Version July 2025
Human African trypanosomiasis (alternative agent):
Note: Use in combination with glucocorticoids to reduce the risk of melarsoprol-related encephalopathy (Ref).
Due to T. b. rhodesiense: Note: Reserve for patients who are unable to receive first-line agent or unable to take oral medications (Ref).
IV: 2.2 mg/kg (maximum dose: 180 to 200 mg) once daily for 10 days (Ref).
Due to T. b. gambiense: Note: Reserve for patients who have recurrent relapse after use of first-line or rescue therapy (Ref).
IV: 2.2 mg/kg (maximum dose: 180 mg) once daily for 10 days (Ref).
(For additional information see "Melarsoprol (United States: Available via CDC drug service investigational drug [IND] protocol only): Pediatric drug information")
African trypanosomiasis (sleeping sickness): Note: Melarsoprol is only available through special distribution programs; refer to Prescribing and Access Restrictions for additional information; defer to CDC and investigational drug protocols. Use concomitantly with prednisolone to reduce the risk of melarsoprol-related encephalopathy; various prednisolone regimens have been reported. Prednisolone doses are typically administered once daily for 10 to 12 days with a taper over the last 3 days (Ref); initiation several days prior to melarsoprol has also been suggested (Ref).
Infants, Children, and Adolescents: IV: 2.2 mg/kg/dose once daily for 10 days; maximum dose: 180 mg/dose (Ref).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Frequency not defined:
Cardiovascular: Cardiac insufficiency, hypertension
Central nervous system: Encephalopathy, headache, hyperthermia
Dermatologic: Urticaria
Endocrine & metabolic: Albuminuria
Gastrointestinal: Diarrhea, vomiting
Hematologic & oncologic: Agranulocytosis
Hepatic: Hepatic insufficiency
Hypersensitivity: Hypersensitivity reaction
Immunologic: Jarisch-Herxheimer reaction
Renal: Renal insufficiency
G6PD deficiency (Kappagoda 2011); pregnancy (depending on the clinical condition of the mother) (WHO 2024).
Concerns related to adverse effects:
• Encephalopathy: Reactive encephalopathy, sometimes fatal, may occur, usually within 7 to 14 days after treatment initiation. Presentation includes abnormal behavior, cerebral edema, seizures, progressive coma, or rapid onset of neurological disorders. Fever and/or headache may be early signs of the disorder (Blum 2001; WHO 2019). Discontinue treatment if signs/symptoms of encephalopathy occur; administration of glucocorticoids may prevent development of this syndrome (CDC 2024; Pépin 1989; WHO 2024).
• Irritant: Melarsoprol is an irritant; avoid extravasation (WHO 1995).
Dosage form specific issues:
• Propylene glycol: Some dosage forms may contain propylene glycol (MSF 2016; WHO 2024); large amounts are potentially toxic and have been associated with hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Zar 2007).
Some dosage forms may contain propylene glycol (MSF 2016; WHO 2019); in neonates, large amounts of propylene glycol delivered orally, intravenously (eg, >3,000 mg/day), or topically have been associated with potentially fatal toxicities which can include metabolic acidosis, seizures, renal failure, and CNS depression; toxicities have also been reported in children and adults including hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Shehab 2009).
Melarsoprol is not commercially available in the US; it is available for the treatment of patients with African trypanosomiasis through the Centers for Disease Control (CDC) Drug Service to be used under an Investigational New Drug (IND) protocol. To obtain treatment advice and obtain melarsoprol, contact the Division of Parasitic Diseases and Malaria (404-718-4745; [email protected]), the CDC Drug Service (404-639-3670; [email protected]), or for emergencies after business hours, on weekends, and on federal holidays, the CDC Emergency Operations Center (770-488-7100). Additional information from the CDC is available at https://www.cdc.gov/laboratory/drugservice/formulary.html.
IV: Administer by slow IV injection (Ref). Melarsoprol is an irritant; avoid extravasation (Ref).
Parenteral: IV: Administer undiluted by slow IV push (Ref). When drawing up dose at the bedside, drug should not come into contact with water; may lead to precipitation. Glass syringes are preferred for administration; following use, syringe must be washed, dried, and sterilized. If sterilization of glass syringe is not possible or reliable, then plastic syringes may be used; however, administration should occur immediately after drawing into syringe as melarsoprol may lead to deterioration of some plastic syringes (Ref). Some experts recommend administration via a microprofuser (butterfly) (Ref). Melarsoprol injection is very painful; in the case of local reaction, another IV site and line should be used for the next dose (Ref). Melarsoprol is an irritant; avoid extravasation (Ref).
Human African trypanosomiasis: Alternative agent for the treatment of second-stage (CNS involvement) human African trypanosomiasis (sleeping sickness) due to Trypanosoma brucei rhodesiense; alternative agent for treatment of human African trypanosomiasis due to Trypanosoma brucei gambiense in patients who have recurrent relapse after use of first-line or rescue therapy (WHO 2024).
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs (contraindicated in pregnancy) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Community/Ambulatory Care Settings).
None known.
There are no known significant interactions.
Other agents are preferred for the treatment of human African trypanosomiasis in pregnant patients when therapy cannot be postponed until after delivery. Melarsoprol is theoretically contraindicated for use during pregnancy, depending on the clinical condition of the mother (WHO 2024).
Signs/symptoms of encephalopathy, hypersensitivity.
Organoarsenic compound that acts on trypanothione (Fairlamb 1989).
Distribution: Vd: >100 L (Burri 1993).
Metabolism: Metabolized to active metabolite, melarsen oxide (Nok 2003).
Half-life elimination: 35 hours (Burri 1993).
Time to peak: 15 minutes (Nok 2003).
