Burosumab

What is Burosumab?

• Burosumab (Crysvita) is a fibroblast growth factor 23 (FGF23) blocking antibody used for the X-linked hypophosphatemia (XLH).

Hcp-0.0-CRYSVITA-antibody rotating 03

What are the uses of this medicine?

This medicine is used for:

• The treatment of X-linked hypophosphatemia (XLH) in adult and pediatric patients 6 months of age and older.
• The treatment of FGF23-related hypophosphatemia in tumor-induced osteomalacia (TIO) associated with phosphaturic mesenchymal tumors that cannot be curatively resected or localized in adult and pediatric patients 2 years of age and older.

How does this medicine work?

• X-linked hypophosphatemia is caused by excess fibroblast growth factor 23 (FGF23) which suppresses renal tubular phosphate reabsorption and the renal production of 1,25 dihydroxy vitamin D.
• Burosumab-twza binds to and inhibits the biological activity of FGF23 restoring renal phosphate reabsorption and increasing the serum concentration of 1,25 dihydroxy vitamin D.

Who Should Not Use this medicine ?

This medicine cannot be used in patients with:

• concomitant use with oral phosphate and/or active vitamin D analogs (e.g. calcitriol, paricalcitol, doxercalciferol, calcifediol) due to the risk of hyperphosphatemia.
• serum phosphorus is within or above the normal range for age.
• severe renal impairment or end stage renal disease because these conditions are associated with abnormal mineral metabolism.

What drug interactions can this medicine cause?

• Avoid co-administration 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.

Is this medicine FDA approved?

• It was approved for use in the United States in 2018.

How should this medicine be used?

• Discontinue oral phosphate and/or active vitamin D analogs (e.g. calcitriol, paricalcitol, doxercalciferol, calcifediol) 1 week prior to initiation of treatment.
• serum phosphorus concentration should be below the reference range for age prior to initiation of treatment.

Recommended Dosage Pediatric Patients with X-linked Hypophosphatemia (6 months to less than 18 years of age):

• For patients who weigh less than 10 kg, starting dose regimen is 1 mg/kg of body weight rounded to the nearest 1 mg, administered every two weeks.
• For patients who weigh 10 kg and greater, starting dose regimen is 0.8 mg/kg of body weight rounded to the nearest 10 mg, administered every two weeks. The minimum starting dose is 10 mg up to a maximum dose of 90 mg.
• Dose may be increased up to approximately 2 mg/kg (maximum 90 mg), administered every two weeks to achieve normal serum phosphorus.

Adult Patients with X-linked Hypophosphatemia (18 years of age and older):

• Dose regimen is 1 mg/kg body weight rounded to the nearest 10 mg up to a maximum dose of 90 mg administered every four weeks.

Pediatric Patients with Tumor-induced Osteomalacia (2 years to less than 18 years of age):

• Starting dose is 0.4 mg/kg of body weight rounded to the nearest 10 mg every 2 weeks.
• Dose may be increased up to 2 mg/kg not to exceed 180 mg, administered every two weeks.

Adult Patients with Tumor-induced Osteomalacia (18 years of age and older):

• Starting dose is 0.5 mg/kg every four weeks.
• Dose may be increased up to 2 mg/kg not to exceed 180 mg, administered every two weeks.

Administration

• Crysvita is administered by subcutaneous injection and should be administered by a healthcare provider.
• The maximum volume of Crysvita per injection is 1.5 mL. If multiple injections are required, administer at different injection sites.
• 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.
• 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.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Injection: 10 mg/mL, 20 mg/mL, or 30 mg/mL in a single-dose vial

This medicine is available in fallowing brand namesː

• Crysvita

What side effects can this medication cause?

The most common side effects of this medicine include: pediatric XLH:

• pyrexia
• injection site reaction
• cough
• vomiting
• pain in extremity
• headache
• tooth abscess
• dental caries

Adult XLH:

• back pain
• headache
• tooth infection
• restless legs syndrome
• vitamin D decreased
• dizziness
• constipation
• muscle spasms
• blood phosphorus increased

In Tumor-induced osteomalacia (TIO):

• tooth abscess
• muscle spasms
• dizziness
• constipation
• injection site reaction
• rash
• headache

What special precautions should I follow?

• Discontinue Crysvita if serious hypersensitivity reactions occur and initiate appropriate medical treatment.
• Increases in serum phosphorus to above the upper limit of normal may be associated with an increased risk of nephrocalcinosis. For patients already taking Crysvita, dose interruption and/or dose reduction may be required based on a patient's serum phosphorus levels.
• Administration of Crysvita may result in local injection site reactions. Discontinue Crysvita if severe injection site reactions occur and administer appropriate medical treatment.

What to do in case of emergency/overdose?

• There have been no reports of overdose with Crysvita.

Management of overdosage:

• In case of overdose, it is recommended that serum phosphorus levels, serum calcium levels and renal function be measured immediately and monitored periodically until resolution to normal/baseline levels.
• In case of hyperphosphatemia, withhold Crysvita and initiate appropriate medical treatment.

Can this medicine be used in pregnancy?

• There are no available data on Crysvita use in pregnant women to inform a drug-associated risk of adverse developmental outcomes.

Can this medicine be used in children?

• Safety and effectiveness of Crysvita have been established in pediatric patients 6 months and older.
• Safety and effectiveness for Crysvita in pediatric patients with XLH below the age of 6 months have not been established.
• Safety and effectiveness for Crysvita in pediatric patients with TIO below the age of 2 years have not been established.

What are the active and inactive ingredients in this medicine?

Active ingredient:

• burosumab

Inactive ingredients:

• sorbitol
• histidine
• methionine
• polysorbate 80
• water
• hydrochloric acid

Who manufactures and distributes this medicine?

Manufactured by: Kyowa Kirin, Inc. Bedminster, NJ 07921 U.S. License No. 2077

Distributed by: Ultragenyx Pharmaceutical Inc. Novato, CA 94949 USA

What should I know about storage and disposal of this medication?

• Crysvita vials must be stored in the original carton until the time of use under refrigerated conditions at 36°F to 46°F (2°C to 8°C). Keep Crysvita vial in the original carton to protect from light until time of use.
• Do not freeze or shake Crysvita.
• Do not use Crysvita beyond the expiration date stamped on the carton.
• Crysvita vials are single-dose only.
• Discard any unused product.

• Dailymed label info on Burosumab
• FDA Burosumab

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