Dosing & Uses
Dosage Forms & Strengths
injectable solution, single-dose vials
- 10mg/mL
- 20mg/mL
- 30mg/mL
X-Linked Hypophosphatemia
Indicated for X-linked hypophosphatemia (XLH), a rare inherited form of rickets
1 mg/kg SC q4Weeks; round dose to nearest 10 mg
Not to exceed 90 mg/dose
Tumor-induced Osteomalacia
Indicated for FGF23-related hypophosphatemia in tumor-induced osteomalacia (TIO) associated with phosphaturic mesenchymal tumors that cannot be curatively resected or localized
0.5 mg SC q4Weeks initially; may increase dose up to 2 mg/kg q2Weeks, not to exceed 180 mg/dose
Dosage Modifications
After treatment initiation, assess fasting serum phosphorus monthly, measured 2 weeks post dose, for the first 3 months of treatment, and thereafter as appropriate
If serum phosphorus is within the reference range, continue with the same dose
Dose decrease
- Reassess fasting serum phosphorus level 2 weeks after dose adjustment
- Do not adjust dose more frequently than q4Weeks
- If serum phosphorus is above the reference range, withhold the next dose and reassess the serum phosphorus level after 4 weeks
- Patient must have serum phosphorus below the reference range to be able to reinitiate drug
- Once serum phosphorus is below the reference range, treatment may be restarted at approximately half the initial starting dose (not to exceed 40 mg q4Weeks) according to the dose schedule listed in the prescribing information
- Reassess serum phosphorus 2 weeks after any change in dose
Renal impairment
- Effect of renal impairment on burosumab pharmacokinetics is unknown
- However, renal impairment can induce abnormal mineral metabolism which will increase phosphate concentrations greater than expected with burosumab; increase may result in hyperphosphatemia which can induce nephrocalcinosis
- CrCl 15-29 mL/min or end stage renal disease (CrCl <15 mL/min): Contraindicated
Dosing Considerations
Discontinue oral phosphate and active vitamin D analogs (eg, calcitriol, paricalcitol, doxercalciferol, calcifediol) 1 week before initiating treatment
Fasting serum phosphorus concentration should be below the reference range for age before treatment initiation
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 treatment
Dosage Forms & Strengths
injectable solution, single-dose vials
- 10mg/mL
- 20mg/mL
- 30mg/mL
X-Linked Hypophosphatemia
Indicated for X-linked hypophosphatemia (XLH), a rare inherited form of rickets, in adults and children aged ≥6 months
<6 months: Safety and efficacy not established
≥6 months
-
<10 kg
- 1 mg/kg SC q2Weeks; round dose to nearest 1 mg
-
≥10 kg
- 0.8 mg/kg SC q2Weeks; round dose to nearest 10 mg
- Minimum weight-based starting dose is 10 mg up to a maximum dose of 90 mg
Tumor-induced Osteomalacia
Indicated for FGF23-related hypophosphatemia in tumor-induced osteomalacia (TIO) associated with phosphaturic mesenchymal tumors that cannot be curatively resected or localized in adults and children aged >2 years
Aged 2 to <18 years
- Initial: 0.4 mg SC q2Weeks; round dose to nearest 10 mg
- May increase up to 2 mg/kg q2Weeks; not to exceed 180 mg/dose
- Do not adjust dose more frequently than q4Weeks
Dose decrease
- If serum phosphorus is above the reference range for age, withhold the next dose and reassess the serum phosphorus level in 4 weeks
- Serum phosphorus must be below the reference range for age to reinitiate
- Once serum phosphorus is below the reference range, may restart at ~50% of the initial starting dose, up to maximum dose of 180 mg q2Weeks
- After dose decrease, reassess serum phosphorus level 4 weeks after dose adjustment
- If level remains below reference range, reinitiate dose and adjust as previously described
Serum phosphorus monitoring
- After initiating, assess fasting serum phosphorus on a monthly basis, measured 2 weeks post-dose, for the first 3 months of treatment, and thereafter as appropriate
- Reassess fasting serum phosphorus level 4 weeks after dose adjustment
Dosage Modifications (X-Linked Hypophosphatemia)
Reassess fasting serum phosphorus level 4 weeks after dose adjustment
Do not adjust dose more frequently than q4Weeks
Dose increase
-
<10 kg
- If serum phosphorus is below the reference range for age, may increase dose to 1.5 mg/kg, rounded to the nearest 1 mg, administered q2Weeks
- If additional dose increases are needed, may increase to maximum of 2 mg/kg, rounded to the nearest 1 mg, administered q2Weeks
-
≥10 kg
- If serum phosphorus is below the reference range for age, may increase dose in stepwise method up to ~2 mg/kg, administered q2Weeks by 5- to 10-mg increments (see prescribing information)
- Not to exceed 90 mg/dose
Dose decrease
- If serum phosphorus is >5 mg/dL, withhold the next dose and reassess the serum phosphorus level in 4 weeks
- Reinitiate drug only when serum phosphorus is below the reference range for age to reinitiate drug
- Once serum phosphorus is below the reference range for age, restart treatment according to the reduced dose schedule described in the prescribing information
- Reassess serum phosphorus level 4 weeks after dose adjustment
- If the level remains below the reference range for age after the reinitiation dose, adjust dose according to initial dose instructions
-
<10 kg
- Restart at 0.5 mg/kg q2Weeks; round dose to nearest 1 mg
-
≥10 kg
- Previous dose of 10-mg: Restart at 5 mg
- Previous dose of 15-mg, 20-mg, or 30-mg: Restart at 10 mg
- Previous dose of 40-mg or 50-mg: Restart at 20 mg
- Previous dose of 60-mg or 70-mg: Restart at 30 mg
- Previous dose of 80-mg or 90-mg: Restart at 40 mg
Dosage Modifications (Other)
Renal impairment
- Effect of renal impairment on burosumab pharmacokinetics is unknown
- However, renal impairment can induce abnormal mineral metabolism which will increase phosphate concentrations greater than expected with burosumab; increase may result in hyperphosphatemia which can induce nephrocalcinosis
- eGFR 15-29 mL/min/1.73m2 or end stage renal disease (eGFR <15 mL/min/1.73m2): Contraindicated
Dosing Considerations
Discontinue oral phosphate and active vitamin D analogs (eg, calcitriol, paricalcitol, doxercalciferol, calcifediol) 1 week before initiating treatment
Fasting serum phosphorus concentration should be below the reference range for age before treatment initiation
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 treatment
Adverse Effects
>10% (Pediatric)
Headache (8-73%)
Injection site reaction (23-67%)
Vomiting (46-48%)
Pyrexia (44-62%)
Pain in extremity (23-46%)
Vitamin D decreased (15-37%)
Rash (8-27%)
Toothache (15-23%)
Hypersensitivity (22%)
Myalgia (8-17%)
Tooth abscess (15-23%)
Dizziness (15%)
>10% (Adults)
Back pain (15%)
Headache (13%)
Tooth infection (13%)
Restless legs syndrome (12%)
Vitamin D decreased (12%)
1-10% (Pediatric)
Injection site rash (6%)
Urticaria (5%)
1-10% (Adults)
Dizziness (10%)
Constipation (9%)
Blood phosphorus increased (6%)
Warnings
Contraindications
Coadministration with oral phosphate and active vitamin D analogs
Serum phosphorus within or above the reference range for age
Severe renal impairment or end-stage renal disease (these conditions associated with abnormal mineral metabolism)
Cautions
Hypersensitivity reactions (eg, rash, urticaria) reported; discontinue if serious hypersensitivity reactions occur and initiate appropriate medical treatment
Increases in serum phosphorus to >ULN may be associated with increased risk of nephrocalcinosis; for patients already taking burosumab and with tumor-induced osteomalacia who undergo treatment of underlying tumor should have dose interrupted or reduced based on serum phosphorus levels to prevent hyperphosphatemia
Local injection site reactions may occur; discontinue if severe injection site reactions occur and administer appropriate medical treatment
Pregnancy
Pregnancy
There are no available data on use in pregnant women to inform a drug-associated risk of adverse developmental outcomes
In utero, burosumab exposure in cynomolgus monkeys did not result in teratogenic effects; adverse effects (eg, late fetal loss, preterm birth) observed in pregnant cynomolgus monkeys; however, these effects are unlikely to indicate clinical risk because they occurred at a drug exposure that was 64-fold higher, by AUC, than the human exposure at 1 mg/kg q4Weeks and were accompanied in the non-XLH monkeys by maternal hyperphosphatemia and placental mineralization
Report pregnancies to the Ultragenyx Adverse Event reporting line at 1-888-756-8657
Lactation
There is no information regarding the presence of burosumab in human milk or the effects on milk production or the breastfed infant
Maternal IgG is present in breast milk; however, the effects of local GI exposure and limited systemic exposure to burosumab in the breastfed infant are unknown
Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for burosumab and any potential adverse effects on the breastfed infant from burosumab or from the underlying maternal condition
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Recombinant fully human monoclonal IgG1 antibody against the phosphaturic hormone, fibroblast growth factor 23 (FGF23)
X-linked hypophosphatemia is a bone disease characterized by phosphate-wasting due to excess activity of FGF23; excess FGF23 suppresses renal tubular phosphate reabsorption and renal production of 1,25 dihydroxy vitamin D
Burosumab binds to and inhibits the biological activity of FGF23, restoring renal phosphate reabsorption and increasing the serum concentration of 1,25 dihydroxy vitamin D
Absorption
Steady-state trough: 5.8 mcg/mL
Peak plasma time: 8-11 days
Distribution
Vd: 8 L
Metabolism
Exact metabolic pathway has not been characterized; expected to degrade into small peptides and amino acids via catabolic pathways
Elimination
Half-life: ~19 days
Clearance: 0.290 L/day
Administration
SC Preparation
Visually inspect solution for particulate matter and discoloration before administration
Burosumab 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
SC Administration
Rotate SC injection sites to a different anatomic location from the previous injection (eg, upper arms, upper thighs, buttocks, any abdominal quadrant)
Do not inject into moles, scars, or areas where the skin is tender, bruised, red, hard, or not intact
Not to exceed 1.5 mL per injection site; if >1.5 mL required on a given dosing day, divide the total volume and split administration between different injection sites
Monitor for signs of reactions
Missed dose
- Resume burosumab 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
Storage
Refrigerate at 36-46°F (2-8°C)
Store vial in original carton until the time of use; protect from light until time of use
Do not freeze or shake
Images
| BRAND | FORM. | UNIT PRICE | PILL IMAGE |
|---|---|---|---|
| Crysvita subcutaneous - | 30 mg/mL vial |  | |
| Crysvita subcutaneous - | 20 mg/mL vial |  | |
| Crysvita subcutaneous - | 10 mg/mL vial |  |
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Formulary
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