Drug reference

melarsoprol

Arsenical · Antiprotozoal

ArsenicalAntiprotozoal

CDSCO approved

EXCRETION

—

not curated

INTERACTIONS

—

none in our sources

PREGNANCY

FDA category + note

Mechanism

Melarsoprol is a prodrug metabolized to melarsen oxide, the active form. Melarsen oxide reacts avidly and reversibly with vicinal sulfhydryl groups, inactivating many enzymes. It also reacts with trypanothione (a spermidine-glutathione adduct unique to parasites), forming a melarsen oxide–trypanothione adduct that inhibits trypanothione reductase.

Indications

Late (CNS) stages of East African trypanosomiasis caused by T. brucei rhodesienseEarly hemolymphatic stage of East African trypanosomiasis caused by T. brucei rhodesiense (reserved for late-stage due to toxicity)Second-stage T. b. rhodesiense HAT

Dosing

Adult: 2.2 mg/kg per day for 10 days (IV)
Pediatric: 2.2 mg/kg per day for 10 days (IV)

Pharmacokinetics

Protein binding

Not explicitly stated for melarsoprol, but for active metabolite. Given the drug affects trypanothione, which is the glutathione version in trypanosomes, it is more about its interaction with the parasite's internal molecules rather than protein binding.

Metabolism

Prodrug, metabolized rapidly (<30 min) to melarsen oxide (active form).

Excretion

~80% of the arsenic found in feces

Side effects

Common

Febrile reaction (especially if parasitemia is high)VomitingAbdominal colicAlbuminuriamyocardial injuryencephalopathyperipheral neuropathyhypertension

Serious

Reactive encephalopathy (9-11 days after treatment, in 5-10% of patients, fatal in about half)
Peripheral neuropathy (about 10% of patients)
Hypertension
Myocardial damage
Shock (rare)
g6pd-induced hemolysis
erythema nodosum leprosum
hypotension
reactive encephalopathy
Reactive encephalopathy (5–18%, 10–70% mortality)
Exfoliative dermatitis
Bloody diarrhea
Peripheral neuropathy
Renal dysfunction
Liver toxicity
Phlebitis
Soft tissue necrosis (if given paravenously)