Source: European Medicines Agency (EU) Revision Year: 2024 Publisher: Rhythm Pharmaceuticals Netherlands B.V., Radarweg 29, 1043NX Amsterdam, Netherlands
IMCIVREE is indicated for the treatment of obesity and the control of hunger associated with genetically confirmed Bardet-Biedl syndrome (BBS), loss-of-function biallelic pro-opiomelanocortin (POMC), including PCSK1, deficiency or biallelic leptin receptor (LEPR) deficiency in adults and children 6 years of age and above.
IMCIVREE should be prescribed and supervised by a physician with expertise in obesity with underlying genetic aetiology.
For adults and children 12 to 17 years of age, the starting dose is a 1 mg once daily subcutaneous injection for 2 weeks. After 2 weeks, if setmelanotide is well-tolerated (see section 4.4), the dose can be increased to a 2 mg once daily subcutaneous injection (Table 1). If dose escalation is not tolerated, patients may maintain administration of the 1 mg once daily dose.
If additional weight loss is desired in adult patients, the dose can be increased to a 2.5 mg once daily subcutaneous injection. If the 2.5 mg once daily dose is well-tolerated, the dose can be increased to 3 mg once daily (Table 1).
In patients aged 12 to 17 years, if weight remains above the 90th percentile with the 2 mg once daily subcutaneous injection and additional weight loss is desired, the dose may be increased to 2.5 mg with a maximum dose of 3 mg once daily (Table 1).
Table 1. Dose titration in adults and paediatric patients 12 years of age or more:
| Week | Daily dose | Volume to be injected |
|---|---|---|
| Weeks 1-2 | 1 mg once daily | 0.1 ml once daily |
| Week 3 and onward | 2 mg once daily | 0.2 ml once daily |
| If clinical response is insufficient and 2 mg dose once daily is well tolerated | 2.5 mg once daily | 0.25 ml once daily |
| If clinical response is insufficient and 2.5 mg dose once daily is well tolerated | 3 mg once daily | 0.3 ml once daily |
For patients aged 6 to <12 years, the starting dose is a 0.5 mg once daily subcutaneous injection for 2 weeks. If tolerated after 2 weeks, the dose can be increased to 1 mg once daily. If dose escalation is not tolerated, paediatric patients may maintain administration of the 0.5 mg once daily dose. If the 1 mg dose is tolerated after 2 weeks, the dose can be increased to 2 mg once daily. If weight remains above the 90th percentile with the 2 mg once daily subcutaneous injection and additional weight loss is desired, the dose may be increased to 2.5 mg once daily (Table 2).
Table 2. Dose titration for paediatric patients from 6 to <12 years of age:
| Week | Daily dose | Volume to be injected |
|---|---|---|
| Patients from 6 to <12 years of age | ||
| Weeks 1-2 | 0.5 mg once daily | 0.05 ml once daily |
| Weeks 3-5 | 1 mg once daily | 0.1 ml once daily |
| Week 6 and onward | 2 mg once daily | 0.2 ml once daily |
| If clinical response is insufficient and 2 mg dose once daily is well tolerated | 2.5 mg once daily | 0.25 ml once daily |
The prescribing physician should periodically assess response to setmelanotide therapy. In growing children, the impact of weight loss on growth and maturation should be evaluated (see section 4.4).
Weight loss and control of hunger associated with setmelanotide can be maintained as long as the therapy is continued uninterrupted. If treatment is discontinued, or if compliance to the dosing regimen is not maintained, symptoms of POMC and LEPR deficiency obesity will return.
For adults and children 16 to 17 years of age, the dose titration in Table 3 should be followed.
Table 3. Dose titration in adults and paediatric patients 16 years of age or more:
| Week | Daily dose | Volume to be injected |
|---|---|---|
| Weeks 1-2 | 2 mg once daily | 0.2 ml once daily |
| Week 3 and onward (if 2 mg dose once daily is well tolerated) | 3 mg once daily | 0.3 ml once daily |
If the 2 mg starting dose is not tolerated, reduce to 1 mg (0.1 ml) once daily. If the 1 mg once daily dose is tolerated, continue dose titration.
Following the starting dose, if a subsequent dose is not tolerated, reduce to the previous dose level. If reduced dose is tolerated, continue dose titration.
For patients aged 6 to <16 years, the dose titration in Table 4 should be followed.
Table 4. Dose titration for paediatric patients from 6 to <16 years of age:
| Week | Daily dose | Volume to be injected |
|---|---|---|
| Week 1 | 1 mg once daily | 0.1 ml once daily |
| Week 2 (if 1 mg dose once daily is well tolerated) | 2 mg once daily | 0.2 ml once daily |
| Week 3 and onward (if 2 mg dose once daily is well tolerated) | 3 mg once daily | 0.3 ml once daily |
If the 1 mg starting dose is not tolerated, reduce to 0.5 mg (0.05 ml) once daily. If the 0.5 mg once daily dose is tolerated, increase the dose to 1 mg once daily and continue dose titration.
Following the starting dose, if a subsequent dose is not tolerated, reduce to the previous dose level. If the reduced dose is tolerated, continue dose titration.
The prescribing physician should periodically assess response to setmelanotide therapy. In growing children, the impact of weight loss on growth and maturation should be evaluated (see section 4.4).
Weight loss and control of hunger associated with setmelanotide can be maintained as long as the therapy is continued uninterrupted. If treatment is discontinued, or if compliance to the dosing regimen is not maintained, symptoms of obesity and/or hunger in BBS will return.
If a dose is missed, the once daily regimen should be resumed at the dose prescribed with the next scheduled dose.
POMC, including PCSK1, deficiency and LEPR deficiency:
For patients with mild or moderate renal impairment (see section 5.2), no dose adjustments are necessary.
For adults and children 12 to 17 years of age with severe renal impairment (see section 5.2), the dose titration in Table 5 should be followed.
Table 5. Dose titration in adults and paediatric patients 12 years of age or more with severe renal impairment:
| Week | Daily dose | Volume to be injected |
|---|---|---|
| Weeks 1-2 | 0.5 mg once daily | 0.05 ml once daily |
| Week 3 and onward (if 0.5 mg dose once daily is well tolerated) | 1 mg once daily | 0.1 ml once daily |
| If clinical response is insufficient and 1 mg dose once daily is well tolerated | 2 mg once daily | 0.2 ml once daily |
| If clinical response is insufficient and 2 mg dose once daily is well tolerated | 2.5 mg once daily | 0.25 ml once daily |
| If clinical response is insufficient and 2.5 mg dose once daily is well tolerated | 3 mg once daily | 0.3 ml once daily |
Following the starting dose, if a subsequent dose is not tolerated, reduce to the previous dose level. If the reduced dose is tolerated, continue dose titration.
For patients aged 6 to <12 years of age with severe renal impairment, the dose titration in Table 6 should be followed.
Table 6. Dose titration for paediatric patients from 6 to <12 years of age with severe renal impairment:
| Week | Daily dose | Volume to be injected |
|---|---|---|
| Weeks 1-2 | 0.25 mg once daily | 0.025 ml once daily |
| Weeks 3-5 (if 0.25 mg dose once daily is well tolerated) | 0.5 mg once daily | 0.05 ml once daily |
| Week 6 and onward (if 0.5 mg once daily is well tolerated) | 1 mg once daily | 0.1 ml once daily |
| If clinical response is insufficient and 1 mg dose once daily is well tolerated | 2 mg once daily | 0.2 ml once daily |
If the 0.25 mg starting dose is not tolerated, treatment should be discontinued.
Following the starting dose, if a subsequent dose is not tolerated, reduce to the previous dose level. If the reduced dose is tolerated, continue dose titration.
Setmelanotide has not been studied in patients with end-stage renal disease. Setmelanotide should not be administered to patients with end-stage renal disease (see section 5.2).
Bardet-Biedl Syndrome:
For patients with mild or moderate renal impairment (see section 5.2), no dose adjustments are necessary.
For adults and children 16 to 17 years of age with severe renal impairment (see section 5.2), the dose titration in Table 7 should be followed.
Table 7. Dose titration in adults and paediatric patients 16 years of age or more with severe renal impairment:
| Week | Daily dose | Volume to be injected |
|---|---|---|
| Weeks 1-2 | 0.5 mg once daily | 0.05 ml once daily |
| Week 3 and onward (if 0.5 mg dose once daily is well tolerated) | 1 mg once daily | 0.1 ml once daily |
| If clinical response is insufficient and 1 mg dose once daily is well tolerated | 2 mg once daily | 0.2 ml once daily |
| If clinical response is insufficient and 2 mg dose once daily is well tolerated | 2.5 mg once daily | 0.25 ml once daily |
| If clinical response is insufficient and 2.5 mg dose once daily is well tolerated | 3 mg once daily | 0.3 ml once daily |
If the 0.5 mg starting dose is not tolerated, reduce to 0.25 mg (0.025 ml) once daily. If the 0.25 mg once daily dose is tolerated, continue dose titration.
Following the starting dose, if a subsequent dose is not tolerated, reduce to the previous dose level. If the reduced dose is tolerated, continue dose titration.
For patients aged 6 to <16 years of age with severe renal impairment, the dose titration in Table 8 should be followed.
Table 8. Dose titration for paediatric patients from 6 to <16 years of age with severe renal impairment:
| Week | Daily dose | Volume to be injected |
|---|---|---|
| Weeks 1-2 | 0.25 mg once daily | 0.025 ml once daily |
| Weeks 3-5 (if 0.25 mg dose once daily is well tolerated) | 0.5 mg once daily | 0.05 ml once daily |
| Week 6 and onward (if 0.5 mg once daily is well tolerated) | 1 mg once daily | 0.1 ml once daily |
| If clinical response is insufficient and 1 mg dose once daily is well tolerated | 2 mg once daily | 0.2 ml once daily |
If the 0.25 mg starting dose is not tolerated, treatment should be discontinued.
Following the starting dose, if a subsequent dose is not tolerated, reduce to the previous dose level. If the reduced dose is tolerated, continue dose titration.
Setmelanotide has not been studied in patients with end-stage renal disease. Setmelanotide should not be administered to patients with end-stage renal disease (see section 5.2).
Setmelanotide has not been studied in patients with hepatic impairment. Setmelanotide should not be administered to patients with hepatic impairment.
The safety and efficacy of setmelanotide in children less than 6 years of age has not yet been established. No data are available.
Although no apparent age-related differences have been observed, data obtained from elderly patients is not sufficient to determine whether they respond differently from younger patients. There is no evidence indicating any special precautions are required for treating an elderly population (see section 5.2).
For subcutaneous use.
Setmelanotide should be injected once daily, at the beginning of the day (to maximise hunger reduction during awake period), without regard to the timing of meals.
Setmelanotide should be injected subcutaneously in the abdomen, alternating the abdominal area each day.
Prior to initiation of treatment, patients should be trained by their healthcare professional on proper injection technique, to reduce the risk of administration errors such as needle sticks and incomplete dosing. Refer to the patient leaflet for complete administration instructions with illustrations.
Setmelanotide should be administered using the syringe volumes and needle sizes shown in Table 9.
Table 9. Administration syringe and needle size, by setmelanotide dose:
| Setmelanotide dose | Syringe | Needle gauge and length |
|---|---|---|
| For doses of: 0.25 mg (0.025 ml or 2.5 units) once daily | 0.3 ml syringe with 0.5 (half) unit increments | 29 to 31 gauge 6 to13 mm needle |
| For doses of: 0.5 mg to 3 mg (0.05 ml to 0.3 ml) once daily | 1 ml syringe with 0.01 ml dosing increments | 28 to 29 gauge 6 to 13 mm needle |
See section 6.6 for instructions on handling IMCIVREE.
The symptoms of setmelanotide overdose may include nausea and penile erection. In the event of overdose, appropriate supportive treatment should be initiated according to the patient’s clinical signs and symptoms. In cases of overdose, blood pressure and heart rate should be monitored regularly over 48 hours or as long as clinically relevant.
3 years.
After first use:
28 days or until the expiry date (whichever is earlier).
Do not store above 30°C.
Chemical and physical in use stability has been demonstrated for 28 days at 2-30°C.
From a microbiological point of view, once opened, the product may be stored for a maximum of 28 days at 2°C to 30°C. Other in-use storage times and conditions are the responsibility of the user.
Store in a refrigerator (2°C to 8°C). Do not freeze. Store in the original carton in order to protect from light.
Unopened vials may be kept at room temperature, not to exceed 30°C, for up to 30 days.
For storage conditions after first opening of the medicinal product, see section 6.3.
2R clear glass type I multidose vial with bromobutyl stopper and aluminium cap.
Packs of:
Not all pack sizes may be marketed.
IMCIVREE should be removed from the refrigerator approximately 15 minutes prior to administration. Alternatively, patients may warm the product prior to administration by rolling the vial gently between the palms of their hands for 60 seconds.
IMCIVREE should be inspected prior to each injection, and the solution should not be used if it is cloudy or contains particles.
If IMCIVREE is exposed to temperatures >30°C, it should be discarded and not used.
Always use a new syringe for each injection to prevent contamination.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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