Powder for injection 300 mg of pentamidine isethionate.
Pentamidine was registered in 1950 as pentamidine mesylate but has been used against Trypanosomiasis since 1937 and against leishmaniasis since 1940. Its effect on Pneumocystis carinii was evidenced by Goa in 1987, and the drug was reevaluated and commercialized in its actual isethionate form in 1984. Pentamidine isethionate is a diamidine compound with antiprotozoal activity. It is administered parenterally since it is unreliably absorbed from the gastrointestinal tract. It does not enter the cerebrospinal fluid at curative levels. Detectable amounts remain in the liver and kidney for many months as a result of selective binding. Only a small fraction is excreted unchanged in the urine within 24 hours.
Used in the treatment of the first stage of T. b. gambiense African trypanosomiasis
Some of the observed adverse effects are mild nephrotoxicity which is usually completely reversible and pancreatic damage resulting in hypoglycaemia due to excessive insulin release, subsequent insulin insufficiency and pancreatitis have been reported. Other adverse effects include hypotension, hypocalcaemia, gastrointestinal effects, cardiac dysrhythmias, local induration and, occasionally, sterile abscess. Rarely, thrombocytopenia, leukopenia, abnormal hepatic function tests and Stevens-Johnson syndrome have been reported.
Storage: Vials of dry powder should be stored below 30°C. Reconstituted sterile solutions should be stored between 2 and 8°C (for short periods) and any unused portion should be discarded within 24 hours of preparation.
Powder for injection 1 g
A complex derivative of urea with antiprotozoal activity that has also been used in the treatment of onchocerciasis. It enters the extracellular space but does not cross the blood-brain barrier. Because it forms stable complexes with protein, suramin is not absorbed from the gastrointestinal tract and must be administered by intravenous injection. It dissociates slowly from plasma proteins and is detectable unchanged in the urine for up to 3 months after the last dose.
Used in the treatment of first stage T. b. rhodesiense African trypanosomiasis
Some of the observed adverse effects are heavy proteinuria, stomal ulceration, exfoliative dermatitis, severe diarrhoea, prolonged high fever and prostration. Lesser symptoms, which are common, include tiredness, anorexia, malaise, polyuria, increased thirst and tenderness of the palms and soles.
Storage: Vials of suramin powder for injection should be kept in well-closed containers protected from light.
Injection 36 mg/ml solution in propylene glycol (1,2 - propanediol), in vials of 5 ml.
Melarsoprol is 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 its solvent 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.
Used in the treatment of confirmed second stage cases (meningoencephalitic involvement) of T. b. gambiense or T. b. rhodesiense African trypanosomiasis. Relapse occurs in less than 5% of cases, however in certain endemic areas rate of relapses have been much higher (up to 20%). Because drug-induced fatalities occasionally occur, melarsoprol should be used only in hospitals and specialized treatment centres.
Some of the observed adverse serious effects are a reactive encephalopathy characterized by headache, tremor, slurring of speech, convulsions and ultimately coma, this is the most serious complication. Frequent, less severe, adverse effects include myocardial damage, albuminuria and hypertension. Agranulocytosis is a particularly dangerous but rare reaction. Dose-related renal and hepatic dysfunction can occur during the later phases of treatment. Other adverse effects include hyperthermia, urticarial rashes, polyneuropathy, headache, diarrhoea and vomiting.
Storage: Ampoules are kept at room temperature and should be protected from light.
Injection 200 mg of eflornithine hydrochloride/ml solution in 100-ml bottle.
Eflornithine is an ornithine derivative with activity that is specific against T. b. gambiense. It acts by inhibiting the enzyme ornithine decarboxylase, which is involved in polyamine synthesis in trypanosomes. The plasma half-life is 3.0-3.5 hours. Eflornithine readily crosses the blood-brain barrier to enter the brain and is mainly excreted by the kidneys.
Used for the treatment of T. b. gambiense African trypanosomiasis the late stage. Eflornithine is not effective for the treatment of T.b. rhodesiense infections.
The most common adverse effects reported include diarrhoea, anaemia, leukopenia, thrombocytopenia and convulsions. Impaired hearing has also been reported. Less commonly, vomiting, anorexia, alopecia, abdominal pain, headache, facial oedema, eosinophilia and dizziness have occurred. These are reversible on withdrawal of the drug.
Storage: Ampoules should be stored at ambient temperatures.
Nifurtimox is a nitrofuran with trypanocidal effects, acting as a inhibitor of the trypaniothione reductase, but also generating free radicals toxic for the trypanosome.
It is used for the treatment of Chagas disease and not registered for human African trypanosomiasis. It is used off-label in the late stage of T. b. gambiense African trypanosomiasis in combination with eflornithine. It is not recommended in monotherapy as its efficacy is limited.
Most frequent adverse effects reported are: anorexia, loss of weight, nausea, vomiting, abdominal pain, insomnia, headache, vertigo, myalgias, convulsions. neuritis, rashes and allergic reactions. Hallucinations, excitatory states and psychosis have been also described.
Storage: They should be stored below 25°C.