Hypersensitivity: Hypersensitivity reactions (e.g. rash, urticaria) have been reported in patients with CRYSVITA. Discontinue CRYSVITA if serious hypersensitivity reactions occur and initiate appropriate medical treatment. [See Clinical Trials Experience under Adverse Reactions.]
Hyperphosphatemia and Risk of Nephrocalcinosis: Increases in serum phosphorus to above the upper limit of normal may be associated with an increased risk of nephrocalcinosis. For patients already taking CRYSVITA, dose interruption and/or dose reduction may be required based on a patient's serum phosphorus levels. [See Dosage & Administration and Clinical Trials Experience under Adverse Reactions.]
Injection Site Reactions: Administration of CRYSVITA may result in local injection site reactions. Discontinue CRYSVITA if severe injection site reactions occur and administer appropriate medical treatment. [See Clinical Trials Experience under Adverse Reactions.]
Renal Impairment: The effect of renal impairment on the pharmacokinetics of burosumab is unknown. However, renal impairment can induce abnormal mineral metabolism which will increase phosphate concentrations greater than expected with CRYSVITA alone. This increase may result in hyperphosphatemia which can induce nephrocalcinosis.
CRYSVITA is contraindicated in patients with severe renal impairment, defined as: Pediatric patients with estimated glomerular filtration rate (eGFR) 15 mL/min/1.73m2 to 29 mL/min/1.73m2 or end stage renal disease (eGFR < 15 mL/min/1.73m2); Adult patients with creatinine clearance (CLcr) 15 mL/min to 29 mL/min or end stage renal disease (CLcr < 15 mL/min).
Use in Children: Safety and effectiveness of CRYSVITA have been established in pediatric patients 1 year and older. Safety and effectiveness in pediatric patients 1 year and older with XLH are based on one phase 3, open-label, active control study [61 patients 1-12 years of age (Study 1)] and two open-label studies [52 patients 5 to 12 years of age (Study 2), and 13 patients 1 to 4 years of age (Study 3) evaluating serum phosphorus and radiographic findings. Efficacy in adolescents is supported by studies in pediatric patients less than 13 years of age. Dosing in this age group was derived using modeling and simulation of adult and pediatric PK and PD data.
Safety and effectiveness for CRYSVITA in pediatric patients with XLH below the age of 1 have not been established [see Pharmacology: Pharmacodynamics: Clinical Studies under Actions and Clinical Trials Experience under Adverse Reactions].
Use in Elderly: Clinical studies of CRYSVITA did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.