Setmelanotide

Dose titration may be performed both upward and downward based on individual tolerability and clinical response, and the dose can be reduced to 0.25 mg if needed. Following the starting dose, if a subsequent dose is not tolerated the dose should be reduced to the previous dose level; if the reduced dose is tolerated, dose titration should be continued. PRESCRIBING RESTRICTION, verbatim: 'IMCIVREE should be prescribed and supervised by physicians experienced in the diagnosis and management of rare forms of obesity with genetic or hypothalamic origin.' DURATION: weight loss and control of hunger can be maintained as long as treatment is continued uninterrupted; if treatment is discontinued, or if compliance to the dosing regimen is not maintained, symptoms of obesity and/or hunger will return. MISSED DOSE: the once daily regimen should be resumed at the dose prescribed with the next scheduled dose. SEVERE RENAL IMPAIRMENT - a separate, lower titration applies. For adults and children 12 years and above (POMC/PCSK1 deficiency, LEPR deficiency or acquired hypothalamic obesity) or 16 years and above (Bardet-Biedl syndrome) with severe renal impairment: weeks 1-2, 0.5 mg once daily; week 3 and onward if tolerated, 1 mg once daily; then 2 mg once daily, then 2.5 mg once daily, then 3 mg once daily, each step only if clinical response is insufficient and the previous dose is well tolerated. Patients with acquired hypothalamic obesity and MODERATE renal impairment should also follow the severe-renal-impairment titration. No dose adjustment is necessary for mild or moderate renal impairment in POMC/PCSK1, LEPR or Bardet-Biedl syndrome, or for mild renal impairment in acquired hypothalamic obesity. Setmelanotide has not been studied in, and should not be administered to, patients with end-stage renal disease. HEPATIC IMPAIRMENT: not studied; setmelanotide should not be administered to patients with hepatic impairment. ELDERLY: no evidence indicating any special precautions is given, though data in patients 65 years and above is not sufficient to determine whether they respond differently. ADMINISTRATION EQUIPMENT (SPC Table 12): for a 0.25 mg (0.025 ml / 2.5 unit) once daily dose, a 0.3 ml syringe with 0.5 (half) unit increments and a 29 to 31 gauge, 6 to 13 mm needle; for doses of 0.5 mg to 3 mg (0.05 ml to 0.3 ml) once daily, a 1 ml syringe with 0.01 ml dosing increments and a 28 to 29 gauge, 6 to 13 mm needle.

NOT A PER-KILOGRAM DRUG - dosePerKg is deliberately null. This SPC doses setmelanotide as a fixed milligram dose titrated by week, with WEIGHT BANDS (not milligrams per kilogram) used only in the youngest age groups. Multiplying any figure here by body weight would be wrong. ACQUIRED HYPOTHALAMIC OBESITY, children 6 years and above: same titration as adults - 0.5 mg once daily week 1, 1 mg week 2, 2 mg week 3, 3 mg week 4 and onward. ACQUIRED HYPOTHALAMIC OBESITY, children 4 to less than 6 years, by weight band: under 20 kg - 0.5 mg week 1, 1 mg week 2, 1.5 mg week 3 and onward; 20 to under 25 kg - 0.5 mg week 1, 1 mg week 2, 1.5 mg week 3, 2 mg week 4 and onward; 25 to under 30 kg - 0.5 mg week 1, 1 mg week 2, 1.5 mg week 3, 2 mg week 4, 2.5 mg week 5 and onward; 30 kg and above - 0.5 mg week 1, 1 mg week 2, 2 mg week 3, 3 mg week 4 and onward (each step only if clinical response is insufficient and the previous dose is well tolerated). POMC (INCLUDING PCSK1) AND LEPR DEFICIENCY, children 12 years and above: 1 mg once daily for 2 weeks, then 2 mg once daily; in patients from 12 to less than 18 years, if weight remains above the 90th percentile with the 2 mg once daily dose and additional weight loss is desired, the dose may be increased to 2.5 mg with a maximum dose of 3 mg once daily. POMC/LEPR, children 6 to less than 12 years: starting dose 0.5 mg once daily for 2 weeks; if tolerated increase to 1 mg once daily; if the 1 mg dose is tolerated after 2 weeks the dose may be increased to 2 mg once daily; if weight remains above the 90th percentile on 2 mg once daily and additional weight loss is desired, the dose may be increased to 2.5 mg once daily. POMC/LEPR, children 2 to less than 6 years, by weight band: under 20 kg - 0.5 mg once daily week 1 and onward; 20 to under 30 kg - 0.5 mg weeks 1-2 then 1 mg week 3 and onward; 30 to under 40 kg - 0.5 mg weeks 1-2, 1 mg weeks 3-4, 1.5 mg week 5 and onward; 40 kg and above - 0.5 mg weeks 1-2, 1 mg weeks 3-4, 1.5 mg weeks 5-6, 2 mg weeks 7-8, 2.5 mg week 9 and onward. If the 0.5 mg starting dose is not tolerated in this age group the dose should be reduced to 0.25 mg (0.025 ml) once daily, and if tolerated titration should continue. BARDET-BIEDL SYNDROME, children 6 to less than 16 years: 1 mg once daily week 1; 2 mg once daily week 2 if the 1 mg dose is well tolerated; 3 mg once daily week 3 and onward if the 2 mg dose is well tolerated. If the 1 mg starting dose is not tolerated it should be reduced to 0.5 mg (0.05 ml) once daily, then increased to 1 mg once daily and titration continued. BARDET-BIEDL SYNDROME, children 2 to less than 6 years: follow the same weight-band table as POMC/LEPR for that age (Table 8), starting at 0.5 mg once daily for 2 weeks. UNDER 2 YEARS, verbatim: 'The safety and efficacy of setmelanotide in children less than 2 years of age has not yet been established. No data are available.' SEVERE RENAL IMPAIRMENT, children 6 to less than 12 years (POMC/PCSK1, LEPR or acquired hypothalamic obesity) or 6 to less than 16 years (Bardet-Biedl syndrome): 0.25 mg once daily weeks 1-2; 0.5 mg once daily weeks 3-4 if tolerated; 1 mg once daily week 5 and onward; then 2 mg once daily if clinical response is insufficient and 1 mg is well tolerated. If the 0.25 mg starting dose is not tolerated, treatment should be discontinued. Children less than 6 years with severe renal impairment have not been studied and follow a separate weight-band table (SPC Table 11) starting at 0.25 mg once daily, with close monitoring.