metreleptin (recombinant methionyl-human leptin)

General

**REMS Drug**

Pronunciation:
met-re-lep-tin


Trade Name(s)

  • Myalept

Ther. Class.
orphan drugs

Pharm. Class.
leptin analogues

Indications

Adjunct to dietary therapy for the management of complications from lipodystrophy due to congenital or acquired leptin deficiency.

Action

Binds to and activates leptin receptors resulting in ↑ insulin sensitivity and ↓ food intake.

Therapeutic Effect(s):

↓ sequelae of lipodystrophy including insulin resistanance, ↑ food intake, hypertriglyceridemia and abnormal fat distribution (liver, muscle).

Pharmacokinetics

Absorption: Well absorbed following subcutaneous administration.

Distribution: Unknown.

Metabolism and Excretion: Elimination is primarily renal. Metabolism is unknown.

Half-life: 3.8–4.7 hr.

TIME/ACTION PROFILE (blood levels)

ROUTEONSETPEAKDURATION
Subcutunknown4.0–4.3 hrunknown

Contraindication/Precautions

Contraindicated in:

  • Hypersensitivity
  • Obesity not associated with leptin deficiency
  • HIV-associated lipodystrophy
  • Lactation: Discontinue metreleptin or discontinue breastfeeding.

Use Cautiously in:

  • Significant hematologic abnormalities;
  • Acquired generalized lipodystrophy (may ↑ risk of lymphoma)
  • History of autoimmune disease (may be exacerbated)
  • History of/risk factors for pancreatitis (dose should be tapered);
  • Geri: Consider age related decrease in renal, hepatic and cardiac function, concurrent disease states and drug therapy (lower initial doses recommended);
  • OB: Use only if potential maternal benefit outweighs fetal risk
  • Pedi: Avoid reconstituting with bacteriostatic water for injection in infants due to known risk of benzyl alcohol causing "gasping syndrome").

Adverse Reactions/Side Effects

CNS: headache, dizziness, fatigue

Endo: hypoglycemia

GI: abdominal pain, diarrhea, nausea

Hemat: anemia

Metabolic: weight loss

MS: arthralgia, back pain

Neuro: paresthesia

Misc: HYPERSENSITIVITY REACTIONS, LYMPHOMA, fever, neutralizing antibodies

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

  • Concurrent use of antidiabetic agents, including insulin ↑ risk of hypoglycemia, dose adjustments may be required.
  • May alter CYP450 enzymes and effects of cyclosporine, hormonal contraceptives, theophylline, warfarin and other substrates, careful clinical and therapeutic monitoring may be necessary.

Route/Dosage

SC: (Adults and Children) > 40 kg): Males–2.5 mg daily, increase or decrease by 1.25 – 2.5 mg/day up to 10 mg/day; Females– 5 mg daily, increase by 1.25 – 2.5 mg/day up to 10 mg/day.

SC: (Adults and Children) ≤ 40 kg): 0.06 mg/kg daily, increase or decrease by 0.02 mg/kg/day up to 0.13 mg/kg/day.

Availability

Lyophylized powder for subcutaneous injection: 11.3 mg/vial

Assessment

  • Test for anti-metreleptin antibodies with neutralizing activity in patients who develop severe infections or show signs suspicious for loss of metreleptin efficacy during treatment. Contact Aegerion Pharmaceuticals, Inc. at 1-866-216-1526 for neutralizing antibody testing of clinical samples.
  • Monitor for signs and symptoms of hypersensitivity reactions (urticaria, rash, hives, swelling of face, lips, tongue, or throat, problems breathing or swallowing, fainting or feeling dizzy, very rapid heartbeat) during therapy. May require discontinuation of therapy.

Lab Test Considerations: Monitor blood glucose closely in patients taking concurrent insulin, especially those on high insulin doses or taking an insulin secretagogue; may cause hypoglycemia.

  • May cause leukopenia, neutropenia, bone marrow abnormalities, lymphoma, lymphadenopathy.
  • Monitor triglycerides when discontinuing metreleptin in patients with risk of pancreatitis (history of pancreatitis, severe hypertriglyceridemia). Taper dose over 1 wk. May need to consider initiating or adjusting the dose of lipid-lowering medications. Monitor for signs of pancreatitis (abdominal pain).

Potential Diagnoses

Implementation

  • Available only through a restricted program, MYALEPT REMS program. Only certified prescribers and pharmacies may prescribe and dispense metreleptin.
  • SC: Administer once daily at the same time each day without regard to meals. Administer first dose under supervision of health care professional. Store vials of powder in refrigerator, do not freeze; powder should be white and intact. Allow vial to warm to room temperature prior to use. Using a 3 mL syringe and 22–gauge or smaller needle, reconstitute vial with 2.2 mL of bacteriostatic water or Sterile Water for injection. Inject toward side of vial and swirl gently; do not shake. Solution should be clear and colorless; do not administer solutions that are discolored or contain particulate matter. Solution is stable up to 3 days if refrigerated, then discard. Reconstitute with preservative free solution for neonates and infants; discard immediately after use. Use a 1 mL syringe and subcut needle, withdraw dose and inject into thigh, abdomen, or upper arm at a 45° angle while pinching skin. Rotate sites with each dose. Avoid IM or IV doses. Doses exceeding 1 mL can be divided into 2 doses. Do not mix with insulin or other medications.
    • May be administered at same time as insulin; do not administer in same site.

Patient/Family Teaching

  • Instruct patient in correct technique for administration, care of medication and equipment, and disposal of syringes and needles. Take missed doses as soon as remembered that day; do not take more than 1 dose/day. Advise patient to read Medication Guide before starting metreleptin and with each Rx refill in case of changes.
  • Inform patient that neutralizing antibodies may result in loss of efficacy of metreleptin. If signs and symptoms (severe infections, worsening of metabolic control [increases in HbA1c and/or triglycerides]) occur, notify health care professional.
  • Advise patients to notify health care professional if signs or symptoms indicating changes in hematologic status (leukopenia, neutropenia, bone marrow abnormalities, lymphoma, lymphadenopathy) occur.
  • Inform patient of risk of lymphoma and hypoglycemia. Review signs and symptoms of hypoglycemia (shakiness, confusion, sweating, irritability, headache, hunger, drowsiness, fast heart beat, weakness, feeling jittery, dizziness) and treatment with patient.
  • Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking any other Rx, OTC, or herbal products.
  • Advise female patients to notify health care professional of pregnancy is planned or suspected or if breastfeeding. Encourage women who become pregnant while taking metreleptin to enroll in the monitoring program by calling 1-855- 6MYALEPT to enroll.
  • Emphasize importance of routine laboratory assessments and monitoring.

Evaluation/Desired Outcomes

Decreased sequelae of lipodystrophy including insulin resistanance, ↑ food intake, hypertriglyceridemia and abnormal fat distribution (liver, muscle).

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