Source: FDA, National Drug Code (US) Revision Year: 2020
CRYSVITA is indicated for the treatment of X-linked hypophosphatemia (XLH) in adult and pediatric patients 6 months of age and older.
CRYSVITA 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.
Discontinue oral phosphate and/or active vitamin D analogs (e.g. calcitriol, paricalcitol, doxercalciferol, calcifediol) 1 week prior to initiation of treatment [see Contraindications (4)].
Fasting serum phosphorus concentration should be below the reference range for age prior to initiation of treatment [see Contraindications (4)].
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.
For patients who weigh less than 10 kg, the recommended starting dose 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.
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 |
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.
The recommended dose 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.
Reassess 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 |
The recommended starting dose for pediatrics is 0.4 mg/kg body weight administered every 2 weeks, rounded to the nearest 10mg, up to a maximum dose of 2 mg/kg not to exceed 180mg, 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.
Reassess fasting serum phosphorus level 4 weeks after dose adjustment.
Do not adjust CRYSVITA more frequently than every 4 weeks.
If 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 Dose* 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 |
* The 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.
If 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.
If 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 4 to maintain serum phosphorus within the reference range for age.
The recommended starting dose 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 180mg, 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.
Reassess fasting serum phosphorus level 2 weeks after dose adjustment.
Do not adjust CRYSVITA more frequently than every 4 weeks.
If serum phosphorus is below the normal range, the dose should be titrated in accordance with Table 5 up 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 Schedule* for Stepwise† Dose Increase for Adults (18 years of age and older):
| Starting Dose | First Dose Increase‡ | 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 weeks | Increase to: 1.5 mg/kg every 4 weeks§ OR 0.75 mg/kg every 2 weeks | Increase to: 2 mg/kg every 4 weeks§ OR 1 mg/kg every 2 weeks | Increase to: 1.5 mg/kg not to exceed 180 mg every 2 weeks | Increase to: 2 mg/kg not to exceed 180 mg every 2 weeks |
* Rounded to the nearest 10 mg.
† Do not adjust CRYSVITA more frequently than every 4 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.
§ In 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.
If 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.
If 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 5 to maintain serum phosphorus within the reference range.
If 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.
Monitor 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)].
Injection 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 (5.3)].
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.
There have been no reports of overdose with CRYSVITA. CRYSVITA has been administered in pediatric clinical trials without dose limiting toxicity using doses up to 2 mg/kg body weight with a maximal dose of 90 mg, administered every two weeks. In XLH adult clinical trials, no dose limiting toxicity has been observed using doses up to 1 mg/kg or a maximal total dose of 128 mg every 4 weeks. In non-XLH rabbits and cynomolgus monkeys, ectopic mineralization in multiple tissues and organs was observed at doses of burosumab-twza that resulted in supra-physiologic serum phosphate levels. Adverse effects on bone including reductions in bone mineral density, bone mineralization and bone strength were also observed at exposure greater than human exposure [see Nonclinical Toxicology (13.2)].
In case of overdose, it is recommended that serum phosphorus levels, serum calcium levels and renal function be measured immediately and monitored periodically until resolution to normal/baseline levels. In case of hyperphosphatemia, withhold CRYSVITA and initiate appropriate medical treatment.
CRYSVITA vials must be stored in the original carton until the time of use under refrigerated conditions at 36°F to 46°F (2°C to 8°C). Keep CRYSVITA vial in the original carton to protect from light until time of use.
Do not freeze or shake CRYSVITA.
Do not use CRYSVITA beyond the expiration date stamped on the carton.
CRYSVITA vials are single-dose only. Discard any unused product.
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