Burosumab
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From MedlinePlus, U.S. National Library of Medicine
Dosing in kidney impairment
Renal Impairment The 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/1.73m 2 to 29 mL/min/1.73m 2 or end stage renal disease (eGFR < 15 mL/min/1.73m 2 ) adult patients with creatinine clearance (CLcr) 15 mL/min to 29 mL/min or end stage renal disease (CLcr < 15 mL/min).
Preparation and administration
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General Considerations for Subcutaneous 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 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 ] .
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.
Drug interactions
Check burosumab against a medication listLabel text (2 paragraphs)
7 DRUG INTERACTIONS
7.1 Oral Phosphate and Active Vitamin D Analogs Concomitant 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.
Contraindications
4 CONTRAINDICATIONS 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 Warnings and Precautions (5.2) and Drug Interactions (7.1) ] . When serum phosphorus is within or above the normal range for age [see Warnings and Precautions (5.2) ] . In patients with severe renal impairment or end stage renal disease because these conditions are associated with abnormal mineral metabolism [see Use In Specific Population (8.6) ] . With oral phosphate and/or active vitamin D analogs.
( 4 ) When serum phosphorus is within or above the normal range for age. ( 4 ) In patients with severe renal impairment or end stage renal disease. ( 4 )
Safety data
Reported adverse events (FAERS)
Liver injury (LiverTox)
ELikelihood score E: Unlikely cause of clinically apparent liver injury.
Burosumab is a human monoclonal antibody to fibroblast growth factor 23 (FGF23) which is used in the treatment of X-linked hypophosphatemia. Burosumab therapy has not been associated with serum enzyme elevations during therapy nor has it been implicated in cases of clinically apparent drug induced liver injury with jaundice.
ABCDEA: well known cause; E: unlikely cause. [HD]: high doses only.
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary 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 ( see Data ).
Serum phosphorus levels should be monitored throughout pregnancy [see Dosage and Administration (2.2) ]. Report pregnancies to the Kyowa Kirin, Inc. Adverse Event reporting line at 1-844-768-3544. 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.
Data Animal Data 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.
Breastfeeding (LactMed)
No information is available on the clinical use of burosumab alfa during breastfeeding. Because burosumab alfa is a large protein molecule with a molecular weight of about 170,000 Da, the amount in milk is likely to be very low. It is also likely to be partially destroyed in the infant's gastrointestinal tract and absorption by the infant is probably minimal. Waiting for at least 2 weeks postpartum to resume therapy may minimize transfer to the infant.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
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