Burosumab

SOURCE: eMC UK SPC, productName 'CRYSVITA 10 mg solution for injection', §4.2 (https://www.medicines.org.uk/emc/product/9779/smpc). WHO INITIATES: 'Treatment should be initiated by a physician experienced in the management of patients with metabolic bone diseases.' BEFORE STARTING: 'Oral phosphate and active vitamin D analogues (e.g. calcitriol) should be discontinued 1 week prior to initiation of treatment.' Vitamin D replacement or supplementation with inactive forms may be started or continued as per local guidelines under monitoring of serum calcium and phosphate. 'At initiation, fasting serum phosphate concentration should be below the reference range for age.' MONITORING (adults): fasting serum phosphate every 2 weeks for the first month, every 4 weeks for the following 2 months, and thereafter as appropriate; serum phosphate should be measured 2 weeks after the previous dose. If serum phosphate is within the normal range, the same dose should be continued. DOSE DECREASE (adults): 'If serum phosphate is above the upper limit of normal range, the next dose should be withheld and the serum phosphate level reassessed within 2 weeks. The patient must have serum phosphate below the normal range before restarting burosumab. Once serum phosphate is below the normal range, treatment may be restarted at half the initial starting dose up to a maximum dose of 40 mg every 4 weeks. Serum phosphate should be reassessed 2 weeks after any change in dose.' NOTE: the fetched §4.2 gives no adult dose-INCREASE step (stepwise increases are described only for the 1–17 year regimen). ALL PATIENTS: 'To decrease the risk for ectopic mineralisation, it is recommended that fasting serum phosphate is targeted in the lower end of the normal reference range for age.' MISSED DOSE: 'Treatments may be administered 3 days either side of the scheduled treatment date if needed for practical reasons. If a patient misses a dose, burosumab should be resumed as soon as possible at the prescribed dose.' TRANSITION: 'At 18 years of age the patient should convert to the adult dose and dosing regimen.' ELDERLY: limited data in patients over 65 years of age. SELF-ADMINISTRATION: for some patients self/carer-administration may be suitable once no immediate dose modifications are anticipated, by an individual trained in injection techniques; the first self-administered dose after initiation or dose change should be under healthcare-professional supervision. §4.8 text was truncated at the source-fetch limit.

SPC §4.2 'Dosing in Children and Adolescents aged 1 to 17 years': 'The recommended starting dose in children and adolescents aged 1 to 17 years is 0.8 mg/kg of body weight given every two weeks. Doses should be rounded to the nearest 10 mg. The maximum dose is 90 mg.' MONITORING: fasting serum phosphate every 2 weeks for the first month, every 4 weeks for the following 2 months and thereafter as appropriate, and 4 weeks after any dose adjustment; if fasting serum phosphate is within the reference range for age, maintain the same dose. 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 dose of 90 mg).' Burosumab should not be adjusted 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. AGE LIMIT: 'The safety and efficacy of burosumab in children aged less than one year have not been established in clinical studies.' Monitoring of plasma alkaline phosphatase, calcium, PTH and creatinine is recommended every 6 months (every 3 months for children 1–2 years). Verify all under-18 dosing against a children's formulary before prescribing.