Version May 2024
African trypanosomiasis, second-stage disease (with CNS involvement):
Due to T. b. rhodesiense: IV: 2 to 3.6 mg/kg once daily for 3 days (dose is progressively increased during this course); after 7 days, 3.6 mg/kg once daily for 3 days, followed by another course of 3.6 mg/kg once daily for 3 days, starting 7 days after completion of the previous course for a total of 3 courses (CDC 2019).
Due to T. b. gambiense (alternative agent): IV: 2.2 mg/kg (maximum dose: 180 mg) once daily for 10 days (Burri 2000; WHO 2019).
(For additional information see "Melarsoprol (United States: Available via CDC drug service investigational drug [IND] protocol only): Pediatric drug information")
African trypanosomiasis (sleeping sickness), second-stage disease (with CNS involvement): Note: Melarsoprol is only available through special distribution programs; refer to Prescribing and Access Restrictions for additional information. Dosing guidance is provided in the investigational new drug (IND) protocol when drug is released by the CDC. Use concomitantly with prednisolone to reduce the risk of melarsoprol-related encephalopathy; various prednisolone regimens have been reported; optimal dose has not been defined; doses are typically administered once daily for 10 to 12 days (Burri 2000; WHO 2019; MSF 2019); initiation of prednisolone for several days prior to melarsoprol has been suggested (Pépin 1989; Pépin 2006); some experts have recommended tapering the dose over 3 to 6 days (Pépin 2006; Schmid 2005; WHO 2019); an alternate approach for prolonged regimens is prednisolone administration only on days on which melarsoprol is administered (Burri 2000).
Due to Trypanosoma brucei rhodesiense: Limited data available.
Abbreviated 10-day regimen: Infants, Children, and Adolescents: IV: 2.2 mg/kg/dose once daily for 10 days; maximum dose: 180 mg/dose. Use concomitantly with prednisolone to reduce the risk of melarsoprol-related encephalopathy (Kuepfer 2012; MSF 2019; Red Book [AAP 2018]).
Prolonged discontinuous regimen: Infants, Children and Adolescents: IV: 2 to 3.6 mg/kg/dose once daily for 3 days, initiating at 2 mg/kg/dose on day 1 and titrating up to 3.6 mg/kg/dose on day 3, followed by a 7-day drug free interval; then a second series consisting of 3.6 mg/kg/dose once daily for 3 days, followed by a 7-day drug free interval; and then a final series of 3.6 mg/kg/dose once daily for 3 days; maximum dose: 180 mg/dose (CDC 2019; Pépin 2006). Use concomitantly with prednisolone to reduce the risk of melarsoprol-related encephalopathy (CDC 2019).
Due to Trypanosoma brucei gambiense (alternative agent): Limited data available: Infants, Children, and Adolescents: IV: 2.2 mg/kg/dose once daily for 10 days; maximum dose: 180 mg/dose. Use concomitantly with prednisolone to reduce the risk of melarsoprol-related encephalopathy (Burri 2000; Eperon 2007; WHO 2019).
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 condition of the mother) (WHO 2019).
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. Closely monitor patients; 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 corticosteroids may prevent development of this syndrome (Pépin 1989).
• 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 2019); 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 (WHO 2019). Melarsoprol is an irritant; avoid extravasation (WHO 1995).
Parenteral: IV: Administer undiluted by slow IV push (MSF 2019; WHO 2019). 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 (MSF 2016; WHO 2019). Some experts recommend administration via a microprofuser (butterfly) (WHO 2019). Melarsoprol is an irritant; avoid extravasation (WHO 1995).
African trypanosomiasis, second stage (with CNS involvement): Treatment of second-stage African trypanosomiasis (sleeping sickness), with involvement of the CNS, due to Trypanosoma brucei rhodesiense or Trypanosoma brucei gambiense.
None known.
There are no known significant interactions.
Other agents are preferred for the treatment of West African trypanosomiasis in pregnant women when therapy cannot be postponed until after delivery. Melarsoprol is theoretically contraindicated for use during pregnancy, depending on the condition of the mother (WHO 2019).
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).
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