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Burosumab-twza

Medically reviewed on August 12, 2018

Pronunciation

(bur oh SUE mab twza)

Dosage Forms

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

Solution, Subcutaneous [preservative free]:

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

Brand Names: U.S.

  • Crysvita

Pharmacologic Category

  • Anti-FGF23 Monoclonal Antibody

Pharmacology

Binds to and inhibits the activity of fibroblast growth factor 23 (FGF23), 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-twza increases with body weight.

Use: Labeled Indications

X-linked hypophosphatemia: Treatment of X-linked hypophosphatemia (XLH) in children ≥1 year of age and adults

Contraindications

Concomitant use of oral phosphate and active vitamin D analogs; serum phosphorus within or above normal range for age; severe renal impairment or end-stage renal disease

Dosing: Adult

Note: Prior to initiating burosumab-twza, oral phosphate and active vitamin D analogs should be discontinued for at least 1 week. Confirm baseline fasting serum phosphorus level is below the reference range for patient age before initiating burosumab-twza.

Hypophosphatemia, X-linked (XLH): 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 phosphorous 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 phosphorous:

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 re-initiate burosumab-twza at approximately one-half the initial starting dose up to a maximum dose of 40 mg every 4 weeks:

Re-Initiation Dosing

Previous Dose (mg/dose) every 4 weeks

Re-Initiation 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

Table has been converted to the following text:

Previous dose: 40 mg/dose every 4 weeks; Re-initiation dose: 20 mg/dose every 4 weeks

Previous dose: 50 mg/dose every 4 weeks; Re-initiation dose: 20 mg/dose every 4 weeks

Previous dose: 60 mg/dose every 4 weeks; Re-initiation dose: 30 mg/dose every 4 weeks

Previous dose: 70 mg/dose every 4 weeks; Re-initiation dose: 30 mg/dose every 4 weeks

Previous dose: ≥80 mg/dose every 4 weeks; Re-initiation dose: 40 mg/dose every 4 weeks

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Prior to initiating burosumab-twza, oral phosphate and active vitamin D analogs should be discontinued for at least 1 week. Confirm baseline fasting serum phosphorus level is below the reference range for patient age before initiating burosumab-twza.

Hypophosphatemia, X-linked (XLH):

Initial: Children and Adolescents ≤17 years: 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.

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 phosphorous:

Children and Adolescents ≤17 years: 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-twza 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: Fixed Dosinga Increases

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

aPresented doses already rounded

10 to 14

10

15

20

15 to 18

10

20

30

19 to 31

20

30

40

32 to 43

30

40

60

44 to 56

40

60

80

57 to 68

50

70

90

69 to 80

60

90

90

81 to 93

70

90

90

94 to 105

80

90

90

≥106

90

90

90

Table has been converted to the following text: Note: Presented doses already rounded.

Weight-band 10 to 14 kg:

Initial dose: 10 mg/dose every 2 weeks

1st dose increase: 15 mg/dose every 2 weeks

2nd dose increase: 20 mg/dose every 2 weeks

Weight-band 15 to 18 kg:

Initial dose: 10 mg/dose every 2 weeks

1st dose increase: 20 mg/dose every 2 weeks

2nd dose increase: 30 mg/dose every 2 weeks

Weight-band 19 to 31 kg:

Initial dose: 20 mg/dose every 2 weeks

1st dose increase: 30 mg/dose every 2 weeks

2nd dose increase: 40 mg/dose every 2 weeks

Weight-band 32 to 43 kg:

Initial dose: 30 mg/dose every 2 weeks

1st dose increase: 40 mg/dose every 2 weeks

2nd dose increase: 60 mg/dose every 2 weeks

Weight-band 44 to 56 kg:

Initial dose: 40 mg/dose every 2 weeks

1st dose increase: 60 mg/dose every 2 weeks

2nd dose increase: 80 mg/dose every 2 weeks

Weight-band 57 to 68 kg:

Initial dose: 50 mg/dose every 2 weeks

1st dose increase: 70 mg/dose every 2 weeks

2nd dose increase: 90 mg/dose every 2 weeks

Weight-band 69 to 80 kg:

Initial dose: 60 mg/dose every 2 weeks

1st dose increase: 90 mg/dose every 2 weeks

2nd dose increase: 90 mg/dose every 2 weeks

Weight-band 81 to 93 kg:

Initial dose: 70 mg/dose every 2 weeks

1st dose increase: 90 mg/dose every 2 weeks

2nd dose increase: 90 mg/dose every 2 weeks

Weight-band 94 to 105 kg:

Initial dose: 80 mg/dose every 2 weeks

1st dose increase: 90 mg/dose every 2 weeks

2nd dose increase: 90 mg/dose every 2 weeks

Weight-band ≥106 kg:

Initial dose: 90 mg/dose every 2 weeks

1st dose increase: 90 mg/dose every 2 weeks

2nd dose increase: 90 mg/dose every 2 weeks

If serum phosphorus above lower limit of the reference range for age and below 5 mg/dL: Continue same dose.

If high serum phosphorous:

Children and Adolescents ≤17 years: If serum phosphorus >5 mg/dL: Hold dose; reassess fasting serum phosphorus in 4 weeks and every 4 weeks thereafter; once serum phosphorus below reference range for age, may reinitiate burosumab-twza at a reduced dose. Recheck fasting serum phosphorus in 4 weeks and follow dosing adjustment recommendations based on result; the following table provides fixed dosing for reduced dosage to re-initiate therapy

Re-Initiation Dosing: Fixed Dosing

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

Table has been converted to the following text:

Previous dose: 10 mg/dose every 2 weeks; Re-initiation dose: 5 mg/dose every 2 weeks

Previous dose: 15 mg/dose every 2 weeks; Re-initiation dose: 10 mg/dose every 2 weeks

Previous dose: 20 mg/dose every 2 weeks; Re-initiation dose: 10 mg/dose every 2 weeks

Previous dose: 30 mg/dose every 2 weeks; Re-initiation dose: 10 mg/dose every 2 weeks

Previous dose: 40 mg/dose every 2 weeks; Re-initiation dose: 20 mg/dose every 2 weeks

Previous dose: 50 mg/dose every 2 weeks; Re-initiation dose: 20 mg/dose every 2 weeks

Previous dose: 60 mg/dose every 2 weeks; Re-initiation dose: 30 mg/dose every 2 weeks

Previous dose: 70 mg/dose every 2 weeks; Re-initiation dose: 30 mg/dose every 2 weeks

Previous dose: 80 mg/dose every 2 weeks; Re-initiation dose: 40 mg/dose every 2 weeks

Previous dose: 90 mg/dose every 2 weeks; Re-initiation dose: 40 mg/dose every 2 weeks

Administration

SubQ: Administer subcutaneously into the upper thighs, any quadrant of abdomen, buttocks, or upper arms; administer each injection at a different anatomic location than a previous injection and avoid areas where the skin is tender, bruised, red, hard, or not intact or where there are scars or moles. The maximum volume per injection site is 1.5 mL.

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-twza. Exceptions: Sodium Glycerophosphate Pentahydrate. Avoid combination

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

Adverse Reactions

>10%:

Central nervous system: Headache (children: 8% to 73%; adults: 13%), dizziness (10% to 15%), restless leg syndrome (adults: 12%)

Dermatologic: Skin rash (children: 8% to 27%)

Endocrine & metabolic: Vitamin D deficiency (children: 15% to 37%; adults: 12%)

Gastrointestinal: Vomiting (children: 46% to 48%), toothache (children: 15% to 23%), tooth infection (adults: 13%)

Infection: Tooth abscess (children: 15% to 23%)

Local: Injection site reaction (children: 23% to 67%; including urticaria, erythema, rash, swelling, bruising, pain, pruritus, and hematoma)

Neuromuscular & skeletal: Limb pain (children: 23% to 46%), myalgia (children: 8% to 17%), back pain (adults: 15%)

Miscellaneous: Fever (children: 44% to 62%)

1% to 10%:

Dermatologic: Rash at injection site (children: 6%), urticaria (children: 5%)

Endocrine & metabolic: Hyperphosphatemia (adults: 6% to 7%)

Gastrointestinal: Constipation (adults: 9%)

Hypersensitivity: Hypersensitivity reaction (6%)

Frequency not defined: Immunologic: Antibody development

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.

• 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 (RLS) has been reported in adults.

Monitoring Parameters

Signs/symptoms of hypersensitivity or injection site reaction.

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 post-dose, for the first 12 weeks of treatment, and as appropriate thereafter (eg, after dosing adjustments).

Pregnancy Considerations

Burosumab-twza 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-twza during pregnancy to the Ultragenyx Adverse Event reporting line (888-756-8657).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience headache, vomiting, painful extremities, tooth pain, muscle pain, dizziness, or constipation. Have patient report immediately to prescriber signs of a kidney stone (back pain, abdominal pain, or hematuria), severe injection site irritation, or restless legs (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Further information

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

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