Miltefosine

Miltefosine Should be taken with food.

Hypersensitivity. Sjogren-Larsson syndrome. Pregnancy.

Indicated for the treatment of visceral (caused by Leishmania donovani), cutaneous (caused by L. braziliensis, L. guyanensis, and L. panamensis) and mucocutaneous (caused by L. braziliensis) leishmaniasis; efficacy of miltefosine in other Leishmania species has not been evaluated. Clinical response and susceptibility of the same Leishmania species to miltefosine may vary based on different geographic regions (refer to detailed local guidelines). Children. Lactation.

Significant: Gastrointestinal effects (e.g. nausea, vomiting, diarrhoea) which may result in volume depletion; Stevens-Johnson syndrome, thrombocytopenia; increased liver transaminases and bilirubin, increased serum creatinine; impaired male fertility (e.g. decreased ejaculate volume, total sperm count, sperm concentration, sperm motility and sperm morphology); ocular complications (e.g. keratitis, iritis, anterior uveitis, acute scleritis, keratopathy).
Blood and lymphatic system disorders: Lymphangitis, anaemia, lymphadenopathy.
Ear and labyrinth disorders: Motion sickness.
Gastrointestinal disorders: Abdominal pain or distension, constipation, flatulence, dysphagia.
General disorders and administration site conditions: Fever, asthenia, malaise.
Hepatobiliary disorders: Jaundice.
Metabolism and nutrition disorders: Decreased appetite.
Nervous system disorders: Headache, dizziness, drowsiness.
Reproductive system and breast disorders: Testicular pain or swelling.
Skin and subcutaneous tissue disorders: Pruritus, rash, urticaria, ecthyma, cellulitis.

PO/Topical: Z (Embryo-foetal death and teratogenicity were observed in animals given oral doses at exposures lower than maximum recommended human doses. Contraindicated.)

Women of childbearing potential must use proven birth control methods during therapy and for 5 months after the last dose; additional non-hormonal or alternative methods of effective contraception should be used if oral contraceptives are taken and vomiting or diarrhoea occur during treatment. Ensure adequate fluid intake during therapy. Avoid breastfeeding during treatment and for 5 months after stopping the treatment.

Evaluate pregnancy status before starting the treatment. Obtain LFTs (e.g. AST, ALT, bilirubin, alkaline phosphatase) and platelet count at baseline and as clinically indicated. Monitor renal function (e.g. serum creatinine, BUN) weekly during treatment and for 4 weeks after the therapy. Assess for signs of exfoliative or bullous rash, bleeding, changes in urine, and ocular complications.

Symptoms: Diarrhoea, vomiting, abdominal pain. Management: Administer adequate hydration and replace electrolytes as needed.

Description:
Mechanism of Action: Miltefosine, an alkyllysophospholipid analogue, is an anti-leishmanial agent with activity against certain Leishmania species. Its exact mechanism of action is unknown; however, it has been proposed to interact with phospholipids and sterols (including membrane lipids) in parasitic cell membranes and inhibit the mitochondrial cytochrome c oxidase enzyme, thereby leading to apoptosis-like cell death.
Pharmacokinetics:
Absorption: Time to peak plasma concentration: 4-7 hours.
Distribution: Plasma protein binding: 98%.
Metabolism: Slowly metabolised in the liver by phospholipases to form choline; fatty alcohol-containing fragments of miltefosine may be oxidised into palmitic acid and undergo fatty acid metabolism.
Excretion: Via urine (<0.2% as unchanged drug). Elimination half-life: >6 days (distribution phase); approx 31 days (terminal elimination phase).

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 3599, Miltefosine. https://pubchem.ncbi.nlm.nih.gov/compound/Miltefosine. Accessed May 27, 2025.

Store between 20-25°C. Protect from moisture.

Other Antiprotozoal Agents

P01CX04 - miltefosine ; Belongs to the class of other agents used in the treatment of leishmaniasis and trypanosomiasis.

Brayfield A, Cadart C (eds). Miltefosine. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 02/04/2025.

Impavido Capsule (Profounda, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 02/04/2025.

Impavido Capsule (Profounda, Inc.). U.S. FDA. https://www.fda.gov. Accessed 02/04/2025.

Leishmaniasis. World Health Organization. https://www.who.int. Accessed 14/05/2025.

Miltefosine. Gold Standard Drug Database in ClinicalKey [online]. Elsevier Inc. https://www.clinicalkey.com. Accessed 02/04/2025.

Miltefosine. UpToDate Lexidrug, AHFS DI (Adult and Pediatric) Online. American Society of Health-System Pharmacists, Inc. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 02/04/2025.

Miltefosine. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 02/04/2025.