Dosing and uses of Impavido (miltefosine)
Adult dosage forms and strengths
capsule
- 50mg
Leishmaniasis
≥45 kg: 50 mg PO TID x28 consecutive days
<45 kg: 50 mg PO BID x28 consecutive days
Indications
- Visceral leishmaniasis due to Leishmania donovani
- Cutaneous leishmaniasis due to Leishmania braziliensis, Leishmania guyanensis, and Leishmania panamensis
- Mucosal leishmaniasis due to Leishmania braziliensis
Dosing Considerations
Leishmania species evaluated in clinical trials were based on epidemiologic data
There may be geographic variation in the response of the same Leishmania species to miltefosine
Efficacy for other Leishmania species has not been evaluated
Administration
Administer with meals to decrease GI adverse effects
Swallow capsule whole; do not chew or break apart
Instruct patient to complete full course of therapy
Pediatric dosage forms and strengths
capsule
- 50mg
Leishmaniasis
<12 years, or ≥12 years weighing <30 kg: Safety and efficacy not established
≥12 years (30-44 kg): 50 mg PO BID x28 consecutive days
≥12 years (≥45 kg): 50 mg PO TID x28 consecutive days
Indications
- Visceral leishmaniasis due to Leishmania donovani
- Cutaneous leishmaniasis due to Leishmania braziliensis, Leishmania guyanensis, and Leishmania panamensis
- Mucosal leishmaniasis due to Leishmania braziliensis
Dosing Considerations
Leishmania species evaluated in clinical trials were based on epidemiologic data
There may be geographic variation in the response of the same Leishmania species to miltefosine
Efficacy for other Leishmania species has not been evaluated
Administration
Administer with meals to decrease GI adverse effects
Swallow capsule whole; do not chew or break apart
Instruct patient to complete full course of therapy
Impavido (miltefosine) adverse (side) effects
>10%
Visceral leishmaniasis
- Increased transaminases, <3 x ULN (94%)
- Decreased platelets <150,000 (62%)
- Vomiting (37.8%)
- Decreased appetite (23.1%)
- Diarrhea (20.4%)
Cutaneous leishmaniasis
- Nausea (35.9-41.7%)
- Motion sickness (29.2%)
- Headache (28.1%)
- Vomiting (4.5-27.5%)
- Increased serum creatinine, 1.5-3 x baseline (25%)
- Diarrhea (15%) Dizziness (4.5-12.5%)
- Abdominal pain (7.5-11.2%)
- Decreased appetite (10.8%)
1-10%
Visceral leishmaniasis
- Increased serum creatinine, ≥1.5 x baseline (10%)
- Asthenia (6.3%)
- Increased transaminases, 3-5 x ULN (6%)
- Decreased platelets <50,000 (2.4%)
Cutaneous leishmaniasis
- Diarrhea (7.9%)
- Lymphangitis (5.8%)
- Pyrexia (5.6%)
- Pruritus (4.5-5.8%)
- Malaise (3.4%)
- Somnolence (3.4%)
Postmarketing Reports
Blood and lymphatics disorders: Thrombocytopenia, agranulocytosis
GI disorders: Melena
General disorders: Generalized edema, peripheral edema
Hepatobiliary disorders: Jaundice
Nervous system disorders: Seizure
Reproductive system and breast disorders: Scrotal pain, decreased ejaculate volume, absent ejaculation
Vascular disorders: Epistaxis
Warnings
Black box warnings
Do not administer to pregnant women; may cause fetal harm
Fetal death and teratogenicity occurred in animals administered at doses lower than the recommended human dose
Obtain a serum or urine pregnancy test in females of reproductive potential prior to prescribing
Advise females of reproductive potential to use effective contraception during therapy and for 5 months after therapy
Contraindications
Pregnancy (see Black box warnings)
Sjögren-Larsson syndrome
Hypersensitivity
Cautions
May cause fetal harm; do not use during pregnancy or become pregnancy within 5 months following therapy completion (see Black box warnings)
Causes impaired fertility in rats and reversible follicular atresia and diestrus in dogs; reduced viable sperm counts and impaired fertility in rats; effects on human fertility have not been studied
Vomiting and/or diarrhea commonly occur; encourage fluid intake to avoid volume depletion
Vomiting and/or diarrhea occurring during therapy may affect oral contraceptive absorption and thereby compromise their efficacy; advise females to use additional nonhormonal or alternative method(s) of effective contraception
Increased serum creatinine, ALT, AST, bilirubin reported; monitor
Thrombocytopenia reported; monitor platelets
Stevens-Johnson syndrome reported; discontinue if an exfoliative or bullous rash occurs
Pregnancy and lactation
Pregnancy category: D (see Black box warnings); Human pregnancy data are not available; however, embryofetal toxicity, including death and teratogenicity, was observed in embryo-fetal studies in rats and rabbits
Clinical considerations: During pregnancy, visceral leishmaniasis may be life-threatening for the mother and may result in adverse fetal outcomes, including spontaneous abortion, congenital disease due to vertical transmission, small for gestational age newborn, and severe anemia
Lactation: Unknown if distributed in human breast milk; avoid breastfeeding during therapy and for 5 months following therapy
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Impavido (miltefosine)
Mechanism of action
Specific mode of action against Leishmania species is unknown; the mechanism is likely to involve interaction with lipids (phospholipids and sterols), including membrane lipids, inhibition of cytochrome C oxidase (mitochondrial function), and apoptosislike cell death
Absorption
Absolute bioavailability not determined
Distribution
Protein bound: >98%
Metabolism
Metabolized by phospholipase D to choline, which is incorporated into tissues, and hexadecanol, which is oxidized to palmitic acid
Not a substrate, inhibitor, or inducer of CYP450 enzymes
Elimination
Excretion: Urine, <0.2% of administered dose
