IMPAVIDO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for IMPAVIDO (IMPAVIDO).
Miltefosine, the active ingredient in IMPAVIDO, is an alkylphosphocholine with antileishmanial activity. It interacts with cell membrane phospholipids, inhibits cytochrome c oxidase, and induces apoptosis-like cell death in Leishmania parasites. It also modulates host immune responses.
| Metabolism | Miltefosine is metabolized primarily via phospholipase cleavage. It undergoes slow hepatic metabolism via hydrolysis, with minimal involvement of cytochrome P450 enzymes. The main metabolites are phosphocholine and choline. |
| Excretion | Primarily renal (over 90% as unchanged drug); fecal excretion is minimal (<5%). |
| Half-life | Terminal elimination half-life is approximately 16-21 days in adults; may be longer in severe hepatic impairment. |
| Protein binding | 99% bound to plasma proteins, primarily albumin and lipoproteins. |
| Volume of Distribution | Vd is large, approximately 5-10 L/kg, indicating extensive tissue distribution and accumulation in organs such as liver, spleen, and bone marrow. |
| Bioavailability | Oral bioavailability is variable, ranging from 10-20% due to extensive first-pass metabolism; absorption is enhanced when taken with fatty food. |
| Onset of Action | Oral: Clinical response (reduction in parasite burden) may be observed within 1-2 weeks; full effect typically requires 4-6 weeks. |
| Duration of Action | Duration of action is prolonged due to long half-life; clinical effects persist for several weeks after discontinuation. |
| Action Class | Anti-Leishmaniasis |
60 mg/kg body weight per day (2.5 mg/kg per hour) by intravenous infusion over 6 hours, up to a maximum of 150 mg/day, for 21 days.
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment; use with caution in severe renal impairment (eGFR <30 mL/min) with monitoring of renal function; no specific dose recommendation available. |
| Liver impairment | Contraindicated in Child-Pugh class C cirrhosis; use with caution and consider dose reduction in Child-Pugh class A or B, as specific dose recommendations are not established. |
| Pediatric use | For visceral leishmaniasis: 2.5 mg/kg per hour (60 mg/kg total dose) intravenously over 6 hours daily for 21 days; for cutaneous leishmaniasis: 2.5 mg/kg per hour (60 mg/kg total dose) intravenously over 6 hours daily for 20 days; safety and efficacy not established in children under 2 years. |
| Geriatric use | No specific dose adjustment recommended; use with caution due to potential age-related renal and hepatic impairment; monitor cardiac and renal function closely. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for IMPAVIDO (IMPAVIDO).
| Breastfeeding | No data on excretion in human milk. M/P ratio unknown. Due to potential for serious adverse reactions in nursing infants, decision should be made to discontinue nursing or drug, considering importance of drug to mother. |
| Teratogenic Risk | FDA Pregnancy Category B. Animal studies show no fetal harm, but no adequate human studies. Risk not ruled out. First trimester: theoretical risk based on antileishmanial action; avoid unless essential. Second/third trimesters: limited data; use only if benefit outweighs potential risk. No specific malformations reported. |
■ FDA Black Box Warning
WARNING: EMBRYOFETAL TOXICITY - IMPAVIDO is contraindicated in pregnant women. It may cause fetal harm when administered to a pregnant woman. Females of reproductive potential must have a negative pregnancy test before starting treatment and must use effective contraception during therapy and for 5 months after treatment discontinuation.
| Serious Effects |
["Pregnancy (absolute contraindication due to embryofetal toxicity).","Women of childbearing potential not using effective contraception.","Severe hypersensitivity to miltefosine or any excipients.","Severe hepatic or renal impairment (relative contraindication; use with caution).","Breastfeeding (discontinue nursing or drug, considering importance to mother)."]
| Precautions | ["Embryofetal toxicity (black box warning): Females must avoid pregnancy during and for 5 months after treatment.","Gastrointestinal adverse reactions: Nausea, vomiting, diarrhea, and abdominal pain are common; severe cases may require antiemetics or dose reduction.","Hepatotoxicity: Monitor liver function tests; elevated transaminases may occur.","Nephrotoxicity: Monitor renal function; miltefosine is primarily excreted renally.","Ocular effects: Retinal degeneration reported in animal studies; advise patients to report visual changes.","Stevens-Johnson syndrome: Rare but serious cutaneous adverse reaction."] |
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| Fetal Monitoring |
| Monitor maternal liver enzymes, renal function, and complete blood counts monthly during treatment. Fetal monitoring: ultrasound for growth and well-being if used in pregnancy. Monitor for signs of maternal hypersensitivity or QT prolongation. |
| Fertility Effects | No specific studies on human fertility. Animal studies show no impairment of fertility. Theoretical risk of gamete toxicity from antileishmanial agents, but not established with miltefosine. |