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 ?
M2 EQUITYBITES-June 29, 2017-Profounda wins US FDA's orphan drug designation for miltefosine for Granulomatous Amebic Encephalitis
M2 PHARMA-June 29, 2017-Profounda wins US FDA's orphan drug designation for miltefosine for Granulomatous Amebic Encephalitis
It is important to highlight that miltefosine is included on the WHO's essential medicines list and in the Pan American Health Organization's guidelines, Leishmaniasis in the Americas: Recommendations for Treatment (Leishmaniasis en las Americas: recomendaciones para el tratamiento) (16,18).
Two known people who have contracted the amoeba have survived -&nbsp;this was after being treated with a cocktail of drugs including miltefosine.
Miltefosine was used to treat one of the survivors ae1/4" a 12-year-old girl in Arkansas, the CDC said.
An effective and safe vaccine is not available so far and hence its treatment relies on drugs like amphotericin B, fluconazole, miltefosine, pentamidine, and pentavalent antimonials [27, 28].
Leishmania promastigotes lac phosphatidylserine but bind Annexin V upon permeabilization or miltefosine treatment.
Drug therapies, including pentavalent antimonials, pentamidine (Nebupent[TM]), amphotericin B (Fungizone[TM]), and miltefosine (Miltex[TM]), are currently employed to treat leishmaniasis, each with different mechanisms of action [8].
Recently, miltefosine, an alkylphosphocholine compound, was approved for visceral Leishmania infections, but teratogenic and gastrointestinal side effects have been reported (Porwal et al.
Orally effective drugs for kala-azar (visceral leishmaniasis): focus on miltefosine and sitamaquine.
Miltefosine, which is still under trial has shown some promising results against this amoeba.