(1995; 152 pages) [French] [Spanish]
Group: antiprotozoal agent
Injection 36 mg/ml solution in propylene glycol (1,2 - propanediol)
An organic arsenical compound that is used in African trypanosomiasis when the central nervous system is involved.
It is administered intravenously because it is unreliably absorbed from the gastrointestinal tract and is too irritant for intramuscular administration. However, it enters the central nervous system in sufficiently high quantities to kill the trypanosomes. It is largely metabolized to nontoxic pentavalent compounds and is excreted in the urine and faeces within a few days.
Treatment of confirmed cases of T. b. gambiense or T. b. rhodesiense African trypanosomiasis with meningoencephalitic involvement. Relapse occurs in less than 5% of cases.
Because drug-induced fatalities occasionally occur, melarsoprol should be used only in hospitals and specialized treatment centres.
Dosage and administration
Melarsoprol should always be administered by slow intravenous injection through a fine needle. The solution is intensely irritant. Particular care must be taken to avoid extravasation.
Several treatment regimens are currently used in the absence of clear evidence that one is better than another. They each comprise three or four series of daily injections with intervening rest periods of 7 to 10 days.
Patients should subsequently be seen every 6 months for at least 2 years. An increase in the leukocyte and protein content of the cerebrospinal fluid or the reappearance of trypanosomes is indicative of relapse. In this event, a second complete course of treatment may be administered. However, this is rarely successful and eflornithine, if available, offers a more effective alternative for the treatment of T. b. gambiense trypanosomiasis. At present, there is no alternative for treatment of T. b. rhodesiense infection.
A Herxheimer reaction resulting from massive destruction of parasites is particularly dangerous during treatment with melarsoprol. For this reason two or three preliminary injections of suramin or pentamidine are often administered to induce the reaction beforehand.
Contraindications and precautions
Melarsoprol should not be administered to pregnant women.
Patients should be hospitalized and remain under close supervision throughout treatment. Most clinicians suspend treatment during episodes of reactive encephalopathy.
Intercurrent infections, such as pneumonia and malaria, should be treated before melarsoprol is administered. Wherever possible, malnutrition should be corrected with a protein-rich diet. Systemic prednisolone at a dose of 1 mg/kg daily has been used to reduce the risk of fatal reactions during treatment but its value is disputed.
Severe haemolytic reactions have occurred in patients deficient in glucose-6-phosphate dehydrogenase.
Use in pregnancy
Treatment should be deferred until immediately after delivery since safety during pregnancy cannot be assured. Pregnant women with meningoencephalitic involvement should receive pentamidine (T. b. gambiense) or suramin (T. b. rhodesiense).
Although up to 95% of patients can be cured without serious complications, 1-5% of patients die during treatment. Reactive encephalopathy characterized by headache, tremor, slurring of speech, convulsions and ultimately coma is the most serious complication. It appears 3-10 days after the first dose of melarsoprol. Hypertonic infusions of mannitol are used to reduce cerebral oedema. Sedatives and anticonvulsants are of value in controlling convulsions.
Frequent severe adverse effects include myocardial damage, albuminuria and hypertension.
Hypersensitivity reactions are uncommon, but when they do occur (usually during a second or subsequent period of treatment) corticosteroid therapy and desensitization with a series of increasing doses can be effective. Agranulocytosis is a particularly dangerous but rare reaction. Dose-related renal and hepatic dysfunction can occur during the later phases of treatment.
Less serious adverse effects include hyperthermia, urticarial rashes, headache, diarrhoea and vomiting.
Ampoules should be kept protected from light.