Burosumab

Treatment should be initiated by a physician experienced in the management of patients with metabolic bone diseases. BEFORE STARTING: discontinue oral phosphate and active vitamin D analogues (e.g. calcitriol) 1 week prior to initiation; vitamin D replacement or supplementation with inactive forms may be started or continued per local guidelines under monitoring of serum calcium and phosphate; at initiation, fasting serum phosphate must be below the reference range for age. MONITORING: measure fasting serum phosphate every 2 weeks for the first month, every 4 weeks for the following 2 months and thereafter as appropriate; in adults measure serum phosphate 2 weeks after the previous dose. If serum phosphate is within the normal range, continue the same dose. ADULT DOSE DECREASE: if serum phosphate is above the upper limit of normal, withhold the next dose and reassess within 2 weeks; the patient must have serum phosphate below the normal range before restarting, and treatment may then be restarted at half the initial starting dose up to a maximum of 40 mg every 4 weeks, with reassessment 2 weeks after any change in dose. ALL PATIENTS: to decrease the risk of ectopic mineralisation, target fasting serum phosphate at the lower end of the normal reference range for age. MISSED DOSE: treatments may be given 3 days either side of the scheduled date if needed for practical reasons; if a dose is missed, resume as soon as possible at the prescribed dose. AGE 18 TRANSITION: patients aged 1–17 years are treated on the paediatric regimen and convert to the adult dose and regimen at 18 years of age. Elderly: limited data in patients over 65 years. Self/carer administration may be suitable for some patients once no immediate dose modifications are anticipated, with the first self-administered dose after initiation or dose change supervised by a healthcare professional.

Recommended starting dose in children and adolescents aged 1 to 17 years; doses should be rounded to the nearest 10 mg. Dose increase: if fasting serum phosphate is below the reference range for age, the dose may be increased stepwise by 0.4 mg/kg up to a maximum dose of 2.0 mg/kg (maximum 90 mg); measure fasting serum phosphate 4 weeks after any dose adjustment and do not adjust more frequently than every 4 weeks. Dose decrease: if fasting serum phosphate is above the reference range for age, withhold the next dose and reassess within 4 weeks; the patient must have fasting serum phosphate below the reference range for age to restart, at half of the previous dose (rounded as above). Safety and efficacy in children aged less than one year have not been established. At 18 years of age convert to the adult dose and regimen. Monitoring of plasma alkaline phosphatase, calcium, PTH and creatinine is recommended every 3 months for children aged 1–2 years (every 6 months otherwise).