Impavido

Last updated on RxList: 6/4/2021
Impavido Side Effects Center

What Is Impavido?

Impavido (miltefosine) is an antileishmanial agent used to treat visceral leishmaniasis caused by Leishmania donovani, cutaneous leishmaniasis caused by Leishmania braziliensis, Leishmania guyanensis, and Leishmania panamensis, and mucosal leishmaniasis caused by Leishmania braziliensis.

What Are Side Effects of Impavido?

Common side effects of Impavido include:

Dosage for Impavido

The dose of Impavido is one 50 mg capsule two or three times daily (based on patient's weight) daily with food for 28 consecutive days.

What Drugs, Substances, or Supplements Interact with Impavido?

Impavido may interact with other drugs. Tell your doctor all medications and supplements you use.

Impavido During Pregnancy or Breastfeeding

Impavido is not recommended for use during pregnancy. It may harm a fetus. It is unknown if this drug passes into breast milk. Breastfeeding should be avoided for 5 months after Impavido therapy. Consult your doctor before breastfeeding.

Additional Information

Our Impavido (miltefosine) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

SLIDESHOW

Fungal Skin Infections: Types, Symptoms, and Treatments See Slideshow
Impavido Consumer Information

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

  • severe or ongoing stomach problems (nausea, vomiting, diarrhea);
  • (in men) pain in the scrotum or testicles, abnormal ejaculation;
  • easy bruising or bleeding (nosebleeds, bleeding gums);
  • signs of a kidney problem--little or no urinating; painful or difficult urination; swelling in your feet or ankles; feeling tired or short of breath;
  • liver problems--nausea, upper stomach pain, tired feeling, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes); or
  • severe skin reaction--fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain, followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

Common side effects may include:

  • nausea, vomiting, stomach pain, loss of appetite;
  • diarrhea;
  • headache, dizziness, drowsiness; or
  • itching.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Impavido (Miltefosine Capsules)

QUESTION

Bowel regularity means a bowel movement every day. See Answer
Impavido Professional Information

SIDE EFFECTS

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.

Clinical 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, CTCAE1 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/day pentavalent antimony (meglumine) parenterally for 20 days.

Table 3: Adverse Reactions Occurring in ≥2% of IMPAVIDO-Treated Patients ≥12 Years of Age with Cutaneous Leishmaniasis in the Placebo-Controlled Trial

System Organ Class
Preferred Term
IMPAVIDO
N = 89
Placebo
N = 44
Ear and Labyrinth Disorders
Motion Sickness 26 (29.2%) 10 (22.7%)
Gastrointestinal Disorders
Abdominal Pain 10 (11.2%) 3 (6.8%)
Diarrhea 7 (7.9%) 2 (4.5%)
Nausea 32 (35.9%) 5 (11.1%)
Vomiting 4 (4.5%) 0
General and Administration Site Disorders
Malaise 3 (3.4%) 1 (2.3%)
Pyrexia 5 (5.6%) 2 (4.5%)
Nervous System Disorders
Dizziness 4 (4.5%) 0
Headache 25 (28.1%) 10 (22.7%)
Somnolence 3 (3.4%) 0
Skin and Subcutaneous Tissue Disorders
Pruritus 4 (4.5%) 0

Table 4: Adverse Reactions Occurring in ≥2% of IMPAVIDO-Treated Patients ≥ 12 Years of Age with Cutaneous Leishmaniasis in Two Comparative Trials

System Organ Class Preferred Term IMPAVIDO
N = 120
Meglumine
N = 58
Gastrointestinal Disorders
Abdominal Pain 9 (7.5%) 3 (5.2%)
Diarrhea 18 (15.0%) 3 (5.2%)
Nausea 50 (41.7%) 3 (5.2%)
Vomiting 33 (27.5%) 0
Infections and Infestations
Lymphangitis 7 (5.8%) 0
Metabolism and Nutrition Disorders
Decreased Appetite 13 (10.8%) 4 (5.8%)
Nervous System Disorders
Dizziness 15 (12.5%) 4 (6.9%)
Skin and Subcutaneous Tissue Disorders
Pruritus 7 (5.8%) 0

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.

Postmarketing 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

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]. The potential of miltefosine to interact with drug transporters has not been evaluated.

REFERENCES

1 Common Terminology Criteria for Adverse Events

Read the entire FDA prescribing information for Impavido (Miltefosine Capsules)

© Impavido Patient Information is supplied by Cerner Multum, Inc. and Impavido Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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