Skip to Content

Burosumab

Medically reviewed by Drugs.com. Last updated on Aug 19, 2020.

Pronunciation

(bur oh SUE mab)

Index Terms

  • Burosumab-twza

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Subcutaneous [preservative free]:

Crysvita: burosumab-twza 10 mg/mL (1 mL); burosumab-twza 20 mg/mL (1 mL); burosumab-twza 30 mg/mL (1 mL) [contains polysorbate 80]

Brand Names: U.S.

  • Crysvita

Pharmacologic Category

  • Anti-FGF23 Monoclonal Antibody
  • Antineoplastic Agent, Monoclonal Antibody
  • Monoclonal Antibody

Pharmacology

Burosumab binds to and inhibits the activity of fibroblast growth factor 23, thereby restoring renal phosphate reabsorption and increasing the serum concentration of 1,25 dihydroxy vitamin D.

Distribution

Vd: 8 L

Metabolism

Degraded into small peptides and amino acids via catabolic pathways

Time to Peak

8 to 11 days

Half-Life Elimination

~19 days

Special Populations Note

Body weight: Clearance and volume of distribution of burosumab increases with body weight.

Use: Labeled Indications

Osteomalacia, tumor-induced: Treatment of fibroblast growth factor 23 (FGF23)-related hypophosphatemia in tumor-induced osteomalacia associated with phosphaturic mesenchymal tumors that cannot be curatively resected or localized in pediatric patients ≥2 years of age and adults.

X-linked hypophosphatemia: Treatment of X-linked hypophosphatemia in pediatric patients ≥6 months of age and adults.

Contraindications

Concomitant use with oral phosphate and/or active vitamin D analogs (eg, calcitriol, paricalcitol, doxercalciferol, calcifediol); serum phosphorus within or above normal range for age; severe renal impairment or end-stage renal disease.

Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to burosumab or any component of the formulation.

Dosing: Adult

Note: Prior to initiating burosumab, oral phosphate and/or active vitamin D analogs (eg, calcitriol, paricalcitol, doxercalciferol, calcifediol) should be discontinued for at least 1 week; do not administer active vitamin D analogs during burosumab treatment. Confirm baseline fasting serum phosphorus level is below the reference range for patient age before initiating burosumab. Monitor serum 25-hydroxy vitamin D levels; if necessary, supplement with cholecalciferol or ergocalciferol to maintain levels in the normal range for age.

Hypophosphatemia, X-linked: SubQ: Initial: 1 mg/kg every 4 weeks; calculated dose should be rounded to the nearest 10 mg; maximum dose: 90 mg.

Dosage adjustment based on serum phosphorus: Evaluate fasting serum phosphorus 2 weeks after treatment initiation and continue every 4 weeks for the first 12 weeks of therapy. Adjust dose accordingly based on fasting serum phosphorus level; see Reference Range for phosphorus age-based normal limits. Do not adjust dose more frequently than every 4 weeks.

If low serum phosphorus: There are no dosage adjustments provided in the manufacturer's labeling.

If normal serum phosphorus: Continue same dose.

If high serum phosphorus:

If fasting serum phosphorus above the normal age-based range, withhold next dose and reassess in 4 weeks; once serum phosphorus falls below the age-based normal range, may reinitiate burosumab at approximately one-half the initial starting dose up to a maximum dose of 40 mg every 4 weeks:

Burosumab Reinitiation Dosing

Previous dose (mg/dose) every 4 weeks

Reinitiation dosea (mg/dose) every 4 weeks

aRecheck fasting serum phosphorus 2 weeks after dose adjustment; based on results, determine if additional dosing adjustment necessary.

40

20

50

20

60

30

70

30

≥80

40

Osteomalacia, tumor-induced: SubQ: Initial: 0.5 mg/kg once every 4 weeks; round dose to the nearest 10 mg; maximum dose: 2 mg/kg (not to exceed 180 mg) every 2 weeks.

Dosage adjustment based on serum phosphorus: Evaluate fasting serum phosphorus monthly, measured 2 weeks postdose, for the first 3 months of treatment and as clinically necessary thereafter. Adjust dose accordingly based on fasting serum phosphorus level; see "Reference Range" for phosphorus age-based normal limits. Reassess fasting serum phosphorus level 2 weeks after dose adjustment; do not adjust dose more frequently than every 4 weeks.

If serum phosphorus is normal: Continue the same burosumab dose.

If serum phosphorus is above the normal range: Withhold the next burosumab dose and reassess serum phosphorus in 4 weeks; the serum phosphorus level must be below the reference range to reinitiate burosumab. Reinitiate at approximately one-half of the initial starting dose (up to a maximum of 180 mg every 2 weeks). Reassess serum phosphorus 2 weeks after the dose adjustment. If the level remains below the reference range, the dose can be adjusted upward (see table: "Burosumab Dose Increase Levels for Tumor-Induced Osteomalacia").

If serum phosphorus is below the normal range: Titrate burosumab dose as follows:

Burosumab Dose Increase Levels For Tumor-Induced Osteomalaciaa,b

Starting dose

First dose increasec

Second dose increasec

Third dose increasec

Fourth dose increase

Fifth dose increase (maximum dose)

aRound dose to the nearest 10 mg.

bDo not adjust burosumab dose more frequently than every 4 weeks.

cIf serum phosphorus is less than the lower limit of the normal range, may consider dividing total dose administered every 4 weeks and administering every 2 weeks.

dIf the calculated dose is >180 mg every 4 weeks, change to a divided dose administered every 2 weeks.

If serum phosphorus is below lower limit of normal 2 weeks postdose adjustment

0.5 mg/kg every 4 weeks

Increase to:

1 mg/kg every 4 weeks

Or

0.5 mg/kg every 2 weeks

Increase to:

1.5 mg/kg every 4 weeksd

Or

0.75 mg/kg every 2 weeks

Increase to:

2 mg/kg every 4 weeksd

Or

1 mg/kg every 2 weeks

Increase to:

1.5 mg/kg (not to exceed 180 mg) every 2 weeks

Increase to:

2 mg/kg (not to exceed 180 mg) every 2 weeks

Dose interruption: Interrupt burosumab therapy if undergoing treatment (eg, surgical excision, radiation therapy) of the underlying tumor; reassess serum phosphorus after underlying tumor treatment is complete. If serum phosphorus remains below the lower limit of normal, reinitiate burosumab at the initiation dose and then adjust as necessary to maintain serum phosphorus within the reference range (see table: "Burosumab Dose Increase Levels for Tumor-Induced Osteomalacia").

Missed dose: If a dose is missed, administer as soon as possible. To avoid missed doses, treatments may be administered 3 days on either side of the scheduled treatment date.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Prior to initiating burosumab, oral phosphates and/or active vitamin D analogs (eg, calcitriol) should be discontinued for at least 1 week. Confirm that baseline fasting serum phosphorus concentration is below the reference range for patient age before initiating burosumab. During burosumab therapy, patients should have 25-hydroxy vitamin D levels monitored; supplement as necessary with cholecalciferol or ergocalciferol to maintain serum 25-hydroxy vitamin D levels in the normal range for age. Dose and interval are age-dependent; use extra precaution.

Hypophosphatemia, X-linked (XLH):

Initial:

Infants ≥6 months, Children, and Adolescents <18 years:

Weight <10 kg: SubQ: 1 mg/kg/dose every 2 weeks; calculated dose should be rounded to the nearest 1 mg.

Weight ≥10 kg: SubQ: 0.8 mg/kg/dose every 2 weeks; minimum dose: 10 mg/dose; calculated dose should be rounded to the nearest 10 mg; maximum dose: 90 mg/dose.

Adolescents ≥18 years: SubQ: 1 mg/kg/dose every 4 weeks; calculated dose should be rounded to the nearest 10 mg; maximum dose: 90 mg/dose.

Monitoring of therapy: Evaluate fasting serum phosphorus every 4 weeks for first 12 weeks of therapy and as appropriate thereafter (eg, after dosing adjustments). Adjust dose accordingly based on fasting serum phosphorus level; see "Reference Range" for phosphorus age-based normal limits.

Dosing adjustment based on serum phosphorus:

If low serum phosphorus:

Infants ≥6 months, Children, and Adolescents <18 years: SubQ:

Weight <10 kg: If serum phosphorus below the reference range for age, increase dose to 1.5 mg/kg/dose every 2 weeks, rounded to the nearest 1 mg. Recheck fasting serum phosphorus 4 weeks after dose adjustment; burosumab should not be adjusted more frequently than every 4 weeks. If needed, dose may be further increased to the maximum dose of 2 mg/kg/dose.

Weight ≥10 kg: If serum phosphorus below the reference range for age, increase dose stepwise based on the following table. Recheck fasting serum phosphorus 4 weeks after dose adjustment; burosumab should not be adjusted more frequently than every 4 weeks. Maximum dose: 2 mg/kg/dose, not to exceed 90 mg/dose.

Weight-Band Dosing for Weight ≥10 kg, Age <18 Years: Fixed DosingA IncreasesB for XLH

Weight-band (kg)

Initial dose (mg/dose) every 2 weeks

1st dose increase to mg/dose every 2 weeks

2nd dose increase to mg/dose every 2 weeks

A Presented doses already rounded

B In trials, dose titration for every-2-week dosing was 0.2 mg/kg or 0.3 mg/kg (Carpenter 2018).

10 to <15

10

15

20

15 to <19

10

20

30

19 to <32

20

30

40

32 to <44

30

40

60

44 to <57

40

60

80

57 to <69

50

70

90

69 to <81

60

90

90

81 to <94

70

90

90

94 to <106

80

90

90

≥106

90

90

90

Adolescents ≥18 years: There are no dosage adjustments provided in the manufacturer's labeling for low serum phosphorus.

If normal serum phosphorus (ie, above the lower limit of reference range for age) and <5 mg/dL: Infants ≥6 months, Children, and Adolescents: Continue current dose; continue to monitor serum phosphorus as appropriate.

If high serum phosphorus:

Infants ≥6 months, Children, and Adolescents <18 years: If serum phosphorus >5 mg/dL: Hold next dose; reassess fasting serum phosphorus in 4 weeks and every 4 weeks thereafter; once serum phosphorus below reference range for age, may reinitiate burosumab at a reduced dose (see the following weight-directed re-initiation recommendations).

Re-initiation dosing: SubQ:

Patient weight <10 kg: Restart at 0.5 mg/kg/dose every 2 weeks; round dose to the nearest 1 mg. Recheck fasting serum phosphorus in 4 weeks and follow dosing adjustment recommendations based on result.

Patient weight ≥10 kg: See the following table. Recheck fasting serum phosphorus in 4 weeks and follow dosing adjustment recommendations based on result.

Re-Initiation Dosing for Weight ≥10 kg, Age <18 Years: Fixed Dosing for XLH

Previous dose (mg/dose) every 2 weeks

Re-initiation dose (mg/dose) every 2 weeks

10

5

15

10

20

10

30

10

40

20

50

20

60

30

70

30

80

40

90

40

Adolescents ≥18 years: If serum phosphorus above normal range: Hold next dose; reassess fasting serum phosphorus every 4 weeks; once serum phosphorus falls below the normal range, may reinitiate burosumab at a reduced dose (approximately half the initial starting dose; see the following table [maximum dose: 40 mg/dose]). Recheck fasting serum phosphorus 2 weeks after dose adjustment; based on results, determine if additional dosing adjustment necessary.

Re-Initiation Dosing: Age ≥18 Years for XLH

Previous dose (mg/dose) every 4 weeks

Re-initiation dose (mg/dose) every 4 weeks

40

20

50

20

60

30

70

30

≥80

40

Osteomalacia, tumor-induced (TIO):

Initial:

Children ≥2 years and Adolescents <18 years: SubQ: 0.4 mg/kg/dose every 2 weeks; calculated dose should be rounded to the nearest 10 mg; maximum dose: 180 mg/dose.

Adolescents ≥18 years: SubQ: 0.5 mg/kg/dose every 4 weeks; calculated dose should be rounded to the nearest 10 mg; maximum dose: 180 mg/dose.

Monitoring of therapy: During the first 12 weeks of therapy, evaluate fasting serum phosphorus 2 weeks postdose and monthly thereafter or more frequently as appropriate (eg, after dosing adjustments). Adjust dose accordingly based on fasting serum phosphorus level; see "Reference Range" for phosphorus age-based normal limits. Do not adjust more frequently than every 4 weeks.

Dosing adjustment based on serum phosphorus:

If low serum phosphorus:

Children ≥2 years and Adolescents <18 years: SubQ: If serum phosphorus below the reference range for age, increase dose stepwise based on the following table. Recheck fasting serum phosphorus 4 weeks after dose adjustment; burosumab should not be adjusted more frequently than every 4 weeks. The following table addresses dose titration only up to 1.5 mg/kg/dose; further increases up to 2 mg/kg/dose may be used; maximum dose: 2 mg/kg/dose, not to exceed 180 mg/dose.

Weight-Band Dosing for Age <18 Years: Fixed DosingA Increases for TIO

Weight-band (kg)

Initial dose (mg/dose) every 2 weeks

1st dose increase to mg/dose every 2 weeks

2nd dose increase to mg/dose every 2 weeks

3rd dose increase to mg/dose every 2 weeks

ATable only includes dose titration only up to 1.5 mg/kg/dose; further increases up to 2 mg/kg/dose may be used.

10 to <15

5

10

15

20

15 to <19

5

10

20

25

19 to <32

10

20

25

30

32 to <44

10

30

40

50

44 to <57

20

40

50

70

57 to <69

20

50

70

90

69 to <81

30

60

80

100

81 to <94

30

70

100

120

94 to <106

40

80

110

140

≥106

40

90

130

160

Adolescents ≥18 years: SubQ: If serum phosphorus below the reference range for age, may increase monthly dose stepwise (see following table) or administer same dose divided every 2 weeks. Burosumab dose should not be adjusted more frequently than every 4 weeks. Maximum dose: 2 mg/kg/dose, not to exceed 180 mg/dose. Recheck fasting serum phosphorus 2 weeks after dose adjustment; burosumab should not be adjusted more frequently than every 4 weeks.

Weight-Based Dosing IncreasesA, B for Age ≥18 years for TIO

Initial dose

1st dose increase

2nd dose increase

3rd dose increase

4th dose increase

5th dose increase

ARound dose to the nearest 10 mg.

BIf the calculated dose is >180 mg every 4 weeks, change to a divided dose administered every 2 weeks. Maximum single dose: 180 mg/dose.

0.5 mg/kg every 4 weeks

1 mg/kg/dose every 4 weeks

OR

0.5 mg/kg/dose every 2 weeks

1.5 mg/kg/dose every 4 weeks

OR

0.75 mg/kg/dose every 2 weeks

2 mg/kg/dose every 4 weeks

OR

1 mg/kg every 2 weeks

1.5 mg/kg/dose every 2 weeks

2 mg/kg/dose every 2 weeks

If normal serum phosphorus:

Children ≥2 years and Adolescents: SubQ: If serum phosphorus within reference range for age, continue current dose; continue to monitor serum phosphorus as appropriate.

If high serum phosphorus:

Children ≥2 years and Adolescents: SubQ: If serum phosphorus above normal reference range for age: hold next dose; reassess fasting serum phosphorus every 4 weeks; once serum phosphorus falls below the reference range for age, may reinitiate burosumab at a reduced dose of approximately half the initial starting dose for age and weight; maximum dose: 180 mg/dose every 2 weeks. Recheck fasting serum phosphorus 4 weeks (if <18 years of age) and 2 weeks (if ≥18 years of age) after dose adjustment; based on results, determine if additional dosing adjustment necessary.

Dose interruption: Children ≥2 years and Adolescents: If underlying tumor is treated (eg, surgical excision or radiation therapy); hold burosumab doses during treatment; after treatment completed, reassess serum phosphorus; if is below the lower limit of normal for age restart burosumab at the original initiation dose for the patient.

Administration

SubQ: Administer SubQ into the upper thighs, any quadrant of abdomen, buttocks, or upper arms. Contents from 2 vials may be combined; however, the maximum volume per injection site is 1.5 mL. Administer each injection at a different anatomic location than a previous injection. Avoid areas where the skin is tender, bruised, red, hard, or not intact, or where there are scars or moles.

Storage

Store at 36°F to 46°F (2°C to 8°C) in the original carton; do not freeze. Protect from light. Do not shake.

Drug Interactions

Phosphate Supplements: May enhance the adverse/toxic effect of Burosumab. Exceptions: Sodium Glycerophosphate Pentahydrate. Avoid combination

Vitamin D Analogs: May enhance the adverse/toxic effect of Burosumab. Exceptions: Calcipotriene; Cholecalciferol; Ergocalciferol. Avoid combination

Adverse Reactions

>10%:

Dermatologic: Eczema (adults: 11%), skin rash (10% to 27%)

Endocrine & metabolic: Vitamin D deficiency (children: 24% to 37%; adults: 7% to 12%)

Gastrointestinal: Constipation (9% to 17%), dental caries (children: 31%), diarrhea (children: 24%), toothache (children: 23%), tooth infection (adults: 13%), vomiting (children: 41% to 48%)

Immunologic: Antibody development (14% to 19%)

Infection: Tooth abscess (15% to 34%)

Local: Injection site reaction (children: 52% to 67%; adults: 15%)

Nervous system: Dizziness (10% to 15%), headache (children: 34% to 73%; adults: 11% to 13%), restless leg syndrome (adults: 7% to 12%)

Neuromuscular & skeletal: Back pain (adults: 15%), limb pain (children: 38% to 46%), muscle spasm (adults: 7% to 19%), myalgia (children: 17%)

Respiratory: Cough (children: 52%)

Miscellaneous: Fever (children: 44% to 55%)

1% to 10%:

Dermatologic: Rash at injection site (children: 10%), urticaria at injection site (children: 7%)

Endocrine & metabolic: Hyperphosphatemia (adults: ≤7%)

Gastrointestinal: Nausea (children: 10%)

Hypersensitivity: Hypersensitivity reaction (adults: 6% to 22%)

Warnings/Precautions

Concerns related to adverse effects:

• Hyperphosphatemia: Elevated serum phosphorus may increase the risk of nephrocalcinosis; dose reduction or interruption of therapy may be required. To prevent hyperphosphatemia, interrupt burosumab therapy in patients with tumor-induced osteomalacia receiving treatment for the underlying tumor. Reassess serum phosphorus after underlying tumor-related treatment has been completed; reinitiate and adjust burosumab dose as clinically necessary.

• Hypersensitivity: May cause hypersensitivity reactions (eg, rash, urticaria). Discontinue therapy immediately if serious hypersensitivity reactions occur.

• Injection site reactions: Local injection site reactions may occur. Most reactions are mild in severity, occur within 1 day of injection, and typically resolve within 1 to 3 days with no treatment. Discontinue use if severe injection site reactions occur.

Disease-related concerns:

• Restless leg syndrome: New onset or worsening of existing restless leg syndrome has been reported in adults.

Dosage form specific issues:

• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.

Other warnings/precautions:

• Vitamin D: May decrease serum vitamin D. Monitor serum 25(OH)D levels; supplement with cholecalciferol or ergocalciferol to maintain age-based normal range. Do NOT administer active vitamin D analogs during burosumab treatment.

Monitoring Parameters

Signs/symptoms of hypersensitivity or injection-site reaction; serum 25-hydroxyvitamin D (25(OH)D) levels.

Serum phosphorus:

Children and adolescents: Evaluate fasting serum phosphorus every 4 weeks for first 12 weeks of therapy and as appropriate thereafter (eg, after dosing adjustments).

Adults: Evaluate fasting serum phosphorus every 4 weeks, measured 2 weeks postdose, for the first 12 weeks of treatment, after any underlying tumor-related treatment (in tumor-induced osteomalacia), and as appropriate thereafter (eg, after dosing adjustments).

Pregnancy Considerations

Burosumab is a human IgG monoclonal antibody and may be transferred across the placenta. Maternal serum phosphorus concentrations should be monitored.

Health care providers are encouraged to report exposures of burosumab during pregnancy to the manufacturer Adverse Event reporting line (888-756-8657).

Patient Education

What is this drug used for?

• It is used to treat low phosphate levels.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Headache

• Vomiting

• Painful extremities

• Tooth pain

• Muscle pain

• Dizziness

• Constipation

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Kidney stone like back pain, abdominal pain, or blood in the urine

• Severe injection site irritation

• Restless legs

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Related questions