Liposomal Amphotericin B

Liposomal amphotericin B packages amphotericin B in unilamellar liposomes, which keeps the drug in the circulation, delivers it to macrophages and reduces kidney toxicity. It is the preferred amphotericin formulation for invasive fungal infection and visceral leishmaniasis. Infusion reactions, hypokalaemia and liver enzyme rises still occur, but nephrotoxicity is much lower than with deoxycholate.

Class. Polyene antifungal; lipid formulation.

Mechanism. Binds ergosterol in fungal membranes, forming pores and causing ion leakage. The liposome is selectively disrupted by fungal enzymes at the site of infection.

Pharmacokinetics. Intravenous only. Peak levels are much higher than with deoxycholate, with a long terminal half life and prolonged tissue levels in liver, spleen and lung. Slow elimination in urine and faeces.

Cryptococcal meningitis (HIV-associated, induction). - Single high dose: 10 mg/kg intravenously once on day 1, with flucytosine 100 mg/kg daily in four divided doses and fluconazole 1200 mg daily for 14 days. - Alternative: 3 to 4 mg/kg daily for 7 to 14 days with flucytosine. - Then consolidation fluconazole 800 mg daily for 2 weeks, then 400 mg daily to complete 8 weeks, and then 200 mg daily.

Invasive candidiasis and aspergillosis. 3 to 5 mg/kg daily until clinical response, then step-down; duration set by the infection.

Mucormycosis. 5 to 10 mg/kg daily, usually 5 mg/kg and up to 10 mg/kg for central nervous system disease, until response.

Severe histoplasmosis and talaromycosis. 3 mg/kg daily for 1 to 2 weeks, then itraconazole.

Visceral leishmaniasis (East Africa). 3 to 5 mg/kg daily over 6 to 10 days to a total of 30 mg/kg in immunocompetent patients; in HIV co-infection a total of 40 mg/kg, often combined with miltefosine, followed by secondary prophylaxis.

Children. Dosed by weight at the same mg/kg doses as adults.

Maximum: 10 mg/kg daily. Loading dose: none. Titration: none.

Contraindications. Hypersensitivity to amphotericin B or any component.

Serious adverse effects. Infusion reactions with chest tightness, back pain and flushing, anaphylaxis, hypokalaemia, hypomagnesaemia, nephrotoxicity (less than deoxycholate), hepatotoxicity and anaemia.

Common adverse effects. Fever, rigors, nausea, headache and raised liver enzymes.

Interactions. Additive nephrotoxicity with ciclosporin, tacrolimus, aminoglycosides and tenofovir disoproxil fumarate; hypokalaemia with corticosteroids and diuretics; digoxin toxicity with hypokalaemia.

Common prescribing errors. Diluting in saline, switching doses one for one with deoxycholate, no electrolyte replacement and no monitoring.

Special groups. - Pregnancy: used when indicated. - Breastfeeding: compatible. - Children: dosed by weight; use for visceral leishmaniasis is well established. - Older adults: usual dose with kidney monitoring. - Kidney impairment: no adjustment; monitor closely. - Liver impairment: no adjustment; monitor liver tests.

Regional points. In East Africa, a single 10 mg/kg dose of liposomal amphotericin B for HIV-associated cryptococcal meningitis, and its use in visceral leishmaniasis, make it a priority for access; supplies may be limited and costs high.

Formulations. Powder for infusion 50 mg vial; store unopened vials at 25 degrees C or under.

Administration. Reconstitute with sterile water, dilute in 5% glucose to 1 to 2 mg/mL (0.2 to 2 mg/mL), pass through a 5 micron filter, and infuse over 1 to 2 hours (30 to 60 minutes if tolerated).

Baseline. Creatinine, potassium, magnesium, liver tests, full blood count.

Monitoring. Creatinine, potassium and magnesium at least 2 to 3 times weekly, with replacement; liver tests weekly.

Stopping thresholds. Stop for anaphylaxis; slow the infusion for infusion reactions; review for creatinine over twice baseline.

Referral and escalation. Specialist review for all invasive mycoses, visceral leishmaniasis or persistent infusion reactions.