Melarsoprol is a medication used in the treatment of African trypanosomiasis, also known as sleeping sickness. This disease is caused by the parasite Trypanosoma brucei gambiense or Trypanosoma brucei rhodesiense, which are transmitted to humans through the bite of infected tsetse flies.

Melarsoprol is an arsenical compound and is considered a second-line treatment for trypanosomiasis, typically used when first-line medications such as pentamidine or suramin are ineffective or when the disease has progressed to the late stage, known as the meningoencephalitic stage.

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 Adult:

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

For T. b. rhodesiense:

• The dose of melarsoprol given through an IV is 2 to 3.6 milligrams per kilogram of body weight once a day for 3 days. During this time, the dose may increase.
• After a break of 7 days, another course of melarsoprol is given at the same dose of 3.6 milligrams per kilogram once a day for 3 days.
• Then, there's another course of the same dose given for 3 days, starting 7 days after the previous course. This makes a total of 3 courses.

For T. b. gambiense (as an alternative treatment):

• The dose of melarsoprol given through an IV is 2.2 milligrams per kilogram of body weight once a day for 10 days. The maximum dose is 180 milligrams.

Melarsoprol Dose in Children:

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

Note:

• Melarsoprol is only available through special distribution programs, and dosing guidance is typically provided through an investigational new drug (IND) protocol released by the CDC.
• It's recommended to use melarsoprol together with prednisolone to lower the risk of melarsoprol-related brain damage.
• Various prednisolone regimens exist, usually given once daily for 10 to 12 days.
• Some experts suggest starting prednisolone several days before melarsoprol, while others recommend gradually reducing the prednisolone dose over 3 to 6 days.
• Another approach for longer treatment regimens is to give prednisolone only on the days when melarsoprol is administered.

For Trypanosoma brucei rhodesiense:

• Abbreviated 10-day regimen:
  • Infants, Children, and Adolescents:
    • Given intravenously (IV) at a dose of 2.2 milligrams per kilogram of body weight once daily for 10 days.
    • The maximum dose per dose is 180 milligrams.
    • It should be used along with prednisolone to decrease the risk of melarsoprol-related encephalopathy.
• Prolonged discontinuous regimen:
  • Infants, Children, and Adolescents:
    • Administered IV at a dose of 2 to 3.6 milligrams per kilogram of body weight once daily for 3 days.
    • The dose starts at 2 milligrams per kilogram on day 1 and increases gradually to 3.6 milligrams per kilogram on day 3.
    • This is followed by a 7-day break without the drug.
    • Then, a second series of 3.6 milligrams per kilogram once daily for 3 days is given, followed by another 7-day break without the drug.
    • Finally, a third series of 3.6 milligrams per kilogram once daily for 3 days is administered.
    • The maximum dose per dose is 180 milligrams.
    • Prednisolone should be used concurrently to decrease the risk of melarsoprol-related encephalopathy.

For Trypanosoma brucei gambiense (as an alternative agent):

• Infants, Children, and Adolescents:
  • IV administration at a dose of 2.2 milligrams per kilogram of body weight once daily for 10 days.
  • The maximum dose per dose is 180 milligrams.
  • It should be used along with prednisolone to reduce the risk of melarsoprol-related encephalopathy.

Melarsoprol Pregnancy Category: D

• For pregnant women with West African trypanosomiasis, other treatments are usually chosen if the infection can't wait until after childbirth.
• Melarsoprol might not be safe during pregnancy, depending on the mother's health condition, so it's generally avoided.

Use during breastfeeding:

• There's no documented evidence regarding the safety of melarsoprol use during lactation.
• Before starting treatment for lactating mothers, it's crucial to carefully consider the potential benefits and risks of exposing infants to the drug.

Melarsoprol Dose in Kidney disease:

No dosage adjustment has been recommended.

Melarsoprol 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:

• Melarsoprol should be used with caution in individuals with G6PD deficiency, as it may exacerbate the condition.
• Additionally, its use during pregnancy depends on the mother's health condition, and it's generally avoided if possible.

Warnings and precautions

Encephalopathy:

• Encephalopathy, a serious brain disorder, can sometimes happen after starting melarsoprol treatment, usually within 7 to 14 days.
• Symptoms may include strange behavior, brain swelling, seizures, worsening unconsciousness, or sudden neurological issues.
• Patients need close monitoring, as fever or headache could be early signs of this problem.
• If encephalopathy signs appear, treatment should stop immediately.
• Corticosteroids might help prevent this syndrome from developing.

Irritating:

• Melarsoprol can irritate the skin and tissues, so it's important to avoid it leaking outside of the vein during administration.

Monitoring parameters:

Signs/Symptoms of Encephalopathy:

• Abnormal behavior
• Cerebral edema (brain swelling)
• Seizures
• Progressive coma
• Rapid onset of neurological disorders
• Fever and/or headache as early signs

Hypersensitivity:

• Skin rash
• Itching
• Swelling
• Difficulty breathing
• Any other signs of allergic reaction

How to administer Melarsoprol?

Administration Method:

• Administer by slow IV injection.

Safety Precaution:

• Melarsoprol is an irritant, so avoid leakage (extravasation) during administration.

Mechanism of action of Melarsoprol:

• Melarsoprol is a type of organoarsenic compound that works by targeting a substance called trypanothione.

Distribution:

• Volume of distribution (V): Greater than 100 liters.

Metabolism:

• Melarsoprol is metabolized in the body to an active metabolite called melarsen oxide.

Half-life Elimination:

• The half-life of elimination for melarsoprol is approximately 35 hours.

Time to Peak:

• It takes about 15 minutes for melarsoprol to reach its peak concentration in the body.

International Brand Names:

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

Melarsoprol Brand Names in Pakistan:

No Brands Available in Pakistan.