Usual Adult Dose for Obesity

Initial dose:
2 mg subcutaneously once a day for 2 weeks

• If 2 mg dose is tolerated and additional weight loss is desired: Increase to 3 mg subcutaneously once a day
• If not tolerated: Reduce to 1 mg subcutaneously once a day; if additional weight loss is desired, titrate to 2 mg subcutaneously once a day

Maintenance dose: 1 to 3 mg per day
Maximum dose: 3 mg per day

Comments:

• Conduct a genetic test to confirm POMC, PCSK1, or LEPR deficiency prior to starting therapy with this drug.
• To assess tolerability, monitor for gastrointestinal adverse reactions.
• Evaluate weight loss after 12 to 16 weeks; if patient has not lost at least 5% of baseline body weight, it is unlikely they will achieve and sustain clinically meaningful weight loss with continued treatment.
• Available tests for the detection of POMC, PCSK1, or LEPR variants have not been approved or cleared by the FDA.

Use: For chronic weight management in adult and pediatric patients 6 years of age and older with obesity due to proopiomelanocortin (POMC), proprotein convertase/subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency confirmed by genetic testing demonstrating variants in POMC, PCSK1, or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance

Usual Pediatric Dose for Obesity

6 to less than 12 years:
Initial dose: 1 mg subcutaneously once a day for 2 weeks

• If not tolerated: Reduce to 0.5 mg subcutaneously once a day
• If 0.5 mg once daily dose is tolerated and additional weight loss is desired, titrate to 1 mg subcutaneously once a day
• If 1 mg dose is tolerated and additional weight loss is desired: Increase to 2 mg subcutaneously once a day
• If 2 mg once daily dose is not tolerated, reduce to 1 mg once a day
• If 2 mg once daily dose is tolerated and additional weight loss is desired, the dose may be increased to 3 mg once a day

Maintenance dose: 0.5 to 3 mg per day
Maximum dose: 3 mg per day

12 years or older:
Initial dose: 2 mg subcutaneously once a day for 2 weeks

• If tolerated and additional weight loss is desired: Increase to 3 mg subcutaneously once a day
• If not tolerated: Reduce to 1 mg subcutaneously once a day; if additional weight loss is desired, titrate to 2 mg subcutaneously once a day

Maintenance dose: 1 to 3 mg per day
Maximum dose: 3 mg per day

Comments:

• Conduct a genetic test to confirm POMC, PCSK1, or LEPR deficiency prior to starting therapy with this drug.
• To assess tolerability, monitor for gastrointestinal adverse reactions.
• Evaluate weight loss after 12 to 16 weeks; if patient has not lost at least 5% of baseline body weight (or 5% of baseline BMI for patients with continued growth potential) it is unlikely they will achieve and sustain clinically meaningful weight loss with continued treatment.
• Available tests for the detection of POMC, PCSK1, or LEPR variants have not been approved or cleared by the FDA.

Use: For chronic weight management in adult and pediatric patients 6 years of age and older with obesity due to proopiomelanocortin (POMC), proprotein convertase/subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency confirmed by genetic testing demonstrating variants in POMC, PCSK1, or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance

Renal Dose Adjustments

Mild renal impairment (eGFR 60 to 89 mL/min/1.73 m2): No dose adjustment recommended
Moderate, severe, and end stage renal impairment (eGFR less than 59 mL/min/1.73 m2): Use is not recommended

Liver Dose Adjustments

No dose adjustments recommended; use caution as the effect on hepatic impairment is unknown.

Precautions

CONTRAINDICATIONS: None

Safety and efficacy have not been established in patients younger than 6 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available; this drug is not recommended in ESRD.

Other Comments

Administration advice:

• Administer with or without food.
• Administer subcutaneously once a day at the beginning of the day.
• Inject into abdomen, thigh, or arm, rotating sites each day.
• Patients should be trained on proper injection technique.
• Do not use if particulate matter or discoloration is seen.
• If a dose is missed, resume with the next scheduled dose.

Storage requirements:

• Unopened vials: Store in refrigerator 36F to 46F (2C to 8C).
• Once removed from the refrigerator, may keep at 36F to 77F (2C to 25C) for up to 30 days with brief excursions to 86F (30C).
• Opened vial should be discarded after 30 days, store vial in original carton.

General:

• This drug is not for the treatment of patients with obesity due to suspected POMC, PCKS1, or LEPR deficiency with POMC, PCSK1, or LEPR variants classified as benign or likely benign or other types of obesity unrelated to POMC, PCSK1, or LEPR deficiency, including obesity associated with other genetic syndromes and general (polygenic) obesity as it is not expected to be effective.
• Periodically assess response to therapy; in pediatric patients, evaluate the impact of weight loss on growth and maturation.
• If weight loss of at least 5% of baseline body weight or 5% of baseline BMI for patients with continued growth potential has not occurred at 12 to 16 weeks, it is unlikely this drug will allow the patient to achieve clinically meaningful weight loss and therapy should be discontinued.

Monitoring:

• Psychiatric: New onset or worsening depression
• Dermatologic: Pre-existing and new pigmentary lesions
• Monitor weight; for pediatric patients, evaluate the impact of weight loss on growth and maturation.

Patient advice:

• Patients should be instructed to read the US FDA-approved patient labeling (Patient Information and Instructions for Use).
• Patients should understand that disturbances in sexual arousal have been reported; male patients should be advised to seek immediate medical attention if they experience an erection that lasts longer than 4 hours.
• Patients should understand that this drug may cause depression or suicidal ideation and they should be instructed to report any new or worsening symptoms of depression.
• Patients should understand that this drug may cause skin darkening.
• Female patients should be instructed to speak with their healthcare provider if they are pregnant or plan to become pregnant.
• Avoid breastfeeding during treatment with this drug.