Sapropterin

Treatment must be initiated and supervised by a physician experienced in the treatment of PKU and BH4 deficiency, with active management of dietary phenylalanine and overall protein intake. Tablets are 100 mg, and the calculated daily dose based on body weight should be rounded to the nearest multiple of 100 (e.g. 401-450 mg rounds down to 400 mg / 4 tablets; 451-499 mg rounds up to 500 mg / 5 tablets). DETERMINATION OF RESPONSE: check blood phenylalanine before administering and after 1 week at the recommended starting dose; if the reduction is unsatisfactory the dose can be increased weekly to a maximum of 20 mg/kg/day with continued weekly monitoring over a one-month period, keeping dietary phenylalanine intake constant. A satisfactory response is a reduction in blood phenylalanine of 30 percent or more, or attainment of the individually defined therapeutic goal; patients who fail to achieve this within the one-month test period should be considered non-responsive, should not be treated with sapropterin, and administration should be discontinued. Once responsiveness is established the dose may be adjusted within 5 to 20 mg/kg/day according to response. Blood phenylalanine and tyrosine should be tested one to two weeks after each dose adjustment and monitored frequently thereafter. Treatment may lower blood phenylalanine below the desired therapeutic level, requiring dose or dietary adjustment. Patients must continue a restricted phenylalanine diet and undergo regular clinical assessment. Discontinuation should only occur under the supervision of a physician. Elderly: safety and efficacy above 65 years have not been established — caution is required.

The SPC states 'The posology is the same in adults, children, and adolescents.' The structured value above is the PKU starting dose — 10 mg/kg body weight once daily — which is then adjusted, usually between 5 and 20 mg/kg/day. For BH4 deficiency the starting dose is 2 to 5 mg/kg total daily dose, adjustable up to a total of 20 mg/kg per day. Children up to 20 kg: the dose is given as a measured volume of dissolved tablet solution using the SPC dosing tables for 2, 5, 10 and 20 mg/kg/day, with the graduated cup (20/40/60/80 mL) and 10 mL or 20 mL oral syringes supplied to specialist paediatric metabolic centres; the solution must be used within 20 minutes and any unused solution discarded. Patients above 20 kg dissolve the prescribed number of tablets in 120 to 240 mL of water. Blood phenylalanine and tyrosine levels should be tested one to two weeks after each dose adjustment, particularly in the paediatric population.