Sodium Stibogluconate

Sodium stibogluconate is a pentavalent antimonial given by injection for visceral and cutaneous leishmaniasis. In East Africa it is combined with paromomycin for visceral leishmaniasis, a regimen that shortens treatment from 30 to 17 days. It is toxic to the heart, pancreas, liver and kidney, and is less effective in HIV co-infection.

Class. Antileishmanial; pentavalent antimonial.

Mechanism. Reduced to the trivalent form within macrophages and amastigotes, where it inhibits trypanothione reductase and glycolysis and disrupts DNA topoisomerase function.

Pharmacokinetics. Not absorbed orally. After intramuscular or intravenous injection, absorbed rapidly. Eliminated by the kidney; terminal half life about 76 hours.

Visceral leishmaniasis (East Africa). Sodium stibogluconate 20 mg of pentavalent antimony/kg intramuscularly or intravenously once daily with paromomycin 15 mg/kg (11 mg base/kg) intramuscularly once daily, both for 17 days.

Visceral leishmaniasis (monotherapy where combination is unavailable). 20 mg/kg daily for 30 days.

Cutaneous leishmaniasis. 20 mg/kg daily for 20 days (or intralesional 1 to 5 mL into the lesion every 1 to 2 weeks, for localised disease).

Mucosal leishmaniasis. 20 mg/kg daily for 28 days, specialist care.

HIV co-infection. Not preferred; liposomal amphotericin B is used instead.

Loading dose, maintenance dose and titration. Not applicable. Maximum: 850 mg of antimony daily in older practice; many programmes now give the full weight-based dose.

Main alternatives. Liposomal amphotericin B, miltefosine, paromomycin.

Contraindications. Hypersensitivity; severe cardiac, kidney or liver disease; pregnancy; QT prolongation; concurrent QT-prolonging drugs.

Serious adverse effects. QT prolongation and fatal arrhythmias, pancreatitis, hepatotoxicity, nephrotoxicity, bone marrow suppression, and severe musculoskeletal pain.

Common adverse effects. Pain at the injection site, arthralgia, myalgia, abdominal pain, nausea and raised liver enzymes.

Interactions. QT-prolonging drugs (macrolides, quinolones, antipsychotics), amiodarone and nephrotoxins add risk; antiretrovirals (efavirenz, ritonavir) can alter levels or add hepatotoxicity.

Common prescribing errors. Under-dosing, stopping early, and not monitoring ECG, amylase and creatinine.

Special groups. - Pregnancy: avoid; liposomal amphotericin B is preferred. - Breastfeeding: avoid. - Children: weight-based dosing; tolerate better than adults. - Older adults: higher risk of cardiotoxicity; consider alternatives. - Kidney impairment: avoid in severe impairment. - Liver impairment: avoid in severe impairment.

Regional points. Visceral leishmaniasis is endemic in north-western Kenya (Pokot), South Sudan, Ethiopia and Uganda; 17-day sodium stibogluconate with paromomycin is the first-line regimen in East Africa, and HIV co-infection requires liposomal amphotericin B (with or without miltefosine) and secondary prophylaxis.

Formulations. Injection 100 mg of pentavalent antimony/mL (30% w/v) in 100 mL vials.

Administration. Intramuscular: deep injection, divided if volume exceeds 5 mL. Intravenous: dilute in 5% glucose and give slowly over at least 5 minutes.

Baseline. ECG, creatinine, liver tests, amylase or lipase, full blood count, HIV test, pregnancy test.

Monitoring. ECG weekly; amylase or lipase, liver tests and creatinine weekly; clinical response (fever, spleen size, haemoglobin) weekly.

Stopping thresholds. Stop for QTc over 500 ms or arrhythmia, amylase or lipase over 3 times the upper limit of normal with symptoms, creatinine rise of more than 50%, or ALT over 3 times the upper limit of normal with symptoms, or over 5 times without.

Referral and escalation. Specialist care for all patients; admission for HIV co-infection, relapse and poor response.