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.
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 (cutaneous, mucosal, visceral):
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.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
(For additional information see "Miltefosine: Pediatric drug information")
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 (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).
There are no dosage adjustments provided in manufacturer's labeling (has not been studied).
There are no dosage adjustments provided in manufacturer's labeling (has not been studied).
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Impavido: 50 mg
No
Ordering and distribution information may be obtained by calling 1-908-635-2326 or visiting http://www.impavido.com/order-page.
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.
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
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.
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.
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).
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.
Free-living ameba infection
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.
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
Hypersensitivity to miltefosine or any component of the formulation; Sjogren-Larsson syndrome; pregnancy
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.
None known.
There are no known significant interactions.
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.
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).
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.
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.
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.
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).
Capsules (Impavido Oral)
50 mg (per each): $713.57
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