burosumab (Rx)

Brand and Other Names:Crysvita, burosumab-twza
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Dosing & Uses

AdultPediatric

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

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
  • eGFR <29 mL/min/1.73m2 or end stage renal disease: Contraindicated

Dosing Considerations

Discontinue oral phosphate and active vitamin D analogs 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

Dosage Modifications

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

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 <29 mL/min/1.73m2 or end stage renal disease: Contraindicated

Dosing Considerations

Discontinue oral phosphate and active vitamin D analogs 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
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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%)

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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, dose interruption and/or dose reduction may be required based serum phosphorus levels

Local injection site reactions may occur; discontinue if severe injection site reactions occur and administer appropriate medical treatment

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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.

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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

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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

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Formulary

FormularyPatient Discounts

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The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

Tier Description
1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
NC NOT COVERED – Drugs that are not covered by the plan.
Code Definition
PA Prior Authorization
Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
QL Quantity Limits
Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
ST Step Therapy
Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
OR Other Restrictions
Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.