Contraindications

AmBisome is contraindicated in those patients who have demonstrated or have 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

Anaphylaxis has been reported with amphotericin B deoxycholate and other amphotericin B containing drugs, including AmBisome. If a severe anaphylactic reaction occurs, the infusion should be immediately discontinued and the patient should not receive further infusions of AmBisome.

Precautions

General
As with any amphotericin B-containing product the drug should be administered by medically trained personnel. During the initial dosing period, patients should be under close clinical observation. AmBisome has been shown to be significantly less toxic than amphotericin B deoxycholate; however, adverse events may still occur.

Laboratory Tests
Patient management should include laboratory evaluation of renal, hepatic and hematopoietic function, and serum electrolytes (particularly magnesium and potassium).

Drug Interactions
No formal clinical studies of drug interactions have been conducted with AmBisome.

Please see the Drug Interactions section for drugs that are known to interact with amphotericin B and may interact with AmBisome.

Carcinogenesis, Mutagenesis, Impairment of Fertility
No long term studies in animals have been performed to evaluate carcinogenic potential of AmBisome. AmBisome has not been tested to determine its mutagenic potential. For more details regarding studies that have been done, see the Prescribing Information section.

Specific Patient Populations
Information specific to certain patient populations can be found in the Prescribing Information section. These populations include: pregnant women, nursing mothers, pediatric patients, and elderly patients.

Adverse Reactions

A clinical study comparing AmBisome to amphotericin B deoxycholate (Study 94-0-002) showed that AmBisome was well tolerated. AmBisome 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, AmBisome had a lower incidence of hypokalemia, chills, vomiting, and hypertension as compared to amphotericin B deoxycholate. The percentage of patients who received drugs either for the treatment or prevention of infusion-related reactions (e.g., acetaminophen, diphenhydramine, meperidine and hydrocortisone) was lower in AmBisome-treated patients compared with amphotericin B deoxycholate-treated patients.

In an empirical therapy study (Study 97-0-034), on Day 1, where no premedication was administered, the overall incidence of infusion-related events of chills/rigors was significantly lower for patients administered AmBisome compared with amphotericin B lipid complex. Fever, chills/rigors and hypoxia were significantly lower for each AmBisome group compared with the amphotericin B lipid complex group.

Despite significantly fewer infusion-related reactions, chills, rigors, fever, nausea, vomiting, and cardiorespiratory events may still be seen with AmBisome.

Anaphylaxis has been reported with amphotericin B formulations including AmBisome.

A comprehensive list of adverse drug reactions, based on clinical trials in various patient groups, and a list of less common adverse events can be found in the Prescribing Information section.

Toxicity and Discontinuation of Dosing

One clinical study (94-0-002) showed a significantly lower incidence of grade 3 or 4 toxicity in the AmBisome group compared with the amphotericin B group. In addition, nearly three times as many patients administered amphotericin B required a reduction in dose due to toxicity or discontinuation of study drug due to an infusion-related reaction compared with those administered AmBisome.

In an empirical therapy study (97-0-034), a greater proportion of patients in the amphotericin B lipid complex group discontinued study drug due to an adverse event than in the AmBisome groups.

For further details, see the Prescribing Information section.

Overdosage

The toxicity of AmBisome 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.

If overdosage should occur, cease administration immediately. Symptomatic supportive measures should be instituted. Particular attention should be given to monitoring renal function.

For complete details regarding the safety and tolerability of AmBisome, please refer to the Prescribing Information section.

Note: Liposomal encapsulation or incorporation into a lipid complex can substantially affect a drug’s functional properties relative to those of the unencapsulated drug or non-lipid associated drug. In addition, different liposomal or lipid-complex products with a common active ingredient may vary from one another in the chemical composition and physical form of the lipid component. Such differences may affect the functional properties of these drug products.