ns of reactions.
Visually inspect CRYSVITA for particulate matter and discoloration prior to administration. CRYSVITA is a sterile, preservative-free, clear to slightly opalescent and colorless to pale brown-yellow solution for subcutaneous injection. Do not use if the solution is discolored or cloudy or if the solution contains any particles or foreign particulate matter.
3 DOSAGE FORMS AND STRENGTHS
Injection: 10 mg/mL, 20 mg/mL, or 30 mg/mL clear to slightly opalescent and colorless to pale brown-yellow solution in a single-dose vial.
4 CONTRAINDICATIONS
Do not use CRYSVITA with oral phosphate and active vitamin D analogs.
Do not initiate CRYSVITA treatment if serum phosphorus is within or above the normal range for age.
CRYSVITA is contraindicated in patients with severe renal impairment or end stage renal disease because these conditions are associated with abnormal mineral metabolism.
5 WARNINGS AND PRECAUTIONS
5.1 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 Adverse Reactions (6.1)].
5.2 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 and Administration (2)].
5.3 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 Adverse Reactions (6.1)].
6 ADVERSE REACTIONS
The following adverse reactions are described below and elsewhere in the labeling:
Hypersensitivity [see Warnings and Precautions (5.1)]
Hyperphosphatemia and Risk of Nephrocalcinosis [see Warnings and Precautions (5.2)]
Injection Site Reactions [see Warnings and Precautions (5.3)]
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Adverse Reactions in Pediatric Patients with XLH
The safety data described below reflect exposure to CRYSVITA in 65 pediatric XLH patients that included 52 exposed for at least 64 weeks (Study 1) and 13 exposed for at least 40 weeks (Study 2). Overall, pediatric XLH patients have been exposed to CRYSVITA for a mean duration of 108 weeks (min 40.9, max 150.0). CRYSVITA was studied in two pediatric open-label phase 2 studies (Study 1, ages 5 to 12 years, n = 52; Study 2, ages ≥ 1 to < 5 years, n = 13). Overall, the patient population was 1-12 years (mean age 7.4 years), 51% male, and 89% white/Caucasian and diagnosed with XLH. In Study 1, 26 of the patients received CRYSVITA at a mean dose of 1.05 mg/kg (range 0.4 – 2.0 mg/kg) every 2 weeks at Week 64; the other 26 patients received CRYSVITA every 4 weeks. In Study 2, patients received CRYSVITA at a mean dose of 0.89 mg/kg (range 0.8 – 1.2 mg/kg) every 2 weeks at Week 40. Adverse reactions reported in more than 10% of CRYSVITA-treated patients from Studies 1 and 2 are shown in Table 4
