elderly population. This experience has not identified differences in response or adverse effects between the elderly and younger patients. However, this drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, which should be based on renal function, and it may be useful to monitor renal function [see Dosage and Administration (2.1)].
                              • Clinical_pharmacology ::
                                  • 0 : 12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action All of digoxin’s actions are mediated through its effects on Na-K ATPase. This enzyme, the “sodium pump,” is responsible for maintaining the intracellular milieu throughout the body by moving sodium ions out of and potassium ions into cells. By inhibiting Na-K ATPase, digoxin •causes increased availability of intracellular calcium in the myocardium and conduction system, with consequent increased inotropy, increased automaticity, and reduced conduction velocity •indirectly causes parasympathetic stimulation of the autonomic nervous system, with consequent effects on the sino-atrial (SA) and atrioventricular (AV) nodes •reduces catecholamine reuptake at nerve terminals, rendering blood vessels more sensitive to endogenous or exogenous catecholamines •increases baroreceptor sensitization, with consequent increased carotid sinus nerve activity and enhanced sympathetic withdrawal for any given increment in mean arterial pressure •increases (at higher concentrations) sympathetic outflow from the central nervous system (CNS) to both cardiac and peripheral sympathetic nerves •allows (at higher concentrations) progressive efflux of intracellular potassium, with consequent increase in serum potassium levels. The cardiologic consequences of these direct and indirect effects are an increase in the force and velocity of myocardial systolic contraction (positive inotropic action), a slowing of the heart rate (negative chronotropic effect), decreased conduction velocity through the AV node, and a decrease in the degree of activation of the sympathetic nervous system and renin-angiotensin system (neurohormonal deactivating effect). 12.2 Pharmacodynamics The times to onset of pharmacologic effect and to peak effect of preparations of DIGOXIN are shown in Table 7. Table 7. Times to Onset of Pharmacologic Effect and to Peak Effect of Preparations of DIGOXIN a Documented for ventricular response rate in atrial fibrillation, inotropic effects and electrocardiographic changes. b Depending upon rate of infusion. Product Time to Onset of Effecta Time to Peak Effecta DIGOXIN Tablets 0.5-2 hours 2-6 hours DIGOXIN Injection/IV 5-30 minutesb 1-4 hours Hemodynamic Effects: Short- and long-term therapy with the drug increases cardiac output and lowers pulmonary artery pressure, pulmonary capillary wedge pressure, and systemic vascular resistance in patients with heart failure. These hemodynamic effects are accompanied by an increase in the left ventricular ejection fraction and a decrease in end-systolic and end-diastolic dimensions. ECG Changes: The use of therapeutic doses of DIGOXIN may cause prolongation of the PR interval and depression of the ST segment on the electrocardiogram. DIGOXIN may produce false positive ST-T changes on the electrocardiogram during exercise testing. These electrophysiologic effects are not indicative of toxicity. DIGOXIN does not significantly reduce heart rate during exercise. 12.3 Pharmacokinetics Note: The following data are from studies performed in adults, unless otherwise stated. Absorption: Following oral administration, peak serum concentrations of digoxin occur at 1 to 3 hours. Absorption of digoxin from DIGOXIN Tablets has been demonstrated to be 60-80% complete compared to an identical intravenous dose of digoxin (absolute bioavailability). When DIGOXIN Tablets are taken after meals, the rate of absorption is slowed, but the total amount of digoxin absorbed is usually unchanged. When taken with meals high in bran fiber, however, the amount absorbed from an oral dose may be reduced. Comparisons of the systemic availability and equivalent doses for oral preparations of DIGOXIN are shown in Dosage and Administration (2.6). Digoxin is a substrate for P-glycoprotein. As an efflux protein on the apical membrane of enterocytes, P-glycoprotein may limit the absorption of digoxin. In some patients, orally administered digoxin is converted to inactive reduction products (e.g., dihydrodigoxin) by colonic bacteria in the gut. Data suggest that 1 in 10 patients treated with digoxin tablets, colonic bacteria will degrade 40% or more of the ingested dose. As a result, certain antibiotics may increase the absorption of digoxin in such patients. Although inactivation of these bacteria by antibiotics is rapid, the serum digoxin concentration will rise at a rate consistent with the elimination half-life of digoxin. Serum digoxin concentration relates to the extent of bacterial inactivation, and may be as much as doubled in some cases [see Drug Interactions (7.2)]. Patients with malabsorption syndromes (e.g., short bowel syndrome, celiac sprue, jejunoileal bypass) may have a reduced ability to absorb orally administered digoxin. Distribution: Following drug administration, a 6-8 hour tissue distribution phase is observed. This is followed by a much more gradual decline in the serum concentration of the drug, which is dependent on the elimination of digoxin from the body. The peak height and slope of the early portion (absorption/distribution phases) of the serum concentration-time curve are dependent upon the route of administration and the absorption characteristics of the formulation. Clinical evidence indicates that the early high serum concentrations do not reflect the concentration of digoxin at its site of action, but that with chronic use, the steady-state post-distribution serum concentrations are in equilibrium with tissue concentrations and correlate with pharmacologic effects. In individual patients, these post-distribution serum concentrations may be useful in evaluating therapeutic and toxic effects [see Dosage and Administration (2.1)]. Digoxin is concentrated in tissues and therefore has a large apparent volume of distribution (approximately 475-500 L). Digoxin crosses both the blood-brain barrier and the placenta. At delivery, the serum digoxin concentration in the newborn is similar to the serum concentration in the mother. Approximately 25% of digoxin in the plasma is bound to protein. Serum digoxin concentrations are not significantly altered by large changes in fat tissue weight, so that its distribution space correlates best with lean (i.e., ideal) body weight, not total body weight. Metabolism: Only a small percentage (13%) of a dose of digoxin is metabolized in healthy volunteers. The urinary metabolites, which include dihydrodigoxin, digoxigenin bisdigitoxoside, and their glucuronide and sulfate conjugates, are polar in nature and are postulated to be formed via hydrolysis, oxidation, and conjugation. The metabolism of digoxin is not dependent upon the cytochrome P-450 system, and digoxin is not known to induce or inhibit the cytochrome P-450 system. Excretion: Elimination of digoxin follows first-order kinetics (that is, the quantity of digoxin eliminated at any time is proportional to the total body content). Following intravenous administration to healthy volunteers, 50-70% of a digoxin dose is excreted unchanged in the urine. Renal excretion of digoxin is proportional to creatinine clearance and is largely independent of urine flow. In healthy volunteers with normal renal function, digoxin has a half-life of 1.5-2 days. The half-life in anuric patients is prolonged to 3.5-5 days. Digoxin is not effectively removed from the body by dialysis, exchange transfusion, or during cardiopulmonary bypass because most of the drug is bound to extravascular tissues. Special Populations: Geriatrics: Because of age-related declines in renal function, elderly patients would be expected to eliminate digoxin more slowly than younger subjects. Elderly patients may also exhibit a lower volume of distribution of digoxin due to age-related loss of lean muscle mass. Thus, the dosage of digoxin should be carefully selected and monitored in elderly patients [see Use in Specific Populations (8.5)]. Gender: In a study of 184 patients, the clearance of digoxin was 12% lower in female than in male patients. This difference is not likely to be clinically important. Hepatic Impairment: Because only a small percentage (approximately 13%) of a dose of digoxin undergoes metabolism, hepatic impairment would not be expected to significantly alter the pharmacokinetics of digoxin. In a small study, plasma digoxin concentration profiles in patients with acute hepatitis generally fell within the range of profiles in a group of healthy subjects. No dosage adjustments are recommended for patients with hepatic impairment; however, serum digoxin concentrations should be used as appropriate to help guide dosing in these patients. Renal Impairment: Since the clearance of digoxin correlates with creatinine clearance, patients with renal impairment generally demonstrate prolonged digoxin elimination half-lives and greater exposures to digoxin. Therefore, titrate carefully in these patients based on clinical response, and based on monitoring of serum digoxin concentrations, as appropriate. Race: The impact of race differences on digoxin pharmacokinetics have not been formally studied. Because digoxin is primarily eliminated as unchanged drug via the kidney and because there are no important differences in creatinine clearance among races, pharmacokinetic differences due to race are not expected. Drug-drug Interactions Based on literature reports no significant changes in digoxin exposure were reported when digoxin was co-administered with the following drugs: alfuzosin, aliskiren, amlodipine, aprepitant, argatroban, aspirin, atorvastatin, benazepril, bisoprolol, black cohosh, bosentan, candesartan, citalopram, clopidogrel, colesevelam, dipyridamole, disopyramide, donepezil, doxazosin, dutasteride, echinacea, enalapril, eprosartan, ertapenem, escitalopram, esmolol, ezetimibe, famciclovir, felodipine, finasteride, flecainide, fluvastatin, fondaparinux, galantamine, gemifloxacin, grapefruit juice, irbesartan, isradipine, ketorlac, levetiracetam, levofloxacin, lisinopril, losartan, lovastatin, meloxicam, mexilitine, midazolam, milk thistle, moexipril, montelukast, moxifloxacin, mycophenolate, nateglinide, nesiritide, nicardipine, nisoldipine, olmesartan, orlistat, pantoprazole, paroxetine, perindopril, pioglitazone, pravastatin, prazosin, procainamide, quinapril, raloxifene, ramipril, repaglinide, rivastigmine, rofecoxib, ropinirole, rosiglitazone, rosuvastatin, sertraline, sevelamer, simvastatin, sirolimus, solifenacin, tamsulosin, tegaserod, terbinafine, tiagabine, ticlopidine, tigecycline, topiramate, torsemide, tramadol, trandolapril, triamterene, trospium, trovafloxacin, valacyclovir, valsartan, varenicline, voriconazole, zaleplon, zolpidem
                                • Clinical_studies ::
                                    • 0 : 14 CLINICAL STUDIES 14.1 Chronic Heart Failure Two 12-week, double-blind, placebo-controlled studies enrolled 178 (RADIANCE trial) and 88 (PROVED trial) adult patients with NYHA Class II or III heart failure previously treated with oral digoxin, a diuretic, and an ACE inhibitor (RADIANCE only) and randomized them to placebo or treatment with DIGOXIN Tablets. Both trials demonstrated better preservation of exercise capacity in patients randomized to DIGOXIN. Continued treatment with DIGOXIN reduced the risk of developing worsening heart failure, as evidenced by heart failure-related hospitalizations and emergency care and the need for concomitant heart failure therapy. DIG Trial of DIGOXIN in Patients with Heart Failure The Digitalis Investigation Group (DIG) main trial was a 37-week, multicenter, randomized, double-blind mortality study comparing digoxin to placebo in 6800 adult patients with heart failure and left ventricular ejection fraction less than or equal to 0.45. At randomization, 67% were NYHA class I or II, 71% had heart failure of ischemic etiology, 44% had been receiving digoxin, and most were receiving a concomitant ACE inhibitor (94%) and diuretics (82%). As in the smaller trials described above, patients who had been receiving open-label digoxin were withdrawn from this treatment before randomization. Randomization to digoxin was again associated with a significant reduction in the incidence of hospitalization, whether scored as number of hospitalizations for heart failure (relative risk 75%), risk of having at least one such hospitalization during the trial (RR 72%), or number of hospitalizations for any cause (RR 94%). On the other hand, randomization to digoxin had no apparent effect on mortality (RR 99%, with confidence limits of 91-107%). 14.2 Chronic Atrial Fibrillation Digoxin has also been studied as a means of controlling the ventricular response to chronic atrial fibrillation in adults. Digoxin reduced the resting heart rate, but not the heart rate during exercise. In 3 different randomized, double-blind trials that included a total of 315 adult patients, digoxin was compared to placebo for the conversion of recent-onset atrial fibrillation to sinus rhythm. Conversion was equally likely, and equally rapid, in the digoxin and placebo groups. In a randomized 120-patient trial comparing digoxin, sotalol, and amiodarone, patients randomized to digoxin had the lowest incidence of conversion to sinus rhythm, and the least satisfactory rate control when conversion did not occur. In at least one study, digoxin was studied as a means of delaying reversion to atrial fibrillation in adult patients with frequent recurrence of this arrhythmia. This was a randomized, double-blind, 43-patient crossover study. Digoxin increased the mean time between symptomatic recurrent episodes by 54%, but had no effect on the frequency of fibrillatory episodes seen during continuous electrocardiographic monitoring.
                                  • Use_in_specific_populations ::
                                      • 0 : •Pregnant patients: It is unknown whether use during pregnancy can cause fetal harm. (8.1) •Pediatric patients: Newborn infants display variability in tolerance to DIGOXIN. (8.4) •Geriatric patients: Consider renal function in dosage selection, and carefully monitor for side effects. (8.5) •Renal impairment: DIGOXIN is excreted by the kidneys. Consider renal function during dosage selection. (8.6) 8.1 Pregnancy Pregnancy Category C. DIGOXIN should be given to a pregnant woman only if clearly needed. It is also not known whether digoxin can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Animal reproduction studies have not been conducted with digoxin. 8.2 Labor and Delivery There are not enough data from clinical trials to determine the safety and efficacy of digoxin during labor and delivery. 8.3 Nursing Mothers Studies have shown that digoxin distributes into breast milk, and that the milk-to-serum concentration ratio is approximately 0.6-0.9. However, the estimated exposure of a nursing infant to digoxin via breastfeeding is far below the usual infant maintenance dose. Therefore, this amount should have no pharmacologic effect upon the infant. 8.4 Pediatric Use The safety and effectiveness of DIGOXIN in the control of ventricular rate in children with atrial fibrillation have not been established. The safety and effectiveness of DIGOXIN in the treatment of heart failure in children have not been established in adequate and well-controlled studies. However, in published literature of children with heart failure of various etiologies (e.g., ventricular septal defects, anthracycline toxicity, patent ductus arteriosus), treatment with digoxin has been associated with improvements in hemodynamic parameters and in clinical signs and symptoms. Newborn infants display considerable variability in their tolerance to digoxin. Premature and immature infants are particularly sensitive to the effects of digoxin, and the dosage of the drug must not only be reduced but must be individualized according to their degree of maturity. 8.5 Geriatric Use The majority of clinical experience gained with digoxin has been in the elderly population. This experience has not identified differences in response or adverse effects between the elderly and younger patients. However, this drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, which should be based on renal function, and it may be useful to monitor renal function [see Dosage and Administration (2.1)]. 8.6 Renal Impairment The clearance of digoxin can be primarily correlated with the renal function as indicated by creatinine clearance. Tables 3 and 5 provide the usual daily maintenance dose requirements for digoxin based on creatinine clearance [see Dosage and Administration (2.3)]. Digoxin is primarily excreted by the kidneys; therefore, patients with impaired renal function require smaller than usual maintenance doses of digoxin [see Dosage and Administration (2.3)]. Because of the prolonged elimination half-life, a longer period of time is required to achieve an initial or new steady-state serum concentration in patients with renal impairment than in patients with normal renal function. If appropriate care is not taken to reduce the dose of digoxin, such patients are at high risk for toxicity, and toxic effects will last longer in such patients than in patients with normal renal function. 8.7 Hepatic Impairment Plasma digoxin concentrations in patients with acute hepatitis generally fall within the range of profiles in a group of healthy subjects. 8.8 Malabsorption The absorption of digoxin is reduced in some malabsorption conditions such as chronic diarrhea.
                                    • Nonclinical_toxicology ::
                                        • 0 : 13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Digoxin showed no genotoxic potential in in vitro studies (Ames test and mouse lymphoma). No data are available on the carcinogenic potential of digoxin, nor have studies been conducted to assess its potential to affect fertility.
                                      • Spl_product_data_elements ::
                                          • 0 : DIGOXIN DIGOXIN DIGOXIN DIGOXIN STARCH, POTATO STARCH, CORN LACTOSE MONOHYDRATE MAGNESIUM STEARATE D&C YELLOW NO. 10 FD&C YELLOW NO. 6 LANOXIN;Y3B
                                        • Overdosage ::
                                            • 0 : 10 OVERDOSAGE 10.1 Signs and Symptoms in Adults and Children The signs and symptoms of toxicity are generally similar to those described in the Adverse Reactions (6.1) but may be more frequent and can be more severe. Signs and symptoms of digoxin toxicity become more frequent with levels above 2 ng/mL. However, in deciding whether a patient’s symptoms are due to digoxin, the clinical state together with serum electrolyte levels and thyroid function are important factors [see Dosage and Administration (2)]. Adults: The most common signs and symptoms of digoxin toxicity are nausea, vomiting, anorexia, and fatigue that occur in 30-70% of patients who are overdosed. Extremely high serum concentrations produce hyperkalemia especially in patients with impaired renal function. Almost every type of cardiac arrhythmia has been associated with digoxin overdose and multiple rhythm disturbances in the same patient are common. Peak cardiac effects occur 3-6 hours following ingestion and may persist for 24 hours or longer. Arrhythmias that are considered more characteristic of digoxin toxicity are new-onset Mobitz type 1 A-V block, accelerated junctional rhythms, non-paroxysmal atrial tachycardia with A-V block, and bi-directional ventricular tachycardia. Cardiac arrest from asystole or ventricular fibrillation is usually fatal. Digoxin toxicity is related to serum concentration. As digoxin serum levels increase above 1.2 ng/mL, there is a potential for increase in adverse reactions. Furthermore, lower potassium levels increases the risk for adverse reactions. In adults with heart disease, clinical observations suggest that an overdose of digoxin of 10-15 mg results in death of half of patients. A dose above 25 mg ingested by an adult without heart disease appeared to be uniformly fatal if no Digoxin Immune Fab (DIGIBIND®, DIGIFAB®) was administered. Among the extra-cardiac manifestations, gastrointestinal symptoms (e.g., nausea, vomiting, anorexia) are very common (up to 80% incidence) and precede cardiac manifestations in approximately half of the patients in most literature reports. Neurologic manifestations (e.g., dizziness, various CNS disturbances), fatigue, and malaise are very common. Visual manifestations may also occur with aberration in color vision (predominance of yellow green) the most frequent. Neurological and visual symptoms may persist after other signs of toxicity have resolved. In chronic toxicity, non-specific extra-cardiac symptoms, such as malaise and weakness, may predominate. Children: In pediatric patients, signs and symptoms of toxicity can occur during or shortly after the dose of digoxin. Frequent non-cardiac effects are similar to those observed in adults although nausea and vomiting are not seen frequently in infants and small pediatric patients. Other reported manifestations of overdose are weight loss in older age groups, failure to thrive in infants, abdominal pain caused by mesenteric artery ischemia, drowsiness, and behavioral disturbances including psychotic episodes. Arrhythmias and combinations of arrhythmias that occur in adult patients can also occur in pediatric patients although sinus tachycardia, supraventricular tachycardia, and rapid atrial fibrillation are seen less frequently in pediatric patients. Pediatric patients are more likely to develop A-V conduction disturbances, or sinus bradycardia. Any arrhythmia in a child treated with digoxin should be considered related to digoxin until otherwise ruled out. In pediatric patients aged 1-3 years without heart disease, clinical observations suggest that an overdose of digoxin of 6-10 mg would result in death of half of the patients. In the same population, a dose above 10 mg resulted in death if no Digoxin Immune Fab were administered. 10.2 Treatment Chronic Overdose If there is suspicion of toxicity, discontinue DIGOXIN and place the patient on a cardiac monitor. Correct factors such as electrolyte abnormalities, thyroid dysfunction, and concomitant medications [see Dosage and Administration (2.5)]. Correct hypokalemia by administering potassium so that serum potassium is maintained between 4.0 and 5.5 mmol/L. Potassium is usually administered orally, but when correction of the arrhythmia is urgent and serum potassium concentration is low, potassium may be administered by the intravenous route. Monitor electrocardiogram for any evidence of potassium toxicity (e.g., peaking of T waves) and to observe the effect on the arrhythmia. Avoid potassium salts in patients with bradycardia or heart block. Symptomatic arrhythmias may be treated with Digoxin Immune Fab. Acute Overdose Patients who have intentionally or accidently ingested massive doses of digoxin should receive activated charcoal orally or by nasogastric tube regardless of the time since ingestion since digoxin recirculates to the intestine by enterohepatic circulation. In addition to cardiac monitoring, temporarily discontinue DIGOXIN until the adverse reaction resolves. Correct factors that may be contributing to the adverse reactions [see Warnings and Precautions (5)]. In particular, correct hypokalemia and hypomagnesemia. Digoxin is not effectively removed from the body by dialysis because of its large extravascular volume of distribution. Life threatening arrhythmias (ventricular tachycardia, ventricular fibrillation, high degree A-V block, bradyarrhythma, sinus arrest) or hyperkalemia requires administration of Digoxin Immune Fab. Digoxin Immune Fab has been shown to be 80-90% effective in reversing signs and symptoms of digoxin toxicity. Bradycardia and heart block caused by digoxin are parasympathetically mediated and respond to atropine. A temporary cardiac pacemaker may also be used. Ventricular arrhythmias may respond to lidocaine or phenytoin. When a large amount of digoxin has been ingested, especially in patients with impaired renal function, hyperkalemia may be present due to release of potassium from skeletal muscle. In this case, treatment with Digoxin Immune Fab is indicated; an initial treatment with glucose and insulin may be needed if the hyperkalemia is life-threatening. Once the adverse reaction has resolved, therapy with DIGOXIN may be reinstituted following a careful reassessment of dose.
                                          • Pharmacodynamics ::
                                              • 0 : 12.2 Pharmacodynamics The times to onset of pharmacologic effect and to peak effect of preparations of DIGOXIN are shown in Table 7. Table 7. Times to Onset of Pharmacologic Effect and to Peak Effect of Preparations of DIGOXIN a Documented for ventricular response rate in atrial fibrillation, inotropic effects and electrocardiographic changes. b Depending upon rate of infusion. Product Time to Onset of Effecta Time to Peak Effecta DIGOXIN Tablets 0.5-2 hours 2-6 hours DIGOXIN Injection/IV 5-30 minutesb 1-4 hours Hemodynamic Effects: Short- and long-term therapy with the drug increases cardiac output and lowers pulmonary artery pressure, pulmonary capillary wedge pressure, and systemic vascular resistance in patients with heart failure. These hemodynamic effects are accompanied by an increase in the left ventricular ejection fraction and a decrease in end-systolic and end-diastolic dimensions. ECG Changes: The use of therapeutic doses of DIGOXIN may cause prolongation of the PR interval and depression of the ST segment on the electrocardiogram. DIGOXIN may produce false positive ST-T changes on the electrocardiogram during exercise testing. These electrophysiologic effects are not indicative of toxicity. DIGOXIN does not significantly reduce heart rate during exercise.
                                            • Warnings_and_cautions ::
                                                • 0 : •Risk of rapid ventricular response leading to ventricular fibrillation in patients with AV accessory pathway. (5.1) •Risk of advanced or complete heart block in patients with sinus node disease and AV block. (5.2) •Digoxin toxicity: Indicated by nausea, vomiting, visual disturbances, and cardiac arrhythmias. Advanced age, low body weight, impaired renal function and electrolyte abnormalities predispose to toxicity. (5.3) •Risk of ventricular arrhythmias during electrical cardioversion. (5.4) •Not recommended in patients with acute myocardial infarction. (5.5) •Avoid DIGOXIN in patients with myocarditis. (5.6) 5.1 Ventricular Fibrillation in Patients With Accessory AV Pathway (Wolff-Parkinson-White Syndrome) Patients with Wolff-Parkinson-White syndrome who develop atrial fibrillation are at high risk of ventricular fibrillation. Treatment of these patients with digoxin leads to greater slowing of conduction in the atrioventricular node than in accessory pathways, and the risks of rapid ventricular response leading to ventricular fibrillation are thereby increased. 5.2 Sinus Bradycardia and Sino-atrial Block DIGOXIN may cause severe sinus bradycardia or sinoatrial block particularly in patients with pre-existing sinus node disease and may cause advanced or complete heart block in patients with pre-existing incomplete AV block. Consider insertion of a pacemaker before treatment with digoxin. 5.3 Digoxin Toxicity Signs and symptoms of digoxin toxicity include anorexia, nausea, vomiting, visual changes and cardiac arrhythmias [first-degree, second-degree (Wenckebach), or third-degree heart block (including asystole); atrial tachycardia with block; AV dissociation; accelerated junctional (nodal) rhythm; unifocal or multiform ventricular premature contractions (especially bigeminy or trigeminy); ventricular tachycardia; and ventricular fibrillation]. Toxicity is usually associated with digoxin levels greater than 2 ng/ml although symptoms may also occur at lower levels. Low body weight, advanced age or impaired renal function, hypokalemia, hypercalcemia, or hypomagnesemia may predispose to digoxin toxicity. Obtain serum digoxin levels in patients with signs or symptoms of digoxin therapy and interrupt or adjust dose if necessary [see Adverse Reactions (6) and Overdosage (10)]. Assess serum electrolytes and renal function periodically. The earliest and most frequent manifestation of digoxin toxicity in infants and children is the appearance of cardiac arrhythmias, including sinus bradycardia. In children, the use of digoxin may produce any arrhythmia. The most common are conduction disturbances or supraventricular tachyarrhythmias, such as atrial tachycardia (with or without block) and junctional (nodal) tachycardia. Ventricular arrhythmias are less common. Sinus bradycardia may be a sign of impending digoxin intoxication, especially in infants, even in the absence of first-degree heart block. Any arrhythmias or alteration in cardiac conduction that develops in a child taking digoxin should initially be assumed to be a consequence of digoxin intoxication. Given that adult patients with heart failure have some symptoms in common with digoxin toxicity, it may be difficult to distinguish digoxin toxicity from heart failure. Misidentification of their etiology might lead the clinician to continue or increase DIGOXIN dosing, when dosing should actually be suspended. When the etiology of these signs and symptoms is not clear, measure serum digoxin levels. 5.4 Risk of Ventricular Arrhythmias During Electrical Cardioversion It may be desirable to reduce the dose of or discontinue DIGOXIN for 1 to 2 days prior to electrical cardioversion of atrial fibrillation to avoid the induction of ventricular arrhythmias, but physicians must consider the consequences of increasing the ventricular response if digoxin is decreased or withdrawn. If digitalis toxicity is suspected, elective cardioversion should be delayed. If it is not prudent to delay cardioversion, the lowest possible energy level should be selected to avoid provoking ventricular arrhythmias. 5.5 Risk of Ischemia in Patients With Acute Myocardial Infarction DIGOXIN is not recommended in patients with acute myocardial infarction because digoxin may increase myocardial oxygen demand and lead to ischemia. 5.6 Vasoconstriction In Patients With Myocarditis DIGOXIN can precipitate vasoconstriction and may promote production of pro-inflammatory cytokines; therefore, avoid use in patients with myocarditis. 5.7 Decreased Cardiac Output in Patients With Preserved Left Ventricular Systolic Function Patients with heart failure associated with preserved left ventricular ejection fraction may experience decreased cardiac output with use of DIGOXIN. Such disorders include restrictive cardiomyopathy, constrictive pericarditis, amyloid heart disease, and acute cor pulmonale. Patients with idiopathic hypertrophic subaortic stenosis may have worsening of the outflow obstruction due to the inotropic effects of digoxin. Patients with amyloid heart disease may be more susceptible to digoxin toxicity at therapeutic levels because of an increased binding of digoxin to extracellular amyloid fibrils. DIGOXIN should generally be avoided in these patients, although it has been used for ventricular rate control in the subgroup of patients with atrial fibrillation. 5.8 Reduced Efficacy In Patients With Hypocalcemia Hypocalcemia can nullify the effects of digoxin in humans; thus, digoxin may be ineffective until serum calcium is restored to normal. These interactions are related to the fact that digoxin affects contractility and excitability of the heart in a manner similar to that of calcium. 5.9 Altered Response in Thyroid Disorders and Hypermetabolic States Hypothyroidism may reduce the requirements for digoxin. Heart failure and/or atrial arrhythmias resulting from hypermetabolic or hyperdynamic states (e.g., hyperthyroidism, hypoxia, or arteriovenous shunt) are best treated by addressing the underlying condition. Atrial arrhythmias associated with hypermetabolic states are particularly resistant to digoxin treatment. Patients with beri beri heart disease may fail to respond adequately to digoxin if the underlying thiamine deficiency is not treated concomitantly.
                                              • Dosage_and_administration_table ::
                                                  • 0 :
                                                    Table 1. Recommended DIGOXIN Oral Loading Dose
                                                    mcg = microgram
                                                    Age Total Oral Loading Dose (mcg/kg) Administer half the total loading dose initially, then ¼ the loading dose every 6 to 8 hours twice
                                                    5 to 10 years 20-45
                                                    Adults and pediatric patients over 10 years 10-15
                                                    • 1 :
                                                      Table 2. Recommended Starting DIGOXIN Maintenance Dosage in Adults and Pediatric Patients Over 10 Years Old
                                                      mcg = microgram
                                                      Age Total Oral Maintenance Dose, mcg/kg/day (given once daily)
                                                      Adults and pediatric patients over 10 years 3.4-5.1
                                                      • 2 : 10 mL/min62.5*125125187.5187.5187.52501920 mL/min125125125187.5187.52502501630 mL/min125125187.5187.5250250312.51440 mL/min125187.5187.5250250312.5312.51350 mL/min125187.5187.5250250312.5312.51260 mL/min125187.5250250312.5312.53751170 mL/min187.5187.5250250312.53753751080 mL/min187.5187.5250312.5312.5375437.5990 mL/min187.5250250312.5375437.5437.58100 mL/min187.5250312.5312.5375437.55007
                                                        Table 3. Recommended Maintenance Dose (in micrograms given once daily) of DIGOXIN in Pediatric Patients Over 10 Years Old and Adults by Lean Body Weight and by Renal Functiona
                                                        a Doses are rounded to the nearest dose possible using whole DIGOXIN tablets. Recommended doses approximately 30 percent lower than the calculated dose are designated with an *. Monitor digoxin levels in patients receiving these initial doses and increase dose if needed. b For adults, creatinine clearance was corrected to 70-kg body weight or 1.73 m2 body surface area. If only serum creatinine concentrations (Scr) are available, a corrected Ccr may be estimated in men as (140 – Age)/Scr. For women, this result should be multiplied by 0.85. For pediatric patients, the modified Schwartz equation may be used. The formula is based on height in cm and Scr in mg/dL where k is a constant. Ccr is corrected to 1.73 m2 body surface area. During the first year of life, the value of k is 0.33 for pre-term babies and 0.45 for term infants. The k is 0.55 for pediatric patients and adolescent girls and 0.7 for adolescent boys. GFR (mL/min/1.73 m2) = (k x Height)/Scr c If no loading dose administered. d The doses listed assume average body composition.
                                                        Corrected Creatinine Clearanceb Lean Body Weightd Number of Days Before Steady State Achievedc
                                                        kg 40 50 60 70 80 90 100
                                                        • 3 :
                                                          Table 4. Recommended Starting DIGOXIN Oral Maintenance Dosage in Pediatric Patients between 5 and 10 Years Old
                                                          Age Oral Maintenance Dose, mcg/kg/dose
                                                          5 years to 10 years 3.2-6.4 Twice daily
                                                          • 4 : 10 mL/min-62.562.5*1251251920 mL/min62.562.51251251251630 mL/min62.562.5*125125187.51440 mL/min62.562.5*125187.5187.51350 mL/min62.5125125187.5187.51260 mL/min62.5125125187.52501170 mL/min62.5125187.5187.52501080 mL/min62.5*125187.5187.5250990 mL/min62.5*125187.52502508100 mL/min62.5*125187.5250312.57
                                                            Table 5. Recommended Maintenance Dose (in micrograms given TWICE daily) of DIGOXIN in Pediatric Patients between 5 and 10 Years of Agea Based upon Lean Body Weight and Renal Functiona,b
                                                            a Recommended are doses to be given twice daily. b The doses are rounded to the nearest dose possible using whole DIGOXIN tablets. Recommended doses approximately 30 percent lower than the calculated dose are designated with an *. Monitor digoxin levels in patients receiving these initial doses and increase dose if needed. c The modified Schwartz equation may be used to estimate creatinine clearance. See footnote b under Table 3. d If no loading dose administered.
                                                            Corrected Creatinine Clearancec Lean Body Weight Number of Days Before Steady State Achievedd
                                                            kg 20 30 40 50 60
                                                            • 5 :
                                                              Table 6. Comparison of the Systemic Availability and Equivalent Doses of Oral and Intravenous DIGOXIN
                                                              Absolute Bioavailability Equivalent Doses (mcg)
                                                              DIGOXIN Tablets 60-80% 62.5 125 250 500
                                                              DIGOXIN Intravenous Injection 100% 50 100 200 400
                                                          • How_supplied ::
                                                              • 0 : 16 HOW SUPPLIED/STORAGE AND HANDLING DIGOXIN Tablets have “LANOXIN” on one side. They are supplied by State of Florida DOH Central Pharmacy as follows: NDC Strength Quantity/Form Color Source Prod. Code 53808-1006-1 0.125 MG 30 Tablets in a Blister Pack YELLOW 49884-514 Store at 25°C (77°F); excursions permitted to 15 to 30°C (59 to 86°F) in a dry place and protect from light. Keep out of reach of children.
                                                            • Nursing_mothers ::
                                                                • 0 : 8.3 Nursing Mothers Studies have shown that digoxin distributes into breast milk, and that the milk-to-serum concentration ratio is approximately 0.6-0.9. However, the estimated exposure of a nursing infant to digoxin via breastfeeding is far below the usual infant maintenance dose. Therefore, this amount should have no pharmacologic effect upon the infant.
                                                              • Set_id : b69e2d2b-725c-4f2c-912d-d068da5c0f31