Abelcet (amphotericin B lipid complex)

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Last reviewed · Source: First Databank (FDB) drug data

Overview

Amphotericin B, a macrocyclic polyene, is an antifungal agent.

Amphotericin B is an antifungal antibiotic produced by Streptomyces nodosus. The drug is commercially available as amphotericin B formulated with sodium desoxycholate (conventional amphotericin B) and amphotericin B liposomal (lipid formulation). The lipid formulation contains a lipid-based drug delivery system that may improve the toxicity profile of amphotericin B, but also can affect pharmacokinetics and functional properties of the drug.

Amphotericin B liposomal contains amphotericin B intercalated into a unilamellar bilayer liposomal membrane composed of hydrogenated soy phosphatidylcholine (HSPC), cholesterol, distearoylphosphatidylglycerol, and alpha-tocopherol.

Amphotericin B usually is fungistatic in action at concentrations obtained clinically, but may be fungicidal in high concentrations or against very susceptible organisms. Amphotericin B exerts its antifungal activity principally by binding to sterols (e.g., ergosterol) in the fungal cell membrane. As a result of this binding, the cell membrane is no longer able to function as a selective barrier and leakage of intracellular contents occurs.

Cell death occurs in part as a result of permeability changes by which monovalent ions (sodium, potassium, hydrogen, and chloride) leak out of the cell. Binding to sterols in mammalian cells (such as certain kidney cells and erythrocytes) may account for some of the toxicities reported with conventional amphotericin B therapy.

The pharmacokinetics of amphotericin B vary substantially depending on whether the drug is administered as conventional amphotericin B (formulated with sodium desoxycholate) or amphotericin B liposomal, and pharmacokinetic parameters reported for one amphotericin B formulation should not be used to predict the pharmacokinetics of any other amphotericin B formulation. The manufacturers' literature and specialized references should be consulted for information regarding the absorption, distribution, or elimination of amphotericin B administered as amphotericin B liposomal.

After an initial IV infusion of 1-5 mg of amphotericin B daily, with dosage gradually increased to 0.4-0.6 mg/kg daily, plasma concentrations ranging from approximately 0.5-2 mcg/mL were reported. Following a rapid initial decrease, plasma concentrations plateau at about 0.5 mcg/mL. The pharmacokinetics of amphotericin B following administration of amphotericin B liposomal are nonlinear, with greater than proportional increases in serum concentrations observed with dosage increases from 1 mg/kg daily to 5 mg/kg daily.

Steady state concentrations of amphotericin B are attained within 4 days of initiating amphotericin B liposomal.

Amphotericin B concentrations attained in inflamed pleura, peritoneum, synovium, and aqueous humor following IV administration of conventional amphotericin B reportedly are about 60% of concurrent plasma concentrations. Penetration into vitreous humor is low. Following administration of amphotericin B liposomal mean trough concentrations of amphotericin B, although variable, generally remain constant with repeated daily administration over the dosage range of 1-5 mg/kg per day.

Following IV administration of conventional amphotericin B, CSF concentrations of the drug rarely exceed 2.5% of concurrent serum concentrations. Low concentrations of amphotericin B are attained in amniotic fluid. It is not known whether amphotericin B is distributed into milk.

Amphotericin B is more than 90% bound to plasma proteins.

The metabolic fate of amphotericin B in humans has not been fully elucidated. Following IV administration of conventional amphotericin B in patients whose renal function is normal prior to therapy, the initial plasma half-life is approximately 24 hours. After the first 24 hours, the rate at which amphotericin B is eliminated decreases and an elimination half-life of approximately 15 days for conventional amphotericin B has been reported.

Conventional amphotericin B is eliminated very slowly (over weeks to months) by the kidneys. Over a 7-day period, the cumulative urinary excretion of a single dose of conventional amphotericin B is about 40% of the administered drug. It has been estimated that only about 2-5% of a total dose of amphotericin B is excreted in urine unchanged.

When conventional IV amphotericin B therapy is discontinued, the drug can be detected in the urine for at least 7 weeks due to its slow disappearance. The elimination half-life of amphotericin B liposomal ranges on average from 7-10 hours, although based on concentrations assessed 49 days after the final dose, mean half-lives ranged from 100-153 hours. This elimination half-life is likely due to a slow redistribution of amphotericin from tissues.

Amphotericin B is not hemodialyzable.

USES: This medication is used to treat a variety of serious fungal infections. It is often used in patients who cannot tolerate or who do not respond to the regular amphotericin treatment. It works by stopping the growth of fungi.

Generic name: amphotericin B lipid complex
Pronunciation: (AM-foe-TER-i-sin/LIP-id)

Reference product & biosimilars

No reference, biosimilar or interchangeable associated with this drug.

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Indications

The following indications are listed for Abelcet:

  • Aspergillosis
  • Blastomycosis
  • Candida Peritonitis
  • Candidal Endocarditis
  • Candidal Meningitis
  • Candidal Septicemia
  • Candidemia
  • Candidiasis
  • Coccidioidomycosis
  • Cryptococcal Septicemia
  • Cryptococcosis
  • Disseminated Candidiasis
  • Disseminated Sporotrichosis
  • Fungal Endocarditis
  • Fungal Infection Of Lung
  • Fungal Meningitis
  • Fungal Sepsis
  • Fungal Urinary Tract Infection
  • Histoplasmosis
  • Leishmaniasis
  • Mucormycosis
  • Pulmonary Cryptococcosis
  • Rhinocerebral Phycomycosis

Also known as: Blastomycotic Infection, Busse-Buschke Disease, California Disease, Candida Species Peritonitis, Candida Spp. Peritonitis, Candidal Infection, Candidal Sepsis, Candidosis, Coccidioidal Granuloma, Cryptococcal Infection, Cryptococcal Sepsis, Darling's Disease, Disseminated Candidosis, Disseminated Moniliasis, Endocardial Candidiasis, Endocardial Moniliasis, Fungal Pneumonia, Fungal Septicemia, Gilchrist's Disease, Infection With Cryptococcus Neoformans, Meningeal Candidiasis, Meningeal Moniliasis, Moniliasis, Mycotic Pneumonia, Mycotic Sepsis, Mycotic Septicemia, North American Blastomycosis, Phycomycetosis, Phycomycosis, Posada-Wernicke Disease, Posadas Disease, Posadas Mycosis, Pulmonary Busse-Buschke Disease, Pulmonary Cryptococcal Infection, Pulmonary Torulosis, Rhinocerebral Mucormycosis, Rhinocerebral Phycomycetosis, Rhinocerebral Zygomycosis, Septic Candidiasis, Septic Moniliasis, Torulosis, Uti Due To A Fungus, Zygomycosis.

Dosing

Amphotericin B is available as conventional amphotericin B (formulated with sodium desoxycholate) or amphotericin B liposomal (AmBisome(R)); dosage is expressed as amphotericin B.

Dosage of amphotericin B varies depending on whether the drug is administered as conventional amphotericin B (formulated with sodium desoxycholate) or amphotericin B liposomal. Dosage recommendations for the specific formulation being administered should be followed.

Drug interactions

Systematic drug interaction studies have not been performed to date using amphotericin B liposomal. The fact that drug interactions reported with conventional IV amphotericin B could also occur with the lipid formulation of the drug should be considered.

Contraindications

*Hypersensitivity to amphotericin B or any other component in the respective formulation. The manufacturers of conventional amphotericin B and amphotericin B liposomal suggest that use of these drugs can be considered in patients with hypersensitivity if the clinician determines that the benefits of such therapy outweigh the risks.

Adverse reactions

The most commonly reported adverse effects reported with conventional amphotericin B include fever (sometimes accompanied by chills), malaise, weight loss, hypotension, tachypnea, anorexia, nausea, vomiting, diarrhea, dyspepsia, cramping epigastric pain, normochromic, normocytic anemia, pain at the injection site (with or without phlebitis or thrombophlebitis), generalized pain (including muscle/joint pains), headache, and decreased renal function and renal function abnormalities (e.g., azotemia, hypokalemia, hyposthenuria, renal tubular acidosis, nephrocalcinosis).

In a study of amphotericin B liposomal as empiric therapy in adults, the only adverse effects reported more frequently than with conventional IV amphotericin B and in >=20% of patients were diarrhea and rash. Amphotericin B liposomal is associated with a lower overall incidence of chills, changes in blood pressure, tachycardia, hypoxia, hypokalemia, and various adverse effects related to renal toxicity than the conventional formulation of the drug.

Precautions

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ICD codes

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Formulary status

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Last reviewed · Source: First Databank (FDB) drug data