Dosing & Uses
Dosage Forms & Strengths
lyophylized powder for reconstitution
- 11.3mg (5mg/mL when reconstituted with 2.2 mL water for injection)
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)
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
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (0)
Monitor Closely (15)
- chlorpropamide
chlorpropamide, metreleptin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of metreleptin with insulin and/or insulin secretagogues (eg, sulfonylureas, meglitinide derivatives) may increase risk for hypoglycemia; may require lower dose of insulin or insulin secretagogue.
- glimepiride
glimepiride, metreleptin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of metreleptin with insulin and/or insulin secretagogues (eg, sulfonylureas, meglitinide derivatives) may increase risk for hypoglycemia; may require lower dose of insulin or insulin secretagogue.
- glipizide
glipizide, metreleptin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of metreleptin with insulin and/or insulin secretagogues (eg, sulfonylureas, meglitinide derivatives) may increase risk for hypoglycemia; may require lower dose of insulin or insulin secretagogue.
- glyburide
glyburide, metreleptin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of metreleptin with insulin and/or insulin secretagogues (eg, sulfonylureas, meglitinide derivatives) may increase risk for hypoglycemia; may require lower dose of insulin or insulin secretagogue.
- insulin aspart
insulin aspart, metreleptin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of metreleptin with insulin and/or insulin secretagogues (eg, sulfonylureas, meglitinide derivatives) may increase risk for hypoglycemia; may require lower dose of insulin or insulin secretagogue.
- insulin detemir
insulin detemir, metreleptin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of metreleptin with insulin and/or insulin secretagogues (eg, sulfonylureas, meglitinide derivatives) may increase risk for hypoglycemia; may require lower dose of insulin or insulin secretagogue.
- insulin glargine
insulin glargine, metreleptin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of metreleptin with insulin and/or insulin secretagogues (eg, sulfonylureas, meglitinide derivatives) may increase risk for hypoglycemia; may require lower dose of insulin or insulin secretagogue.
- insulin glulisine
insulin glulisine, metreleptin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of metreleptin with insulin and/or insulin secretagogues (eg, sulfonylureas, meglitinide derivatives) may increase risk for hypoglycemia; may require lower dose of insulin or insulin secretagogue.
- insulin lispro
insulin lispro, metreleptin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of metreleptin with insulin and/or insulin secretagogues (eg, sulfonylureas, meglitinide derivatives) may increase risk for hypoglycemia; may require lower dose of insulin or insulin secretagogue.
- insulin NPH
insulin NPH, metreleptin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of metreleptin with insulin and/or insulin secretagogues (eg, sulfonylureas, meglitinide derivatives) may increase risk for hypoglycemia; may require lower dose of insulin or insulin secretagogue.
- insulin regular human
insulin regular human, metreleptin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of metreleptin with insulin and/or insulin secretagogues (eg, sulfonylureas, meglitinide derivatives) may increase risk for hypoglycemia; may require lower dose of insulin or insulin secretagogue.
- nateglinide
nateglinide, metreleptin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of metreleptin with insulin and/or insulin secretagogues (eg, sulfonylureas, meglitinide derivatives) may increase risk for hypoglycemia; may require lower dose of insulin or insulin secretagogue.
- repaglinide
repaglinide, metreleptin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of metreleptin with insulin and/or insulin secretagogues (eg, sulfonylureas, meglitinide derivatives) may increase risk for hypoglycemia; may require lower dose of insulin or insulin secretagogue.
- tolazamide
tolazamide, metreleptin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of metreleptin with insulin and/or insulin secretagogues (eg, sulfonylureas, meglitinide derivatives) may increase risk for hypoglycemia; may require lower dose of insulin or insulin secretagogue.
- tolbutamide
tolbutamide, metreleptin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of metreleptin with insulin and/or insulin secretagogues (eg, sulfonylureas, meglitinide derivatives) may increase risk for hypoglycemia; may require lower dose of insulin or insulin secretagogue.
Minor (0)
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%)
Postmarketing Reports
Incorrect dose administered, accidental overdose
Injection-site reaction (eg, inflammation, hyperpigmentation)
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
Pregnancy & Lactation
Pregnancy
A program monitors outcomes in women exposed to MYALEPT during pregnancy; women who become pregnant during MYALEPT treatment are encouraged to enroll; patients or their physicians should call 1-855-669-2537 to enroll
Available pharmacovigilance reports in pregnant women are insufficient to evaluate for any drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes; these reports describe similar adverse pregnancy outcomes as those documented in women with lipodystrophy
Drug contains benzyl alcohol when reconstituted with BWFI; it contains no preservative when reconstituted with WFI; because benzyl alcohol is rapidly metabolized by a pregnant woman, benzyl alcohol exposure in the fetus is unlikely; however, adverse reactions have occurred in premature neonates and low birth weight infants who received intravenously administered benzyl alcohol-containing drugs; if therapy is needed during pregnancy, consider using preservative-free WFI when reconstituting
Lipodystrophy in pregnancy can result in an increased rate of gestational diabetes, macrosomia, eclampsia, intrauterine growth retardation, intrauterine death, and miscarriage
Effects on labor and delivery in pregnant women are unknown; in a published in vitro study of human myometrial tissue exposed to a recombinant leptin, human uterine contractility was inhibited; in animal studies, prolonged gestation and dystocia were observed
Animal data
- In an animal reproduction study, no adverse developmental effects were observed with subcutaneous administration of drug to pregnant mice during organogenesis at doses 7-and 15-fold maximum recommended clinical dose, based on body surface area of a 20-and 60-kg patient, respectively
- In a pre-and postnatal development study in mice, subcutaneous administration caused prolonged gestation and dystocia resulting in maternal death during parturition and lower survival of offspring in immediate postnatal period at doses starting approximately at maximum recommended clinical dose
Lactation
There are no available data on presence of drug in human milk; however, endogenous leptin is present in human milk; there are no available data on effects of drug on breastfed infant or effects on milk production
Developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed child from drug or from underlying maternal condition
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.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
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
Images
Patient Handout
metreleptin subcutaneous
NO MONOGRAPH AVAILABLE AT THIS TIME
USES: Consult your pharmacist.
HOW TO USE: Consult your pharmacist.
SIDE EFFECTS: Consult your pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.
PRECAUTIONS: Consult your pharmacist.
DRUG INTERACTIONS: Consult your pharmacist.Keep a list of all your medications with you, and share the list with your doctor and pharmacist.
OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.
NOTES: No monograph available at this time.
MISSED DOSE: Consult your pharmacist.
STORAGE: Consult your pharmacist.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.
Information last revised July 2016. Copyright(c) 2023 First Databank, Inc.
IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.
Formulary
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