Version May 2024
Anti-metreleptin 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 metreleptin efficacy. Severe infection and/or worsening metabolic control have been reported. 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 Amryt Pharmaceuticals DAC 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 metreleptin. Carefully consider the benefits and risks of treatment with metreleptin in patients with significant hematologic abnormalities and/or acquired generalized lipodystrophy.
Because of these risks associated with the development of anti-metreleptin antibodies that neutralize endogenous leptin and/or metreleptin and the risk for lymphoma, metreleptin is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Myalept REMS Program.
Lipodystrophy:
Baseline weight ≤40 kg: SUBQ: Initial: 0.06 mg/kg once daily; adjust dose by 0.02 mg/kg daily based on response and tolerability (maximum: 0.13 mg/kg once daily).
Baseline weight >40 kg: SUBQ: Initial: 2.5 mg (males) or 5 mg (females) once daily; adjust dose by 1.25 to 2.5 mg daily based on response and tolerability (maximum: 10 mg once daily).
Discontinuation: If metreleptin is to be discontinued in a patient who also has risk factors for pancreatitis (eg, history of pancreatitis, severe hypertriglyceridemia), taper the dose over a 1-week period and monitor triglyceride levels; consider initiating or adjusting the dose of lipid-lowering medications as needed.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Refer to adult dosing.
(For additional information see "Metreleptin: Pediatric drug information")
Lipodystrophy: Infants, Children, and Adolescents: The manufacturer’s labeling describes use in infants; however, in trials, the minimal inclusion age was 6 months and the youngest subjects reported in trials and case series were at least 1 year of age (Ref). Note: Increase or decrease dose based on clinical response (eg, inadequate metabolic control) or other considerations (eg, tolerability issues, excessive weight loss).
Baseline weight ≤40 kg, male and female patients: SubQ: Initial: 0.06 mg/kg/dose once daily; adjust dose (increase or decrease) in 0.02 mg/kg increments based on response or adverse effects. Maximum daily dose: 0.13 mg/kg/day
Baseline weight >40 kg:
Female patients: SubQ: Initial: 5 mg once daily, adjust dose (increase or decrease) in 1.25 to 2.5 mg increments based on response or adverse effects; maximum daily dose: 10 mg/day
Male patients: SubQ: Initial: 2.5 mg once daily, adjust dose (increase or decrease) in 1.25 to 2.5 mg increments based on response or adverse effects; maximum daily dose: 10 mg/day
Discontinuation: When discontinuing therapy in patients with risk factors for pancreatitis (eg, history of pancreatitis, severe hypertriglyceridemia), taper the dose over a 1-week period and monitor triglyceride levels; consider initiating or adjusting the dose of lipid-lowering medications as needed.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Endocrine & metabolic: Hypoglycemia (13%; includes adjunctive insulin use), weight loss (13%)
Immunologic: Antibody development (84%; neutralizing: 6%)
Nervous system: Headache (13%)
1% to 10%:
Dermatologic: Urticaria at injection site (≤4%)
Gastrointestinal: Abdominal pain (10%), diarrhea (6%), nausea (8%)
Genitourinary: Ovarian cyst (8%), proteinuria (6%)
Hematologic & oncologic: Anemia (6%)
Local: Erythema at injection site (≤4%)
Nervous system: Dizziness (8%), fatigue (8%), paresthesia (6%)
Neuromuscular & skeletal: Arthralgia (8%), back pain (6%)
Otic: Otic infection (8%)
Respiratory: Upper respiratory tract infection (8%)
Miscellaneous: Fever (6%)
Frequency not defined:
Hepatic: Autoimmune hepatitis (progression)
Hypersensitivity: Anaphylaxis, hypersensitivity reaction
Renal: Membranoproliferative glomerulonephritis (progression)
Postmarketing:
Hematologic & oncologic: Anaplastic large cell lymphoma, T-cell lymphoma
Local: Injection site reaction (including inflammation at injection site and local skin hyperpigmentation)
Hypersensitivity (eg, anaphylaxis, urticaria, generalized rash) to metreleptin or any component of the formulation; general obesity (not associated with congenital leptin deficiency)
Concerns related to adverse effects:
• Antibody development: [US Boxed Warning]: Antimetreleptin antibodies with neutralizing activity have been identified with metreleptin use. Consequences could include inhibition of endogenous leptin action and/or loss of metreleptin efficacy; severe infection and/or worsening of metabolic control have been reported. Test patients who develop severe infections or show signs of loss of metreleptin efficacy for anti-metreleptin antibodies with neutralizing activity. Contact the manufacturer (1-866-216-1526) for neutralizing antibody testing of clinical samples.
• Hypersensitivity reactions: Generalized hypersensitivity (eg, urticaria, generalized rash) has been reported; instruct patients to promptly seek medical advice regarding discontinuation of metreleptin if hypersensitivity reaction occurs.
• Lymphomas: [US Boxed Warning]: T-cell lymphoma has been reported in patients with acquired generalized lipodystrophy (both treated and not treated with metreleptin). Consider the benefits and risks of metreleptin treatment in patients with significant hematologic abnormalities and/or acquired generalized lipodystrophy. A causal relationship has not been established; acquired lipodystrophies are associated with autoimmune disorders, and autoimmune disorders are associated with increased risk of malignancy (including lymphoma).
Disease-related concerns:
• Autoimmune disorders: Progression of autoimmune hepatitis and membranoproliferative glomerulonephritis associated with massive proteinuria and renal failure have been observed; causal relationship with metreleptin treatment has not been established; acquired lipodystrophies themselves are associated with autoimmune disorders. Consider the benefits/risks of metreleptin treatment in patients with autoimmune disease.
• Pancreatitis: In patients with risk factors for pancreatitis (eg, history of pancreatitis, severe hypertriglyceridemia) who require discontinuation of metreleptin, taper the dose over a 1-week period and monitor triglyceride levels; evaluate signs/symptoms of pancreatitis. Consider initiating or adjusting the dose of lipid-lowering medications.
Dosage form specific issues:
• Benzyl alcohol and derivatives: Injection contains benzyl alcohol when reconstituted with bacteriostatic water for injection (BWFI); large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC, 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors, 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer’s labeling.
Other warnings/precautions:
• Appropriate use: Safety and effectiveness have not been established for the treatment of partial lipodystrophy or liver disease, including nonalcoholic steatohepatitis. Not indicated for use in patients with HIV-related lipodystrophy or for use in patients with metabolic disease (eg, diabetes mellitus, hypertriglyceridemia) without concurrent evidence of congenital or acquired generalized lipodystrophy.
• REMS program: [US Boxed Warning]: Access is restricted through a REMS program. Prescribers and pharmacies must be certified with the program; information is available at www.myaleptrems.com or 1-855-669-2537.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Subcutaneous:
Myalept: 11.3 mg (1 ea)
No
Solution (reconstituted) (Myalept Subcutaneous)
11.3 mg (per each): $7,393.08
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
SUBQ: Administer SUBQ into the abdomen, thigh, or upper arm once daily at the same time every day; administer any time of day without regard to the timing of meals. Rotate injection sites daily. Doses exceeding 1 mL may be administered as 2 equally divided injections.
Parenteral: SubQ: Using a 1 mL syringe or smaller, withdraw desired dose. Smaller syringes may be appropriate for patients ≤25 kg as small volumes for administration can result in medication errors when measured incorrectly; ensure proper syringe size is selected. Administer subcutaneously into the abdomen, thigh, or upper arm once daily at the same time every day; administer any time of day without regard to the timing of meals. Rotate injection sites daily. Doses exceeding 1 mL may be administered as 2 equally divided injections. Do not mix with insulin. If administered at the same time of day as insulin, the same body area may be used for injection; however, use 2 different injection sites.
Note: If using an insulin syringe to administer metreleptin, the volume conversion is 100 units/mL (eg, 0.1 mg [0.02 mL] = 2 units).
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/125390s024lbl.pdf#page=16, must be dispensed with this medication.
Lipodystrophy: Replacement therapy to treat the complications of leptin deficiency, in addition to diet, in patients with congenital or acquired generalized lipodystrophy.
Limitations of use: Not indicated for use in patients with HIV-related lipodystrophy or for use in patients with metabolic disease (eg, diabetes mellitus, hypertriglyceridemia) without concurrent evidence of congenital or acquired generalized lipodystrophy.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Insulins: Metreleptin may enhance the hypoglycemic effect of Insulins. Management: Insulin dosage adjustments (including potentially large decreases) may be required to minimize the risk for hypoglycemia with concurrent use of metreleptin. Monitor closely for signs and symptoms of hypoglycemia. Risk D: Consider therapy modification
Sulfonylureas: Metreleptin may enhance the hypoglycemic effect of Sulfonylureas. Management: Sulfonylurea dosage adjustments (including potentially large decreases) may be required to minimize the risk for hypoglycemia with concurrent use of metreleptin. Monitor closely for signs or symptoms of hypoglycemia. Risk D: Consider therapy modification
Because metreleptin can restore metabolic and endocrine function, normal menses may be restored in women with previous amenorrhea; fertility may be restored and pregnancies may occur (Chou 2011; Chou 2013; Maguire 2012).
Reports of use of metreleptin during pregnancy are limited (Chou 2011; Chou 2013; Maguire 2012).
Adverse pregnancy outcomes are associated with lipodystrophy in pregnant women, including eclampsia, gestational diabetes, intrauterine growth retardation, intrauterine death, macrosomia, and miscarriage. Based on in vitro data, metreleptin may inhibit uterine contractility during labor. If use is needed during pregnancy, reconstitution with a preservative-free diluent is recommended; solutions containing benzyl alcohol should be avoided in pregnant women due to association with gasping syndrome in premature infants.
Data collection to monitor pregnancy and infant outcomes following exposure to metreleptin is ongoing. Pregnant women or their health care provider may enroll by calling 1-855-669-2537.
It is not known if metreleptin is present in breast milk; however, endogenous leptin is present.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
Test for antimetreleptin antibodies with neutralizing activity in patients who develop severe infections or show signs of loss of efficacy (eg, worsened metabolic control). Closely monitor blood glucose in patients on concomitant insulin or insulin secretagogue (sulfonylurea, meglitinide) therapy. If tapering metreleptin in patients at risk for pancreatitis, monitor triglyceride levels.
Recombinant human leptin analog that 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) to treat complications of leptin deficiency associated with generalized lipodystrophy.
Distribution: Vd: 4-5 times plasma volume
Metabolism: No apparent systemic metabolism
Half-life elimination: 3.8-4.7 hours
Time to peak: 4 hours (range: 2-8 hours)
Excretion: Renal (major route); clearance delayed in the presence of leptin antibodies and may be delayed in renal impairment
Altered kidney function: Pharmacokinetics may be altered in subjects with renal impairment.
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