FDA Advise-ERR: Taking Crysvita with active vitamin D analogs is contraindicated
CRYSVITA (burosumab-twza) injection, approved by the US Food and Drug Administration (FDA) in April 2018, is a fibroblast growth factor 23 (FGF23) blocking antibody used to treat X-linked hypophosphatemia (XLH) in patients 6 months and older. XLH is caused by excess FGF23, which suppresses renal tubular phosphate reabsorption and renal production of 1,25-dihydroxyvitamin D. Before Crysvita, treatment with oral phosphates and active vitamin D was the standard of care for XLH.
Crysvita is contraindicated with concomitant use of oral phosphates and/or active vitamin D analogs (Table 1). Concomitant use will increase phosphate concentrations greater than with Crysvita alone, which may result in hyperphosphatemia that can induce nephrocalcinosis. Cholecalciferol (D3) and ergocalciferol (D2), used for nutritional vitamin D deficiency, are not contraindicated with Crysvita. In fact, supplementation with cholecalciferol or ergocalciferol is recommended to maintain normal 25-hydroxyvitamin D levels.
|Active Vitamin D Analogs|
FDA has received 70 reports of concomitant use of Crysvita and a vitamin D product. Of the 58 reports that specify the product involved, 57% describe cholecalciferol or ergocalciferol, which are not contraindicated, and 43% describe a true contraindication with an active vitamin D analog, mainly calcitriol. Thus, more than half of the reports indicate a lack of understanding of which vitamin D products are contraindicated.
In September 2019, FDA updated the Crysvita prescribing information to specify the active vitamin D analogs to discontinue 1 week prior to initiation (Table 1). A drug interaction section was also added describing possible hyperphosphatemia, which can induce nephrocalcinosis as a result of increased phosphate concentrations from concomitant use of Crysvita with oral phosphates and/or active vitamin D analogs.
To help prevent the concomitant use of Crysvita and oral phosphates and/or active vitamin D analogs:
For Prescribers, Pharmacists, and Nurses
Educate practitioners about active vitamin D analogs (calcitriol, paricalcitol, doxercalciferol, calcifediol) and their contraindication for use with Crysvita.
Prior to prescribing, dispensing, and administering Crysvita, determine whether patients are taking oral phosphates and/or active vitamin D analogs. Review the patients’ medication regimen in the medical record and with the patient, and conduct a thorough medication reconciliation.
Ensure that patients have discontinued oral phosphates or active vitamin D analogs for 1 week before starting Crysvita, and that they do not restart these products while taking Crysvita. (Crysvita is administered every 2 or 4 weeks; oral phosphates and active vitamin D analogs should be avoided throughout this time and until fasting serum phosphorus has been reassessed.)
Work with information technology (IT) to create order entry system alerts for concomitant use of Crysvita and oral phosphates or active vitamin D analogs.
Educate patients about the importance of not taking oral phosphates or active vitamin D analogs while receiving Crysvita injections (even between injections).
Create alerts to warn against the concomitant use of Crysvita and oral phosphates or active vitamin D analogs (calcitriol, paricalcitol, doxercalciferol, calcifediol) when claims are submitted for both drugs.
ISMP thanks Celeste Karpow, PharmD, MPH, FISMP, and Briana Rider, PharmD, CPPS, FISMP, from the FDA Division of Medication Error Prevention and Analysis, for contributing this article.