Usual Adult Dose for Lipodystrophy

Weight 40 kg or less (males and females):

• Initial dose: 0.06 mg/kg subcutaneously once a day
• Adjust dose in 0.02 mg/kg increments based on clinical response
• Maximum dose: 0.13 mg/kg/day

Weight greater than 40 kg:

• Initial dose: Males: 2.5 mg subcutaneously once a day
• Initial dose: Females: 5 mg subcutaneously once a day
• Adjust dose in 1.25 to 2.5 mg increments based on clinical response
• Maximum dose: 10 mg/day

Comments: Dose adjustments should be made based on clinical response (e.g., metabolic control) or other considerations (e.g., tolerability issues, excessive weight loss).

Use: As an adjunct to diet, used as replacement therapy to treat the complications of leptin deficiency in patients with congenital or acquired generalized lipodystrophy.

Usual Pediatric Dose for Lipodystrophy

Weight 40 kg or less (males and females):

• Initial dose: 0.06 mg/kg subcutaneously once a day
• Adjust dose in 0.02 mg/kg increments based on clinical response
• Maximum dose: 0.13 mg/kg/day

Weight greater than 40 kg:

• Initial dose: Males: 2.5 mg subcutaneously once a day
• Initial dose: Females: 5 mg subcutaneously once a day
• Adjust dose in 1.25 to 2.5 mg increments based on clinical response
• Maximum dose: 10 mg/day

Comments: Dose adjustments should be made based on clinical response (e.g., metabolic control) or other considerations (e.g., tolerability issues, excessive weight loss).

Use: As an adjunct to diet, used as replacement therapy to treat the complications of leptin deficiency in patients with congenital or acquired generalized lipodystrophy.

Renal Dose Adjustments

Dose adjustment may be required; however, no specific guidelines have been suggested. Caution is recommended

Liver Dose Adjustments

No adjustment recommended

Dose Adjustments

Dose adjustments of medications known to cause hypoglycemia:

• Reduction of insulin or insulin secretagogue (e.g., sulfonylurea) may be necessary to minimize the risk of hypoglycemia.
• Closely monitor blood glucose in patients on concomitant insulin therapy, especially those on high doses, or insulin secretagogue

Discontinuation in patients at risk for pancreatitis:

• Tapering of the dose over a one-week period is recommended when discontinuing therapy in patients with risk factors for pancreatitis (e.g., history of pancreatitis, severe hypertriglyceridemia).
• Monitor triglyceride levels and consider initiating or adjusting dose of lipid-lowering medications as needed during tapering phase.
• Signs/symptoms consistent with pancreatitis should prompt appropriate clinical evaluation.

Precautions

The US FDA requires a Risk Evaluation and Mitigation Strategy (REMS) for Metreleptin. It includes elements to assure safe use, and implementation system. For additional information: http://www.accessdata.fda.gov/scripts/cder/rems/index.cfm.

US BOXED WARNINGS: 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 metreleptin. The consequences could be inhibition of endogenous leptin action and loss of metreleptin 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 metreleptin treatment. Contact Aegerion Pharmaceuticals, Inc. 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 this drug. Carefully consider the benefits and risk of treatment in patients with significant hematologic abnormalities and/or acquired generalized lipodystrophy.
• Because of the risks associated with the development of anti-metreleptin antibodies and the risk for lymphoma, this drug is only available through a restricted program under a REMS called the Myalept REMS Program.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• For subcutaneous use only; do not administer IM or IV
• Proper training should be provided to patients and caregivers and the first dose should be prepared and administered under the supervision of a qualified healthcare professional.
• Inject subcutaneously into abdomen, thigh, or upper arm, at any time, with or without meals; rotate injection sites daily; consult the manufacturer product information.
• Doses exceeding 1 mL can be administered as separate injections to minimize injection-site discomfort.
• Missed dose: Administer as soon as noticed and resume normal dosing schedule the next day.

Reconstitution/preparation techniques:

• Neonates and infants: Reconstitute with preservative-free sterile water for injection (WFI ) subcutaneous injection
• Adults and older children: Reconstitute with bacteriostatic water for injection (BWFI); contains 0.9%benzyl alcohol
• Allow vial to warm to room temperature prior to reconstitution
• Reconstitute lyophilized powder with 2.2 mL of BWFI or WFI, gently swirl until clear and free of clumps; do not shake or vigorously agitate.
• When reconstituted in sterile WFI, administer immediatley.
• Any unused reconstituted solution should be discarded and not saved for later.
• The manufacturer product information should be consulted for further reconstitution techniques.

Storage:

• Unopened vials: Store in their carton in the refrigerator 36F to 46F (2C to 8C)
• Vials reconstituted with BWFI can be used for up to 3 days when stored in the refrigerator and protected from light; discard unused solution after 3 days

Compatibility:

• Do not mix insulin; may be injected using a separate syringe for each medication in the same body area using 2 different injection sites.

General: Limitations of use:

• The safety and effectiveness for the treatment of complications of partial lipodystrophy have not been established.
• The safety and effectiveness for the treatment of liver disease, including nonalcoholic steatohepatitis (NASH), have not been established.
• Not indicated for use in patients with HIV-related lipodystrophy.
• Not indicated for use in patients with metabolic disease, including diabetes mellitus and hypertriglyceridemia, without concurrent evidence of congenital or acquired generalized lipodystrophy.

Monitoring:

• Metabolic: Monitor blood glucose and triglyceride levels as appropriate; additional monitoring of triglyceride levels and possible initiation or dose adjustment of lipid lowering medications may be considered when discontinuing metreleptin in patients with a history of pancreatitis and or severe hypertriglyceridemia.

Patient advice:

• Report any symptoms or signs that would warrant antibody testing and changes in hematologic status.
• Routine laboratory and physician monitoring is important.
• Risk of hypoglycemia is increased when metreleptin is used in combination with insulin or insulin secretagogues. Blood glucose should be closely monitored and hypoglycemia management should be reviewed when initiating therapy with metreleptin.
• Seek medical advice if symptoms of hypersensitivity reactions occur.