metreleptin

Contraindicated in:

Hypersensitivity;
Obesity not associated with leptin deficiency;
HIV-associated lipodystrophy.

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);
OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant.
Pedi: Avoid reconstituting with bacteriostatic water for injection in infants due to known risk of benzyl alcohol causing “gasping syndrome”);
Geri: Consider age related ↓ in renal, hepatic and cardiac function, concurrent disease states and drug therapy (lower initial doses recommended).

Adv. Reactions/Side Effects ⬆ ⬇

Endo: hypoglycemia

GI: abdominal pain, diarrhea, nausea

Hemat: anemia

Metab: weight loss

MS: arthralgia, back pain

Neuro: headache, dizziness, fatigue, paresthesia

Misc: fever, HYPERSENSITIVITY REACTIONS, LYMPHOMA, neutralizing antibodies

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.

Availability ⬆ ⬇

Lyophylized powder for injection: 11.3 mg/vial

Route/Dosage ⬆ ⬇

SC (Adults and Children > 40 kg): Males: 2.5 mg once daily;↑ or ↓ by 1.25 – 2.5 mg/day (max dose = 10 mg/day); Females: 5 mg once daily, ↑ or ↓ by 1.25 – 2.5 mg/day (max dose = 10 mg/day).
SC (Adults and Children ≤40 kg): 0.06 mg/kg once daily, ↑ or ↓ by 0.02 mg/kg/day (max dose = 0.13 mg/kg/day).

US Brand Names ⬆ ⬇

Action ⬆ ⬇

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

Therapeutic effects:

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

Classifications ⬆ ⬇

Therapeutic Classification: orphan drugs

Pharmacologic Classification: leptin analogues

Pharmacokinetics ⬆ ⬇

Absorption: Well absorbed following SUBQ administration.

Distribution: Unknown.

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

Half-Life: 3.8–4.7 hr.

Time/Action Profile ⬆ ⬇

(blood levels)

ROUTE	ONSET	PEAK	DURATION
SUBQ	unknown	4.0–4.3 hr	unknown

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.
Rep: 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 1-855-669-2537 to enroll.
Emphasize importance of routine laboratory assessments and monitoring.

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Indications ⬇

Contraind./Precautions ⬆ ⬇