Caspofungin

Caspofungin is an intravenous echinocandin used for candidaemia and invasive candidiasis, oesophageal candidiasis, empirical therapy in persistent febrile neutropenia, and salvage therapy for invasive aspergillosis. It is fungicidal against Candida and fungistatic against Aspergillus, and it is inactive against Cryptococcus. It is well tolerated and has few interactions.

Class. Echinocandin antifungal.

Mechanism. Non-competitive inhibition of 1,3-beta-D-glucan synthase, blocking cell wall synthesis. Resistance arises through FKS mutations. Candida parapsilosis is less susceptible.

Pharmacokinetics. Intravenous only. Highly protein bound, half life 9 to 11 hours, slow hydrolysis and N-acetylation (not CYP-mediated), excreted in urine and faeces. Negligible cerebrospinal fluid and urine penetration.

Invasive candidiasis and candidaemia (adults). - Loading: 70 mg intravenously on day 1. - Maintenance: 50 mg once daily; 70 mg daily if over 80 kg. - Duration: 14 days after the first negative blood culture and resolution of symptoms; step down to oral fluconazole when stable and susceptible.

Oesophageal candidiasis. 50 mg daily (no loading dose in some labels) for 7 to 14 days after symptom resolution.

Empirical therapy in febrile neutropenia. Load 70 mg, then 50 mg daily until neutrophil recovery.

Salvage invasive aspergillosis. Load 70 mg, then 50 mg daily, with 70 mg daily in specialist practice.

Children (3 months to 17 years). Load 70 mg/m2 (maximum 70 mg), then 50 mg/m2 daily (maximum 70 mg); neonates 25 mg/m2 daily.

Titration. 70 mg daily with enzyme inducers (rifampicin, efavirenz, nevirapine, phenytoin, carbamazepine, dexamethasone). Maximum: 70 mg daily.

Contraindications. Hypersensitivity to echinocandins.

Serious adverse effects. Hepatotoxicity, anaphylaxis, severe skin reactions and haemolysis (rare).

Common adverse effects. Infusion-site phlebitis, fever, rash, flushing (histamine-mediated), raised liver enzymes and hypokalaemia.

Interactions. Ciclosporin raises caspofungin levels and transaminases, so combine only with monitoring; tacrolimus levels fall by about 20%; inducers lower caspofungin.

Common prescribing errors. Using it for cryptococcal or central nervous system infection, forgetting the loading dose, diluting in glucose, and not adjusting for liver impairment.

Special groups. - Pregnancy: avoid unless essential; embryotoxic in animals. - Breastfeeding: limited data. - Children: body-surface-area dosing. - Older adults: no adjustment. - Kidney impairment: no adjustment. - Liver impairment: Child-Pugh B: after the 70 mg load, give 35 mg daily; Child-Pugh C: limited data.

Regional points. Cryptococcus is intrinsically resistant, so echinocandins have no role in cryptococcal meningitis, the commonest invasive fungal infection in advanced HIV in the region.

Formulations. Powder for infusion 50 mg and 70 mg vials; store at 2 to 8 degrees C.

Administration. Reconstitute with sterile water and dilute in 0.9% sodium chloride; infuse over about 1 hour. Do not use glucose.

Baseline. Liver tests, potassium, creatinine.

Monitoring. Liver tests weekly; blood cultures until clear; potassium.

Stopping thresholds. Stop for anaphylaxis, severe skin reaction or marked hepatotoxicity (ALT over five times the upper limit of normal with symptoms).

Referral and escalation. Specialist review for candidaemia, ophthalmology review for candidaemia (retinal and endophthalmitis), and treatment failure.