Metreleptin
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From MedlinePlus, U.S. National Library of Medicine
Boxed warning
WARNING: RISK OF ANTI-METRELEPTIN ANTIBODIES WITH NEUTRALIZING ACTIVITY AND RISK OF LYMPHOMA Anti-metreleptin 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-metreleptin antibodies with neutralizing activity in patients who develop severe infections or show signs suspicious for loss of MYALEPT efficacy during treatment. Contact Chiesi Farmaceutici S.p.A.
at 1-866-216-1526 for neutralizing antibody testing of clinical samples [see Contraindications (4.1) and Warnings and Precautions (5.1) ]. 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 [see Warnings and Precautions (5.2) ].
Because of these risks associated with the development of anti-metreleptin 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 [see Warnings and Precautions (5.3) ]. WARNING: RISK OF ANTI-METRELEPTIN ANTIBODIES WITH NEUTRALIZING ACTIVITY AND RISK OF LYMPHOMA See full prescribing information for complete boxed warning. Anti-metreleptin antibodies with neutralizing activity have been identified in patients treated with MYALEPT.
The consequences are not well characterized but could include inhibition of endogenous leptin action and loss of MYALEPT efficacy. Worsening metabolic control and/or severe infection have been reported. Test for anti-metreleptin antibodies with neutralizing activity in patients with severe infections or loss of efficacy during MYALEPT treatment. Contact Chiesi Farmaceutici S.p.A. at 1-866-216-1526 for neutralizing antibody testing. ( 4.1 ), ( 5.1 ) 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. ( 5.2 ) MYALEPT is available only through a restricted program called the MYALEPT REMS PROGRAM. ( 5.3 )
Leptin Analog
Dosing in kidney impairment
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 MYALEPT. A causal relationship between MYALEPT treatment and the development and/or progression of autoimmune disease has not been established.
Preparation and administration
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MYALEPT Preparation and Storage Healthcare practitioners should provide proper training to patients and caregivers regarding how to prepare and administer the correct dose of MYALEPT prior to self-use. The patients and caregivers should prepare and administer the first dose of MYALEPT under the supervision of a qualified healthcare professional.
Instruct patients to store the vials of lyophilized powder in their carton in the refrigerator as soon as received [see How Supplied/Storage and Handling ]. MYALEPT can be reconstituted aseptically with 2.2 mL of sterile Bacteriostatic Water for Injection (BWFI), USP (0.9% benzyl alcohol), or with 2.2 mL of sterile Water for Injection (WFI).
When reconstituted in BWFI, MYALEPT solution can be used within 3 days when stored in the refrigerator between 36°F and 46°F (2°C and 8°C) and protected from light [see How Supplied/Storage and Handling ]. Discard unused reconstituted solution after 3 days. Attach the supplied sticker to the vial and enter the discard date.
For use in neonates and infants, reconstitute with preservative-free sterile WFI [see Warnings and Precautions and Use in Specific Populations ]. When reconstituted in sterile WFI, MYALEPT should be administered immediately. Unused reconstituted solution cannot be saved for later use and should be discarded. Reconstitution of the Lyophilized Powder Instruct patients to follow the directions below for reconstitution of the lyophilized powder: Remove the vial containing the MYALEPT lyophilized powder from the refrigerator and allow the vial to warm to room temperature prior to use.
Visually inspect the vial containing MYALEPT. The cake of lyophilized powder should be intact and white in color. Using a 3-mL syringe with a 22-gauge or smaller diameter needle withdraw 2.2 mL of sterile Bacteriostatic Water for Injection (BWFI) or preservative-free sterile Water for Injection (WFI). Do not reconstitute MYALEPT with other diluents.
Inject the BWFI or WFI into the vial containing the lyophilized powder of MYALEPT, slowly injecting down the side of the vial. It is normal for some bubbles to form. Remove the needle and syringe from the vial and gently swirl the contents to reconstitute. Do not shake or vigorously agitate. When properly mixed, the MYALEPT reconstituted solution should be clear and free of clumps or dry powder, bubbles or foam.
Do not use the solution if discolored or cloudy, or if particulate matter remains. Regarding the compatibility of MYALEPT reconstituted solution with other solutions: Do not mix with, or transfer into, the contents of another vial of MYALEPT. Do not add other medications, including insulin. Use a separate syringe for insulin injections.
See the MYALEPT Instructions for Use for complete administration instructions. The instructions can also be found at www.myalept.com .
Administration Instructions Healthcare practitioners should instruct patients and caregivers on the proper subcutaneous injection technique with care to avoid intramuscular injection in patients with minimal subcutaneous adipose tissue. Never administer MYALEPT intravenously or intramuscularly. Instruct patients to follow the recommended injection technique: Using a 1-mL or smaller syringe with a needle appropriate for subcutaneous injection, withdraw the prescribed dose of MYALEPT 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 MYALEPT into the subcutaneous 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-degree angle, inject the MYALEPT reconstituted solution subcutaneously.
Avoid intramuscular injection, especially in patients with minimal subcutaneous adipose tissue. Doses exceeding 1 mL can be administered as two 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.
In pediatric patients, small volumes for administration can result in medication errors when measured incorrectly. Smaller syringe sizes may be more appropriate for pediatric patients weighing less than or equal to 25 kg. Ensure the proper size syringe is selected. Table 2 provides example doses and volumes by weight [see Dosage and Administration , Adverse Reactions ].
Do not mix MYALEPT with insulin. Use a separate syringe for each medication. If MYALEPT and insulin are administered at the same time of day, they may be injected in the same body area using two different injection sites. See the MYALEPT Instructions for Use for complete administration instructions. The instructions can also be found at www.myalept.com .
| Baseline weight | Starting daily dose (injection volume) | Dose adjustments (injection volume) | Maximum daily dose (injection volume) |
|---|---|---|---|
| Less than or equal to 40 kg (males and females) | 0.06 mg/kg (0.012 mL/kg) | 0.02 mg/kg (0.004 mL/kg) | 0.13 mg/kg (0.026 mL/kg) |
| Males greater than 40 kg | 2.5 mg (0.5 mL) | 1.25 mg (0.25 mL) to 2.5 mg (0.5 mL) | 10 mg (2 mL) |
| Females greater than 40 kg | 5 mg (1 mL) | 1.25 mg (0.25 mL) to 2.5 mg (0.5 mL) | 10 mg (2 mL) |
Drug interactions
Check metreleptin against a medication listLabel text (2 paragraphs)
No formal drug interaction studies were performed. Leptin is a cytokine and may have the potential to alter the formation of cytochrome P450 (CYP450) enzymes. This should be taken into account when prescribing concomitant drugs metabolized by CYP450 (e.g., oral contraceptives and drugs with a narrow therapeutic index). The effect of metreleptin on CYP450 enzymes may be clinically relevant for CYP450 substrates with narrow therapeutic index, where the dose is individually adjusted.
Upon initiation or discontinuation of MYALEPT, in patients being treated with these types of agents, therapeutic monitoring of effect (e.g., warfarin) or drug concentration (e.g., cyclosporine or theophylline) should be performed and the individual dose of the agent adjusted as needed.
Contraindications
General obesity not associated with congenital leptin deficiency. ( 4.1 ) Hypersensitivity to metreleptin. ( 4.2 )
4.1 General Obesity MYALEPT is contraindicated in patients with general obesity not associated with congenital leptin deficiency. MYALEPT has not been shown to be effective in treating general obesity, and the development of anti-metreleptin antibodies with neutralizing activity has been reported in obese patients treated with MYALEPT [see Warnings and Precautions (5.1) ].
4.2 Hypersensitivity MYALEPT is contraindicated in patients with prior severe hypersensitivity reactions to metreleptin or to any of the product components. Known hypersensitivity reactions have included anaphylaxis, urticaria and generalized rash [see Warnings and Precautions (5.6) ].
Safety data
Reported adverse events (FAERS)
Liver injury (LiverTox)
LiverTox has no chapter for metreleptin. Check the label's hepatic warnings.
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Pregnancy Exposure Registry There is a program that 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. Risk Summary Available pharmacovigilance reports with the use of MYALEPT 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 (see Clinical Considerations ) .
In an animal reproduction study, no adverse developmental effects were observed with subcutaneous administration of metreleptin to pregnant mice during organogenesis at doses 7- and 15-fold the 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 of metreleptin caused prolonged gestation and dystocia resulting in maternal death during parturition and lower survival of offspring in the immediate postnatal period at doses starting approximately at the maximum recommended clinical dose (see Data ) . MYALEPT contains benzyl alcohol when reconstituted with BWFI.
MYALEPT 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 [see Warnings and Precautions (5.7) and Use in Specific Populations (8.4) ]. Therefore, if therapy with MYALEPT is needed during pregnancy, consider using preservative-free WFI when reconstituting [see Dosage and Administration (2.2) ]. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.
In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Disease-Associated Maternal and Fetal Risk Lipodystrophy in pregnancy can result in an increased rate of gestational diabetes, macrosomia, eclampsia, intrauterine growth retardation, intrauterine death, and miscarriage. Labor and Delivery The effects of MYALEPT on labor and delivery in pregnant women are unknown. In a published in vitro study of human myometrial tissue exposed…
For breastfeeding, also see LactMed (National Library of Medicine), which summarizes milk levels and infant effects.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
Price ladder
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