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Impavido miltefosine 50 mg Capsule, 28-count — NDC 69051-0300-01 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

Impavido miltefosine 50 mg Capsule, 28-count — NDC 69051-300-01 (Billing 69051-0300-01)

by Profounda, Inc. · 2 BLISTER PACK in 1 CARTON / 14 CAPSULE in 1 BLISTER PACK

This is a package of 28 capsules of Impavido miltefosine 50 mg Capsule from Profounda, Inc., no longer marketed (first marketed Oct 2015), no longer in the FDA NDC Directory, this package's marketing ended Sep 2026. It is this product's only package size.

NDC 69051-0300-01
🏷️ FDA NDC (as labeled) 69051-300-01 billing pads the product segment with a zero
Rx only Brand Discontinued Non-controlled ⚠ Discontinued by firm ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 1, 2026 · this listing last changed Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

NDC database record

One package, one record: these facts belong to NDC 69051-300-01 alone.

Record
FDA NDC Directory package listing · Human prescription drug
Code segments
69051 labeler · 300 product · 01 package
Package marketed since
Oct 29, 2015
Package marketing ended
Sep 26, 2026
Sample package
No — commercial package
Billing quantity
28 EA per package
Barcode (UPC-A, from the NDC)
3 6905130001 0
FDA record last changed
Jul 24, 2026
⚠️
Excluded from the active FDA NDC Directory. The labeler reported this product as discontinued, so it is excluded from the active NDC Directory. The listing was last certified through Sep 2026. A label may still appear on DailyMed, but the NDC is no longer in the current FDA NDC Directory. Search the FDA NDC Directory ↗

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 69051-300-01
Product NDC 69051-300
11-digit billing NDC 69051030001
NCPDP billing unit EA — each (per item)
RxCUI 1494071, 1495070
UNII 53EY29W7EC
Application # NDA204684
SPL Set ID bcb387ac-2e90-4f5e-94b2-d3635190678e
Established class (EPC) Antileishmanial
DEA schedule Non-controlled
Marketing category NDA
Marketing status Discontinued
FDA listing status Discontinued by firm (certified through Sep 2026)
Marketing start 2015-10-29
Marketing end 2026-09-26
Route ORAL
Dosage form CAPSULE
Substance MILTEFOSINE

Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification

GPI-14 16000036000120
GPI class Impavido
GCN Seq No 072164
GCN 36283
HICL code 016200
Ingredient (HICL) Miltefosine
HIC1 code W
Therapeutic class — broad (HIC1) Anti-Infecting Agents
HIC2 code W4
Therapeutic class — intermediate (HIC2) Antiparasitics
HIC3 code W4K
Therapeutic class — specific (HIC3) Antiprotozoal Drugs,Miscellaneous
AHFS code 08:30.16.08
AHFS class Nitroimidazole Derivative, Anti-Leishmal
FDB label name IMPAVIDO 50 MG CAPSULE
FDB brand name Impavido
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 072164
  • GCN: 36283
  • GPI-14 (Medi-Span): 16000036000120
  • HICL (First Databank): 016200
  • AHFS class code: 08:30.16.08
  • RxCUI (RxNorm): 1494071
Why two NDCs? The FDA registers this code as 69051-300-01 — a 5-3-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the product segment → 69051-0300-01. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

RxNorm drug class

This medicine belongs to the Antileishmanial class.

Pharmacologic class Antileishmanial
Drug family (ATC) Other agents against leishmaniasis and trypanosomiasis
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

Clinical

Label name IMPAVIDO 50 MG CAPSULE Ingredient Miltefosine
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

Pricing

A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.

Price systemPer eachPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data.
Medicare drug plans payPart D · Q2 2026 $599.17 $16,776.74 / 28 capsules
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
69051-0300-01 You're viewing this Main listing 2 BLISTER PACK in 1 CARTON / 14 CAPSULE in 1 BLISTER PACK 2015-10-29 Sep 26, 2026 Discontinued by firm

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Impavido 50 mgthis 69051-0300-01 Profounda, 28 capsules — — Discontinued —
Impavido 50 mg 71863-0135-28 Eton 28 capsules — — FDA listed —
About this product: this is the brand-name version. We did not find an FDA-approved generic match for this exact strength, form and route.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & generic status

🏛️
2015
On the market since
Oct 2015
📍
2026
Currently FDA-listed
11 years listed
🔒
·
No generic listed yet
brand only
ℹ️No FDA-approved generic found

We did not find an FDA-approved generic match for this exact strength, form and route.

Where does this data come from?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

Inactive Ingredients / Excipients

Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.

💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.

  • UNII OP1R32D61U
    Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
  • UNII 1K09F3G675
    Ferric oxide red is an inorganic iron compound used as a colorant in medicines. It gives tablets, capsules, or other dosage forms a red or reddish tint for identification and appearance.
  • UNII 2G86QN327L
    Gelatin is a protein derived from animal collagen, commonly used in medicines as a gelling agent and capsule material. It helps create soft or hard capsule shells that hold and release medication, and can also thicken liquid formulations.
  • UNII EWQ57Q8I5X
    Lactose monohydrate is a natural sugar derived from milk. It serves as a filler and binder in tablets and capsules, helping create the proper size, texture, and consistency of the medicine.
  • UNII 70097M6I30
    Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
  • UNII ETJ7Z6XBU4
    Silicon dioxide is a naturally occurring mineral used as a glidant and anti-caking agent. It helps powder ingredients flow smoothly and prevents clumping during manufacturing and storage.
  • UNII 7SEV7J4R1U
    A powder made from a naturally occurring mineral. In medicines, talc works as a glidant and anti-caking agent, helping tablets and capsules flow smoothly during manufacturing and preventing clumping.
  • UNII 15FIX9V2JP
    Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
  • UNII 059QF0KO0R
    Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.

9 inactive ingredients listed in the exact product block matched to this NDC.

Where does this data come from?
Data sourced from official FDA Structured Product Labeling (SPL) via DailyMed — ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.

Inactive ingredient FAQ

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

Manufacturer & labeler

LabelerProfounda, Inc.
Application holderKNIGHT THERAPEUTICS USA INC
FDA applicationNDA204684 (NDA)
Labeler code69051
First marketedOct 2015
Product typeHuman Prescription Drug
The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Very long sections are excerpted here and marked; the full text is on DailyMed (linked in the sources below). Jump with a chip, search within the label, or expand everything.
🚨 Boxed Warning 🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients 💬 Medication Guide 🍼 Nursing Mothers 🧬 Pharmacokinetics 🔬 Clinical Studies 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📄 Package Label / Principal Display Panel
🚨 Boxed Warning 179 words ▾

WARNING: EMBRYO-FETAL TOXICITY IMPAVIDO may cause fetal harm. Fetal death and teratogenicity occurred in animals administered miltefosine at doses lower than the recommended human dose. Do not administer IMPAVIDO to pregnant women.

Obtain a serum or urine pregnancy test in females of reproductive potential prior to prescribing IMPAVIDO. Females of reproductive potential should be advised to use effective contraception during IMPAVIDO therapy and for 5 months after therapy [see Contraindications ( 4.1 ), Warnings and Precautions ( 5.1 ), Use in Specific Populations ( 8.1 , 8.8 ) and Nonclinical Toxicology ( 13.1 )] . WARNING: EMBRYO-FETAL TOXICITY See full prescribing information for complete boxed warning.

IMPAVIDO may cause fetal harm. Fetal death and teratogenicity, occurred in animals administered miltefosine at doses lower than the recommended human dose. Do not administer IMPAVIDO to pregnant women.

Obtain a serum or urine pregnancy test in females of reproductive potential prior to prescribing IMPAVIDO. Advise females of reproductive potential to use effective contraception during therapy and for 5 months after therapy ( 4.1 , 5.1 , 8.1 , 8.8 , 13.1 ).

🎯 Indications and Usage ~1 min read ▾

1 INDICATIONS AND USAGE IMPAVIDO (miltefosine) capsules are indicated in adults and adolescents ≥12 years of age weighing ≥ 30 kg for the treatment of: Visceral leishmaniasis caused by Leishmania donovani [see Clinical Trials ( 14.1 )] . Cutaneous leishmaniasis caused by Leishmania braziliensis , Leishmania guyanensis , and Leishmania panamensis [see Clinical Trials ( 14.2 )] . Mucosal leishmaniasis caused by Leishmania braziliensis [see Clinical Trials ( 14.3 )] .

Limitations of Use: Leishmania species studied in clinical trials evaluating IMPAVIDO were based on epidemiologic data [see Clinical Trials ( 14.1 , 14.2 )] . There may be geographic variation in clinical response of the same Leishmania species to IMPAVIDO [see Clinical Trials ( 14.1 , 14.2 )] . The efficacy of IMPAVIDO in the treatment of other Leishmania species has not been evaluated.

IMPAVIDO is an antileishmanial drug indicated in adults and adolescents ≥12 years of age weighing ≥30 kg (66 lbs) for treatment of: Visceral leishmaniasis due to Leishmania donovani ( 1 ). Cutaneous leishmaniasis due to Leishmania braziliensis, Leishmania guyanensis, and Leishmania panamensis ( 1 ). Mucosal leishmaniasis due to Leishmania braziliensis ( 1 ).

Limitations of use : 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 IMPAVIDO ( 1 , 14 ). The efficacy of IMPAVIDO in the treatment of other Leishmania species has not been evaluated.

⏱️ Dosage and Administration 103 words ▾

2 DOSAGE AND ADMINISTRATION The treatment duration is 28 consecutive days. Administer with food to ameliorate gastrointestinal adverse reactions. Table 1: Miltefosine Dosage Weight Dosage and Administration 30 kg to 44 kg One 50 mg capsule twice daily with food (breakfast and dinner) 45 kg or greater One 50 mg capsule three times daily with food (breakfast, lunch, and dinner) Administer with food to ameliorate gastrointestinal adverse reactions.

30 to 44 kg: one 50 mg capsule twice daily for 28 consecutive days ( 2 ). 45 kg or greater: one 50 mg capsule three times daily for 28 consecutive days ( 2 ).

💊 Dosage Forms and Strengths 65 words ▾

3 DOSAGE FORMS AND STRENGTHS IMPAVIDO® (miltefosine) oral capsules are opaque, red, hard gelatin capsules with “PLB” imprinted on the capsule body and “MILT 50” imprinted on the cap using a white ink. Each capsule contains 50 mg miltefosine [see Description ( 11 ), How Supplied/Storage and Handling ( 16 )] . Each IMPAVIDO capsule for oral use contains 50 mg miltefosine ( 3 ).

⛔ Contraindications 98 words ▾

4 CONTRAINDICATIONS Pregnancy ( 4.1 , 8.1 , 8.8 , 13.1 ). Sjögren-Larsson-Syndrome ( 4.2 , 12.3 ). Hypersensitivity to miltefosine or any of its excipients ( 4.3 ).

4.1Pregnancy IMPAVIDO may cause fetal harm. IMPAVIDO is contraindicated in pregnant women. Obtain a urine or serum pregnancy test prior to prescribing IMPAVIDO [see Boxed Warning and Use in Specific Populations ( 8.1 )] .

4.2Sjögren-Larsson-Syndrome IMPAVIDO is contraindicated in patients who have Sjögren-Larsson-Syndrome [see Clinical Pharmacology ( 12.3 )] .

4.3Hypersensitivity IMPAVIDO is contraindicated in patients who are hypersensitive to miltefosine or any IMPAVIDO excipients.

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS Embryo-Fetal Toxicity. Do not use in pregnant women. Obtain a urine or serum pregnancy test prior to initiation of therapy.

Advise use of effective contraception in females of reproductive potential ( Boxed Warning , 5.1 , 8.1 , 8.8 , 13.1 ). Reproductive effects. Miltefosine caused testicular atrophy and impaired fertility in male rats and impaired fertility in female rats.

Advise patients of reproductive toxicities in animal studies and that the potential effects on human fertility have not been adequately evaluated ( 13.1 ). Renal Effects. Monitor serum creatinine during therapy and for 4 weeks after end of therapy ( 5.3 , 6.1 ).

Hepatic Effects. Monitor transaminases and bilirubin during therapy ( 5.4 , 6.1 ). Gastrointestinal Effects.

Encourage fluid intake ( 5.5 ). Thrombocytopenia. Monitor platelet count during therapy for visceral leishmaniasis ( 5.6 , 6.1 ).

Absorption of Oral Contraceptives. Advise use of alternative method of contraception if vomiting and/or diarrhea occur ( 5.7 ). Stevens-Johnson syndrome.

Discontinue IMPAVIDO ( 5.8 ).

5.1Embryo-Fetal Toxicity Miltefosine may cause fetal harm. Embryo-fetal toxicity, including death and teratogenicity, was observed in animals administered miltefosine prior to mating, during early pregnancy, and during organogenesis at doses lower than the maximum recommended human dose (MRHD). Do not use IMPAVIDO in pregnant women.

Obtain a urine or serum pregnancy test prior to prescribing IMPAVIDO to females of reproductive potential. Advise females of reproductive potential to use effective contraception during IMPAVIDO therapy and for 5 months after completion of therapy [see Boxed Warning , Contraindications ( 4.1 ) and Use in Specific Populations ( 8.1 , 8.8 )] .

5.2Reproductive Effects Females Miltefosine caused impaired fertility in rats and reversible follicular atresia and diestrus in dogs at doses approximately 1.0 and 0.2 times respectively the MRHD based on body surface area comparisons [see Nonclinical Toxicology ( 13.1 )] . Effects on human female fertility have not been formally studied. Males Miltefosine caused reduced viable sperm counts and impaired fertility in rats at doses approximately 0.4 times the MRHD [see Nonclinical Toxicology ( 13.1 ) ] .

A higher dose in rats, approximately 1.0 times the MRHD, caused testicular atrophy and impaired fertility that did not fully reverse 10 weeks after drug administration ended. Scrotal pain and decreased or absent ejaculation during therapy have been reported during IMPAVIDO therapy [see Adverse Reactions ( 6.2 ) ] . The effects of IMPAVIDO on human male fertility have not been adequately studied.

Advise women and men of the animal fertility findings, and that the potential for impaired fertility with IMPAVIDO therapy in humans has not been adequately evaluated.

5.3Renal Effects Elevations of serum creatinine (Cr) were noted in clinical trials evaluating IMPAVIDO in the treatment of cutaneous, mucosal and visceral leishmaniasis. Monitor renal function weekly in patients receiving IMPAVIDO during therapy and for 4 weeks after end of therapy [see Adverse Reactions ( 6.1 )] .

5.4Hepatic Effects Elevations in liver transaminases (ALT, AST) and bilirubin were noted in clinical trials evaluating IMPAVIDO in the treatment of visceral leishmaniasis. Monitor liver transaminases (ALT, AST) and bilirubin during therapy in patients receiving IMPAVIDO [see Adverse Reactions ( 6.1 )] .

5.5Gastrointestinal Effects Vomiting and/or diarrhea commonly occur during IMPAVIDO administration and may result in volume depletion. Encourage fluid intake to avoid volume depletion [see Adverse Reactions ( 6.1 )] .

5.6Thrombocytopenia Thrombocytopenia during therapy has been reported in patients treated for visceral leishmaniasis. Monitor platelet count during therapy for visceral leishmaniasis [see Adverse Reactions ( 6.1 , 6.2 )] .

5.7Absorption of Oral Contraceptives Vomiting and/or diarrhea occurring during IMPAVI… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse reactions occurring in ≥2% of patients include nausea, vomiting, diarrhea, headache, decreased appetite, dizziness, abdominal pain, pruritus, somnolence, elevated transaminases, and elevated creatinine (6.1). To report SUSPECTED ADVERSE REACTIONS, contact Profounda, Inc. at 1-866-588-5405 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical Trials Experience Visceral Leishmaniasis One Phase 3 trial was conducted in patients ≥ 12 years of age in India. Two-hundred and ninety-nine (299) patients (211 men and 88 women) received oral IMPAVIDO at a target dose of 2.5 mg/kg/day for 28 days (50 mg capsule once daily if weight was less than 25 kg and 50 mg capsule twice daily if weight was 25 kg or greater). Patients ranged between 12 and 64 years of age.

Weight ranged between 15 and 67 kg (mean weight 38.6 kg) and BMI ranged between 8.2 and 24 (mean 16.1). Ninety-nine (99) patients received 1 mg/kg/day amphotericin B deoxycholate intravenously every other day for 15 doses. A statistically significant higher percentage of men received IMPAVIDO compared to amphotericin B.

Less than 1% of patients who received IMPAVIDO died (2/299) and no patient who received amphotericin B died. Serious adverse reactions were reported in 2% of IMPAVIDO recipients (6/299) and 1% of amphotericin B recipients (1/99). Approximately 3% of patients discontinued treatment in each treatment arm due to an adverse reaction.

Serious adverse reactions and adverse reactions leading to drug discontinuation that were thought to be related or possibly related to IMPAVIDO included Stevens-Johnson syndrome, melena and thrombocytopenia, arthritis and skin rash, CTCAE Common Terminology Criteria for Adverse Events Grade 4 diarrhea (≥10 stools per day) and CTCAE Grade 4 hyperbilirubinemia (≥10x upper limit of normal ULN). Table 2: Treatment Emergent Adverse Reactions Occurring in ≥2% of Visceral Leishmaniasis Patients Receiving IMPAVIDO System Organ Class Preferred Term IMPAVIDO N = 299 Amphotericin B Deoxycholate N = 99 Gastrointestinal Disorders Diarrhea 61 (20.4%) 6 (6.1%) Vomiting 113 (37.8%) 20 (20.0%) General Disorders Asthenia 19 (6.3%) 4 (4.0%) Metabolism and Nutrition Disorders Decreased Appetite 69 (23.1%) 22 (22.2%) In this study, creatinine (Cr) elevations ≥ 1.5 times above baseline occurred in approximately 10% of IMPAVIDO recipients and in 40% of amphotericin B recipients at the end of therapy.

Ten percent of subjects in each arm had Cr elevations ≥1.5 times above baseline at 6 months follow up. No IMPAVIDO recipient discontinued therapy due to Cr elevation. Elevations of transaminases during therapy occurred in up to half of IMPAVIDO recipients and up to a third of amphotericin B recipients.

The elevations were mild (< 3x ULN) or moderate (3-5x ULN) in 94% and 6% respectively of IMPAVIDO-treated patients who experienced an elevation. No patient discontinued therapy due to elevations in transaminases. At the end of therapy, 62% and 2.4% of IMPAVIDO recipients and 54% and 2% of amphotericin B recipients had platelet count < 150,000 and < 50,000 respectively.

Cutaneous Leishmaniasis The efficacy of IMPAVIDO in the treatment of cutaneous leishmaniasis was evaluated in one placebo-controlled trial conducted in Colombia and Guatemala and in two comparative trials conducted in Bolivia and Brazil respectively. In the placebo-controlled trial, eighty-nine (89) patients ≥12 years of age received a target IMPAVIDO dose of 2.5 mg/kg/day for 28 days and forty-four (44) received placebo. In the comparative trials, one hundred and twenty (120) patients ≥12 years of age received a target IMPAVIDO dose of 2.5 mg/kg/day for 28 days and fifty eight (58) patients received 20 mg/kg/… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions 70 words ▾

7 DRUG INTERACTIONS In vitro and animal metabolism studies showed that miltefosine did not markedly induce or inhibit the activity of the major human cytochrome P450 enzymes [see Clinical Pharmacology ( 12.3 )] . The potential of miltefosine to interact with drug transporters has not been evaluated. IMPAVIDO did not inhibit human cytochrome P450 enzymes in vitro. IMPAVIDO did not induce cytochrome 3A activity in rats( 7 , 12.3 ).

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS Pregnancy: IMPAVIDO should not be used during pregnancy. Obtain a urine or serum pregnancy test in females of reproductive potential prior to prescribing ( 4.1 , 5.1 , 8.1 , 8.8 , 13.1 ). Nursing Mothers: Discontinue drug or nursing depending on importance of drug to mother.

Avoid breastfeeding for 5 months after IMPAVIDO therapy ( 8.3 ). Females and Males of Reproductive Potential: Advise females to use effective contraception during therapy and for 5 months after therapy. Advise patients of reproductive toxicities in animals, and that the potential for impaired fertility in humans has not been adequately evaluated ( 5.1 , 5.2 , 8.8 ).

8.1Pregnancy Pregnancy Category D Risk Summary IMPAVIDO may cause fetal harm. Human pregnancy data are not available, however, embryo-fetal toxicity including death and teratogenicity, was observed in embryo-fetal studies in rats and rabbits administered oral miltefosine during organogenesis at doses that were respectively 0.06 and 0.2 times the maximum recommended human dose (MRHD), based on body surface area (BSA) comparison. Numerous visceral and skeletal fetal malformations were observed in a fertility study in female rats administered miltefosine prior to mating through day 7 of pregnancy at doses 0.3 times the MRHD.

Do not administer IMPAVIDO to pregnant women. 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. During pregnancy, cutaneous leishmaniasis may manifest with larger and atypical appearing lesions and may be associated with increased risk for adverse fetal outcomes, including preterm births and stillbirths.

Animal Data Miltefosine administration in rat embryo-fetal toxicity studies during early embryonic development (Day 6 to Day 15 of gestation) caused embryo-fetal toxicity including death and teratogenicity at dosages of ≥ 1.2 mg/kg/day (0.06 times the MRHD based on BSA comparison). Teratogenic effects included undeveloped cerebrum, hemorrhagic fluid filling the lumina of the skull, cleft palate and generalized edema. Embryo-fetal toxicity was also observed in rabbits after oral administration of miltefosine during organogenesis (Day 6 to Day 18 of gestation) at doses ≥ 2.4 mg/kg/day (0.2 times the MRHD based on BSA comparison).

In both rats and rabbits, there were no viable litters at miltefosine doses ≥ 6.0 mg/kg/day (0.3 or 0.6 times the MRHD based on BSA comparisons for rats and rabbits respectively). In a separate female fertility study in rats, miltefosine doses ≥ 6.81 mg/kg/day (0.3 times the MRHD based on BSA comparison) administered for four weeks before mating and up to Day 7 of pregnancy produced numerous visceral (misshapen cerebral structures, dilated ventricles filled with brown masses, misshapen spinal cord, misshapen and malpositioned eyes, hypophysis, and absent inner ear) and skeletal (cleft palate, dumbbell-shaped ossification of thoracic vertebral centers, markedly enlarged skull bones, and markedly dilated suturae) fetal malformations. [see Contraindications ( 4.1 ), Nonclinical Toxicology ( 13.1 )] .

8.3Nursing Mothers It is not known whether IMPAVIDO is present in human milk. Because many drugs are present in human milk and because of the potential for serious adverse reactions in nursing infants from IMPAVIDO, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. Breastfeeding should be avoided for 5 months after IMPAVIDO therapy.

8.4Pediatric Use Safety and effectiveness in pediatric patients < 12 years have not been established. Juvenile rats were more sensitive to the miltefosine-induced effects, especially retinal and kidney effects, than adult rats [see Indications and Usage ( 1 )] .

8.5Geriatric Use… [Excerpted — this section continues on DailyMed.]

🤰 Pregnancy ~2 min read ▾

8.1Pregnancy Pregnancy Category D Risk Summary IMPAVIDO may cause fetal harm. Human pregnancy data are not available, however, embryo-fetal toxicity including death and teratogenicity, was observed in embryo-fetal studies in rats and rabbits administered oral miltefosine during organogenesis at doses that were respectively 0.06 and 0.2 times the maximum recommended human dose (MRHD), based on body surface area (BSA) comparison. Numerous visceral and skeletal fetal malformations were observed in a fertility study in female rats administered miltefosine prior to mating through day 7 of pregnancy at doses 0.3 times the MRHD.

Do not administer IMPAVIDO to pregnant women. 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. During pregnancy, cutaneous leishmaniasis may manifest with larger and atypical appearing lesions and may be associated with increased risk for adverse fetal outcomes, including preterm births and stillbirths.

Animal Data Miltefosine administration in rat embryo-fetal toxicity studies during early embryonic development (Day 6 to Day 15 of gestation) caused embryo-fetal toxicity including death and teratogenicity at dosages of ≥ 1.2 mg/kg/day (0.06 times the MRHD based on BSA comparison). Teratogenic effects included undeveloped cerebrum, hemorrhagic fluid filling the lumina of the skull, cleft palate and generalized edema. Embryo-fetal toxicity was also observed in rabbits after oral administration of miltefosine during organogenesis (Day 6 to Day 18 of gestation) at doses ≥ 2.4 mg/kg/day (0.2 times the MRHD based on BSA comparison).

In both rats and rabbits, there were no viable litters at miltefosine doses ≥ 6.0 mg/kg/day (0.3 or 0.6 times the MRHD based on BSA comparisons for rats and rabbits respectively). In a separate female fertility study in rats, miltefosine doses ≥ 6.81 mg/kg/day (0.3 times the MRHD based on BSA comparison) administered for four weeks before mating and up to Day 7 of pregnancy produced numerous visceral (misshapen cerebral structures, dilated ventricles filled with brown masses, misshapen spinal cord, misshapen and malpositioned eyes, hypophysis, and absent inner ear) and skeletal (cleft palate, dumbbell-shaped ossification of thoracic vertebral centers, markedly enlarged skull bones, and markedly dilated suturae) fetal malformations. [see Contraindications ( 4.1 ), Nonclinical Toxicology ( 13.1 )] .

🧒 Pediatric Use 41 words ▾

8.4Pediatric Use Safety and effectiveness in pediatric patients < 12 years have not been established. Juvenile rats were more sensitive to the miltefosine-induced effects, especially retinal and kidney effects, than adult rats [see Indications and Usage ( 1 )] .

🧓 Geriatric Use 29 words ▾

8.5Geriatric Use Clinical studies of IMPAVIDO did not include sufficient numbers of subjects 65 years of age and over to determine if they respond differently than younger subjects.

🆘 Overdosage 66 words ▾

10 OVERDOSAGE The common adverse effects of vomiting, diarrhea, and abdominal pain are likely in case of overdose. Institute adequate hydration to prevent the risk of impaired renal function, and replace electrolytes as necessary. Because miltefosine is only slightly excreted in the urine, forced diuresis will not increase miltefosine excretion. Gastrointestinal lavage is of unknown value. A specific antidote to treat miltefosine overdose is not known.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Miltefosine is an anti-leishmanial agent [see Clinical Pharmacology ( 12.4 )] .

12.3Pharmacokinetics The pharmacokinetic parameters of miltefosine in patients with visceral and cutaneous leishmaniasis treated for 28 days with IMPAVIDO are listed in Table 5. Due to the long half-life of miltefosine (> 6 days), trough plasma concentrations did not appear to reach a steady state at the end of treatment (i.e., Day 28). Table 5: Mean (%CV) Pharmacokinetic Parameters for Miltefosine Following Oral Capsule Administration to Adult Patients with Visceral and Cutaneous Leishmaniasis a: Adolescent (≥12 years)/Adults, mean dose per kg was 3.1 mg/kg/day b: Adolescent (≥12 years)/Adults, mean dose per kg was 3.6 mg/kg/day c: Adults, mean dose per kg was 1.8 mg/kg/day d: median (range) e: AUC 0-12h for BID, AUC 0-8h for TID f: t 1/2, α = distribution phase half-life; t 1/2,β = terminal elimination phase half-life g: Estimates based on a population PK model h: mean (% standard error) Dose C max (µg/mL) T max d (hr) AUC tau e (µg∙hr/mL) t 1/2,α f (day) t 1/2,β g (day) Visceral Leishmaniasis (on Day 23) 50 mg BID (4 wks) a 66.2 (28.5) 7(2-12) 636 (26.7) 6.4 (31.1) 50 mg BID (1 wk)/ 50 mg TID (3 wks) b 75.9 (17.6) 4 (2-8) 486 (18.1) 8.5 (28.9) Cutaneous Leishmaniasis c (on Day 27) 50 mg TID (4 wks) 37.3 (22) f 295 (22) f 6.8 (5.8) g,h 30.7 (18.3) g,h Absorption Absolute bioavailability of miltefosine has not been determined.

In patients with visceral leishmaniasis, maximum miltefosine concentrations following oral administration of IMPAVIDO capsules were reached right before the next dose in many patients, indicating that the absorption of miltefosine may proceed throughout the dosing interval. Distribution The distribution of miltefosine has not been studied in humans. Human plasma protein binding of miltefosine, evaluated by an ultracentrifugation method, was 98% over the drug concentration range from 0.1 to 10 µg/mL.

In rats, radioactivity of [ 14 C] miltefosine is widely distributed after both single and repeated oral administration with highest uptake of radioactivity in kidney, liver, and spleen. Placental transfer and excretion into milk have not been investigated. Metabolism and Excretion No in vitro oxidative metabolism by 15 different human cytochrome P450 enzymes (1A1, 1A2, 1B1, 2A6, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, 3A4, 3A5, 3A7, and 4A1) was observed.

A slow metabolic breakdown could be shown in human hepatocytes, resulting in the release of choline by phospholipase D-like cleavage of the miltefosine molecule. The fatty alcohol-containing fragment of miltefosine can enter the metabolism of fatty acids after being oxidized to palmitic acid. This oxidation is blocked in patients with Sjögren-Larsson syndrome, which is caused by a genetic defect in fatty aldehyde dehydrogenase activity.

IMPAVIDO is contraindicated in patients who have Sjögren-Larsson-Syndrome [see Contraindications ( 4.2 )] . There was little or no evidence of time or metabolism dependent inhibition of the cytochrome P450 enzymes examined at up to approximately 40 µg/mL miltefosine. Oral administration of miltefosine did not markedly induce the content of hepatic CYP3A assayed by demethylation activity of erythromycin in rats.

In visceral leishmaniasis patients, <0.2% of the administered dose was excreted into the urine.

12.4Microbiology Mechanism of Action The specific mode of action of miltefosine against Leishmania species is unknown. The mechanism of action of miltefosine is likely to involve interaction with lipids (phospholipids and sterols), including membrane lipids, inhibition of cytochrome c oxidase (mitochondrial function), and apoptosis-like cell death. Activity In Vitro and In Vivo Miltefosine has anti-leishmanial activity in vitro and in clinical infections [see Clinical Studies ( 14 )] .

Sensitivity of different Leishmania species as well as different strains of a Leishmania species to miltefosine m… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 16 words ▾

12.1Mechanism of Action Miltefosine is an anti-leishmanial agent [see Clinical Pharmacology ( 12.4 )] .

📦 How Supplied / Storage and Handling 71 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING Each IMPAVIDO capsule contains 50 mg miltefosine in an opaque, red, hard gelatin capsule. IMPAVIDO capsules are supplied in a folded peel/push-through child-resistant blister card. Each blister card contains 14 capsules.

Each carton contains two blister cards (NDC 69051-300-01). Store at 20-25 °C (68-77 °F); excursions permitted to 15-30 °C (59-86 °F). [See USP Controlled Room Temperature]. Protect from moisture.

Dispense only in the original carton.

📋 Description 93 words ▾

11 DESCRIPTION IMPAVIDO capsules contain the active ingredient miltefosine, an antileishmanial agent. The chemical name of miltefosine is 2-[[(hexadecyloxy)hydroxyphosphenyl]oxy]-N,N,N-trimethylethylammonium inner salt. Miltefosine is a white powder that is freely soluble in water,

0.1N HCl or NaOH, methanol, and ethanol. It has the empirical formula of C 21 H 46 NO 4 P with a molecular weight of 407.6 and the following structural formula: The inactive ingredients are colloidal silicon dioxide, microcrystalline cellulose, lactose monohydrate, talc, and magnesium stearate. The capsule shell contains gelatin, titanium dioxide, ferric oxide, and purified water. Structural Formula

💬 Information for Patients ~1 min read ▾

17 PATIENT COUNSELING INFORMATION See the FDA-approved Medication Guide

17.1Dosing Instructions IMPAVIDO is administered with food to ameliorate gastrointestinal side effects. Instruct the patient to swallow the capsule whole and not to chew it or break it apart. Instruct the patient to complete the full course of therapy.

Inform the patient that abdominal pain, nausea, vomiting, and diarrhea are common side effects of therapy with IMPAVIDO and instruct the patient to inform their healthcare provider if these gastrointestinal side effects are severe or persistent. Instruct the patient to consume sufficient fluids to avoid dehydration and, consequently, the risk of kidney injury.

17.2Females and Males of Reproductive Potential Advise women of reproductive potential to use effective contraception during IMPAVIDO therapy and for 5 months after therapy ends [see Boxed Warning and Use in Specific Populations ( 8.1 , 8.8 )] . Advise women who use oral contraceptives to use additional non-hormonal or alternative method(s) of effective contraception during IMPAVIDO therapy if vomiting and/or diarrhea occurs [see Warnings and Precautions ( 5.7 ) and Use in Specific Populations ( 8.8 )] . Advise nursing mothers not to breastfeed during IMPAVIDO therapy and for 5 months after therapy is completed [see Use in Specific Populations ( 8.3 )] .

Advise women and men that IMPAVIDO caused infertility in male rats, impaired fertility in female rats, and caused atresia in ovarian follicles in female dogs. Advise patients that the potential of impaired fertility in humans has not been adequately evaluated [see Warnings and Precautions ( 5.2 ) and Use in Specific Populations ( 8.8 )] . Distributed by: Profounda, Inc.

5790 Hoffner Avenue, Suite 507 Orlando, FL 32822 USA PR033

💬 Medication Guide ~3 min read ▾

Medication Guide IMPAVIDO® (Im-PA-vee-do) (miltefosine) Capsules Read this Medication Guide before you receive IMPAVIDO. This information does not take the place of talking to your healthcare provider about you medical condition or treatment. What is the most important information I should know about IMPAVIDO?

IMPAVIDO may cause serious risks to pregnancy: Do not take IMPAVIDO if you are pregnant. If you take IMPAVIDO during pregnancy, your baby is at risk for death or serious birth defects. Women who can become pregnant should use effective birth control (contraception) during IMPAVIDO treatment and for 5 months after stopping IMPAVIDO treatment.

Discuss with your healthcare provider which birth control method is right for you. If you become pregnant while taking IMPAVIDO, tell your healthcare provider right away. Talk to your healthcare provider about taking part in the IMPAVIDO Pregnancy Registry.

This is a study to learn how IMPAVIDO affects pregnancy and babies. You can enroll in this registry by calling 1-866-588-5405. What is IMPAVIDO?

IMPAVIDO is prescription medicine used to treat certain types of leishmaniasis: visceral leishmaniasis (affecting your internal organs) cutaneous leishmaniasis (affecting the skin) mucosal leishmaniasis (affecting the nose, mouth and throat) It is not known if IMPAVIDO is safe and effective in children under 12 years of age. Who should not take IMPAVIDO? Do not take IMPAVIDO if you: are pregnant have Sjögren-Larsson-Syndrome are allergic to miltefosine or any of the ingredients in IMPAVIDO.

See the end of this leaflet for a list of the ingredients in IMPAVIDO. are a woman who can become pregnant and have not had a pregnancy test. Women who can get pregnant must have a urine or blood pregnancy test before taking IMPAVIDO. are a woman who can become pregnant and you are not willing to use effective birth control during IMPAVIDO treatment and for 5 months after treatment Before you take IMPAVIDO, tell your healthcare provider about all of your medical conditions, including if you: have kidney or liver problems.

Your healthcare provider should do blood tests to check your kidneys and liver before you start, during and after your treatment with IMPAVIDO. are pregnant or planning to become pregnant. IMPAVIDO may harm your unborn baby. are breastfeeding or plan to breastfeed. It is not known if IMPAVIDO passes into your breast milk.

Talk to your healthcare provider about the best way to feed your baby if you take IMPAVIDO. You should avoid breastfeeding while you take IMPAVIDO and for 5 months after you stop taking IMPAVIDO. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

How should I take IMPAVIDO? Take IMPAVIDO exactly as your healthcare provider tells you to. Complete your full 28 day IMPAVIDO treatment.

Take IMPAVIDO capsules whole. Do not break, crush, dissolve, or chew IMPAVIDO before swallowing. Take IMPAVIDO with food to help reduce stomach problems.

What are the possible side effects of IMPAVIDO? IMPAVIDO may cause serious side effects, including: See “What is the most important information I should know about IMPAVIDO?” Fertility problems in male and female rats and abnormal menstrual cycle in female dogs. It is not known if IMPAVIDO causes fertility problems in men or women Testicular pain and absent or decreased ejaculation Kidney and liver problems Stomach problems .

IMPAVIDO can cause vomiting, diarrhea, and dehydration. Call your healthcare provider right away if you have severe vomiting and diarrhea that does not go away. Drink a lot of water to help prevent dehydration while you are having vomiting and diarrhea.

Decreased effectiveness of oral contraceptive pills . Vomiting and diarrhea may cause your birth control pills to be less effective at preventing pregnancy. Use an extra method of birth control, such as male condoms with spermicide, until you are no longer having vomi… [Excerpted — this section continues on DailyMed.]

🍼 Nursing Mothers 70 words ▾

8.3Nursing Mothers It is not known whether IMPAVIDO is present in human milk. Because many drugs are present in human milk and because of the potential for serious adverse reactions in nursing infants from IMPAVIDO, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. Breastfeeding should be avoided for 5 months after IMPAVIDO therapy.

🧬 Pharmacokinetics ~2 min read ▾

12.3Pharmacokinetics The pharmacokinetic parameters of miltefosine in patients with visceral and cutaneous leishmaniasis treated for 28 days with IMPAVIDO are listed in Table 5. Due to the long half-life of miltefosine (> 6 days), trough plasma concentrations did not appear to reach a steady state at the end of treatment (i.e., Day 28). Table 5: Mean (%CV) Pharmacokinetic Parameters for Miltefosine Following Oral Capsule Administration to Adult Patients with Visceral and Cutaneous Leishmaniasis a: Adolescent (≥12 years)/Adults, mean dose per kg was 3.1 mg/kg/day b: Adolescent (≥12 years)/Adults, mean dose per kg was 3.6 mg/kg/day c: Adults, mean dose per kg was 1.8 mg/kg/day d: median (range) e: AUC 0-12h for BID, AUC 0-8h for TID f: t 1/2, α = distribution phase half-life; t 1/2,β = terminal elimination phase half-life g: Estimates based on a population PK model h: mean (% standard error) Dose C max (µg/mL) T max d (hr) AUC tau e (µg∙hr/mL) t 1/2,α f (day) t 1/2,β g (day) Visceral Leishmaniasis (on Day 23) 50 mg BID (4 wks) a 66.2 (28.5) 7(2-12) 636 (26.7) 6.4 (31.1) 50 mg BID (1 wk)/ 50 mg TID (3 wks) b 75.9 (17.6) 4 (2-8) 486 (18.1) 8.5 (28.9) Cutaneous Leishmaniasis c (on Day 27) 50 mg TID (4 wks) 37.3 (22) f 295 (22) f 6.8 (5.8) g,h 30.7 (18.3) g,h Absorption Absolute bioavailability of miltefosine has not been determined.

In patients with visceral leishmaniasis, maximum miltefosine concentrations following oral administration of IMPAVIDO capsules were reached right before the next dose in many patients, indicating that the absorption of miltefosine may proceed throughout the dosing interval. Distribution The distribution of miltefosine has not been studied in humans. Human plasma protein binding of miltefosine, evaluated by an ultracentrifugation method, was 98% over the drug concentration range from 0.1 to 10 µg/mL.

In rats, radioactivity of [ 14 C] miltefosine is widely distributed after both single and repeated oral administration with highest uptake of radioactivity in kidney, liver, and spleen. Placental transfer and excretion into milk have not been investigated. Metabolism and Excretion No in vitro oxidative metabolism by 15 different human cytochrome P450 enzymes (1A1, 1A2, 1B1, 2A6, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, 3A4, 3A5, 3A7, and 4A1) was observed.

A slow metabolic breakdown could be shown in human hepatocytes, resulting in the release of choline by phospholipase D-like cleavage of the miltefosine molecule. The fatty alcohol-containing fragment of miltefosine can enter the metabolism of fatty acids after being oxidized to palmitic acid. This oxidation is blocked in patients with Sjögren-Larsson syndrome, which is caused by a genetic defect in fatty aldehyde dehydrogenase activity.

IMPAVIDO is contraindicated in patients who have Sjögren-Larsson-Syndrome [see Contraindications ( 4.2 )] . There was little or no evidence of time or metabolism dependent inhibition of the cytochrome P450 enzymes examined at up to approximately 40 µg/mL miltefosine. Oral administration of miltefosine did not markedly induce the content of hepatic CYP3A assayed by demethylation activity of erythromycin in rats.

In visceral leishmaniasis patients, <0.2% of the administered dose was excreted into the urine.

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES

14.1Treatment of Visceral Leishmaniasis One randomized, open-label, active-controlled study was conducted to evaluate the efficacy of IMPAVIDO in the treatment of visceral leishmaniasis in Bihar, India, an area where L. donovani is known epidemiologically to be the prevalent infecting species. Patients ≥ 12 years of age with clinical signs and symptoms compatible with visceral leishmaniasis (fever, splenomegaly, and cytopenia) confirmed by the presence of Leishmania amastigotes in aspirates of spleen or bone marrow were randomized to receive oral IMPAVIDO or intravenous amphotericin B deoxycholate in a 3:1 ratio.

Patients weighing ≥ 25 kg received an IMPAVIDO 50 mg capsule with meals twice a day. Patients weighing < 25 kg received an IMPAVIDO 50 mg capsule with meals once a day in the morning. Weight ranged between 15 and 67 kg (mean weight 38.6 kg) and BMI ranged between 8.2 and 24 (mean 16.1).

No patient weighed more than 70kg. Amphotericin B was administered intravenously over 6 continuous hours at 1 mg/kg every other day for 15 doses. Patients were hospitalized for the duration of therapy.

Exclusion criteria included platelet count <50 × 10 9 /L, white cell count <1 × 10 9 /L, hemoglobin <6 g/100 mL, AST or ALT ≥3 times upper limit of the normal range, bilirubin ≥2 times upper limit of the normal range, serum creatinine or BUN >1.5 times upper limit of the normal range, prothrombin time >5 seconds above control, and any non-compensated or uncontrolled condition including human immunodeficiency virus (HIV) infection. Women of reproductive potential were required to use effective contraception for the duration of therapy and for 2 months post therapy.

Final cure was defined as initial cure at end of therapy plus absence of signs and symptoms of visceral leishmaniasis at 6 months follow up. Initial cure at the end of therapy was evaluated by repeat spleen or bone marrow aspiration. Patients with initial parasitologic cure were followed for 6 months; patients without absence of clinical signs and symptoms of visceral leishmaniasis were to be evaluated with repeat spleen or bone marrow aspiration to determine final cure.

Two hundred and ninety nine (299) patients received IMPAVIDO and 99 patients received amphotericin B. Approximately, 70% of patients in each arm had previously failed treatment with pentavalent antimony. Initial cure was achieved in 98% of patients in each treatment arm.

At 6 months after therapy, 88 (29.5%) IMPAVIDO recipients and 12 (12.1%) amphotericin B recipients continued to have signs and symptoms suggestive of visceral leishmaniasis. These signs or symptoms were attributed to alternative diagnosis in 73 patients. The remaining 27 patients, all in the IMPAVIDO arm, underwent evaluation with splenic or bone marrow aspiration, and 9 (3.0%) were positive for Leishmania amastigotes, indicating relapse.

The final cure rates for IMPAVIDO and amphotericin B were 94% and 97%, respectively. Table 6: Efficacy of IMPAVIDO in Visceral Leishmaniasis in Patients ≥12 years of Age in India IMPAVIDO N = 299 Amphotericin B Deoxycholate N = 99 End of therapy Initial Cure 293 (98%) 97 (98%) 6 months after therapy Final Cure The 95% exact confidence interval for the difference (IV Amphotericin B – IMPAVIDO) in final cure is (-3.0%, 6.8%). 282 (94%) 96 (97%) Treatment Failure 9 (3%) 0 (0) Not Assessable 8 (3%) 3 (3%)

14.2Treatment of Cutaneous Leishmaniasis A placebo controlled study was performed in Colombia where L. panamensis and L. braziliensis are epidemiologically known to be the prevalent infecting Leishmania species, and in Guatemala where L. braziliensis is epidemiologically known to be the prevalent infecting species. The study included male and female patients older than 12 years of age who had newly diagnosed or relapsing cutaneous leishmaniasis without mucosal involvement, parasitologically confirmed, presenting with at least one skin ulcer with minimum area of 50 mm 2 .

Exclusion criteria w… [Excerpted — this section continues on DailyMed.]

🧪 Nonclinical Toxicology ~2 min read ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Mutagenicity/Carcinogenicity: Miltefosine tested negative in the AMES-Salmonella test, DNA-amplification test, chromosomal aberration test in vitro , UDS-test in vivo/in vitro , and oral mouse micronucleus test in vivo . The V 79 mammalian cell HPRT gene mutation test showed an increase in mutant frequency without dose dependency. In view of all mutagenicity test results, the single positive finding in the V 79 HPRT test is considered to be not of toxicological relevance with respect to a mutagenic risk to humans.

Carcinogenicity studies were not performed. In a 52-week oral rat toxicity study, testicular Leydig cell adenoma was observed in 3 of 30 male rats with daily administration of 21.5 mg/kg/day miltefosine (1.0 times the MRHD based on BSA comparison). The carcinogenic potential of miltefosine in humans is unknown.

In a Segment I fertility study in male rats, testicular atrophy, reduced numbers of viable sperm, and impaired fertility were observed in rats following daily oral doses of ≥ 8.25 mg/kg (0.4 times the MRHD based on BSA comparison). These findings were reversible within a recovery period of 10 weeks except at the highest dose tested, 21.5 mg/kg/day (1.0 times the MRHD based on BSA comparison), where effects were not fully reversible. In a female fertility study in rats, estrus cycle arrest in the metestrus or diestrus phases occurred with the high-dose of 21.5 mg/kg (1.0 times the MRHD based on BSA comparison).

At doses of 6.81 and 21.5 mg/kg (0.3 and 1.0 times the MRHD respectively based on BSA comparison) increased numbers of embryonic and fetal resorptions and dead fetuses were observed. In a 52-week toxicology study in dogs, increased numbers of atretic follicles in the ovaries, and cycle arrest in the uterus, vagina, and mammary gland with morphology consistent with anestrus or diestrus was observed at doses ≥ 1 mg/kg/day (0.2 times the MRHD based on BSA comparison). The effects in dogs were fully reversible after a recovery period of 6 weeks.

13.2Animal Toxicology and/or Pharmacology Toxicological studies with miltefosine have been performed in mice, rats, dogs, and rabbits. Adverse reactions not observed in clinical studies but seen in animals at exposure levels similar to clinical exposure levels and with possible relevance to clinical use were as follows: Acute and chronic toxicity: The oral administration of miltefosine in rats was associated with lesions affecting the eyes (retinal degeneration). Retinal degeneration was observed after 8-weeks treatment at doses of 10 mg/kg/day (0.5 times the MRHD based on BSA comparison).

Juvenile rats were more sensitive to the miltefosine-induced effects, especially on eyes and kidneys, than adult rats with retinal degeneration occurring at doses ≥ 2.15 mg/kg/day (0.1 times the MRHD based on BSA comparison), and reversible damage to proximal tubule epithelium occurring at doses ≥ 4.64 mg/kg/day (0.2 times the MRHD based on BSA comparison).

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ~1 min read ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Mutagenicity/Carcinogenicity: Miltefosine tested negative in the AMES-Salmonella test, DNA-amplification test, chromosomal aberration test in vitro , UDS-test in vivo/in vitro , and oral mouse micronucleus test in vivo . The V 79 mammalian cell HPRT gene mutation test showed an increase in mutant frequency without dose dependency. In view of all mutagenicity test results, the single positive finding in the V 79 HPRT test is considered to be not of toxicological relevance with respect to a mutagenic risk to humans.

Carcinogenicity studies were not performed. In a 52-week oral rat toxicity study, testicular Leydig cell adenoma was observed in 3 of 30 male rats with daily administration of 21.5 mg/kg/day miltefosine (1.0 times the MRHD based on BSA comparison). The carcinogenic potential of miltefosine in humans is unknown.

In a Segment I fertility study in male rats, testicular atrophy, reduced numbers of viable sperm, and impaired fertility were observed in rats following daily oral doses of ≥ 8.25 mg/kg (0.4 times the MRHD based on BSA comparison). These findings were reversible within a recovery period of 10 weeks except at the highest dose tested, 21.5 mg/kg/day (1.0 times the MRHD based on BSA comparison), where effects were not fully reversible. In a female fertility study in rats, estrus cycle arrest in the metestrus or diestrus phases occurred with the high-dose of 21.5 mg/kg (1.0 times the MRHD based on BSA comparison).

At doses of 6.81 and 21.5 mg/kg (0.3 and 1.0 times the MRHD respectively based on BSA comparison) increased numbers of embryonic and fetal resorptions and dead fetuses were observed. In a 52-week toxicology study in dogs, increased numbers of atretic follicles in the ovaries, and cycle arrest in the uterus, vagina, and mammary gland with morphology consistent with anestrus or diestrus was observed at doses ≥ 1 mg/kg/day (0.2 times the MRHD based on BSA comparison). The effects in dogs were fully reversible after a recovery period of 6 weeks.

📄 Package Label / Principal Display Panel 110 words ▾

PRINCIPAL DISPLAY PANEL - CARTON NDC 69051-300-01 28 Capsules Impavido® (miltefosine) capsules 50 mg per Capsule Rx only PROFOUNDA Contains 2 blister cards, 14 blisters per card, 1 capsule per blister. Active ingredient: miltefosine Inactive ingredients: colloidal silicon dioxide, lactose monohydrate, magnesium stearate, microcrystalline cellulose, talc. The capsule shell contains gelatin, titanium dioxide, ferric oxide and purified water.

Usual dosage: see enclosed package insert for complete prescribing information. Keep out of reach of children. Store at 20-25 °C (68-77 °F); excursions permitted to 15-30 °C (59-86 °F). [See USP Controlled Room Temperature].

Distributed by: Profounda, Inc. 5790 Hoffner Avenue, Suite 507 Orlando, Florida 32822 USA Principal Display Panel - Carton

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗

Medicare Part D spend CMS · PART D · 2025 (Q1-Q4)

Medicare Part D (outpatient prescription) spending for Impavido — the program that covers self-administered drugs. 1 manufacturer.
⚠️ Drug-level data: CMS publishes Part D spending by drug, not by NDC — these figures combine every manufacturer, strength and package size sold under the name Impavido. That’s a different level of aggregation than the Medicaid card above, which is specific to this exact 11-digit NDC (pack size included), so the two aren’t directly comparable.
Total Part D spend
$2.23M
Claims incl. refills
48
Beneficiaries
34
Spend / beneficiary
$65,629.45
Spend / claim
$46,487.53
💵 About the dollar figures: spending is what Part D plans paid before confidential manufacturer rebates, so the program’s real net cost is lower. A blank patient count means fewer than 11 people — CMS hides counts that small to protect privacy. Source: CMS Medicare Quarterly Part D Spending by Drug (data.cms.gov), updated quarterly.

About this NDC listing & data coverage

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Labeler ✓ Available
Product & package description ✓ Available
Marketing category & status ✓ Available
Active ingredient / dosage form / route ✓ Available
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Package photos ✓ Available
Inactive ingredients (structured) ✓ Available
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Questions about this listing

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
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The labeler reported a marketing end date (or the listing was delisted), so this specific package is no longer actively marketed. Remaining stock may still be dispensed for a time, and the NDC stays valid for historical records and claims — but data feeds (pricing, labeling) typically stop updating for it. Other package sizes or other manufacturers' versions of the same medication may still be marketed — see the equivalents section where available.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The form printed on the packaging and shown on DailyMed is the one the FDA registered. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero and the dashes are dropped. The Identity section at the top of this page lists each form of this code.
Who lists this product with the FDA?
Profounda, Inc. is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.
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For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.