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Miltefosine: Drug information

Miltefosine: Drug information
(For additional information see "Miltefosine: Patient drug information" and see "Miltefosine: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US Boxed Warning
Embryo-fetal toxicity:

Miltefosine is contraindicated in pregnancy. Based on animal data, miltefosine may cause fetal harm. Verify pregnancy status prior to initiating miltefosine. To prevent pregnancy, patients of reproductive potential should use effective contraception during treatment and for 5 months after the last dose.

Brand Names: US
  • Impavido
Pharmacologic Category
  • Antiparasitic Agent
Dosing: Adult
Free-living ameba infection

Free-living ameba infection (granulomatous amebic encephalitis [Acanthamoeba spp., B. mandrillaris] and primary amebic meningoencephalitis [N. fowleri]) (off-label use): Oral:

<45 kg: 50 mg twice daily (CDC 2019b; Drugs for Parasitic Infections 2013).

≥45 kg: 50 mg 3 times daily (CDC 2019b; Drugs for Parasitic Infections 2013).

Leishmaniasis

Leishmaniasis (cutaneous, mucosal, visceral):

Monotherapy: Note: Efficacy is species and locale dependent. For visceral leishmaniasis, reserve use for patients who are unable to use preferred therapy (Drugs for Parasitic Infections 2013; HHS [OI adult 2021]; IDSA/ASTMH [Aronson 2016]).

30 to 44 kg: Oral: 50 mg twice daily for 28 days.

≥45 kg: Oral: 50 mg 3 times daily for 28 days.

Combination therapy (off-label): Note: For patients with HIV and visceral leishmaniasis acquired in East Africa or Southeast Asia (WHO 2022).

Oral: 50 mg twice daily in combination with liposomal amphotericin B. Duration of miltefosine is 14 days for patients in Southeast Asia and 28 days for patients in East Africa (Abongomera 2018; Burza 2022; Diro 2019; Mahajan 2015; WHO 2022).

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Miltefosine: Pediatric drug information")

Leishmaniasis

Leishmaniasis: Children ≥12 years and Adolescents weighing ≥30 kg: Oral: Cutaneous, mucosal, visceral leishmaniasis: Note: Efficacy is species- and locale-dependent.

30 to 44 kg: 50 mg twice daily for 28 days.

≥45 kg: 50 mg 3 times daily 28 days.

Naegleria fowleri infection

Naegleria fowleri infection (free-living ameba): Very limited data available; efficacy results variable; Note: Due to the poor prognosis of infection and lack of successful treatment options, expert recommendations suggest adding miltefosine as a component of treatment regimen (CDC 2020; Cope 2016; Linam 2015; Red Book [AAP 2018]):

Children and Adolescents: Oral:

<45 kg: 50 mg twice daily for 28 days (CDC 2020; Linam 2015); an 8-year-old (weight not reported) received 50 mg 3 times daily (Cope 2016).

≥45 kg: 50 mg 3 times daily for 28 days (Cope 2016; Linam 2015).

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in manufacturer's labeling (has not been studied).

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in manufacturer's labeling (has not been studied).

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Gastrointestinal: Abdominal pain (8% to 11%), decreased appetite (11% to 23%), diarrhea (8% to 20%), motion sickness (29%), nausea (36% to 42%), vomiting (5% to 38%)

Genitourinary: Asthenospermia, decreased ejaculate volume, oligospermia, scrotal pain (tenderness), spermatozoa disorder (reduction in sperm morphology)

Hematologic & oncologic: Decreased platelet count (<150,000: 62%; <50,000: 2%)

Hepatic: Increased serum transaminases (<3 × ULN: 94%; ≥3 × ULN: 6%)

Nervous system: Dizziness (5% to 13%), headache (28%)

Renal: Increased serum creatinine (≥1.5 × above baseline: 10% to 25%)

1% to 10%:

Dermatologic: Cellulitis (<2%), ecthyma (<2%), pruritus (5% to 6%), pyoderma (<2%), skin rash (<2%), Stevens-Johnson syndrome (<2%), urticaria (<2%)

Gastrointestinal: Abdominal distention (<2%), constipation (<2%), dysphagia (<2%), flatulence (<2%)

Genitourinary: Dry ejaculation, epididymitis, testicular pain (<2%), testicular swelling (<2%)

Hematologic & oncologic: Anemia (<2%), lymphadenopathy (<2%), lymphangitis (6%)

Infection: Abscess (<2%)

Nervous system: Drowsiness (3%), fatigue (<2%), malaise (3%), paresthesia (<2%)

Neuromuscular & skeletal: Asthenia (6%)

Miscellaneous: Fever (6%)

Frequency not defined: Hepatic: Increased serum bilirubin

Postmarketing:

Cardiology: Edema, peripheral edema

Gastrointestinal: Melena

Hematologic & oncologic: Agranulocytosis, thrombocytopenia

Hepatic: Jaundice

Nervous system: Seizure

Respiratory: Epistaxis

Contraindications

Hypersensitivity to miltefosine or any component of the formulation; Sjogren-Larsson syndrome; pregnancy

Warnings/Precautions

Concerns related to adverse effects:

• Dermatologic toxicity: Stevens-Johnson syndrome has been reported; discontinue miltefosine if an exfoliative or bullous rash occurs during therapy.

• Gastrointestinal effects: Nausea, vomiting and diarrhea may occur with use; administer with food to decrease GI effects. Ensure adequate fluid intake during therapy to prevent dehydration.

• Hematologic toxicity: Thrombocytopenia has been reported during therapy for visceral leishmaniasis; monitor platelet count during therapy in these patients.

• Hepatic effects: Increased liver transaminases and bilirubin have been reported during therapy for visceral leishmaniasis. Assess ALT, AST, and bilirubin during therapy.

• Renal toxicity: May increase serum creatinine. Assess kidney function weekly while on therapy and for 4 weeks after the end of therapy.

Product Availability

Ordering and distribution information may be obtained by calling 1-908-635-2326 or visiting http://www.impavido.com/order-page.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral:

Impavido: 50 mg

Generic Equivalent Available: US

No

Pricing: US

Capsules (Impavido Oral)

50 mg (per each): $713.57

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Prescribing and Access Restrictions

Miltefosine may be ordered directly from Profunda by any licensed pharmacy; it is not available through wholesalers. For ordering and distribution information call 1-908-635-2326 or visit http://www.impavido.com/order-page.

Administration: Adult

Oral: Administer with food to decrease GI distress. Twice daily dosing should be administered with breakfast and dinner; 3 times daily dosing with breakfast, lunch, and dinner.

Administration: Pediatric

Oral: Administer with food to decrease GI distress. Twice-daily dosing should be administered with breakfast and dinner; 3-times daily dosing with breakfast, lunch, and dinner.

Hazardous Drugs Handling Considerations

This medication is not on the NIOSH (2016) list; however, it may meet the criteria for a hazardous drug. Miltefosine may cause teratogenicity and reproductive toxicity. Assess risk to determine appropriate containment strategy (USP-NF 2017).

Use appropriate precautions for receiving, handling, administration, and disposal. Gloves (single) should be worn during receiving, unpacking, and placing in storage. NIOSH recommends single gloving for administration of intact tablets or capsules (NIOSH 2016).

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:

Impavido: http://www.fda.gov/downloads/Drugs/DrugSafety/UCM390972.pdf

Use: Labeled Indications

Leishmaniasis: Treatment of visceral (caused by Leishmania donovani), cutaneous (caused by L. braziliensis, L. guyanensis, and L. panamensis), and mucosal leishmaniasis (caused by L. braziliensis) in adults and adolescents ≥12 years of age weighing ≥30 kg.

Limitations of use: Efficacy of miltefosine in the treatment of other Leishmania species has not been evaluated; there may be geographic variation in clinical response of the same Leishmania species to miltefosine.

Use: Off-Label: Adult

Free-living ameba infection

Medication Safety Issues
High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs that have a heightened risk of causing significant patient harm when used in error.

Metabolism/Transport Effects

None known.

Drug Interactions

There are no known significant interactions.

Reproductive Considerations

Verify pregnancy status prior to treatment initiation. Patients who may become pregnant should use effective contraception during therapy and for 5 months after the last dose of miltefosine. If oral contraceptives are used and nausea, vomiting, and/or diarrhea occur during therapy, additional nonhormonal or alternative methods of effective contraception should be used.

Miltefosine may reduce ejaculate volume, total sperm count, sperm concentration, sperm morphology, and sperm motility, resulting in impaired fertility. Duration of adverse events is unknown. However, improvements of most parameters occurred within 3 to 6 months following the last miltefosine dose.

Pregnancy Considerations

Based on data from animal reproduction studies, in utero exposure to miltefosine may cause fetal harm. Embryo-fetal toxicity was observed in animal studies with doses less than the maximum recommended human dose. Use is contraindicated in pregnant patients.

Leishmaniasis is also associated with adverse pregnancy outcomes. Untreated visceral leishmaniasis may be life-threatening to the mother and may result in adverse fetal outcomes (eg, spontaneous abortion, congenital disease due to vertical transmission, small for gestational age newborn, severe anemia); untreated cutaneous leishmaniasis may manifest with larger and atypical appearing lesions and may be associated with adverse fetal outcomes (eg, preterm births, stillbirths).

Agents other than miltefosine are recommended for the treatment of leishmaniasis during pregnancy (Fontenele e Silva 2013; IDSA/ASTMH [Aronson 2016]).

Data collection to monitor pregnancy and infant outcomes following exposure to miltefosine is ongoing. Health care providers are encouraged to enroll patients exposed to miltefosine during pregnancy in the pregnancy registry (1-866-588-5405).

Breastfeeding Considerations

It is not known if miltefosine is present in breast milk.

Agents other than miltefosine are recommended for the treatment of leishmaniasis in breastfeeding patients (Fontenele e Silva 2013; IDSA/ASTMH [Aronson 2016]).

Due to the potential for serious adverse reactions in the breastfeeding infant, breastfeeding is not recommended by the manufacturer during treatment and for 5 months after the last miltefosine dose.

Monitoring Parameters

Baseline and as clinically indicated during therapy: liver function tests (AST, ALT, alkaline phosphatase, bilirubin) and BUN/serum creatinine; platelet count.

Evaluate pregnancy status prior to use in patients who may become pregnant.

Mechanism of Action

Exact mechanism unknown; likely interaction with phospholipids and steroids in parasitic cell membranes, inhibition of cytochrome c oxidase (mitochondrial function), and apoptosis-like cell death.

Pharmacokinetics (Adult Data Unless Noted)

Protein binding: 98%.

Metabolism: Hepatic; phospholipase D-like cleavage of miltefosine releases choline. Fatty alcohol-containing fragment may be oxidized to palmitic acid and undergo fatty acid metabolism.

Half-life elimination: t½ alpha: >6 days; t½ beta: ~31 days.

Time to peak, serum: 4 to 7 hours.

Excretion: Urine (<0.2% as unchanged drug).

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (CO) Colombia: Antylex | Impavido;
  • (CZ) Czech Republic: Impavido;
  • (DE) Germany: Impavido;
  • (EC) Ecuador: Impavido;
  • (IN) India: Impavido;
  • (NO) Norway: Impavido;
  • (PK) Pakistan: Leish | Miltefo | Visral;
  • (PR) Puerto Rico: Impavido;
  • (PY) Paraguay: Impavido
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Topic 91793 Version 105.0

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