Crysvita
(Burosumab)Crysvita Prescribing Information
Warnings and Precautions, Hypercalcemia (5.3 Hypercalcemia Increases in serum calcium have been reported in patients treated with CRYSVITA. Patients with risk factors such as, pre-existing hyperparathyroidism, prolonged immobilization, dehydration, hypervitaminosis D, or renal impairment, are at higher risk of hypercalcemia. Monitor these patients for serum calcium and parathyroid hormone levels before and during CRYSVITA treatment for moderate to severe hypercalcemia. In patients with moderate to severe hypercalcemia, CRYSVITA should not be administered until hypercalcemia is adequately managed. | 8/2025 |
CRYSVITA is a fibroblast growth factor 23 (FGF23) blocking antibody indicated for:
- The treatment of X-linked hypophosphatemia (XLH) in adult and pediatric patients 6 months of age and older. ()
1.1 X-linked HypophosphatemiaCRYSVITA is indicated for the treatment of X-linked hypophosphatemia (XLH) in adult and pediatric patients 6 months of age and older.
- The treatment of FGF23-related hypophosphatemia in tumor-induced osteomalacia (TIO) associated with phosphaturic mesenchymal tumors that cannot be curatively resected or localized in adult and pediatric patients 2 years of age and older. ()
1.2 Tumor-induced OsteomalaciaCRYSVITA is indicated for the treatment of FGF23-related hypophosphatemia in tumor-induced osteomalacia (TIO) associated with phosphaturic mesenchymal tumors that cannot be curatively resected or localized in adult and pediatric patients 2 years of age and older.
- For subcutaneous use only ()
2 DOSAGE AND ADMINISTRATION- For subcutaneous use only
- Prior to starting CRYSVITA, discontinue oral phosphate and/or active vitamin D analogs for one week
- Pediatric XLH (6 months and older):
- For patients who weigh less than 10 kg, starting dose regimen is 1 mg/kg of body weight rounded to the nearest 1 mg, administered every two weeks
- For patients who weigh 10 kg and greater, starting dose regimen is 0.8 mg/kg of body weight rounded to the nearest 10 mg, administered every two weeks. The minimum starting dose is 10 mg up to a maximum dose of 90 mg.
- Adult XLH:Dose regimen is 1 mg/kg body weight rounded to the nearest 10 mg up to a maximum dose of 90 mg administered every four weeks.
- Pediatric TIO (2 years and older):Starting dose is 0.4 mg/kg of body weight rounded to the nearest 10 mg every 2 weeks. Dose may be increased up to 2 mg/kg not to exceed 180 mg, administered every two weeks.
- Adult TIO:Starting dose is 0.5 mg/kg every four weeks. Dose may be increased up to 2 mg/kg not to exceed 180 mg, administered every two weeks.
2.1 Important Information Prior to Initiation of CRYSVITAPrior to starting CRYSVITA, discontinue oral phosphate and/or active vitamin D analogs (e.g. calcitriol, paricalcitol, doxercalciferol, calcifediol) for one week
[see Contraindications (4), Warnings and Precautions (5.3)].Prior to starting CRYSVITA, fasting serum phosphorus concentration should be below the reference range for age
[see Contraindications (4)].In patients at high risk for hypercalcemia (e.g., pre-existing hyperparathyroidism, prolonged immobilization, dehydration, hypervitaminosis D, or renal impairment) assess serum calcium and parathyroid hormone levels prior to starting CRYSVITA
[see Warnings and Precautions (5.3)].CRYSVITA is administered by subcutaneous injection and should be administered by a healthcare provider.
The maximum volume of CRYSVITA per injection is 1.5 mL. If multiple injections are required, administer at different injection sites.
2.2 Recommended Dosage for Pediatric Patients with X-linked Hypophosphatemia (6 months to less than 18 years of age)For patients who weigh less than 10 kg, the recommended starting dosage is 1 mg/kg of body weight, rounded to the nearest 1 mg, administered every two weeks.
For patients who weigh 10 kg and greater, the recommended starting dose regimen is 0.8 mg/kg of body weight, rounded to the nearest 10 mg, administered every two weeks. The minimum starting dose is 10 mg up to a maximum dose of 90 mg.
After initiation of treatment with CRYSVITA, measure fasting serum phosphorus every 4 weeks for the first 3 months of treatment, and thereafter as appropriate. If serum phosphorus is above the lower limit of the reference range for age and below 5 mg/dL, continue treatment with the same dose. Follow dose adjustment schedule below to maintain serum phosphorus within the reference range for age.
Dose AdjustmentReassess fasting serum phosphorus level 4 weeks after dose adjustment.
Do not adjust CRYSVITA more frequently than every 4 weeks.
Dose Increase:For patients who weigh less than 10 kg, if serum phosphorus is below the reference range for age, the dose may be increased to 1.5 mg/kg, rounded to the nearest 1 mg, administered every two weeks. If additional dose increases are needed, the dose may be increased to the maximum dose of 2 mg/kg, rounded to the nearest 1 mg, administered every two weeks.
For patients who weigh 10 kg or greater, if serum phosphorus is below the reference range for age, the dose may be increased stepwise up to approximately 2 mg/kg, administered every two weeks (maximum dose of 90 mg) according to the dosing schedule shown in Table 1.
Table 1: XLH Pediatric Dose Schedule for Stepwise Dose Increase for Patients Weighing 10 kg or More Body Weight (kg) Starting Dose (mg) First Dose Increase to (mg) Second Dose Increase to (mg) 10 – 14 10 15 20 15 – 18 10 20 30 19 – 31 20 30 40 32 – 43 30 40 60 44 – 56 40 60 80 57 – 68 50 70 90 69 – 80 60 90 90 81 – 93 70 90 90 94 – 105 80 90 90 106 and greater 90 90 90 Dose Decrease:If serum phosphorus is above 5 mg/dL, withhold the next dose and reassess the serum phosphorus level in 4 weeks. The patient must have serum phosphorus below the reference range for age to reinitiate CRYSVITA. Once serum phosphorus is below the reference range for age, treatment may be restarted.
For patients who weigh less than 10 kg, restart CRYSVITA at 0.5 mg/kg of body weight, rounded to the nearest 1 mg, administered every two weeks. For patients who weigh 10 kg or more, restart CRYSVITA according to the dose schedule shown in Table 2.
Table 2: XLH Pediatric Dose Schedule for Re-Initiation of Therapy for Patients Weighing 10 kg or More Previous Dose (mg) Re-Initiation Dose (mg) 10 5 15 10 20 10 30 10 40 20 50 20 60 30 70 30 80 40 90 40 After a dose decrease, reassess serum phosphorus level 4 weeks after the dose adjustment. If the level remains below the reference range for age after the re-initiation dose, the dose can be adjusted as outlined under Dose Increase.
2.3 Recommended Dosage for Adult Patients with X-linked Hypophosphatemia (18 years of age and older)The recommended dosage regimen in adults is 1 mg/kg body weight, rounded to the nearest 10 mg up to a maximum dose of 90 mg, administered every four weeks.
After initiation of treatment with CRYSVITA, assess fasting serum phosphorus on a monthly basis, measured 2 weeks post-dose, for the first 3 months of treatment, and thereafter as appropriate. If serum phosphorus is within the normal range, continue with the same dose.
Dose DecreaseReassess fasting serum phosphorus level 2 weeks after dose adjustment.
Do not adjust CRYSVITA more frequently than every 4 weeks.
If serum phosphorus is above the normal range, withhold the next dose and reassess the serum phosphorus level after 4 weeks. The patient must have serum phosphorus below the normal range to be able to reinitiate CRYSVITA. Once serum phosphorus is below the normal range, treatment may be restarted at approximately half the initial starting dose up to a maximum dose of 40 mg every 4 weeks according to the dose schedule shown in Table 3. Reassess serum phosphorus 2 weeks after any change in dose.
Table 3: XLH Adult Dose Schedule for Re-Initiation of Therapy Previous Dose (mg) Re-Initiation Dose (mg) 40 20 50 20 60 30 70 30 80 and greater 40 2.4 Recommended Dosage for Pediatric Patients with Tumor-induced Osteomalacia (2 years to less than 18 years of age)The recommended starting dosage for pediatrics is 0.4 mg/kg body weight administered every 2 weeks, rounded to the nearest 10 mg, up to a maximum dose of 2 mg/kg not to exceed 180 mg, administered every 2 weeks.
After initiation of treatment with CRYSVITA, assess fasting serum phosphorus on a monthly basis, measured 2 weeks post-dose, for the first 3 months of treatment, and thereafter as appropriate. If serum phosphorus is within the reference range for age, continue with the same dose. Follow the dose adjustment schedule below to maintain serum phosphorus within the reference range for age.
Dose AdjustmentReassess fasting serum phosphorus level 4 weeks after dose adjustment.
Do not adjust CRYSVITA more frequently than every 4 weeks.
Dose IncreaseIf serum phosphorus is below the reference range for age, the dose should be titrated in accordance with Table 4 up to the maximum dose of 2 mg/kg every 2 weeks. The maximum dose should not exceed 180 mg.
Table 4: TIO Pediatric Dose Schedule for Stepwise Dose Increase for Patients Weighing 10 kg or more Body Weight
(kg)Starting Dose
(mg)First Dose Increase to
(mg)Second Dose Increase to
(mg)Third DoseThe table shows a dose increase up to 1.5 mg/kg. Further dose increases to a maximum of 2 mg/kg not to exceed 180 mg, administered every 2 weeks should be calculated by the physician.Increase to
(mg)10 – 14 5 10 15 20 15 – 18 5 10 20 25 19 – 31 10 20 25 30 32 – 43 10 30 40 50 44 – 56 20 40 50 70 57 – 68 20 50 70 90 69 – 80 30 60 80 100 81 – 93 30 70 100 120 94 – 105 40 80 110 140 106 and greater 40 90 130 160 Dose DecreaseIf serum phosphorus is above the reference range for age, withhold the next dose and reassess the serum phosphorus level in 4 weeks. The patient must have serum phosphorus below the reference range for age to reinitiate CRYSVITA. Once serum phosphorus is below the reference range for age, treatment may be restarted at approximately half the initial starting dose, up to a maximum dose of 180 mg administered every 2 weeks for pediatrics. After a dose decrease, reassess serum phosphorus level 4 weeks after the dose adjustment. If the level remains below the reference range for age after the re-initiation dose, the dose can be adjusted as outlined per Table 4.
Dose InterruptionIf a patient undergoes treatment of the underlying tumor (i.e., surgical excision or radiation therapy) CRYSVITA treatment should be interrupted and serum phosphorus reassessed after treatment has been completed. CRYSVITA dose should be restarted at the patient's initiation dose if serum phosphorus remains below the lower limit of normal. Follow dose adjustment per Table 4to maintain serum phosphorus within the reference range for age.
2.5 Recommended Dosage for Adult Patients with Tumor-induced Osteomalacia (18 years of age and older)The recommended starting dosage for adults is 0.5 mg/kg body weight administered every 4 weeks, rounded to the nearest 10 mg, up to a maximum dose of 2 mg/kg not to exceed 180 mg, administered every 2 weeks.
After initiation of treatment with CRYSVITA, assess fasting serum phosphorus on a monthly basis, measured 2 weeks post-dose, for the first 3 months of treatment, and thereafter as appropriate. If serum phosphorus is within the normal range, continue with the same dose. Follow the dose adjustment schedule below to maintain serum phosphorus within the reference range.
Dose AdjustmentReassess fasting serum phosphorus level 2 weeks after dose adjustment.
Do not adjust CRYSVITA more frequently than every 4 weeks.
Dose IncreaseIf serum phosphorus is below the normal range, the dose should be titrated in accordance with Table 5up to the maximum dose of 2 mg/kg not to exceed 180 mg, administered every 2 weeks. For those individuals not reaching a serum phosphorus greater than the lower limit of the normal range, physicians may consider dividing total dose administered every 4 weeks and administering every 2 weeks.
Table 5: TIO Dose ScheduleRounded to the nearest 10 mg.for StepwiseDo not adjust CRYSVITA more frequently than every 4 weeks.Dose Increase for Adults (18 years of age and older) Starting Dose First Dose IncreaseFor those individuals not reaching a serum phosphorus greater than the lower limit of the normal range, physicians may consider dividing total dose administered every 4 weeks and administering every 2 weeks. Second Dose Increase Third Dose Increase Fourth Dose Increase Fifth Dose Increase
(maximum dose)If serum phosphorus 2 weeks post-dose adjustment is below lower limit of normal 0.5 mg/kg every 4 weeks Increase to:
1 mg/kg every 4 weeks
OR
0.5 mg/kg every 2 weeksIncrease to:
1.5 mg/kg every 4 weeksIn patients with high body weight, if the calculated dose is greater than 180 mg every 4 weeks, move to a divided dose every 2 weeks.
OR
0.75 mg/kg every 2 weeksIncrease to:
2 mg/kg every 4 weeks
OR
1 mg/kg every 2 weeksIncrease to:
1.5 mg/kg not to exceed 180 mg every 2 weeksIncrease to:
2 mg/kg not to exceed 180 mg every 2 weeksDose DecreaseIf serum phosphorus is above the normal range, withhold the next dose and reassess the serum phosphorus level in 4 weeks. The patient must have serum phosphorus below the reference range to reinitiate CRYSVITA. Once serum phosphorus is below the reference range, treatment may be restarted at approximately half the initial starting dose, up to a maximum dose of 180 mg administered every 2 weeks for adults. After a dose decrease, reassess serum phosphorus level 2 weeks after the dose adjustment. If the level remains below the reference range after the re-initiation dose, the dose can be adjusted as outlined per Table 5.
Dose InterruptionIf a patient undergoes treatment of the underlying tumor (i.e., surgical excision or radiation therapy) CRYSVITA treatment should be interrupted and serum phosphorus reassessed after treatment has been completed. CRYSVITA dose should be restarted at the patient’s initiation dose if serum phosphorus remains below the lower limit of normal. Follow dose adjustment per Table 5to maintain serum phosphorus within the reference range.
2.6 Missed DoseIf a patient misses a dose, resume CRYSVITA as soon as possible at the prescribed dose. To avoid missed doses, treatments may be administered 3 days either side of the scheduled treatment date.
2.7 25-Hydroxy Vitamin D SupplementationMonitor 25-hydroxy vitamin D levels. Supplement with cholecalciferol or ergocalciferol to maintain 25-hydroxy vitamin D levels in the normal range for age. Do not administer active Vitamin D analogs during CRYSVITA treatment
[see Contraindications (4)].2.8 General Considerations for Subcutaneous AdministrationInjection sites should be rotated with each injection administered at a different anatomic location (upper arms, upper thighs, buttocks, or any quadrant of abdomen) than the previous injection. Do not inject into moles, scars, or areas where the skin is tender, bruised, red, hard, or not intact. If a given dose on a dosing day requires multiple vials of CRYSVITA, contents from two vials can be combined for injection. The maximum volume of CRYSVITA per injection is 1.5 mL. If multiple injections are required on a given dosing day, administer at different injection sites. Monitor for signs of reactions
[see Warnings and Precautions (5.4)].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.
- Prior to starting CRYSVITA, discontinue oral phosphate and/or active vitamin D analogs for one week ()
2.1 Important Information Prior to Initiation of CRYSVITAPrior to starting CRYSVITA, discontinue oral phosphate and/or active vitamin D analogs (e.g. calcitriol, paricalcitol, doxercalciferol, calcifediol) for one week
[see Contraindications (4), Warnings and Precautions (5.3)].Prior to starting CRYSVITA, fasting serum phosphorus concentration should be below the reference range for age
[see Contraindications (4)].In patients at high risk for hypercalcemia (e.g., pre-existing hyperparathyroidism, prolonged immobilization, dehydration, hypervitaminosis D, or renal impairment) assess serum calcium and parathyroid hormone levels prior to starting CRYSVITA
[see Warnings and Precautions (5.3)].CRYSVITA is administered by subcutaneous injection and should be administered by a healthcare provider.
The maximum volume of CRYSVITA per injection is 1.5 mL. If multiple injections are required, administer at different injection sites.
- Pediatric XLH (6 months and older):
- For patients who weigh less than 10 kg, starting dose regimen is 1 mg/kg of body weight rounded to the nearest 1 mg, administered every two weeks ()
2.2 Recommended Dosage for Pediatric Patients with X-linked Hypophosphatemia (6 months to less than 18 years of age)For patients who weigh less than 10 kg, the recommended starting dosage is 1 mg/kg of body weight, rounded to the nearest 1 mg, administered every two weeks.
For patients who weigh 10 kg and greater, the recommended starting dose regimen is 0.8 mg/kg of body weight, rounded to the nearest 10 mg, administered every two weeks. The minimum starting dose is 10 mg up to a maximum dose of 90 mg.
After initiation of treatment with CRYSVITA, measure fasting serum phosphorus every 4 weeks for the first 3 months of treatment, and thereafter as appropriate. If serum phosphorus is above the lower limit of the reference range for age and below 5 mg/dL, continue treatment with the same dose. Follow dose adjustment schedule below to maintain serum phosphorus within the reference range for age.
Dose AdjustmentReassess fasting serum phosphorus level 4 weeks after dose adjustment.
Do not adjust CRYSVITA more frequently than every 4 weeks.
Dose Increase:For patients who weigh less than 10 kg, if serum phosphorus is below the reference range for age, the dose may be increased to 1.5 mg/kg, rounded to the nearest 1 mg, administered every two weeks. If additional dose increases are needed, the dose may be increased to the maximum dose of 2 mg/kg, rounded to the nearest 1 mg, administered every two weeks.
For patients who weigh 10 kg or greater, if serum phosphorus is below the reference range for age, the dose may be increased stepwise up to approximately 2 mg/kg, administered every two weeks (maximum dose of 90 mg) according to the dosing schedule shown in Table 1.
Table 1: XLH Pediatric Dose Schedule for Stepwise Dose Increase for Patients Weighing 10 kg or More Body Weight (kg) Starting Dose (mg) First Dose Increase to (mg) Second Dose Increase to (mg) 10 – 14 10 15 20 15 – 18 10 20 30 19 – 31 20 30 40 32 – 43 30 40 60 44 – 56 40 60 80 57 – 68 50 70 90 69 – 80 60 90 90 81 – 93 70 90 90 94 – 105 80 90 90 106 and greater 90 90 90 Dose Decrease:If serum phosphorus is above 5 mg/dL, withhold the next dose and reassess the serum phosphorus level in 4 weeks. The patient must have serum phosphorus below the reference range for age to reinitiate CRYSVITA. Once serum phosphorus is below the reference range for age, treatment may be restarted.
For patients who weigh less than 10 kg, restart CRYSVITA at 0.5 mg/kg of body weight, rounded to the nearest 1 mg, administered every two weeks. For patients who weigh 10 kg or more, restart CRYSVITA according to the dose schedule shown in Table 2.
Table 2: XLH Pediatric Dose Schedule for Re-Initiation of Therapy for Patients Weighing 10 kg or More Previous Dose (mg) Re-Initiation Dose (mg) 10 5 15 10 20 10 30 10 40 20 50 20 60 30 70 30 80 40 90 40 After a dose decrease, reassess serum phosphorus level 4 weeks after the dose adjustment. If the level remains below the reference range for age after the re-initiation dose, the dose can be adjusted as outlined under Dose Increase.
- For patients who weigh 10 kg and greater, starting dose regimen is 0.8 mg/kg of body weight rounded to the nearest 10 mg, administered every two weeks. The minimum starting dose is 10 mg up to a maximum dose of 90 mg. ()
2.2 Recommended Dosage for Pediatric Patients with X-linked Hypophosphatemia (6 months to less than 18 years of age)For patients who weigh less than 10 kg, the recommended starting dosage is 1 mg/kg of body weight, rounded to the nearest 1 mg, administered every two weeks.
For patients who weigh 10 kg and greater, the recommended starting dose regimen is 0.8 mg/kg of body weight, rounded to the nearest 10 mg, administered every two weeks. The minimum starting dose is 10 mg up to a maximum dose of 90 mg.
After initiation of treatment with CRYSVITA, measure fasting serum phosphorus every 4 weeks for the first 3 months of treatment, and thereafter as appropriate. If serum phosphorus is above the lower limit of the reference range for age and below 5 mg/dL, continue treatment with the same dose. Follow dose adjustment schedule below to maintain serum phosphorus within the reference range for age.
Dose AdjustmentReassess fasting serum phosphorus level 4 weeks after dose adjustment.
Do not adjust CRYSVITA more frequently than every 4 weeks.
Dose Increase:For patients who weigh less than 10 kg, if serum phosphorus is below the reference range for age, the dose may be increased to 1.5 mg/kg, rounded to the nearest 1 mg, administered every two weeks. If additional dose increases are needed, the dose may be increased to the maximum dose of 2 mg/kg, rounded to the nearest 1 mg, administered every two weeks.
For patients who weigh 10 kg or greater, if serum phosphorus is below the reference range for age, the dose may be increased stepwise up to approximately 2 mg/kg, administered every two weeks (maximum dose of 90 mg) according to the dosing schedule shown in Table 1.
Table 1: XLH Pediatric Dose Schedule for Stepwise Dose Increase for Patients Weighing 10 kg or More Body Weight (kg) Starting Dose (mg) First Dose Increase to (mg) Second Dose Increase to (mg) 10 – 14 10 15 20 15 – 18 10 20 30 19 – 31 20 30 40 32 – 43 30 40 60 44 – 56 40 60 80 57 – 68 50 70 90 69 – 80 60 90 90 81 – 93 70 90 90 94 – 105 80 90 90 106 and greater 90 90 90 Dose Decrease:If serum phosphorus is above 5 mg/dL, withhold the next dose and reassess the serum phosphorus level in 4 weeks. The patient must have serum phosphorus below the reference range for age to reinitiate CRYSVITA. Once serum phosphorus is below the reference range for age, treatment may be restarted.
For patients who weigh less than 10 kg, restart CRYSVITA at 0.5 mg/kg of body weight, rounded to the nearest 1 mg, administered every two weeks. For patients who weigh 10 kg or more, restart CRYSVITA according to the dose schedule shown in Table 2.
Table 2: XLH Pediatric Dose Schedule for Re-Initiation of Therapy for Patients Weighing 10 kg or More Previous Dose (mg) Re-Initiation Dose (mg) 10 5 15 10 20 10 30 10 40 20 50 20 60 30 70 30 80 40 90 40 After a dose decrease, reassess serum phosphorus level 4 weeks after the dose adjustment. If the level remains below the reference range for age after the re-initiation dose, the dose can be adjusted as outlined under Dose Increase.
)2.2 Recommended Dosage for Pediatric Patients with X-linked Hypophosphatemia (6 months to less than 18 years of age)For patients who weigh less than 10 kg, the recommended starting dosage is 1 mg/kg of body weight, rounded to the nearest 1 mg, administered every two weeks.
For patients who weigh 10 kg and greater, the recommended starting dose regimen is 0.8 mg/kg of body weight, rounded to the nearest 10 mg, administered every two weeks. The minimum starting dose is 10 mg up to a maximum dose of 90 mg.
After initiation of treatment with CRYSVITA, measure fasting serum phosphorus every 4 weeks for the first 3 months of treatment, and thereafter as appropriate. If serum phosphorus is above the lower limit of the reference range for age and below 5 mg/dL, continue treatment with the same dose. Follow dose adjustment schedule below to maintain serum phosphorus within the reference range for age.
Dose AdjustmentReassess fasting serum phosphorus level 4 weeks after dose adjustment.
Do not adjust CRYSVITA more frequently than every 4 weeks.
Dose Increase:For patients who weigh less than 10 kg, if serum phosphorus is below the reference range for age, the dose may be increased to 1.5 mg/kg, rounded to the nearest 1 mg, administered every two weeks. If additional dose increases are needed, the dose may be increased to the maximum dose of 2 mg/kg, rounded to the nearest 1 mg, administered every two weeks.
For patients who weigh 10 kg or greater, if serum phosphorus is below the reference range for age, the dose may be increased stepwise up to approximately 2 mg/kg, administered every two weeks (maximum dose of 90 mg) according to the dosing schedule shown in Table 1.
Table 1: XLH Pediatric Dose Schedule for Stepwise Dose Increase for Patients Weighing 10 kg or More Body Weight (kg) Starting Dose (mg) First Dose Increase to (mg) Second Dose Increase to (mg) 10 – 14 10 15 20 15 – 18 10 20 30 19 – 31 20 30 40 32 – 43 30 40 60 44 – 56 40 60 80 57 – 68 50 70 90 69 – 80 60 90 90 81 – 93 70 90 90 94 – 105 80 90 90 106 and greater 90 90 90 Dose Decrease:If serum phosphorus is above 5 mg/dL, withhold the next dose and reassess the serum phosphorus level in 4 weeks. The patient must have serum phosphorus below the reference range for age to reinitiate CRYSVITA. Once serum phosphorus is below the reference range for age, treatment may be restarted.
For patients who weigh less than 10 kg, restart CRYSVITA at 0.5 mg/kg of body weight, rounded to the nearest 1 mg, administered every two weeks. For patients who weigh 10 kg or more, restart CRYSVITA according to the dose schedule shown in Table 2.
Table 2: XLH Pediatric Dose Schedule for Re-Initiation of Therapy for Patients Weighing 10 kg or More Previous Dose (mg) Re-Initiation Dose (mg) 10 5 15 10 20 10 30 10 40 20 50 20 60 30 70 30 80 40 90 40 After a dose decrease, reassess serum phosphorus level 4 weeks after the dose adjustment. If the level remains below the reference range for age after the re-initiation dose, the dose can be adjusted as outlined under Dose Increase.
- For patients who weigh less than 10 kg, starting dose regimen is 1 mg/kg of body weight rounded to the nearest 1 mg, administered every two weeks (
- Adult XLH:Dose regimen is 1 mg/kg body weight rounded to the nearest 10 mg up to a maximum dose of 90 mg administered every four weeks. ()
2.3 Recommended Dosage for Adult Patients with X-linked Hypophosphatemia (18 years of age and older)The recommended dosage regimen in adults is 1 mg/kg body weight, rounded to the nearest 10 mg up to a maximum dose of 90 mg, administered every four weeks.
After initiation of treatment with CRYSVITA, assess fasting serum phosphorus on a monthly basis, measured 2 weeks post-dose, for the first 3 months of treatment, and thereafter as appropriate. If serum phosphorus is within the normal range, continue with the same dose.
Dose DecreaseReassess fasting serum phosphorus level 2 weeks after dose adjustment.
Do not adjust CRYSVITA more frequently than every 4 weeks.
If serum phosphorus is above the normal range, withhold the next dose and reassess the serum phosphorus level after 4 weeks. The patient must have serum phosphorus below the normal range to be able to reinitiate CRYSVITA. Once serum phosphorus is below the normal range, treatment may be restarted at approximately half the initial starting dose up to a maximum dose of 40 mg every 4 weeks according to the dose schedule shown in Table 3. Reassess serum phosphorus 2 weeks after any change in dose.
Table 3: XLH Adult Dose Schedule for Re-Initiation of Therapy Previous Dose (mg) Re-Initiation Dose (mg) 40 20 50 20 60 30 70 30 80 and greater 40 - Pediatric TIO (2 years and older):Starting dose is 0.4 mg/kg of body weight rounded to the nearest 10 mg every 2 weeks. Dose may be increased up to 2 mg/kg not to exceed 180 mg, administered every two weeks. ()
2.4 Recommended Dosage for Pediatric Patients with Tumor-induced Osteomalacia (2 years to less than 18 years of age)The recommended starting dosage for pediatrics is 0.4 mg/kg body weight administered every 2 weeks, rounded to the nearest 10 mg, up to a maximum dose of 2 mg/kg not to exceed 180 mg, administered every 2 weeks.
After initiation of treatment with CRYSVITA, assess fasting serum phosphorus on a monthly basis, measured 2 weeks post-dose, for the first 3 months of treatment, and thereafter as appropriate. If serum phosphorus is within the reference range for age, continue with the same dose. Follow the dose adjustment schedule below to maintain serum phosphorus within the reference range for age.
Dose AdjustmentReassess fasting serum phosphorus level 4 weeks after dose adjustment.
Do not adjust CRYSVITA more frequently than every 4 weeks.
Dose IncreaseIf serum phosphorus is below the reference range for age, the dose should be titrated in accordance with Table 4 up to the maximum dose of 2 mg/kg every 2 weeks. The maximum dose should not exceed 180 mg.
Table 4: TIO Pediatric Dose Schedule for Stepwise Dose Increase for Patients Weighing 10 kg or more Body Weight
(kg)Starting Dose
(mg)First Dose Increase to
(mg)Second Dose Increase to
(mg)Third DoseThe table shows a dose increase up to 1.5 mg/kg. Further dose increases to a maximum of 2 mg/kg not to exceed 180 mg, administered every 2 weeks should be calculated by the physician.Increase to
(mg)10 – 14 5 10 15 20 15 – 18 5 10 20 25 19 – 31 10 20 25 30 32 – 43 10 30 40 50 44 – 56 20 40 50 70 57 – 68 20 50 70 90 69 – 80 30 60 80 100 81 – 93 30 70 100 120 94 – 105 40 80 110 140 106 and greater 40 90 130 160 Dose DecreaseIf serum phosphorus is above the reference range for age, withhold the next dose and reassess the serum phosphorus level in 4 weeks. The patient must have serum phosphorus below the reference range for age to reinitiate CRYSVITA. Once serum phosphorus is below the reference range for age, treatment may be restarted at approximately half the initial starting dose, up to a maximum dose of 180 mg administered every 2 weeks for pediatrics. After a dose decrease, reassess serum phosphorus level 4 weeks after the dose adjustment. If the level remains below the reference range for age after the re-initiation dose, the dose can be adjusted as outlined per Table 4.
Dose InterruptionIf a patient undergoes treatment of the underlying tumor (i.e., surgical excision or radiation therapy) CRYSVITA treatment should be interrupted and serum phosphorus reassessed after treatment has been completed. CRYSVITA dose should be restarted at the patient's initiation dose if serum phosphorus remains below the lower limit of normal. Follow dose adjustment per Table 4to maintain serum phosphorus within the reference range for age.
- Adult TIO:Starting dose is 0.5 mg/kg every four weeks. Dose may be increased up to 2 mg/kg not to exceed 180 mg, administered every two weeks. ()
2.5 Recommended Dosage for Adult Patients with Tumor-induced Osteomalacia (18 years of age and older)The recommended starting dosage for adults is 0.5 mg/kg body weight administered every 4 weeks, rounded to the nearest 10 mg, up to a maximum dose of 2 mg/kg not to exceed 180 mg, administered every 2 weeks.
After initiation of treatment with CRYSVITA, assess fasting serum phosphorus on a monthly basis, measured 2 weeks post-dose, for the first 3 months of treatment, and thereafter as appropriate. If serum phosphorus is within the normal range, continue with the same dose. Follow the dose adjustment schedule below to maintain serum phosphorus within the reference range.
Dose AdjustmentReassess fasting serum phosphorus level 2 weeks after dose adjustment.
Do not adjust CRYSVITA more frequently than every 4 weeks.
Dose IncreaseIf serum phosphorus is below the normal range, the dose should be titrated in accordance with Table 5up to the maximum dose of 2 mg/kg not to exceed 180 mg, administered every 2 weeks. For those individuals not reaching a serum phosphorus greater than the lower limit of the normal range, physicians may consider dividing total dose administered every 4 weeks and administering every 2 weeks.
Table 5: TIO Dose ScheduleRounded to the nearest 10 mg.for StepwiseDo not adjust CRYSVITA more frequently than every 4 weeks.Dose Increase for Adults (18 years of age and older) Starting Dose First Dose IncreaseFor those individuals not reaching a serum phosphorus greater than the lower limit of the normal range, physicians may consider dividing total dose administered every 4 weeks and administering every 2 weeks. Second Dose Increase Third Dose Increase Fourth Dose Increase Fifth Dose Increase
(maximum dose)If serum phosphorus 2 weeks post-dose adjustment is below lower limit of normal 0.5 mg/kg every 4 weeks Increase to:
1 mg/kg every 4 weeks
OR
0.5 mg/kg every 2 weeksIncrease to:
1.5 mg/kg every 4 weeksIn patients with high body weight, if the calculated dose is greater than 180 mg every 4 weeks, move to a divided dose every 2 weeks.
OR
0.75 mg/kg every 2 weeksIncrease to:
2 mg/kg every 4 weeks
OR
1 mg/kg every 2 weeksIncrease to:
1.5 mg/kg not to exceed 180 mg every 2 weeksIncrease to:
2 mg/kg not to exceed 180 mg every 2 weeksDose DecreaseIf serum phosphorus is above the normal range, withhold the next dose and reassess the serum phosphorus level in 4 weeks. The patient must have serum phosphorus below the reference range to reinitiate CRYSVITA. Once serum phosphorus is below the reference range, treatment may be restarted at approximately half the initial starting dose, up to a maximum dose of 180 mg administered every 2 weeks for adults. After a dose decrease, reassess serum phosphorus level 2 weeks after the dose adjustment. If the level remains below the reference range after the re-initiation dose, the dose can be adjusted as outlined per Table 5.
Dose InterruptionIf a patient undergoes treatment of the underlying tumor (i.e., surgical excision or radiation therapy) CRYSVITA treatment should be interrupted and serum phosphorus reassessed after treatment has been completed. CRYSVITA dose should be restarted at the patient’s initiation dose if serum phosphorus remains below the lower limit of normal. Follow dose adjustment per Table 5to maintain serum phosphorus within the reference range.
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.
There are no available data on CRYSVITA use in pregnant women to inform a drug-associated risk of adverse developmental outcomes. In utero, burosumab-twza exposure in cynomolgus monkeys did not result in teratogenic effects. Adverse effects such as late fetal loss and preterm birth were observed in pregnant cynomolgus monkeys, however, these effects are unlikely to indicate clinical risk because they occurred at a drug exposure that was 15-fold higher, by AUC, than the human exposure at the maximum recommended human dose (MRHD) of 2 mg/kg every 2 weeks and were accompanied by maternal hyperphosphatemia and placental mineralization (
For patients who weigh less than 10 kg, the recommended starting dosage is 1 mg/kg of body weight, rounded to the nearest 1 mg, administered every two weeks.
For patients who weigh 10 kg and greater, the recommended starting dose regimen is 0.8 mg/kg of body weight, rounded to the nearest 10 mg, administered every two weeks. The minimum starting dose is 10 mg up to a maximum dose of 90 mg.
After initiation of treatment with CRYSVITA, measure fasting serum phosphorus every 4 weeks for the first 3 months of treatment, and thereafter as appropriate. If serum phosphorus is above the lower limit of the reference range for age and below 5 mg/dL, continue treatment with the same dose. Follow dose adjustment schedule below to maintain serum phosphorus within the reference range for age.
Reassess fasting serum phosphorus level 4 weeks after dose adjustment.
Do not adjust CRYSVITA more frequently than every 4 weeks.
For patients who weigh less than 10 kg, if serum phosphorus is below the reference range for age, the dose may be increased to 1.5 mg/kg, rounded to the nearest 1 mg, administered every two weeks. If additional dose increases are needed, the dose may be increased to the maximum dose of 2 mg/kg, rounded to the nearest 1 mg, administered every two weeks.
For patients who weigh 10 kg or greater, if serum phosphorus is below the reference range for age, the dose may be increased stepwise up to approximately 2 mg/kg, administered every two weeks (maximum dose of 90 mg) according to the dosing schedule shown in Table 1.
| Body Weight (kg) | Starting Dose (mg) | First Dose Increase to (mg) | Second Dose Increase to (mg) |
|---|---|---|---|
| 10 – 14 | 10 | 15 | 20 |
| 15 – 18 | 10 | 20 | 30 |
| 19 – 31 | 20 | 30 | 40 |
| 32 – 43 | 30 | 40 | 60 |
| 44 – 56 | 40 | 60 | 80 |
| 57 – 68 | 50 | 70 | 90 |
| 69 – 80 | 60 | 90 | 90 |
| 81 – 93 | 70 | 90 | 90 |
| 94 – 105 | 80 | 90 | 90 |
| 106 and greater | 90 | 90 | 90 |
If serum phosphorus is above 5 mg/dL, withhold the next dose and reassess the serum phosphorus level in 4 weeks. The patient must have serum phosphorus below the reference range for age to reinitiate CRYSVITA. Once serum phosphorus is below the reference range for age, treatment may be restarted.
For patients who weigh less than 10 kg, restart CRYSVITA at 0.5 mg/kg of body weight, rounded to the nearest 1 mg, administered every two weeks. For patients who weigh 10 kg or more, restart CRYSVITA according to the dose schedule shown in Table 2.
| Previous Dose (mg) | Re-Initiation Dose (mg) |
|---|---|
| 10 | 5 |
| 15 | 10 |
| 20 | 10 |
| 30 | 10 |
| 40 | 20 |
| 50 | 20 |
| 60 | 30 |
| 70 | 30 |
| 80 | 40 |
| 90 | 40 |
After a dose decrease, reassess serum phosphorus level 4 weeks after the dose adjustment. If the level remains below the reference range for age after the re-initiation dose, the dose can be adjusted as outlined under Dose Increase.
The background risk of major birth defects and miscarriage for the indicated population is unknown; however, the estimated background risk in the U.S. general population of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies.
In a reproductive toxicity study in pregnant cynomolgus monkeys, burosumab-twza was administered intravenously once every two weeks from Day 20 of pregnancy to parturition or cesarean section on Day 133, which includes the period of organogenesis, at doses of 0.2-, 2- and 15-fold human exposure at the adult MRHD of 2 mg/kg every 2 weeks. The treatment did not result in teratogenic effects in fetuses or offspring. An increase in late fetal loss, a shortened gestation period, and an increased incidence of preterm births were observed at 15-fold human exposure at the adult MRHD of 2 mg/kg every 2 weeks, concomitant with maternal hyperphosphatemia and placental mineralization. Burosumab-twza was detected in serum from fetuses indicating transport across the placenta. Hyperphosphatemia but no ectopic mineralization was present in fetuses and offspring of dams exposed to 15-fold human exposure at the MRHD of 2 mg/kg dose every 2 weeks. Burosumab-twza did not affect pre- and postnatal growth including survivability of the offspring.
CRYSVITA is contraindicated:
- In concomitant use with oral phosphate and/or active vitamin D analogs (e.g. calcitriol, paricalcitol, doxercalciferol, calcifediol) due to the risk of hyperphosphatemia [see.and
5.2 Hyperphosphatemia and Risk of NephrocalcinosisIncreases 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. Patients with tumor-induced osteomalacia who undergo treatment of the underlying tumor should have dosing interrupted and adjusted to prevent hyperphosphatemia
[see Dosage and Administration (2)and Adverse Reactions (6.1)].]7.1 Oral Phosphate and Active Vitamin D AnalogsConcomitant use of CRYSVITA with oral phosphate and/or active vitamin D analogs will increase phosphate concentrations greater than expected with CRYSVITA alone. This increase may result in hyperphosphatemia which can induce nephrocalcinosis.
Concomitant use of CRYSVITA with oral phosphate and/or active vitamin D analogs is contraindicated.
- When serum phosphorus is within or above the normal range for age [see.]
5.2 Hyperphosphatemia and Risk of NephrocalcinosisIncreases 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. Patients with tumor-induced osteomalacia who undergo treatment of the underlying tumor should have dosing interrupted and adjusted to prevent hyperphosphatemia
[see Dosage and Administration (2)and Adverse Reactions (6.1)]. - In patients with severe renal impairment or end stage renal disease because these conditions are associated with abnormal mineral metabolism [see.]
8.6 Renal ImpairmentThe effect of renal impairment on the pharmacokinetics of burosumab-twza 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/1.73m2to 29 mL/min/1.73m2or 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).