Posology : מינונים

4.2    Posology and method of administration

IMCIVREE should be prescribed and supervised by a physician with expertise in obesity with underlying genetic aetiology.


Posology
POMC, including PCSK1, deficiency and LEPR deficiency

Adult population and children more than 12 years of age

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.


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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   2.5 mg once daily       0.25 ml once daily once daily is well tolerated
If clinical response is insufficient and 2.5 mg dose 3 mg once daily         0.3 ml once daily once daily is well tolerated

Paediatric population (children aged 6 to <12 years)

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 2.5 mg once daily            0.25 ml once daily once daily is well tolerated

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.

Evaluate weight loss after 12-16 weeks of treatment. If a patient has not lost at least 5% of baseline body weight or 5% of baseline BMI for patients with continued growth potential, discontinue IMCIVREE as it is unlikely that the patient will achieve and sustain clinically meaningful weight loss with continued treatment.

Bardet-Biedl Syndrome

Adult population and children more than 16 years of age
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 IMCIVREE-SPC-0124-V1
Weeks 1-2                                            2 mg once daily            0.2 ml once daily Week 3 and onward (if 2 mg dose once daily is        3 mg once daily            0.3 ml once daily well tolerated)

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.

Paediatric population (children aged 6 to <16 years)

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      3 mg once daily              0.3 ml once daily well tolerated)

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.


Missed dose
If a dose is missed, the once daily regimen should be resumed at the dose prescribed with the next scheduled dose.

Special populations

Renal impairment
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.



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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 1 mg once daily              0.1 ml once daily well tolerated)
If clinical response is insufficient and 1 mg dose   2 mg once daily         0.2 ml once daily once daily is well tolerated
If clinical response is insufficient and 2 mg dose   2.5 mg once daily       0.25 ml once daily once daily is well tolerated
If clinical response is insufficient and 2.5 mg dose 3 mg once daily         0.3 ml once daily once daily is well tolerated

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 <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      0.5 mg once daily         0.05 ml once daily tolerated)
Week 6 and onward (if 0.5 mg once daily is well 1 mg once daily              0.1 ml once daily tolerated)
If clinical response is insufficient and 1 mg dose 2 mg once daily           0.2 ml once daily once daily is well tolerated

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 
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Week 3 and onward (if 0.5 mg dose once daily is        1 mg once daily            0.1 ml once daily well tolerated)
If clinical response is insufficient and 1 mg dose     2 mg once daily            0.2 ml once daily once daily is well tolerated
If clinical response is insufficient and 2 mg dose     2.5 mg once daily          0.25 ml once daily once daily is well tolerated
If clinical response is insufficient and 2.5 mg dose   3 mg once daily            0.3 ml once daily once daily is well tolerated

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.



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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      0.5 mg once daily       0.05 ml once daily tolerated)
Week 6 and onward (if 0.5 mg once daily is well 1 mg once daily            0.1 ml once daily tolerated)
If clinical response is insufficient and 1 mg dose 2 mg once daily         0.2 ml once daily once daily is well tolerated

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).

Hepatic impairment

Setmelanotide has not been studied in patients with hepatic impairment. Setmelanotide should not be administered to patients with hepatic impairment.

Paediatric population (<6 years)

The safety and efficacy of setmelanotide in children less than 6 years of age has not yet been established. No data are available.

Elderly

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).

Method of administration

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.



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Table 9 Administration syringe and needle size, by setmelanotide dose Setmelanotide dose                   Syringe                             Needle gauge and length For doses of:                        0.3 ml syringe with 0.5 (half) unit 29 to 31 gauge 0.25 mg (0.025 ml or 2.5 units) once increments                          6 to13 mm needle daily
For doses of:                            1 ml syringe with 0.01 ml dosing     28 to 29 gauge daily
0.5 mg to 3 mg (0.05 ml to 0.3 ml)                                            6 to 13 mm needle increments once daily


See section 6.6 for instructions on handling IMCIVREE.