Myalept

Myalept is a prescription medication used to treat complications related to leptin deficiency in patients with congenital or acquired generalized lipodystrophy.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

WARNING: RISK OF ANTI-MYALEPT ANTIBODIES WITH NEUTRALIZING ACTIVITY AND RISK OF LYMPHOMA

Anti-Myalept antibodies with neutralizing activity have been identified in patients treated with MYALEPT. The consequences of these neutralizing antibodies are not well characterized but could include inhibition of endogenous leptin action and/or loss of MYALEPT efficacy. Severe infection and/or worsening metabolic control have been reported. Test for anti-Myalept antibodies with neutralizing activity in patients who develop severe infections or show signs suspicious for loss of MYALEPT efficacy during treatment. Contact AstraZeneca at 1-866-216-1526 for neutralizing antibody testing of clinical samples.

T-cell lymphoma has been reported in patients with acquired generalized lipodystrophy, both treated and not treated with MYALEPT. Carefully consider the benefits and risks of treatment with MYALEPT in patients with significant hematologic abnormalities and/or acquired generalized lipodystrophy.

Because of these risks associated with the development of anti-Myalept antibodies that neutralize endogenous leptin and/or MYALEPT and the risk for lymphoma, MYALEPT is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the MYALEPT REMS PROGRAM.

Recombinant analog of human leptin.1 4

Generalized Lipodystrophy

Replacement therapy as an adjunct to diet for treatment of complications of leptin deficiency in patients with congenital or acquired generalized lipodystrophy;1 2 4 21 designated an orphan drug by FDA for treatment of metabolic disorders secondary to lipodystrophy.3

Metreleptin therapy associated with reductions in glycosylated hemoglobin (HbA1c), fasting glucose, and fasting triglyceride concentrations in patients with generalized lipodystrophy.1 2

Manufacturer states that drug not indicated for use in patients with HIV-related lipodystrophy.1

Manufacturer also states that drug not indicated for use in patients with general obesity or metabolic disease, including diabetes mellitus and hypertriglyceridemia, without concurrent evidence of congenital or acquired generalized lipodystrophy.1 5 (See Contraindications under Cautions.)

Efficacy and safety not established for the treatment of complications of partial lipodystrophy.1 2 4

Efficacy and safety not established for treatment of liver disease, including nonalcoholic steatohepatitis (NASH).1

Absorption

Bioavailability

Patients with lipodystrophy: peak plasma concentrations achieved in approximately 4 hours.1 4

Distribution

Extent

Endogenous leptin crosses the blood-brain barrier.12

Not known whether distributed into milk; endogenous leptin is distributed into milk.1

Elimination

Metabolism

None apparent; formal pharmacokinetic studies lacking.1

Elimination Route

Renal excretion.1

Half-life

Healthy individuals: 3.8–4.7 hours.1

• Before mixing, store in the refrigerator.
• Do not freeze.
• Protect from light.
• Store vials in carton.
• After mixing, be sure you know how long the product is good for and how to store it. Ask your doctor or pharmacist if you are not sure.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

There were no reports of overdose in the lipodystrophy clinical trial program of Myalept. In the event of an overdose, patients should be monitored and appropriate supportive treatment be initiated as dictated by the patient’s clinical status.

Myalept (metreleptin) for injection is a recombinant human leptin analog for injection that binds to and activates the leptin receptor. Metreleptin (recombinant methionyl-human leptin) is produced in E. coli and differs from native human leptin by the addition of a methionine residue at its amino terminus. Metreleptin is a 147-amino acid, nonglycosylated, polypeptide with one disulfide bond between Cys-97 and Cys-147 and a molecular weight of approximately 16.15 kDa.

Myalept is supplied as a sterile, white, solid, lyophilized cake containing 11.3 mg that is reconstituted with 2.2 mL of BWFI or WFI to a final formulation of 5 mg/mL metreleptin for subcutaneous injection. Inactive ingredients are: glutamic acid (1.47 mg/mL), glycine (20 mg/mL), polysorbate 20 (0.1 mg/mL), and sucrose (10 mg/mL), pH 4.25.

Usual Adult Dose for Lipodystrophy:

40 Kg or less:
-Initial dose: 0.06 mg/kg/day subcutaneously. Increase or decrease by 0.02 mg/kg
-Maximum dose: 0.13 mg/kg/day

Greater than 40 Kg:
Males:
-Initial dose: 2.5 mg/day subcutaneously. Increase or decrease by 1.25 to 2.5 mg/day
-Maximum dose: 10 mg/day

Female:
-Initial dose: 5 mg/day subcutaneously. Increase or decrease by 1.25 to 2.5 mg/day
-Maximum dose: 10 mg/day

Uses: Replacement therapy for leptin deficiency in patients with congenital or acquired generalized lipodystrophy, as adjunct to diet.

Usual Pediatric Dose for Lipodystrophy:

40 Kg or less:
-Initial dose: 0.06 mg/kg/day subcutaneously. Increase or decrease by 0.02 mg/kg
-Maximum dose: 0.13 mg/kg/day

Greater than 40 Kg:
Males:
-Initial dose: 2.5 mg/day subcutaneously. Increase or decrease by 1.25 to 2.5 mg/day
-Maximum dose: 10 mg/day

Female:
-Initial dose: 5 mg/day subcutaneously. Increase or decrease by 1.25 to 2.5 mg/day
-Maximum dose: 10 mg/day

Comments: Use preservative-free sterile water for injection (WFI) to reconstitute metreleptin for pediatric injection.

Uses: Replacement therapy for leptin deficiency in patients with congenital or acquired generalized lipodystrophy, as adjunct to diet.

Do not stop using Myalept suddenly. Stopping suddenly may cause serious medical problems. Follow your doctor's instructions about tapering your dose.

Applies to metreleptin: subcutaneous powder for injection

Metabolic

Very common (10% or more): Hypoglycemia (13%), decreased weight (13%)[Ref]

Nervous system

Very common (10% or more): Headache (13%)
Common (1% to 10%): Dizziness, paresthesia[Ref]

Gastrointestinal

It has been reported that two patients (4%) had symptoms of pancreatitis. Both had a medical history of pancreatitis.[Ref]

Very common (10% or more): Abdominal pain (10%)
Common (1% to 10%): Nausea, diarrhea, pancreatitis[Ref]

Genitourinary

Common (1% to 10%): Ovarian cyst

Hematologic

Common (1% to 10%): Anemia[Ref]

Hypersensitivity

Common (1% to 10%): Injection-site erythema, urticaria
Frequency not reported: Generalized rash[Ref]

Immunologic

In vitro neutralizing activity anti-metreleptin (the active ingredient contained in Myalept) antibodies were identified in 2 patients (n=33) with generalized lipodystrophy who showed severe infections and worsening metabolic control (increases in HbA1c and/or triglycerides). Three patients with anti-metreleptin antibodies without lipodystrophy showed excessive weight gain, and/or development of glucose intolerance or diabetes.

In clinical trials, anti-metreleptin antibodies were detected in 36 of 43 generalized lipodystrophy patients, with titers ranging from 1:5 to 1:1,953, 125; however, these numbers may be misleading as detection of antibody formation is highly dependent on the sensitivity and specificity of the assay (the assays utilized in clinical trials lacked sensitivity), handling of the sample, concomitant drugs, and underlying disease. Due to incompleteness of the immunogenicity data, the clinical significance and the magnitude and persistence of the anti-drug responses are not well characterized.[Ref]

Frequency not reported: Autoimmune disorder, immunogenicity[Ref]

Musculoskeletal

Common (1% to 10%): Arthralgia, back pain[Ref]

Other

Common (1% to 10%): Pyrexia, ear infection, fatigue[Ref]

Renal

Common (1% to 10%): Proteinuria[Ref]

Respiratory

Common (1% to 10%): Upper respiratory tract infection[Ref]

Oncologic

Frequency not reported: T-cell lymphoma, anaplastic large cell lymphoma

Three cases of T-cell lymphoma were reported among patients with acquired generalized lipodystrophy; 2 patients diagnosed with peripheral T-cell lymphoma during treatment had immunodeficiency and significant hematologic abnormalities including severe bone marrow abnormalities prior to starting treatment. Anaplastic large cell lymphoma was reported in 1 patient receiving this drug who did not have hematologic abnormalities before treatment.

Some side effects of Myalept may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.