Melarsoprol is available as an intravenous formulation through a special distribution program from the CDC. It is indicated for the treatment of the second stage of African trypanosomiasis with central nervous system involvement.

Melarsoprol Uses:

• African trypanosomiasis, the second stage (with CNS involvement):

  • Melarsoprol is used for the treatment of second-stage African trypanosomiasis, a sleeping sickness involving the CNS, which is caused by Trypanosoma brucei rhodesiense or Trypanosoma brucei gambiense.

Melarsoprol Dose in Adults:

Melarsoprol Dose in the treatment of the second stage of African trypanosomiasis with CNS involvement:

• Due to T. b. rhodesiense:

  • 2 to 3.6 mg per kg IV once a day for straight 3 days
  • The dose is progressively increased during this course.
  • After 7 days, 3.6 mg per kg once a day for 3 days, followed by another course of 3.6 mg per kg once a day for 3 days, starting 7 days after completion of the previous course for a total of 3 courses.

• Due to T. b. gambiense (alternative agent):

  • 2.2 mg/kg IV. The maximum dose is 180 mg once daily for 10 days.

Melarsoprol Dose in Childrens:

Melarsoprol Dose in second-stage African trypanosomiasis with CNS involvement (sleeping sickness):

Note:

• Melarsoprol is only available through special distribution programs.
• Dosing guidance is provided in the investigational new drug (IND) protocol when the drug is released by the CDC.
• Prednisolone should be used concomitantly to reduce the risk of melarsoprol-related encephalopathy.
• The optimal dose of the drug has not been defined.
• Typically, doses are administered once a day for ten to twelve days.
• Most experts suggest initiating prednisolone treatment several days before melarsoprol therapy.
• Tapering the dose over 3 to 6 days may be advised as some experts suggest.
• Prednisolone is alternately prescribed for prolonged regimens only on those days on which melarsopol is administrated.

• Due to Trypanosoma brucei rhodesiense:

  • Abbreviated 10-day regimen:

    • Infants, Children, and Adolescents:
    • IV: 2.2 mg/kg per dose once daily for 10 days.
    • The maximum dose is 180 mg/dose.
    • Use concomitantly with prednisolone to reduce the risk of melarsoprol-related encephalopathy.

  • Prolonged discontinuous regimen:

    • Infants, Children, and Adolescents:
    • IV: 2 to 3.6 mg/kg per dose once daily for three days.
    • Initially starting at 2 mg/kg per dose on day one and titrating up to 3.6 mg/kg per dose on day three followed by a 7-day drug-free interval.
    • Then a second series consisting of 3.6 mg/kg per dose once a day for three days followed by a 7-day drug-free interval.
    • Then a final series of 3.6 mg/kg per dose once daily for three days.
    • The maximum dose can be 180 mg per dose.
    • Use concomitantly with prednisolone to reduce the risk of melarsoprol-related encephalopathy.

• Due to Trypanosoma brucei gambiense (alternative agent):

  • Infants, Children, and Adolescents:
    • IV: 2.2 mg/kg per dose once daily for ten days.
    • The maximum dose is 180 mg per dose.
    • Use concomitantly with prednisolone to reduce the risk of melarsoprol-related encephalopathy.

Melarsoprol Pregnancy Category: D

• Theoretically, it is contraindicated during pregnancy.
• For the treatment of West African trypanosomiasis among pregnant women, other preferred medications should also be used (if the treatment cannot wait until after the delivery).

Use during breastfeeding:

• Its use during lactation has not been documented. 
• Before starting treatment for lactating mothers, it is important to weigh the benefits and risks of drug exposure in infants.

Dose in Renal Impairment:

No dosage adjustment has been recommended.

Dose in Liver disease:

No dosage adjustment has been recommended.

Side effects of Melarsoprol:

• 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

Contraindication to Melarsoprol:

• G6PD deficiency
• Pregnancy (depending upon the health of the mother).

Warnings and precautions

• Encephalopathy:

  • Initial treatment may result in Life-threatening Encephalopathy.
  • Encephalopathy is usually diagnosed within one to two weeks after treatment begins.
  • The clinical signs of cerebral edema include fits, abnormal behavior and coma.
  • Patients could also present with rapid onset neurological disorders.
  • It is important to monitor patients closely, especially for early signs of encephalopathy such as fever and headaches.
  • If encephalopathy is suspected, treatment must be stopped immediately
  • To prevent this syndrome from developing, patients may need corticosteroids.

• Irritating:

  • Extravasation of the drug is a problem.

Monitoring parameters:

• Clinical features of encephalopathy,
• Monitor for allergic reactions.

How to administer Melarsoprol?

IV:

• It should be administered by a slow intravenous injection.
• Since it is an irritant, extravasation should be avoided.

Mechanism of action of Melarsoprol:

• It is an Organoarsenic compound that acts on trypanothione.

Metabolism:

• It is metabolized to melarsen oxide which is the active metabolite.

Half-life elimination:

• 35 hours.

Time to peak:

• 15 minutes.

International Brand Names:

It is available only in specialized centers and provided by CDC.

Melarsoprol Brand Names in Pakistan:

No Brands Available in Pakistan.