Brand Name
Impavido
Generic Name
Miltefosine
View Brand Information FDA approval date: October 29, 2015
Classification: Antileishmanial
Form: Capsule
What is Impavido (Miltefosine)?
IMPAVIDO 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 ( 1.
Approved To Treat
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Brand Information
IMPAVIDO (miltefosine)
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
1INDICATIONS 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
- Cutaneous leishmaniasis caused by
- Mucosal leishmaniasis caused by
Limitations of Use:
- Leishmania species studied in clinical trials evaluating IMPAVIDO were based on epidemiologic data [see Clinical Trials ( .
- There may be geographic variation in clinical response of the same
- The efficacy of IMPAVIDO in the treatment of other
2DOSAGE AND ADMINISTRATION
The treatment duration is 28 consecutive days. Administer with food to ameliorate gastrointestinal adverse reactions.
3DOSAGE 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
4ADVERSE 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.
4.1Clinical 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
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/day pentavalent antimony (meglumine) parenterally for 20 days.
In the placebo controlled trial, 12/89 (13.4%) IMPAVIDO subjects had Cr increases of 1.5-3 times above baseline, compared to 2/44 (4.5%) placebo subjects at end of therapy. In the comparative trial, a similar percentage of subjects who received IMPAVIDO or pentavalent antimony had Cr elevations above baseline at 3 and 6 months after therapy (approximately 5%). Approximately 25% of IMPAVIDO subjects and 11% of pentavalent antimony subjects had Cr elevations 1.5-3 times above baseline at the end of therapy in the two active controlled trials. The frequency of AST and ALT increase above upper limit of normal at end of therapy was similar in IMPAVIDO and placebo recipients (approximately 5%).
Other adverse events seen at <2% incidence in the IMPAVIDO group included anemia, lymphadenopathy, abdominal distension, constipation, dysphagia, flatulence, fatigue, malaise, abscess, cellulitis, ecthyma, paresthesia, testicular pain, testicular swelling, Stevens-Johnson syndrome, urticaria, rash, pyoderma.
4.2Postmarketing Experience
The following adverse reactions have been identified during use of IMPAVIDO worldwide. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Blood and Lymphatics Disorders: thrombocytopenia, agranulocytosis
Gastrointestinal Disorders: melena
General Disorders: generalized edema, peripheral edema
Hepatobiliary Disorders: jaundice
Nervous System Disorders: seizure
Reproductive System and Breast Disorders: scrotal pain, decreased ejaculate volume, absent ejaculation.
Vascular Disorders: epistaxis
5DRUG 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 ( . The potential of miltefosine to interact with drug transporters has not been evaluated.
6OVERDOSAGE
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.
7DESCRIPTION
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, 0.1 N HCl or NaOH, methanol, and ethanol. It has the empirical formula of C
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.
8HOW 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.
9PATIENT COUNSELING INFORMATION
See the FDA-approved Medication Guide
9.1Dosing 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.
9.2Females and Males of Reproductive Potential
- Advise women of reproductive potential to use effective contraception during IMPAVIDO therapy and for 5 months after therapy ends
- 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
- Advise nursing mothers not to breastfeed during IMPAVIDO therapy and for 5 months after therapy is completed
- 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
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PR033
10Medication Guide
IMPAVIDO® (Im-PA-vee-do)
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 vomiting and diarrhea.
- Decrease in platelets (which are blood cells that help blood clot).
- Serious Skin Problems. IMPAVIDO can cause a serious skin problem called Stevens-Johnson Syndrome. If you develop a skin rash with blisters while taking IMPAVIDO, stop taking IMPAVIDO right away and call your healthcare provider.
The most common side effects of IMPAVIDO include: nausea, vomiting and diarrhea. Other side effects include abdominal pain, decreased appetite, dizziness, headache, sleepiness, skin itching, and abnormalities in liver or kidney tests.
Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of IMPAVIDO. For more information, ask your healthcare provider.
You may report side effects to FDA at 1-800-FDA-1088.
How should I store IMPAVIDO?
- Store IMPAVIDO at room temperature between 68°F to 77°F (20°C to 25°C).
- Protect IMPAVIDO from moisture.
Keep IMPAVIDO and all medicines out of the reach of children.
General information about the safe and effective use of IMPAVIDO.
Medicines are sometimes prescribed for purposes other than those listed in this Medication Guide. Do not use IMPAVIDO for a condition for which it was not prescribed. This Medication Guide summarizes the most important information about IMPAVIDO. If you would like more information, talk to your healthcare provider or pharmacist. You can ask your healthcare or pharmacist for information about IMPAVIDO that is written for health professionals. Do not give IMPAVIDO to other people, even if they have the same symptoms that you have. For more information, go to www.IMPAVIDO.com or www.dailymed.nlm.nih.gov, or call 1-866-588-5405.
What are the ingredients in IMPAVIDO?
Active ingredient: miltefosine
Inactive ingredients: colloidal silicon dioxide, microcrystalline cellulose, lactose monohydrate, talc, and magnesium stearate. The capsule shell contains gelatin, titanium dioxide, ferric oxide, and purified water.
Distributed by: Profounda, Inc.
This Medication Guide has been approved by the U.S. Food and Drug Administration.
Issued: Oct 2015
PR034
11PRINCIPAL DISPLAY PANEL - CARTON
NDC 69051-300-01 28 Capsules
Impavido®
(miltefosine) capsules
50 mg per Capsule
(miltefosine) capsules
50 mg per Capsule
Rx only PROFOUNDA
Contains 2 blister cards, 14 blisters per card, 1 capsule per blister.
Usual dosage: see enclosed package insert for complete
prescribing information.
prescribing information.
Keep out of reach of children.
Store at 20-25 °C (68-77 °F); excursions permitted
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