metreleptin (Rx)

Brand and Other Names:Myalept
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

lyophylized powder for reconstitution

  • 11.3mg (5mg/mL when reconstituted with 2.2 mL water for injection)
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Lipodystrophy

Indicated as replacement therapy (in addition to diet) for the complications of leptin deficiency in patients with congenital generalized or acquired generalized lipodystrophy

Administer by SC injection once daily at the same time each day

≤40 kg (males or females)

  • Initial daily dose: 0.06 mg/kg (0.012 mL/kg) SC
  • Dose adjustments: 0.02 mg/kg (0.004 mL/kg)
  • Maximum daily dose: 0.13 mg/kg (0.026 mL/kg)

Males >40 kg

  • Initial daily dose: 2.5 mg (0.5 mL) SC
  • Dose adjustments: 1.25-2.5 mg (0.25-0.5 mL)
  • Maximum daily dose: 10 mg (2 mL)

Females >40 kg

  • Initial daily dose: 5 mg (1 mL) SC
  • Dose adjustments: 1.25-2.5 mg (0.25-0.5 mL)
  • Maximum daily dose: 10 mg (2 mL)

Dosage Modifications

Coadministration with insulin or insulin secretagogue (eg, sulfonylurea, meglitinide derivatives): Dosage adjustments, including possible large reductions, of insulin or insulin secretagogue may be necessary in some patients to minimize the risk of hypoglycemia

Dosing Considerations

Safety and efficacy not established for

  • Treatment of complications of partial lipodystrophy
  • Treatment of liver disease, including nonalcoholic steatohepatitis (NASH)
  • HIV-related lipodystrophy
  • Use in patients with metabolic disease, including diabetes mellitus and hypertriglyceridemia, without concurrent evidence of generalized lipodystrophy

Discontinuing due to pancreatitis risk

  • When discontinuing therapy in patients with risk factors for pancreatitis (eg, history of pancreatitis, severe hypertriglyceridemia), taper the dose over a 1-week period
  • During tapering, monitor triglyceride levels and consider initiating or adjusting the dose of lipid-lowering medications as needed
  • Signs and/or symptoms consistent with pancreatitis should prompt an appropriate clinical evaluation

Dosage Forms & Strengths

lyophylized powder for reconstitution

  • 11.3mg (5mg/mL when reconstituted with 2.2 mL water for injection)
more...

Lipodystrophy

Indicated as replacement therapy (in addition to diet) for the complications of leptin deficiency in patients with congenital generalized or acquired generalized lipodystrophy

Administer by SC injection once daily at the same time each day

≤40 kg (males or females)

  • Initial daily dose: 0.06 mg/kg (0.012 mL/kg) SC
  • Dose adjustments: 0.02 mg/kg (0.004 mL/kg)
  • Maximum daily dose: 0.13 mg/kg (0.026 mL/kg)

Males >40 kg

  • Initial daily dose: 2.5 mg (0.5 mL) SC
  • Dose adjustments: 1.25-2.5 mg (0.25-0.5 mL)
  • Maximum daily dose: 10 mg (2 mL)

Females >40 kg

  • Initial daily dose: 5 mg (1 mL) SC
  • Dose adjustments: 1.25-2.5 mg (0.25-0.5 mL)
  • Maximum daily dose: 10 mg (2 mL)

Dosage Modifications

Coadministration with insulin or insulin secretagogue (eg, sulfonylurea, meglitinide derivatives): Dosage adjustments, including possible large reductions, of insulin or insulin secretagogue may be necessary in some patients to minimize the risk of hypoglycemia

Dosing Considerations

Safety and efficacy not established for

  • Treatment of complications of partial lipodystrophy
  • Treatment of liver disease, including nonalcoholic steatohepatitis (NASH)
  • HIV-related lipodystrophy
  • Use in patients with metabolic disease, including diabetes mellitus and hypertriglyceridemia, without concurrent evidence of generalized lipodystrophy

Discontinuing due to pancreatitis risk

  • When discontinuing therapy in patients with risk factors for pancreatitis (eg, history of pancreatitis, severe hypertriglyceridemia), taper the dose over a 1-week period
  • During tapering, monitor triglyceride levels and consider initiating or adjusting the dose of lipid-lowering medications as needed
  • Signs and/or symptoms consistent with pancreatitis should prompt an appropriate clinical evaluation
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Interactions

Interaction Checker

and metreleptin

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            Adverse Effects

            >10%

            Headache (13%)

            Hypoglycemia (13%)

            Decreased weight (13%)

            1-10%

            Abdominal pain (10%)

            Arthralgia (8%)

            Dizziness (8%)

            Ear infection (8%)

            Fatigue (8%)

            Nausea (8%)

            Ovarian cyst (8%)

            Upper respiratory tract infection (8%)

            Anemia (6%)

            Back pain (6%)

            Diarrhea (6%)

            Paresthesia (6%)

            Proteinuria (6%)

            Pyrexia (6%)

            Antibodies with neutralizing activity (6%)

            Injection site erythema and urticaria (4%)

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            Warnings

            Black Box Warnings

            Neutralizing antibodies

            • Antimetreleptin antibodies with neutralizing activity have been identified in patients treated with metreleptin
            • The consequences of these neutralizing antibodies are not well characterized but could include inhibition of endogenous leptin action and/or loss of efficacy
            • Severe infection and/or worsening metabolic control reported
            • Test for antimetreleptin antibodies with neutralizing activity in patients who develop severe infections or show signs suspicious for loss of efficacy during treatment

            Lymphoma

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

            Myalept Risk Evaluation and Mitigation Strategy (REMS) Program

            • Because of the risk for autoantibodies and lymphoma, prescribers must be certified with the Myalept REMS Program by enrolling in and completing training
            • Pharmacies must be certified with the program and only dispense metreleptin after receipt of the REMS prescription authorization form for each new prescription

            Contraindications

            Hypersensitivity, including urticaria and generalized rash

            General obesity not associated with congenital leptin deficiency; has not been shown to be effective in treating general obesity, and the development of antimetreleptin antibodies with neutralizing activity has been reported in obese patients treated with metreleptin

            Cautions

            For SC injection only; instruct patients and caregivers on the proper SC injection technique (see Administration)

            Neutralizing antibody activity to leptin and/or metreleptin may develop, which could result in severe infections or loss of treatment effectiveness (see Black Box Warnings)

            T-cell lymphoma reported in patients with acquired generalized lipodystrophy, both treated and not treated with metreleptin (see Black Box Warnings)

            Dosage adjustments, including possible large reductions, of insulin or insulin secretagogue (eg, sulfonylurea, meglitinide derivatives) may be necessary in some patients to minimize the risk of hypoglycemia (see Dosage Modifications)

            Hypersensitivity reported; promptly discontinue if hypersensitivity occurs

            Benzoyl alcohol

            • Contains benzyl alcohol when reconstituted with bacteriostatic water for injection
            • Reconstitute with preservative-free water for injection when used in neonates and infants
            • Benzoyl alcohol doses >99 mg/kg/day in neonates and low-birth-weight infants is associated with gasping syndrome
            • Gasping syndrome is characterized by CNS depression, metabolic acidosis, gasping respirations, and high levels of benzyl alcohol and its metabolites found in the blood and urine

            Autoimmunity

            • Leptin plays a role in immune system homeostasis
            • Acquired lipodystrophies are associated with autoimmune disorders (eg, autoimmune hepatitis, membranoproliferative glomerulonephritis)
            • Cases of progression of autoimmune hepatitis and membranoproliferative glomerulonephritis (associated with massive proteinuria and renal failure) were observed in some patients with acquired generalized lipodystrophy treated with metreleptin
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            Pregnancy & Lactation

            Pregnancy Category: C

            Women who become pregnant during treatment are encouraged to enroll in an outcomes monitoring; patients or their physicians should call 1-855-6MYALEPT to enroll

            Lactation: Unknown if distributed in human breast milk; endogenous leptin is present in human milk

            Because of the potential for serious adverse reactions (including possible adverse reactions related to passage of antimetreleptin antibodies) in nursing infants, a decision should be made whether to discontinue nursing or discontinue the drug

            Pregnancy Categories

            A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA:Information not available.

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            Pharmacology

            Mechanism of Action

            Recombinant analog of the human hormone leptin; binds to and activates the human leptin receptor (ObR), which belongs to the class I cytokine family of receptors that signals through the JAK/STAT transduction pathway

            Deficiency of adipose tissue leads to hypertriglyceridemia and ectopic deposition of fat in nonadipose tissues (eg, liver, muscle), contributing to metabolic abnormalities including insulin resistance

            Native leptin is a hormone predominantly secreted by adipose tissue that informs the CNS of the status of energy stores in the body; in patients with generalized lipodystrophy, leptin deficiency, resulting from the loss of adipose tissue, contributes to excess caloric intake, which exacerbates the metabolic abnormalities

            Absorption

            Peak plasma time: 4-4.3 hr

            Distribution

            Vd: 370, 398, and 463 mL/kg for 0.3, 1, and 3 mg/kg/day doses, respectively

            Metabolism

            No formal metabolism studies have been conducted

            Nonclinical data indicate renal clearance is the major route of metreleptin elimination, with no apparent contribution of systemic metabolism or degradation

            Elimination

            Half-life: 3.8-4.7 hr

            Clearance delayed in presence of leptin antibodies

            Excretion: Predominantly renal

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            Administration

            SC Preparation

            Remove the vial from the refrigerator and allow vial to warm to room temperature prior to use

            Do not use if the white lyophilized cake is discolored

            Reconstitute aseptically with 2.2 mL of sterile bacteriostatic water for injection (BWFI) USP (0.9% benzyl alcohol) or 2.2 mL of sterile water for injection (WFI)

            For use in neonates and infants, reconstitute with preservative-free sterile WFI (see Cautions)

            Slowly inject diluent down the side of the vial; it is normal for some bubbles to form

            Gently swirl the contents to reconstitute; do not shake or vigorously agitate

            When properly mixed, the reconstituted solution should be clear and free of clumps or dry powder, bubbles, or foam

            After reconstitution, the mixture should be clear and colorless; do not use if visible particulates are present in the solution

            After reconstitution, the vials should not be frozen (below 0°C) or shaken vigorously; if the reconstituted product is inadvertently frozen, it should be thrown away

            SC Administration

            Instruct patients and caregivers on the proper SC injection technique with care to avoid IM injection in patients with minimal subcutaneous adipose tissue

            Never administer IV or IM

            Do not mix with insulin; use a separate syringe for each medication

            If metreleptin and insulin are administered at the same time of day, they may be injected in the same body area using 2 different injection sites

            Can be administered without regard to the timing of meals

            If a dose is missed, administer the dose as soon as noticed, and resume the normal dosing schedule the next day

            SC injection technique

            • Using a 1-mL syringe with a needle appropriate for SC injection, withdraw the prescribed dose of metreleptin reconstituted solution
            • Remove any large air pockets or large bubbles from the filled syringe prior to administration; some small bubbles may remain in the syringe
            • Administer into the SC tissue of the abdomen, thigh, or upper arm
            • Advise patients to use a different injection site each day when injecting in the same region
            • After choosing an injection site, pinch the skin and at a 45° angle, inject SC
            • Avoid IM injection, especially in patients with minimal subcutaneous adipose tissue
            • Doses exceeding 1 mL can be administered as 2 injections (the total daily dose divided equally) to minimize potential injection-site discomfort due to injection volume
            • When dividing doses due to volume, doses can be administered one after the other

            Storage

            Unopened vials

            • Store refrigerated between 2-8°C (36-46°F) in original carton
            • Do not freeze

            Reconstituted vials

            • Reconstituted with water for injection (no preservatives): Use for a single dose and should be administered immediately; unused reconstituted solution cannot be saved for later use and should be discarded
            • Reconstituted with bacteriostatic water for injection: Can be used for multiple doses within 3 days when refrigerated at 2-8°C (36-46°F) and protected from light; do not freeze
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            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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