CRYSVITA has a simple dosing schedule
Starting dose:
Every 4 weeks for adults (18 years of age and older)1
Every 2 weeks for children (2 years to <18 years of age)1,*
*Safety and effectiveness of CRYSVITA in pediatric patients 2 years of age and older with TIO are supported by evidence from the studies in adult patients with TIO with additional modeling and simulation of pharmacokinetic (PK) data from adult and pediatric patients with XLH and adult patients with TIO to inform dosing. Safety and effectiveness for CRYSVITA in pediatric patients with TIO below the age of 2 years have not been established.
All patients should discontinue oral phosphate and/or active vitamin D analogs (e.g., calcitriol, paricalcitol, doxercalciferol, calcifediol) 1 week prior to initiation of treatment.
Fasting serum phosphorus concentration should be below the reference range for age prior to initiation of treatment.
Dosing for adults
The recommended starting dose regimen in adults is 0.5 mg/kg of body weight, rounded to the nearest 10 mg, up to a maximum dose of 180 mg.1
After initiating CRYSVITA, monitor fasting serum phosphorus every 4 weeks, measured 2 weeks post-dose for the first 3 months of treatment and thereafter, as appropriate. If serum phosphorus is within the normal reference range, continue with the same dose. To maintain serum phosphorus within the normal range, adjust the dose up to a maximum dose of 2 mg/kg, not to exceed 180 mg, administered every 2 weeks, as indicated in the full Prescribing Information.1
Dose adjustments in adults
Reassess fasting serum phosphorus level 2 weeks after dose adjustment.1
Do not adjust CRYSVITA more frequently than every 4 weeks.1
Dose increase: If serum phosphorus is below the normal range, the CRYSVITA dose may be increased stepwise up to a maximum dose of 2 mg/kg, not to exceed 180 mg, administered every 2 weeks, according to the dose schedule in Table 1.1
| Table 1. Dose Schedulea for Stepwiseb Dose Increase for Adults(18 Years of Age and Older) | ||||||
|---|---|---|---|---|---|---|
| If serum phosphorus 2 weeks post-dose adjustment is below lower limit of normal | ||||||
| Starting dose | 0.5 mg/kg every 4 weeks | |||||
| First dose increasec | Increase to: 1 mg/kg every 4 weeks OR 0.5 mg/kg every 2 weeks | |||||
| Second dose increasec | Increase to: 1.5 mg/kg every 4 weeksd OR 0.75 mg/kg every 2 weeks | |||||
| Third dose increasec | Increase to: 2 mg/kg every 4 weeksd OR 1 mg/kg every 2 weeks | |||||
| Fourth dose increase | Increase to: 1.5 mg/kg every 2 weeks | |||||
| Fifth dose increase (maximum dose) | Increase to: 2 mg/kg every 2 weeks | |||||
- aRounded to the nearest 10 mg.
- bDo not adjust CRYSVITA more frequently than every 4 weeks.
- cFor 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.
- dIn patients with high body weight, if the calculated dose is greater than 180 mg every 4 weeks, move to a divided dose of every 2 weeks.
Dose decrease: If serum phosphorus is above the normal range, withhold the next dose and reassess fasting 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.
After a dose decrease, reassess fasting serum phosphorus level 2 weeks after the dose adjustment. If the level remains below the reference range after the reinitiation dose, the dose can be adjusted, as outlined in Table 1.1
Dose interruption: If a patient undergoes treatment of the underlying tumor, such as surgical excision or radiation therapy, CRYSVITA treatment should be interrupted and serum phosphorus reassessed after treatment has been completed. If serum phosphorus level remains below the lower limit of normal, CRYSVITA dose should be restarted at the patient’s initiation dose. The dose may be adjusted following the dose schedule in Table 1 to maintain serum phosphorus levels within the reference range.1
Dosing for children
The recommended starting dose regimen for children is 0.4 mg/kg of body weight, rounded to the nearest 10 mg, up to a maximum dose of 180 mg.1
After initiating CRYSVITA, monitor fasting serum phosphorus every 4 weeks, measured 2 weeks post-dose for the first 3 months of treatment and thereafter, as appropriate. If serum phosphorus is within the normal reference range for age, continue with the same dose. To maintain serum phosphorus within the reference range for age, adjust the dose up to a maximum dose of 2 mg/kg, not to exceed 180 mg, administered every 2 weeks, as indicated in the full Prescribing Information.1
Dose adjustments in children
Reassess fasting serum phosphorus level 4 weeks after dose adjustment.1
Do not adjust CRYSVITA more frequently than every 4 weeks.1
Dose increase: If serum phosphorus is below the reference range for age, the CRYSVITA dose may be increased stepwise up to the maximum dose of 2 mg/kg, not to exceed 180 mg, administered every 2 weeks, according to the dose schedule shown in Table 2.1
| Table 2. 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 Dosea 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 |
- aThe 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.
Dose decrease: If serum phosphorus is above the reference range for age, withhold the next dose and reassess fasting 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.
After a dose decrease, reassess fasting serum phosphorus level 4 weeks after the dose adjustment. If the level remains below the reference range for age after the reinitiation dose, the dose can be adjusted, as outlined in Table 2.1
Dose interruption: If a patient undergoes treatment of the underlying tumor, such as surgical excision or radiation therapy, CRYSVITA treatment should be interrupted and serum phosphorus reassessed after treatment has been completed. If serum phosphorus level remains below the lower limit of normal, CRYSVITA dose should be restarted at the patient’s initiation dose. The dose may be adjusted following the dose schedule in Table 2 to maintain serum phosphorus level within the reference range for age.1
Missed dose
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 on either side of the scheduled treatment date.1
25-Hydroxy vitamin D supplementation
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.1
Download the CRYSVITA Start Guide for additional information on initiating, dosing, and administering CRYSVITA
How CRYSVITA is supplied
CRYSVITA injection for subcutaneous administration is supplied as a sterile, preservative-free, clear to slightly opalescent and colorless to pale brown-yellow solution. The product is available as 1 single-dose vial per carton in the following strengths: 10 mg/mL, 20 mg/mL, and 30 mg/mL.1
Administration
CRYSVITA is administered by subcutaneous injection and should be administered by a healthcare provider.
Discontinue oral phosphate and/or active vitamin D analogs (e.g., calcitriol, paricalcitol, doxercalciferol, calcifediol) 1 week prior to initiation of treatment. Fasting serum phosphorus concentration should be below the reference range for age prior to initiation of treatment.
General considerations for administration
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 2 vials can be combined for injection. The maximum volume of CRYSVITA per injection site is 1.5 mL. If multiple injections are required, administer at different injection sites. Monitor for signs of reactions.
Visually inspect CRYSVITA for particulate matter and discoloration prior to administration. Do not use if the solution is discolored or cloudy or if the solution contains any particles or foreign particulate matter.
CRYSVITA storage
Store in original carton to protect from light and under refrigerated conditions at 36°F to 46°F (2°C to 8°C) until time of use.1
Do not freeze or shake. Do not use CRYSVITA beyond the expiration date stamped on the carton. CRYSVITA vials are single-dose only. Discard any unused product.1
Reference
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CRYSVITA (burosumab-twza) US Prescribing Information; June 2020.