amphotericin b

High Alert

IV: Treatment of progressive, potentially fatal fungal infections. The lipid complex, and liposome formulations should be considered for patients who are intolerant (e.g., renal dysfunction) or refractory to amphotericin B deoxycholate.

Amphotericin B liposome

Management of suspected fungal infections in febrile neutropenic patients:
- Treatment of visceral leishmaniasis,
- Treatment of cryptococcal meningitis in HIV patients.

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Lactation: Potential for distribution into breast milk and toxicity in infant; discontinue nursing.

Use Cautiously in:

Renal impairment or electrolyte abnormalities;
Patients receiving concurrent leukocyte transfusions (↑ risk of pulmonary toxicity);
OB: Has been used safely.

Adv. Reactions/Side Effects ⬆ ⬇

CV: chest pain, hypotension, edema, hypertension, tachycardia

Derm: pruritus, rashes

F and E: hyperglycemia, hypocalcemia, hypokalemia, hypomagnesemia

GI: ↑liver enzymes, diarrhea, hyperbilirubinemia, nausea, vomiting, abdominal pain

GU: nephrotoxicity, hematuria

Hemat: anemia, leukopenia, thrombocytopenia

Local: phlebitis

MS: arthralgia, myalgia

Neuro: anxiety, confusion, headache, insomnia

Resp: dyspnea, hypoxia, wheezing

Misc: chills, fever, acute infusion reactions, HYPERSENSITIVITY REACTIONS

Interactions ⬆ ⬇

Drug-drug:

↑risk of nephrotoxicity, bronchospasm, and hypotension with antineoplastics.
Concurrent use with corticosteroids↑ risk of hypokalemia.
Concurrent use with zidovudine may ↑ the risk of myelotoxicity and nephrotoxicity.
Concurrent use with flucytosine↑ antifungal activity but may ↑ the risk of toxicity from flucytosine.
Combined use with azole antifungals may induce fungal resistance.
↑risk of nephrotoxicity with other nephrotoxic agents such as aminoglycosides, cyclosporine, or tacrolimus.
Hypokalemia from amphotericin ↑ the risk of digoxin toxicity.
Hypokalemia may enhance the curariform effects of neuromuscular blocking agents.

Availability ⬆ ⬇

(Generic available)

Amphotericin Deoxycholate

Powder for injection: 50 mg/vial

Amphotericin B Lipid Complex

Suspension for injection: 5 mg/mL

Amphotericin B Liposome

Powder for injection: 50 mg/vial

Route/Dosage ⬆ ⬇

Conventional and lipid-based formulations are NOT interchangeable

Amphotericin Deoxycholate

IV (Adults ): Give test dose of 1 mg. If test dose tolerated, initiate therapy with 0.25 mg/kg/day (doses up to 1.5 mg/kg/day may be used, depending on type of infection) (alternate-day dosing may also be used); Bladder irrigation: Instill 50 mcg/mL solution into bladder daily for 5–10 days.
IV (Infants and Children): Give test dose of 0.1 mg/kg (maximum dose 1 mg) or may administer initial dose of 0.25–1 mg/kg/day over 6 hr (without test dose) (some infections may require 1.5 mg/kg/day; alternate-day dosing may be used).
IT (Adults ): 25–300 mcg every 48–72 hr, ↑ to 500 mcg–1 mg as tolerated (maximum total dose = 15 mg).
IT (Children ): 25–100 mcg every 48–72 hr; ↑ to 500 mcg as tolerated.

Amphotericin B Lipid Complex (Abelcet)

IV (Adults and Children ): 2.5–5 mg/kg every 24 hr (no test dose needed).

Amphotericin B Liposome (AmBisome)

IV (Adults and Children ): Empiric therapy: 3 mg/kg every 24 hr; Documented infections: 3–5 mg/kg every 24 hr; Visceral leishmaniasis (immunocompetent patients): 3 mg/kg every 24 hr on days 1–5, then 3 mg/kg every 24 hr on days 14 and 21; Visceral leishmaniasis (immunosuppressed patients): 4 mg/kg every 24 hr on days 1–5, then 4 mg/kg every 24 hr on days 10, 17, 24, 31, and 38; Cryptococcal meningitis in HIV patients: 6 mg/kg every 24 hr.

US Brand Names ⬆ ⬇

amphotericin B lipid complex: Abelcet,

amphotericin B liposome: AmBisome

Action ⬆ ⬇

Binds to fungal cell membrane, allowing leakage of cellular contents.
Toxicity (especially acute infusion reactions and nephrotoxicity) is less with lipid formulations.

Therapeutic effects:

Can be fungistatic or fungicidal (depends on concentration achieved and susceptibility of organism).

Spectrum:

Active against:
- Aspergillosis,
- Blastomycosis,
- Candidiasis,
- Coccidioidomycosis,
- Cryptococcosis,
- Histoplasmosis,
- Leishmaniasis (liposomal formulation only),
- Mucormycosis.

Classifications ⬆ ⬇

Therapeutic Classification: antifungals

Pharmacokinetics ⬆ ⬇

Absorption: IV administration results in complete bioavailability.

Distribution: Extensively distributed to body tissues and fluids. Poor penetration into CSF.

Metabolism/Excretion: Elimination is very prolonged. Detectable in urine up to 7 wk after discontinuation.

Half-Life: Biphasic—initial phase, 24–48 hr; terminal phase, 15 days. Lipid complex: 174 hr. Liposomal: 100–153 hr.

Canadian Brand Names ⬆ ⬇

amphotericin B deoxycholate: Fungizone

Time/Action Profile ⬆ ⬇

(blood levels)

ROUTE	ONSET	PEAK	DURATION
IV	rapid	end of infusion	24 hr

Patient/Family Teaching ⬆ ⬇

Explain need for long duration of IV therapy.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected and to avoid breast feeding during therapy.
IV: Inform patient of potential side effects and discomfort at IV site. Advise patient to notify health care professional if side effects occur.
Home Care Issue: Instruct family or caregiver on dilution, rate, and administration of drug and proper care of IV equipment.

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Indications ⬇