Lanoxin Injection Pediatric

— THERAPEUTIC CATEGORIES —
  • CHF and arrhythmias
PAGE CONTENTS
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  • Generic Name & Formulations
  • Indications
  • Dosage and Administration
  • Contraindications
  • Boxed Warnings
  • Warnings/Precautions
  • Pharmacokinetics
  • Interactions
  • Adverse Reactions
  • Clinical Trials
  • Note
  • Patient Counseling

    • Lanoxin Injection Pediatric Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Digoxin 0.1mg/mL; soln for IV or IM inj.

    Pharmacological Class

    Cardiac glycoside.

    See Also

    How Supplied

    Tabs—100, 1000; Inj 0.25mg/mL (2mL amps)—10; Inj Pediatric (1mL amp)—10

    How Supplied

    Lanoxin Tablets have “LANOXIN” on one side and are supplied as follows: 

    • Strength: 62.5mcg. Scored: No. Color: Peach. Imprint: U3A.

    • Strength: 125mcg. Scored: Yes. Color: Yellow. Imprint: Y3B.

    • Strength: 187.5mcg. Scored: No. Color: Blue. Imprint: F3F.

    • Strength: 250mcg. Scored: Yes. Color: White. Imprint: X3A.

    Lanoxin (digoxin) Injection, 500 mcg (0.5 mg) in 2 mL (250 mcg [0.25 mg] per mL); box of 10 ampules or 10 vials.

    Lanoxin (digoxin) Injection Pediatric, 100 mcg (0.1 mg) in 1 mL; box of 10 ampules or 10 vials.

    Storage

    Lanoxin Tablets: Store at 25°C (77°F); excursions permitted to 15 to 30°C (59 to 86°F) [See USP Controlled Room Temperature] in a dry place and protect from light. Keep out of reach of children. Dispense in tight, light-resistant container.

    Lanoxin (digoxin) Injection and Lanoxin (digoxin) Injection Pediatric: Store at 25 °C (77 °F); excursions permitted to 15 °C to 30 °C (59 °F to 86 °F) [see USP Controlled Room Temperature] and protect from light

    Manufacturer

    Covis Pharmaceuticals, Inc.

    Lanoxin Injection Pediatric Indications

    Indications

    Mild-to-moderate heart failure (with a diuretic and an ACE inhibitor when possible). Increase myocardial contractility in pediatrics with heart failure. Control of ventricular response rate in chronic atrial fibrillation.

    Lanoxin Injection Pediatric Dosage and Administration

    Adults and Children

    Individualize: see full labeling. Reduce dose in premature and immature infants. Children usually need proportionally larger doses (based on body weight or surface area) than adults. Use divided doses for children <10yrs. Retitrate when changing formulations (esp. oral tabs to or from other dose forms).

    Adults and Children

    Important Dosing and Administration Information

    • Consider factors that affect digoxin blood levels (e.g., body weight, age, renal function, concomitant drugs).

    • Consider interrupting or reducing Lanoxin dose prior to electrical cardioversion. Use digoxin solution to obtain appropriate dose in infants, young paediatric patients, or patients with very low body weight.

    Loading Dosing Regimen in Adults and Pediatric Patients

    • Give ½ the total loading dose initially, then ¼ the loading dose every 6 to 8 hours twice. Before each dose, carefully assess the patient's clinical response and toxicity.

    • For patients 5 to 10 years of age: total oral loading dose is 20–45 mcg/kg.

    • For patients over 10 years of age: total oral loading dose is 10–15 mcg/kg.

    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.

    • The recommended starting maintenance dose in patients over 10 years of age with normal renal function: total oral maintenance dose is 3.4–5.1 mcg/kg/day (given once daily). May increase doses every 2 weeks according to clinical response. Serum drug levels and toxicity.

    • The recommended (once daily) maintenance dose for patients over 10 years of age is according to lean body weight and renal function: see Table 3 in full labeling.

      • The maintenance dose can be estimated with 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 Lanoxin in patients whose lean weight is an abnormally small fraction of their total body mass due to obesity or edema.

    Maintenance Dosing in Pediatric Patients Less Than 10 Years Old

    • The maintenance dose is based on lean body weight, renal function, age, and concomitant products.

    • The recommended starting maintenance dose in patients between 5 and 10 years of age with normal renal function: total oral maintenance dose is 3.2–6.4 mcg/kg/day (to be given twice daily). May increase doses every 2 weeks according to clinical response. Serum drug levels and toxicity.

    • The recommended maintenance dose (in micrograms given twice daily) for patients  between 5 and 10 years of age is based upon lean body weight and renal function: see Table 5 in full labeling.

    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. The Lanoxin Tablets have 60–80% absolute bioavailability when compared with 100% absolute bioavailability of Lanoxin Intravenous Injection.

    • The following are the equivalent doses (mcg) for the oral to intravenous digoxin formulations, respectively:

      • 62.5 = 50

      • 125 = 100

      • 250 = 200

      • 500 = 400

    Lanoxin Injection Pediatric Contraindications

    Contraindications

    Ventricular fibrillation.

    Lanoxin Injection Pediatric Boxed Warnings

    Not Applicable

    Lanoxin Injection Pediatric Warnings/Precautions

    Warnings/Precautions

    Renal dysfunction: reduce dose. Sinus node disease. Incomplete AV block. Accessory AV pathway (Wolff-Parkinson-White syndrome). Heart failure with preserved LV ejection fraction (eg, restrictive cardiomyopathy, constrictive pericarditis, amyloid heart disease, acute cor pulmonale, idiopathic hypertrophic subaortic stenosis). Electrical cardioversion. Acute MI. Avoid in myocarditis. Toxicity risk increased by hypokalemia, hypomagnesemia, hypercalcemia. Hypocalcemia may nullify effects. Thyroid disease. Hypermetabolic states. Monitor digoxin levels, electrolytes, renal function. Premature infants. Neonates. Labor & Delivery. Pregnancy; monitor. Nursing mothers.

    Warnings/Precautions

    Ventricular Fibrillation in Patients With Accessory AV Pathway (Wolff-Parkinson-White Syndrome)  

    • Increased risk of ventricular fibrillation in patients with Wolff-Parkinson-White syndrome who develop atrial fibrillation. 

    Sinus Bradycardia and Sino-atrial Block

    • 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.

    Digoxin Toxicity  

    • While symptoms for digoxin toxicity may occur at lower levels, toxicity is usually associated with digoxin levels >2 ng/ml

    • Obtain serum digoxin levels in patients with signs or symptoms of digoxin therapy and interrupt or adjust dose if necessary. 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.

      • Sinus bradycardia may be a sign of impending digoxin intoxication, especially in infants, even in the absence of first-degree heart block.

      • Initially assume digoxin intoxication if a child taking digoxin develops any arrhythmias or alteration in cardiac conduction.

      • The most common are conduction disturbances or supraventricular tachyarrhythmias, such as atrial tachycardia (with or without block) and junctional (nodal) tachycardia.

    • In adults with heart failure, it may be difficult to distinguish digoxin toxicity from heart failure.

      • Measure serum digoxin levels when the etiology of these signs and symptoms is not clear.

    Risk of Ventricular Arrhythmias During Electrical Cardioversion 

    • To avoid the induction of ventricular arrhythmias, may be desirable to reduce the dose or discontinue Lanoxin for 1 to 2 days prior to electrical cardioversion of atrial fibrillation.

    • Physicians must consider the consequences of increasing the ventricular response if digoxin is decreased or withdrawn.

    • Delay elective cardioversion if digitalis toxicity is suspected. Use the lowest possible energy level to avoid provoking ventricular arrhythmias if it is not prudent to delay cardioversion.

    Risk of Ischemia in Patients With Acute Myocardial Infarction 

    • Not recommended for use in patients with acute myocardial infarction because digoxin may increase myocardial oxygen demand and lead to ischemia. 

    Vasoconstriction In Patients With Myocarditis 

    • Avoid use in patients with myocarditis because Lanoxin may precipitate vasoconstriction and may promote production of pro-inflammatory cytokines.

    Decreased Cardiac Output in Patients With Preserved Left Ventricular Systolic Function 

    • Avoid use in patients with heart failure associated with preserved left ventricular ejection fraction, patients with idiopathic hypertrophic subaortic stenosis, and patients with amyloid heart disease.

    • Patients with heart failure associated with preserved left ventricular ejection fraction may experience decreased cardiac output with use of Lanoxin. 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. 

    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.

    Altered Response in Thyroid Disorders and Hypermetabolic States

    • Hypothyroidism may reduce the requirements for digoxin. 

    • 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.  

    Pregnancy Considerations

    Risk Summary 

    • According to published retrospective clinical studies and case reports, experience with digoxin in pregnant women over several decades has not led to the identification of a drug associated risk of major birth defects, miscarriage or adverse maternal and fetal outcomes. 

    • Untreated underlying maternal conditions, such as heart failure and atrial fibrillation, during pregnancy pose a risk to the mother and fetus.

    Clinical Considerations

    • Disease-associated maternal and/or embryo/fetal risk: Pregnant women with heart failure are at increased risk for preterm birth. Pregnant women with atrial fibrillation are at an increased risk of delivering a low birth weight infant. Clinical classification of heart disease or atrial fibrillation may worsen with pregnancy and lead to maternal or fetal death. 

    • Fetal/neonatal adverse reactions: Monitor neonates for signs and symptoms of digoxin toxicity, including vomiting, and cardiac arrhythmias.

    • Dose adjustments during pregnancy and the postpartum period: Monitor serum digoxin levels during pregnancy and the postpartum period.

    • Labor or Delivery: Risk of arrhythmias may increase during the labor and delivery. Monitor continuously during labor and delivery.

    Nursing Mother Considerations

    Risk Summary 

    • No data on the effects of digoxin on the breastfed infant or the effects on milk production. 

    Pediatric Considerations

    The safety and effectiveness of Lanoxin in the control of ventricular rate in children with atrial fibrillation have not been established.

    The safety and effectiveness of Lanoxin in the treatment of heart failure in children have not been established in adequate and well-controlled studies.

    Geriatric Considerations

    Care should be taken in dose selection in elderly patients due to a higher likelihood of decreased renal function. May be useful to monitor renal function. 

    Renal Impairment Considerations

    Digoxin is primarily excreted by the kidneys. Patients with impaired renal function require smaller than usual maintenance doses of digoxin.

    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. 

    Hepatic Impairment Considerations

    Plasma digoxin concentrations in patients with acute hepatitis generally fall within the range of profiles in a group of healthy subjects.

    Other Considerations for Specific Populations

    Malabsorption

    • Reduced absorption of digoxin in some malabsorption conditions such as chronic diarrhea.

    Lanoxin Injection Pediatric Pharmacokinetics

    Absorption

    Following oral administration, peak serum concentrations of digoxin occur at 1 to 3 hours. Absorption of digoxin from Lanoxin Tablets has been demonstrated to be 60-80% complete compared to an identical intravenous dose of digoxin (absolute bioavailability). 

    When taken with meals high in bran fiber, however, the amount absorbed from an oral dose may be reduced. 

    Patients with malabsorption syndromes (e.g., short bowel syndrome, celiac sprue, jejunoileal bypass) may have a reduced ability to absorb orally administered digoxin. 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.

    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. 

    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.

    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.

    Elimination

    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.

    Lanoxin Injection Pediatric Interactions

    Interactions

    Toxicity risk increased by potassium-depleting drugs (eg, diuretics, amphotericin B, corticosteroids). Digoxin levels increased by antibiotics (eg, macrolides, tetracyclines), amiodarone, dronedarone, propafenone, quinidine, quinine, ritonavir, verapamil, indomethacin, itraconazole, lapatinib, mirabegron, spironolactone, telaprevir, drugs that reduce GI motility (eg, propantheline, diphenoxylate), thyroid antagonists, drugs that reduce renal function, others. Digoxin levels decreased by thyroid hormones, antacids, kaolin-pectin, cholestyramine, neomycin, penicillamine, rifampin, sulfasalazine, drugs that increase GI motility (eg, metoclopramide), certain antineoplastics, others. Digoxin levels possibly affected by alprazolam, cyclosporine, diclofenac, others. Arrhythmias with sympathomimetics, succinylcholine, or rapid calcium infusion. Heart block with drugs that affect cardiac conduction (eg, calcium channel blockers, β-blockers). Increased risk of bradycardia with ivabradine.

    Lanoxin Injection Pediatric Adverse Reactions

    Adverse Reactions

    GI upset, anorexia, CNS effects (eg, blurred or yellow vision, or mental disturbances, confusion, headache, weakness, dizziness, apathy), gynecomastia, rash, heart block, arrhythmias (esp. children).

    Lanoxin Injection Pediatric Clinical Trials

    Clinical Trials

    Chronic Heart Failure

    Lanoxin was evaluated in 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). In both trials, patients who received Lanoxin demonstrated better preservation of exercise capacity. Patients who continued treatment with Lanoxin experienced a risk reduction in 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 Lanoxin in Patients with Heart Failure

    The 37-week, multicenter, randomized, double-blind, Digitalis Investigation Group (DIG) trial compared digoxin to placebo in 6800 adults with heart failure and left ventricular ejection fraction less than or equal to 0.45. As in the smaller trials described above, patients who had been receiving open-label digoxin were withdrawn from this treatment before randomization. 

    Patients who were randomized to digoxin was 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, there was no apparent effect on mortality (RR 99%, with confidence limits of 91-107%) for patients randomized to digoxin. 

     

    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. 

    The effects of digoxin were compared to placebo in 3 different randomized, double-blind trials that included a total of 315 adult patients for the conversion of recent-onset atrial fibrillation to sinus rhythm. The incidence of conversion in the digoxin and placebo treatment arms were equally likely and equally rapid.

    In a randomized 120-patient trial, patients who received digoxin had the lowest incidence of conversion to sinus rhythm, and the least satisfactory rate control when conversion did not occur compared with sotalol and amiodarone.

    In a randomized, double-blind, 43-patient crossover study, digoxin was studied as a means of delaying reversion to atrial fibrillation in adult patients with frequent recurrence of this arrhythmia. Findings showed that 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. 

    Lanoxin Injection Pediatric Note

    Not Applicable

    Lanoxin Injection Pediatric Patient Counseling

    Patient Counseling

    • Many drugs can interact with Lanoxin. Inform your doctor and pharmacist if you are taking any over the counter medications, including herbal medication, or are started on a new prescription.

    • Contact your doctor or a health care professional if you 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 Lanoxin may be too high.

    • Symptoms of having too high Lanoxin 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. 

    • Monitor and record your heart rate and blood pressure daily. 

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