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. DESCRIPTION OF CLINICAL STUDIES Eleven clinical studies supporting the efficacy and safety of amphotericin B were conducted.
This clinical program included both controlled and uncontrolled studies . These studies, which involved 2,171 patients, included patients with confirmed systemic mycoses, empirical therapy, and visceral leishmaniasis. Nineteen hundred and forty-six (1,946) episodes were evaluable for efficacy, of which 1,280 (302 pediatric and 978 adults) were treated with amphotericin B. Three controlled empirical therapy trials compared the efficacy and safety of amphotericin B liposome for injection to amphotericin B.
One of these studies was conducted in a pediatric population, one in adults, and a third in patients aged 2 years or more. In addition, a controlled empirical therapy trial comparing the safety of amphotericin B liposome for injection to Abelcet ® (amphotericin B lipid complex) was conducted in patients aged 2 years or more. One controlled trial compared the efficacy and safety of amphotericin B liposome for injection to amphotericin B in HIV patients with cryptococcal meningitis.
One compassionate use study enrolled patients who had failed amphotericin B deoxycholate therapy or who were unable to receive amphotericin B deoxycholate because of renal insufficiency. Empirical Therapy in Febrile Neutropenic Patients Study 94-0-002, a randomized, double-blind, comparative multi-center trial, evaluated the efficacy of amphotericin B liposome for injection (1.5 to 6 mg/kg/day) compared with amphotericin B deoxycholate (0.3 to 1.2 mg/kg/day) in the empirical treatment of 687 adult and pediatric neutropenic patients who were febrile despite having received at least 96 hours of broad spectrum antibacterial therapy.
Therapeutic success required (a) resolution of fever during the neutropenic period, (b) absence of an emergent fungal infection, (c) patient survival for at least 7 days post therapy, (d) no discontinuation of therapy due to toxicity or lack of efficacy, and (e) resolution of any study-entry fungal infection. The overall therapeutic success rates for amphotericin B liposome for injection and the amphotericin B deoxycholate were equivalent.
Results are summarized in the following table. Note: The categories presented below are not mutually exclusive. Empirical Therapy in Febrile Neutropenic Patients: Randomized, Double-Blind Study in 687 Patients * 8 and 10 patients, respectively, were treated as failures due to premature discontinuation alone. Amphotericin B Liposome for Injection 3 mg/kg/day Amphotericin B 0.6 mg/kg/day Number of patients receiving at least one dose of study drug 343 344 Overall Success 171 (49.9%) 169 (49.1%) Fever resolution during neutropenic period 199 (58%) 200 (58.1%) No treatment-emergent fungal infection 300 (87.5%) 301 (87.7%) Survival through 7 days post study drug 318 (92.7%) 308 (89.5%) Study drug not prematurely discontinued due to toxicity or lack of efficacy* 294 (85.7%) 280 (81.4%) This therapeutic equivalence had no apparent relationship to the use of prestudy antifungal prophylaxis or concomitant granulocytic colony-stimulating factors.
The incidence of mycologically-confirmed, and clinically-diagnosed, emergent fungal infections are presented in the following table. Amphotericin B liposome for injection and amphotericin B were found to be equivalent with respect to the total number of emergent fungal infections. Empirical Therapy in Febrile Neutropenic Patients: Emergent Fungal Infections Amphotericin B Liposome for Injection 3 mg/kg/day Amphotericin B 0.6 mg/kg/day Number of patients receiving at least one dose of study drug 343 344 Mycologically-confirmed fungal infection 11 (3.2%) 27 (7.8%) Clinically-diagnosed fungal infection 32 (9.3%) 16 (4.7%) Total emergent fungal infections 43 (12.5%) 43 (12.5%) Mycologically-confirmed fungal infections at study entry were cured in 8 of 11 patients in the amphotericin B liposome for injection group and 7 of 10 in the amphotericin B group.
Study 97-0-034, a randomized, double-blind, comparative multi-center trial, evaluated the safety of amphotericin B liposome for injection (3 and 5 mg/kg/day) compared with amphotericin B lipid complex (5 mg/kg/day) in the empirical treatment of 202 adult and 42 pediatric neutropenic patients. One hundred and sixty-six (166) patients received amphotericin B liposome for injection (85 patients received 3 mg/kg/day and 81 received 5 mg/kg/day) and 78 patients received amphotericin B lipid complex.
The study patients were febrile despite having received at least 72 hours of broad spectrum antibacterial therapy. The primary endpoint of this study was safety. The study was not designed to draw statistically meaningful conclusions related to comparative efficacy and, in fact, Abelcet is not labeled for this indication. Two supportive, prospective, randomized, open-label, comparative multi-center studies examined the efficacy of two dosages of amphotericin B liposome for injection (1 and 3 mg/kg/day) compared to amphotericin B deoxycholate (1 mg/kg/day) in the treatment of neutropenic patients with presumed fungal infections.
These patients were undergoing chemotherapy as part of a bone marrow transplant or had hematological disease. Study 104-10 enrolled adult patients (n = 134). Study 104-14 enrolled pediatric patients (n = 214). Both studies support the efficacy equivalence of amphotericin B liposome for injection and amphotericin B as empirical therapy in febrile neutropenic patients. Treatment of Cryptococcal Meningitis in HIV-Infected Patients Study 94-0-013, a randomized, double-blind, comparative multi-center trial, evaluated the efficacy of amphotericin B liposome for injection at doses (3 and 6 mg/kg/day) compared with amphotericin B deoxycholate (0.7 mg/kg/day) for the treatment of cryptococcal meningitis in 266 adult and one pediatric HIV-positive patients (the pediatric patient received amphotericin B deoxycholate).
Of the 267 treated patients, 86 received amphotericin B liposome for injection 3 mg/kg/day, 94 received 6 mg/kg/day and 87 received amphotericin B deoxycholate; cryptococcal meningitis was documented by a positive CSF culture at baseline in 73, 85 and 76 patients, respectively. Patients received study drug once daily for an induction period of 11 to 21 days. Following induction, all patients were switched to oral fluconazole at 400 mg/day for adults and 200 mg/day for patients less than 13 years of age to complete 10 weeks of protocol-directed therapy.
For mycologically evaluable patients, defined as all randomized patients who received at least one dose of study drug, had a positive baseline CSF culture, and had at least one follow-up culture, success was evaluated at week 2 (i.e., 14 ± 4 days), and was defined as CSF culture conversion. Success rates at 2 weeks for amphotericin B liposome for injection and amphotericin B deoxycholate are summarized in the following table: Success Rates at 2 Weeks (CSF Culture Conversion) Study 94-0-013 * 97.5% Confidence Interval for the difference between amphoteri
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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.
Warnings and precautions
Anaphylaxis has been reported with amphotericin B deoxycholate and other amphotericin B-containing drugs, including amphotericin B liposome for injection. If a severe anaphylactic reaction occurs, the infusion should be immediately discontinued and the patient should not receive further infusions of amphotericin B liposome for injection.
Interactions
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 administered concomitantly, serum potassium levels should be closely monitored.
Pregnancy and breastfeeding
Pregnancy There have been no adequate and well-controlled studies of amphotericin B liposome for injection in pregnant women. Systemic fungal infections have been successfully treated in pregnant women with amphotericin B deoxycholate, but the number of cases reported has been small. Segment II studies in both rats and rabbits have concluded that amphotericin B liposome for injection had no teratogenic potential in these species.
In rats, the maternal non-toxic dose of amphotericin B liposome for injection was estimated to be 5 mg/kg (equivalent to 0.16 to 0.8 times the recommended human clinical dose range of 1 to 5 mg/kg) and in rabbits, 3 mg/kg (equivalent to 0.2 to 1 times the recommended human clinical dose range), based on body surface area correction. Rabbits receiving the higher doses, (equivalent to 0.5 to 2 times the recommended human dose) of amphotericin B liposome for injection experienced a higher rate of spontaneous abortions than did the control groups.
Amphotericin B liposome for injection should only be used during pregnancy if the possible benefits to be derived outweigh the potential risks involved.
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, multi-center 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
17.2 Nervous System Anxiety 13.7 11 Confusion 11.4
13.4 Headache 19.8
20.9 Insomnia 17.2
14.2Respiratory 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 Sweating 7
10.8Urogenital System Hematuria 14 14 Amphotericin
B liposome for injection was well tolerated. Amphotericin B liposome for injection had a lower incidence of chills, hypertension, hypotension, tachycardia, hypoxia, hypokalemia, and various events related to decreased kidney function as compared to amphotericin B deoxycholate. In pediatric patients (16 years of age or less) in this double-blind study, amphotericin B liposome for injection compared to amphotericin B deoxycholate, had a lower incidence of hypokalemia (37% versus 55%), chills (29% versus 68%), vomiting (27% versus 55%), and hypertension (10% versus 21%).
Similar trends, although with a somewhat lower incidence, were observed in open-label, randomized Study 104-14 involving 205 febrile neutropenic pediatric patients (141 treated with amphotericin B liposome for injection and 64 treated with amphotericin B deoxycholate). Pediatric patients appear to have more tolerance than older individuals for the nephrotoxic effects of amphotericin B deoxycholate. The following adverse events are based on the experience of 244 patients (202 adult and 42 pediatric patients) of whom 85 patients were treated with amphotericin B liposome for injection 3 mg/kg, 81 patients were treated with amphotericin B liposome for injection 5 mg/kg and 78 patients were treated with amphotericin B lipid complex 5 mg/kg in Study 97-0-034, a randomized, double-blind, multi-center study in febrile, neutropenic patients.
Amphotericin B liposome for injection and amphotericin B lipid complex were infused over two hours. The incidence of adverse events occurring in more than 10% of subjects in one or more arms, regardless of relationship to study drug, are summarized in the following table: Empirical Therapy Study 97-0-034 Common Adverse Events Adverse Event by Body System Amphotericin B Liposome for Injection 3 mg/kg/day N = 85 % Amphotericin B Liposome for Injection 5 mg/kg/day N = 81 % Amphotericin B Lipid Complex 5 mg/kg/day N = 78 % Body as a Whole Abdominal pain 12.9 9.9
11.5 Asthenia 8.2 6.2
11.5 Chills/rigors 40 48.1
89.7 Sepsis 12.9 7.4
11.5 Transfusion reaction 10.6 8.6
5.1Cardiovascular System
Chest pain 8.2 11.1
6.4 Hypertension 10.6 19.8
23.1 Hypotension 10.6 7.4
19.2 Tachycardia 9.4 18.5
23.1 Digestive System Diarrhea 15.3 17.3
14.1 Nausea 25.9 29.6
37.2 Vomiting 22.4 25.9
30.8Metabolic and Nutritional Disorders
Alkaline phosphatase increased 7.1 8.6
12.8 Bilirubinemia 16.5 11.1
11.5 BUN increased 20 18.5
28.2 Creatinine increased 20 18.5
48.7 Edema 12.9 12.3
12.8 Hyperglycemia 8.2 8.6
14.1 Hypervolemia 8.2 11.1
14.1 Hypocalcemia 10.6 4.9
5.1 Hypokalemia 37.6 43.2
39.7 Hypomagnesemia 15.3 25.9
15.4 Liver function tests abnormal 10.6 7.4
11.5 Nervous System Anxiety 10.6 7.4 9 Confusion 12.9 8.6
3.8 Headache 9.4 17.3
10.3 Respiratory System Dyspnea 17.6 22.2
23.1 Epistaxis 10.6 8.6
14.1 Hypoxia 7.1 6.2
20.5 Lung disorder 14.1 13.6
15.4 Skin and Appendages Rash 23.5 22.2
14.1 The following adverse events are based on the experience of 267 patients (266 adult patients and 1 pediatric patient) of whom 86 patients were treated with amphotericin B liposome for injection 3 mg/kg, 94 patients were treated with amphotericin B liposome for injection 6 mg/kg and 87 patients were treated with amphotericin B deoxycholate 0.7 mg/kg in Study 94-0-013 a randomized, double-blind, comparative multi-center trial, in the treatment of cryptococcal meningitis in HIV-positive patients.
The incidence of adverse events occurring in more than 10% of subjects in one or more arms regardless of relationship to study drug are summarized in the following table: Cryptococcal Meningitis Therapy Study 94-0-013 Common Adverse Events Adverse Event by Body System Amphotericin B Liposome for Injection 3 mg/kg/day N = 86 % Amphotericin B Liposome for Injection 6 mg/kg/day N = 94 % Amphotericin B 0.7 mg/kg/day N = 87 % Body as a Whole Abdominal pain 7 7.4
10.3 Infection 12.8 11.7
6.9 Procedural Complication 8.1 9.6
10.3 Cardiovascular System Phlebitis 9.3 10.6
25.3 Digestive System Anorexia 14 9.6
11.5 Constipation 15.1 14.9
20.7 Diarrhea 10.5 16
10.3 Nausea 16.3 21.3
25.3 Vomiting 10.5 21.3
20.7 Hemic and Lymphatic System Anemia 26.7 47.9
43.7 Leukopenia 15.1 17
17.2 Thrombocytopenia 5.8 12.8
6.9 Metabolic and Nutritional Disorders Bilirubinemia 0 8.5
12.6 BUN increased 9.3 7.4
10.3 Creatinine increased 18.6 39.4
43.7 Hyperglycemia 9.3 12.8
17.2 Hypocalcemia 12.8 17
13.8 Hypokalemia 31.4 51.1
48.3 Hypomagnesemia 29.1 48.9
40.2 Hyponatremia 11.6 8.5
9.2 Liver Function Tests Abnormal 12.8 4.3
9.2 Nervous System Dizziness 7 8.5
10.3 Insomnia 22.1 17
20.7 Respiratory System Cough Increased 8.1 2.1
10.3 Skin and Appendages Rash 4.7 11.7
4.6Infusion-Related Reactions In Study 94-0-002,
the large, double-blind study of pediatric and adult febrile neutropenic patients, no premedication to prevent infusion-related reaction was administered prior to the first dose of study drug (Day 1). Amphotericin B liposome for injection-treated patients had a lower incidence of infusion-related fever (17% versus 44%), chills/rigors (18% versus 54%) and vomiting (6% versus 8%) on Day 1 as compared to amphotericin B deoxycholate-treated patients.
The incidence of infusion-related reactions on Day 1 in pediatric and adult patients is summarized in the following table: Incidence of Day 1 Infusion-Related Reactions (IRR) By Patient Age * Day 1 body temperature increased above the temperature taken within 1 hour prior to infusion (preinfusion temperature) or above the lowest infusion value (no preinfusion temperature recorded). Pediatric Patients (≤ 16 years of age) Adult Patients (>16 years of age) Amphotericin B Liposome for Injection 3 mg/kg/day Amphotericin B 0.6 mg/kg/day Amphotericin B Liposome for Injection 3 mg/kg/day Amphotericin B 0.6 mg/kg/day Total number of patients receiving at least one dose of study drug 48 47 295 297 Patients with fever * increase ≥1.0ºC 6 (13%) 22 (47%)
Our copy of this section ends here. The full text is in the official label at the FDA. Open Drugs@FDA
Composition
Active ingredients
AMPHOTERICIN B 50MG/VIAL
Strengths and forms
The FDA lists each strength of a product separately; these pages share one label.
AMPHOTERICIN B 50MG/VIAL · Injectable, liposomalThis page
Prognia shows this product information for reference and learning. It is not treatment advice and can lag behind the official text. Always check the current product information and local protocols before prescribing.
At a glance
Brand name
Amphotericin B
Drug class
Antiinfectives and antiseptics for local oral treatment, Antibiotics
