miltefosine


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miltefosine

(mil-te-fos-een),

Impavido

(trade name)

Classification

Therapeutic: temporary class
Pharmacologic: temporary class
Pregnancy Category: D

Indications

Treatment visceral leishmaniasis, cutaneous leishmaniasis and mucocal leishmanisis in adults and adolescents.

Action

Interacts with lipids and sterols in the Leismania membrane resulting in inhibition of mitochondria and apoptotic cell death.

Therapeutic effects

Resolution of Leismania infections.

Pharmacokinetics

Absorption: Absorption is prolonged and may persist for 8–12 hr.
Distribution: Unknown.
Protein Binding: 98%.
Metabolism and Excretion: Slowly broken in the liver, releasing choline; remaining portion is further metabolized and enters fatty acid metabolism ; <0.2% excreted in urine.
Half-life: >6 days.

Time/action profile

ROUTEONSETPEAKDURATION
POunknown4–7 hr (blood level)unknown†
† Persists in the body for up to 5 mos.

Contraindications/Precautions

Contraindicated in: Hypersensitvity; Sjögren-Larsson-Syndrome (due to metabolic defect); Obstetric: Pregnancy (may cause fetal harm); Obstetric: Discontinue miltefosine or discontinue breastfeeding during treatment and for 5 mos following treatment.
Use Cautiously in: Renal impairment (BUN or Cr ≥1.5 x upper limit of normal); Hepatic impairment (ALT or AST ≥3 x upper limit of normal); Patients with reproductive potential..) Pediatric: Safe and effective use in children <12 yr has not been established.

Adverse Reactions/Side Effects

Central nervous system

  • dizziness (most frequent)
  • drowsiness
  • headache
  • weakness

Gastrointestinal

  • abdominal pain (most frequent)
  • ↓ appetite (most frequent)
  • diarrhea (most frequent)
  • vomiting (most frequent)
  • abdominal distention
  • constipation
  • dysphagia
  • flatulence
  • ↑ liver enzymes
  • nausea

Genitourinary

  • ↑ creatinine
  • testicular pain/swelling

Dermatologic

  • pruritus
  • rash including Stevens-Johnson Syndrome (life-threatening)
  • urticaria

Fluid and Electrolyte

  • volume depletions (due to GI effects)

Hematologic

  • anemia
  • thrombocytopenia

Miscellaneous

  • fever
  • lymphadenopathy
  • lymphangitis
  • malaise

Interactions

Drug-Drug interaction

May ↓ absorption and effectiveness of oral hormonal contraceptives..

Route/Dosage

Oral (Adults and adolescents ≥45 kg) 50 mg three times daily for 28 consecutive days.
Oral (Adults and adolescents 30–44 kg) 50 mg twice daily for 28 consecutive days.

Availability

Capsules: 50 mg

Nursing implications

Nursing assessment

  • Assess visible lesions periodically during therapy.
  • Monitor for vomiting and diarrhea. Encourage fluid intake to avoid dehydration.
  • Lab Test Considerations: Obtain a negative urine pregnancy test prior to beginning therapy.
    • Monitor renal function weekly and for 4 wks after completion of therapy. May ↑ serum creatinine.
    • Monitor AST, ALT, and serum bilirubin periodically during therapy. May cause ↑ in AST, ALT, and bilirubin.
    • Monitor platelet count periodically during therapy. May cause thrombocytopenia and agranulocytosis.

Potential Nursing Diagnoses

Impaired skin integrity (Indications)
Deficient knowledge, related to disease process and medication regimen (Patient/Family Teaching)

Implementation

  • Administer with food to decrease GI side effects for 28 consecutive days. Swallow capsule whole; do not open, dissolve or chew.

Patient/Family Teaching

  • Instruct patient to take miltefosine as directed for 28 consecutive days. Advise patient to read the Medication Guide before beginning therapy and with each Rx refill in case of changes.
  • Advise patient to notify health care professional immediately if skin rash with blisters occurs. Discontinue therapy if exfoliative or bullous rash occurs.
  • May cause dizziness and drowsiness. Caution patient to avoid driving and other activities requiring alertness until response t medication is known.
  • Instruct patient to notify healthcare professional if abdominal pain, nausea, vomiting, or diarrhea are persistent or severe. Advise to maintain hydration to prevent kidney damage.
  • Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
  • Caution patient that miltefosine may cause teratogenic effects during pregnancy and may impair fertility. Advise female patient to use effective contraception during and for at least 5 mo after completion of therapy. Nausea and vomiting may decrease absorption of hormonal contraceptives. Advise patient to use a non-hormonal or alternative method of effective contraception. May cause scrotal pain and decreased or absent ejaculation in males. Advise females to avoid breastfeeding during and for at least 5 mo after completion of therapy.

Evaluation/Desired Outcomes

  • Resolution of signs and symptoms of leishmaniasis.

miltefosine

An oral alkyl phosphocholine analogue used to treat cutaneous and visceral leishmaniasis.

Adverse events
Nausea, vomiting, diarrhoea, rigors, increased transaminases, grade-III hepatotoxicity and renal damage.

Mechanism
Miltefosine interferes with cell-signalling pathways and membrane synthesis of Leishmania donovani and L infantum, as well as with mitogenic signal transduction; it also induces apoptosis. It has been used in treating HIV disease because miltefosine inhibits the PI3K/Akt pathway, removing HIV-infected macrophages from circulation without affecting normal cells.
References in periodicals archive ?
Isoproterenol (Injection 1mg/ml), Labetalol (Injection 5mg/ml), Meglumine Antimoniate (Injection 30%), Mercaptopurine (Tablets 50mg), Miltefosine Solid (Oral Dosage Form 10mg and 50mg), Phenoxymethylpenicillin (Powder for Oral Liquid 250mg/5ml), Procaine Penicillin (Injection 1MIU and 3MIU).
Treatment of ML was carried out as follows: 10 patients received IV L-AmB at a dose of 3 mg/kg/day for 6-10 days (total 18-30 mg/kg); 6 patients received IV SSG at a dose of 20 mg/kg/day for 20-30 days; and 1 patient was given oral miltefosine at a dose of 150 mg/day for 28 days.
We aimed to investigate in-vitro anticancer activity of two transition metal compounds of derived Schiff bases; NM-3 (Tetrakis (2-{(E)-[(2- {[(Z)-(2-hydroxynapthyl) methylidene]amino} phenyl)imino] methyl}phenol) Copper(II) and NM-4 (Tetrakis (2-{(E)-[(2- {[(Z)-(2-hydroxynapthyl) methylidene] amino}phenyl)imino]methyl} phenol) zinc(II)), against human THP-1 leukemia cell line in-relation to miltefosine (standard chemotherapy).
An anti-parasitic drug called miltefosine (sold as Impavido) has been used to treat patients and even, in two cases in 2013, was credited with saving lives.
Miltefosine a new compound, derived from alkyl-phospholipids, has demonstrated its antileishmanial and antineoplastic efficacy.4 Miltefosine is the first and still the only oral agent that is being used against all types of leishmaniasis since its registration in 2002.4 Drug was approved in India first and has been used for the past decade in 14 countries for the treatment of leishmaniasis.2 The chemical name of miltefosine is hexadecylphosphocholine and the empirical formula is C21H46NO4P, yielding a molecular weight of 407.57 g/mol.4 Miltefosine acts primarily on Leishmania by affecting the promastigote and amastigote stages of the species.
Activities of hexadecylphosphocholine (miltefosine), AmBisome, and sodium stibogluconate (Pentostam) against Leishmania donovani in immunodeficient scid mice.
(2, 7) Also, the clinical management of VL is undergoing rapid changes with the use of liposomal forms of Amphotericin B and also due to the use of various combinations of miltefosine, amphotericin B, paromomycin etc.
El tratamiento en seis pacientes fue con miltefosine inicialmente, cinco presentaron fracaso terapeutico, por lo que se escalono a anfotericina B; dos ninos recibieron tratamiento exitoso con anfotericina B liposomal y tres con anfotericina de-oxicolato.
Other drugs, such as pentamidine, miltefosine, and amphotericin B, have been used as alternative medications towards resistant parasites.
The AgNPs augmented antileishmanial effect of miltefosine by ~2-folds, even though AgNPs alone did not show any inhibition against leishmanial parasite [33].
Drug resistance has been reported in various species of Leishmania against various antileishmanial drugs like antimonials, amphotericin B, pentamidine, miltefosine, and so forth.