burosumab

General

Trade Name(s)

  • Crysvita

Ther. Class.
none assigned

Pharm. Class.
monoclonal antibodies

Indications

X-linked hypophosphatemia.

Action

Binds to and inhibits the activity of fibroblast growth factor 23 (FGF23). Excess levels of FGF23 are present in X-linked hypophosphatemia which leads to inhibition of the reabsorption of phosphate by the renal tubules and the production of 1,25 dihydroxy vitamin D by the kidneys.

Therapeutic Effect(s):

Increased serum phosphorus and 1,25 dihydroxy vitamin D concentrations.

Pharmacokinetics

Absorption: Extent of absorption following subcutaneous injection unknown.

Distribution: Well distributed to tissues.

Metabolism and Excretion: Broken down by catabolic processes into peptides and amino acids.

Half-life: 19 days.

TIME/ACTION PROFILE (plasma concentrations)

ROUTEONSETPEAKDURATION
Subcutunknown8–11 days14 days

Contraindication/Precautions

Contraindicated in:

  • Hypersensitivity
  • Concurrent use with oral phosphate and active vitamin D analogs;
  • Serum phosphorus concentrations within or above the normal range for age;
  • Severe renal impairment or end-stage renal disease.

Use Cautiously in:

  • Geri: Choose dose carefully, considering concurrent disease states, drug therapy, and age-related ↓ in hepatic and renal function;
  • OB: Use only if potential maternal benefit justifies potential risk to fetus;
  • Lactation: Use only if potential maternal benefit justifies potential risk to infant
  • Pedi: Children <1 yr (safety and effectiveness not established).

Adverse Reactions/Side Effects

CNS: dizziness, headache

Derm: rash

Endo: ↓ vitamin D concentrations

F and E: hyperphosphatemia

GI: toothache, tooth abscess, vomiting, constipation

GU: nephrocalcinosis

Local: injection site reactions

MS: musculoskeletal pain, restless leg syndrome

Misc: hypersensitivity reactions (rash, urticaria), fever

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

None known.

Route/Dosage

SC (Adults) 1 mg/kg (rounded up to nearest 10 mg) every 4 wk (min dose = 10 mg; max dose = 90 mg). Adjust dose based on fasting serum phosphorus concentrations (not to be adjusted more frequently than every 4 wk).

SC (Children ≥1 yr) 0.8 mg/kg (rounded up to nearest 10 mg) every 2 wk (max dose = 90 mg). Adjust dose based on fasting serum phosphorus concentrations (not to be adjusted more frequently than every 4 wk).

Availability

Solution for subcutaneous injection: 10 mg/mL, 20 mg/mL, 30 mg/mL

Assessment

  • Monitor for signs of injection site reactions (injection site urticaria, erythema, rash, swelling, bruising, pain, pruritus, hematoma). Reactions are usually mild in severity, occur within 1 day of injection, last 1–3 days and rarely require treatment.
  • Monitor for signs and symptoms of hypersensitivity reactions (rash, injection site rash, urticaria) during therapy.

Lab Test Considerations:

Adults: Monitor fasting serum phosphorus monthly, measured 2 weeks post-dose, for 1st 3 mo of therapy, and after as needed. If serum phosphorus is within normal range, continue with same dose. Reassess fasting serum phosphorus level 2 weeks after dose adjustment. Do not adjust more frequently than every 4 wks. If serum phosphorus is >normal range, withhold next dose and reassess serum phosphorus level after 4 wks. Serum phosphorus must be <normal range to restart therapy. Once serum phosphorus is <normal range, therapy may be restarted at approximately half the initial starting dose up to a maximum dose of 40 mg every 4 wks according to manufacturer's guidelines. Reassess serum phosphorus 2 wks after any change in dose.

  • Children: Monitor fasting serum phosphorus every 4 wks for 1st 3 mo of therapy, and after as needed. If serum phosphorus is >lower limit of reference range for age and below 5 mg/dL, continue with same dose. If serum phosphorus is <reference range for age, dose may be ↑ stepwise up to 2 mg/kg, every 2 wks (maximum dose of 90 mg) to maintain serum phosphorous level. If serum phosphorus is >5 mg/dL, withhold next dose and reassess serum phosphorus level in 4 wks. Serum phosphorus must below the reference range for age to restart therapy; base dose on manufacturer's guidelines. Reassess serum phosphorus level 4 wks after dose adjustment. If level remains below reference range for age after restarting therapy, dose can be adjusted based on manufacturer's guidelines.

Potential Diagnoses

Implementation

  • Injection should be administered a health care professional.
    • Discontinue oral phosphate and active vitamin D analogs 1 wk prior to starting therapy. Fasting serum phosphorus concentration should be below reference range for age prior to starting therapy.
  • SC Rotate sites with each injection (upper arms, upper thighs, buttocks, or any quadrant of abdomen). Do not inject into moles, scars, or areas where the skin is tender, bruised, red, hard, or not intact. The maximum volume per injection site is 1.5 mL. If more than 1.5 mL is required, divide total volume and administer at 2 different injection sites. Solution is clear to slightly opalescent and colorless to pale brown-yellow; do not administer solutions that are discolored, cloudy or contain particulate matter.
    • If a dose is missed, resume as soon as possible at prescribed dose.

Patient/Family Teaching

  • Explain purpose of injections to patient and family.
  • Advise patient to notify health care professional if signs and symptoms of hypersensitivity or injection site reactions occur.
  • Advise female patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Serum phosphorus levels should be monitored throughout pregnancy.

Evaluation/Desired Outcomes

Increased serum phosphorus and 1,25 dihydroxy vitamin D concentrations.

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