Amphotericin B (5 brand names, 7 dosage forms, 3 routes)
Available dosage forms: INJECTABLE, SUSPENSION, INJECTABLE, LIPID COMPLEX, CREAM, INJECTABLE, LIPOSOMAL, OINTMENT, LOTION.
Routes of administration: INJECTION, ORAL, TOPICAL.
Brand Names
- ABELCET
- AMBISOME
- AMPHOTEC
- AMPHOTERICIN B
- FUNGIZONE
Indications and Usage
Amphotericin B liposome for injection is indicated for the following: Empirical therapy for presumed fungal infection in febrile, neutropenic patients. Treatment of Cryptococcal Meningitis in HIV-infected patients (see DESCRIPTION OF CLINICAL STUDIES). Treatment of patients with Aspergillus species, Candida species and/or Cryptococcus species infections (see above for the treatment of Cryptococcal Meningitis) refractory to amphotericin B deoxycholate, or in patients where renal impairment or unacceptable toxicity precludes the use of amphotericin B deoxycholate. Treatment of visceral leishmaniasis. In immunocompromised patients with visceral leishmaniasis treated with amphotericin B liposome for injection, relapse rates were high following initial clearance of parasites (see DESCRIPTION OF CLINICAL STUDIES). See DOSAGE AND ADMINISTRATION for recommended doses by indication.
Dosage and Administration
Amphotericin B liposome for injection is not interchangeable or substitutable on a mg per mg basis with other amphotericin B products. Different amphotericin B products are not equivalent in terms of pharmacodynamics, pharmacokinetics and dosing. Amphotericin B liposome for injection should be administered by intravenous infusion, using a controlled infusion device, over a period of approximately 120 minutes. An in-line membrane filter may be used for the intravenous infusion of amphotericin B liposome for injection, provided THE MEAN PORE DIAMETER OF THE FILTER IS NOT LESS THAN 1.0 MICRON. NOTE: An existing intravenous line must be flushed with 5% Dextrose Injection prior to infusion of amphotericin B liposome for injection. If this is not feasible, amphotericin B liposome for injection must be administered through a separate line. Infusion time may be reduced to approximately 60 minutes in patients in whom the treatment is well-tolerated. If the patient experiences discomfort during infusion, the duration of infusion may be increased. The recommended initial dose of amphotericin B liposome for injection for each indication for adult and pediatric patients is as follows: Indication Dose (mg/kg/day) Empirical therapy 3 Systemic fungal infections: Aspergillus Candida Cryptococcus 3 to 5 Cryptococcal meningitis in HIV-infected patients (see DESCRIPTION OF CLINICAL STUDIES) 6 Dosing and rate of infusion should be individualized to the needs of the specific patient to ensure maximum efficacy while minimizing systemic toxicities or adverse events. Doses recommended for visceral leishmaniasis are presented below: Visceral Leishmaniasis Dose (mg/kg/day) Immunocompetent patients 3 (days 1 to 5) and3 on days 14, 21 Immunocompromised patients 4 (days 1 to 5) and4 on days 10, 17, 24, 31, 38 For immunocompetent patients who do not achieve parasitic clearance with the recommended dose, a repeat course of therapy may be useful. For immunocompromised patients who do not clear para
Contraindications
Amphotericin B liposome for injection is contraindicated in those patients who have demonstrated or have a known hypersensitivity to amphotericin B deoxycholate or any other constituents of the product unless, in the opinion of the treating physician, the benefit of therapy outweighs the risk.
Adverse Reactions
The following adverse events are based on the experience of 592 adult patients (295 treated with amphotericin B liposome for injection and 297 treated with amphotericin B deoxycholate) and 95 pediatric patients (48 treated with amphotericin B liposome for injection and 47 treated with amphotericin B deoxycholate) in Study 94-0-002, a randomized double-blind, multicenter study in febrile, neutropenic patients. Amphotericin B liposome for injection and amphotericin B were infused over two hours. The incidence of common adverse events (incidence of 10% or greater) occurring with amphotericin B liposome for injection compared to amphotericin B deoxycholate, regardless of relationship to study drug, is shown in the following table: Empirical Therapy Study 94-0-002 Common Adverse Events Adverse Event by Body System Amphotericin B Liposome for Injection N=343 % Amphotericin B N=344 % Body as a Whole Abdominal pain 19.8 21.8 Asthenia 13.1 10.8 Back pain 12 7.3 Blood product transfusion reaction 18.4 18.6 Chills 47.5 75.9 Infection 11.1 9.3 Pain 14 12.8 Sepsis 14 11.3 Cardiovascular System Chest pain 12 11.6 Hypertension 7.9 16.3 Hypotension 14.3 21.5 Tachycardia 13.4 20.9 Digestive System Diarrhea 30.3 27.3 Gastrointestinal hemorrhage 9.9 11.3 Nausea 39.7 38.7 Vomiting 31.8 43.9 Metabolic and Nutritional Disorders Alkaline phosphatase increased 22.2 19.2 ALT (SGPT) increased 14.6 14 AST (SGOT) increased 12.8 12.8 Bilirubinemia 18.1 19.2 BUN increased 21 31.1 Creatinine increased 22.4 42.2 Edema 14.3 14.8 Hyperglycemia 23 27.9 Hypernatremia 4.1 11 Hypervolemia 12.2 15.4 Hypocalcemia 18.4 20.9 Hypokalemia 42.9 50.6 Hypomagnesemia 20.4 25.6 Peripheral edema 14.6 17.2 Nervous System Anxiety 13.7 11 Confusion 11.4 13.4 Headache 19.8 20.9 Insomnia 17.2 14.2 Respiratory System Cough increased 17.8 21.8 Dyspnea 23 29.1 Epistaxis 14.9 20.1 Hypoxia 7.6 14.8 Lung disorder 17.8 17.4 Pleural effusion 12.5 9.6 Rhinitis 11.1 11 Skin and Appendages Pruritus 10.8 10.2 Rash 24.8 24.4 Sweatin
Drug Interactions
No formal clinical studies of drug interactions have been conducted with amphotericin B liposome for injection; however, the following drugs are known to interact with amphotericin B and may interact with amphotericin B liposome for injection: Antineoplastic Agents Concurrent use of antineoplastic agents may enhance the potential for renal toxicity, bronchospasm, and hypotension. Antineoplastic agents should be given concomitantly with caution. Corticosteroids and Corticotropin (ACTH) Concurrent use of corticosteroids and ACTH may potentiate hypokalemia, which could predispose the patient to cardiac dysfunction. If used concomitantly, serum electrolytes and cardiac function should be closely monitored. Digitalis Glycosides Concurrent use may induce hypokalemia and may potentiate digitalis toxicity. When administered concomitantly, serum potassium levels should be closely monitored. Flucytosine Concurrent use of flucytosine may increase the toxicity of flucytosine by possibly increasing its cellular uptake and/or impairing its renal excretion. Azoles (e.g., ketoconazole, miconazole, clotrimazole, fluconazole, etc.) In vitro and in vivo animal studies of the combination of amphotericin B and imidazoles suggest that imidazoles may induce fungal resistance to amphotericin B. Combination therapy should be administered with caution, especially in immunocompromised patients. Leukocyte Transfusions Acute pulmonary toxicity has been reported in patients simultaneously receiving intravenous amphotericin B and leukocyte transfusions. Other Nephrotoxic Medications Concurrent use of amphotericin B and other nephrotoxic medications may enhance the potential for drug-induced renal toxicity. Intensive monitoring of renal function is recommended in patients requiring any combination of nephrotoxic medications. Skeletal Muscle Relaxants Amphotericin B-induced hypokalemia may enhance the curariform effect of skeletal muscle relaxants (e.g. tubocurarine) due to hypokalemia. When admini
Overdosage
The toxicity of amphotericin B liposome for injection due to overdose has not been defined. Repeated daily doses up to 10 mg/kg in pediatric patients and 15 mg/kg in adult patients have been administered in clinical trials with no reported dose-related toxicity. Management If overdosage should occur, cease administration immediately. Symptomatic supportive measures should be instituted. Particular attention should be given to monitoring renal function. Hemodialysis or peritoneal dialysis do not appear to significantly affect the elimination of amphotericin B liposome for injection.