Amphotericin B
Synonyms :
Conventional Amphotericin B, Liposomal Amphotericin B
Mechanism :
Amphotericin B is a polyene fungistatic drug. It does not reach fungicidal concentrations in body fluids. It acts by binding to the sterol component of fungal cell membrane leading to alterations in cell permeability and 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. It is effective against a wide variety of fungi and is used to treat systemic fungal infections causes by Aspergillus, Mucor species, Candida, Cryptococcus and Blastomyces. It has also been used in protozoal infections like Kala-Azar.
Indication :
- Cryptococcosis
- Blastomycosis
- Histoplasmosis
- Candidiasis
- Aspergillosis
- Coccidioidomycosis
- Visceral leishmaniasis
Contraindications :
Any known hypersensitivity to amphotericin or any of its constituents is a contraindication for use. Renal impairment may occur. Monitor serum potassium, magnesium and phosphate levels, as they may be lowered. Also, LFT should be monitored, and the drug should be discontinued in case of severe liver dysfunction. Avoid concurrent use of other nephrotoxic drugs.
Dosing :
A test dose of 0.1 mg/kg/dose to a maximum of 1 mg is infused over 20-60 minutes. An initial dose of 0.25-0.5 mg/kg IV on day 1. From day 2: 1 mg/kg/day once daily, infuse over 2-6 hours. Total dose of 30-40 mg/kg is given over 3-6 weeks.
Intrathecal, intraventricular: 25-100 mcg every 48-72 hours; increase to 500 mcg as tolerated. Dose reduction may be advisable if amphotericin is suspected of causing nephrotoxicity.
Liposomal amphotericin B:
3-5 mg/kg/day IV infusion for 7-10 days.
Visceral leishmaniasis:
Liposomal amphotericin B if given at 10 mg/kg IV as a single dose.
Adverse Effect :
Fever, chills, malaise, weight loss, hypotension; tachypnea, anorexia, nausea, vomiting, diarrhea, abdominal pain, anemia, headache, azotemia, hypokalemia, renal tubular acidosis, and nephrocalcinosis. The liposomal preparation of amphotericin B is well tolerated, and has a lower incidence of chills, hypertension, hypotension, tachycardia, hypoxia, hypokalemia, hypomagnesemia and nephrotoxicity B.
Interaction :
Digitalis: Hypokalemia induces by amphotericin can potentiate digitalis toxicity.
Skeletal Muscle Relaxants: Increased effects.
Nephrotoxic drugs: Concurrent use increases nephrotoxic potential.
Corticosteroids: Enhance potassium depletion.
Zidovudine: Enhances effects on bone marrow and renal function.
Flucytosine: Enhanced toxicity.
Cyclosporin: Increased levels.
Renal Dose :
Dose in Renal Impairment GFR (mL/min)
| 20-50 | Dose as in normal renal function |
| 10-20 | Dose as in normal renal function |
| <10 | Dose as in normal renal function |
Dose in Patients undergoing Renal Replacement Therapies
| CAPD | Not dialysed. Dose as in normal renal function |
| HD | Not dialysed. Dose as in normal renal function |
| HDF/High flux | Unknown dialysability. Dose as in normal renal function |
| CAV/VVHD | Not dialysed. Dose as in normal renal function |
Hepatic Dose :
No dosage adjustments are recommended.