Get your patient on Amphotericin B Liposome - Amphotericin B Liposome injection, Powder, Lyophilized, For Suspension (Amphotericin B Liposome)

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.

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:

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:

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 parasites or who experience relapses, expert advice regarding further treatment is recommended. For additional information, see DESCRIPTION OF CLINICAL STUDIES .

Directions for Reconstitution, Filtration and Dilution

Read This Entire Section Carefully Before Beginning Reconstitution

Amphotericin B liposome for injection must be reconstituted using Sterile Water for Injection, USP (without a bacteriostatic agent). Vials of amphotericin B liposome for injection containing 50 mg of amphotericin B are prepared as follows:

Reconstitution

1. Aseptically add 12 mL of Sterile Water for Injection, USP to each amphotericin B liposome for injection vial to yield a preparation containing 4 mg amphotericin B/mL.
   CAUTION: DO NOT RECONSTITUTE WITH SALINE OR ADD SALINE TO THE RECONSTITUTED CONCENTRATION, OR MIX WITH OTHER DRUGS. The use of any solution other than those recommended, or the presence of a bacteriostatic agent in the solution, may cause precipitation of amphotericin B liposome for injection.
2. Immediately after the addition of water, SHAKE THE VIAL VIGOROUSLY for 30 seconds to completely disperse the amphotericin B liposome for injection. Amphotericin B liposome for injection forms a yellow, translucent suspension. Visually inspect the vial for particulate matter and continue shaking until completely dispersed.

Filtration and Dilution

1. Calculate the amount of reconstituted (4 mg/mL) amphotericin B liposome for injection to be further diluted.
2. Withdraw this amount of reconstituted amphotericin B liposome for injection into a sterile syringe.
3. Attach the 5 micron filter provided to the syringe. Inject the syringe contents through the filter, into the appropriate amount of 5% Dextrose Injection (use only one filter per vial of amphotericin B liposome for injection).
4. Amphotericin B liposome for injection must be diluted with 5% Dextrose Injection to a final concentration of 1 to 2 mg/mL prior to administration. Lower concentrations (0.2 to 0.5 mg/mL) may be appropriate for infants and small children to provide sufficient volume for infusion. DISCARD PARTIALLY USED VIALS.

STORAGE OF AMPHOTERICIN B LIPOSOME FOR INJECTION

Unopened vials of lyophilized material are to be stored at temperatures up to 25°C (77°F).

Storage of Reconstituted Product Concentrate

The reconstituted product concentrate may be stored for up to 24 hours at 2° to 8°C (36° to 46°F) following reconstitution with Sterile Water for Injection, USP. Do not freeze.

Storage of Diluted Product

Injection of amphotericin B liposome for injection should commence within 6 hours of dilution with 5% Dextrose Injection.

As with all parenteral drug products, the reconstituted amphotericin B liposome for injection should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use material if there is any evidence of precipitation or foreign matter. Aseptic technique must be strictly observed in all handling, since no preservative or bacteriostatic agent is present in amphotericin B liposome for injection or in the materials specified for reconstitution and dilution.

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.

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:

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:

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:

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:

Amphotericin B liposome for injection is a sterile, non-pyrogenic, yellow lyophilized product for intravenous infusion. Each vial contains amphotericin B, USP, 50 milligrams (mg), intercalated into a liposomal membrane consisting of alpha tocopherol, USP approximately 0.64 mg; cholesterol, NF, 52 mg; distearoyl phosphatidylglycerol sodium salt 86.48 mg; hydrogenated soy phosphatidylcholine 213 mg, together with disodium succinate hexahydrate, NF, 27 mg; and sucrose, NF, 900 mg. Amphotericin B liposome for injection may also contain hydrochloric acid and/or sodium hydroxide as pH adjusters. Each 1 mL of reconstituted Amphotericin B liposome for injection contains 1 mg of sodium and less than 5 mg of phosphorus. Following reconstitution with Sterile Water for Injection, USP, the resulting pH of the suspension is between 5-6.

Amphotericin B liposome for injection is a true single bilayer liposomal drug delivery system. Liposomes are closed, spherical vesicles created by mixing specific proportions of amphophilic substances such as phospholipids and cholesterol so that they arrange themselves into multiple concentric bilayer membranes when hydrated in aqueous solutions. Single bilayer liposomes are then formed by microemulsification of multilamellar vesicles using a homogenizer. Amphotericin B liposome for injection consists of these unilamellar bilayer liposomes with amphotericin B intercalated within the membrane. Due to the nature and quantity of amphophilic substances used, and the lipophilic moiety in the amphotericin B molecule, the drug is an integral part of the overall structure of the amphotericin B liposomes. Amphotericin B liposome for injection contains true liposomes that are less than 100 nm in diameter. A schematic depiction of the liposome is presented below.

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.

Amphotericin B is a macrocyclic, polyene, antifungal antibiotic produced from a strain of Streptomyces nodosus . Amphotericin B is designated chemically as: [1R-(1R•,3S•,5R•,6R•,9R•,11R•,15S•,16R•,17R•,18S•,19E,21E,23E,25E,27E,29E,31E,33R•,35S•,36R•,37S•)]-33-[(3-Amino-3,6-dideoxy-β-D-mannopyranosyl)oxy]-1,3,5,6,9,11,17,37-octahydroxy-15,16,18-trimethyl-13-oxo-14,39-dioxabicyclo[33.3.1]nonatriaconta-19,21,23,25, 27,29,31-heptaene-36-carboxylic acid (CAS No.1397-89-3).

Amphotericin B has a molecular formula of C ₄₇ H ₇₃ NO ₁₇ and a molecular weight of 924.08.

The structure of amphotericin B is shown below:

Amphotericin B liposome for injection is a sterile, non-pyrogenic, yellow lyophilized product for intravenous infusion and is available as an individual carton (NDC 67457-926-50) and in packs of ten individual cartons (NDC 67457-926-99).

Each individual carton contains one pre-packaged, disposable sterile 5 micron filter.

All other trademarks and registered trademarks are the property of their respective owners.

Rx only

Manufactured for:
Mylan Institutional LLC
Morgantown, WV 26505 U.S.A.

Manufactured by:
Mylan Laboratories Limited
Bangalore, India

50105038

JUNE 2025

Amphotericin B, the active ingredient of amphotericin B liposome for injection, acts by binding to the sterol component, ergosterol, of the cell membrane of susceptible fungi. It forms transmembrane channels leading to alterations in cell permeability through which monovalent ions (NA+, K+, H+, and Cl-) leak out of the cell resulting in cell death. While amphotericin B has a higher affinity for the ergosterol component of the fungal cell membrane, it can also bind to the cholesterol component of the mammalian cell leading to cytotoxicity. Amphotericin B liposome for injection, the liposomal preparation of amphotericin B, has been shown to penetrate the cell wall of both extracellular and intracellular forms of susceptible fungi.