Burosumab is a fibroblast growth factor 23 (FGF23) blocking antibody. It is indicated for the treatment of X-linked hypophosphatemia (XLH) in adult and pediatric patients 6 months of age and older. Burosumab is also indicated for the treatment of tumor-induced osteomalacia (TIO) in adult and pediatric patients 2 years of age and older. In a placebo-controlled study involving 134 adult patients with XLH, 94% of adults receiving burosumab once a month achieved normal phosphorus concentrations compared to 8% of those receiving placebo. In pediatric studies, 94% to 100% of patients treated with burosumab every 2 weeks achieved normal phosphorus concentrations. Additionally, there was an improvement in X-ray findings associated with XLH in both children and adults receiving burosumab therapy. In 2 single-arm, phase 2 trials (n = 14 and n = 13), the mean serum phosphorus levels increased to above the lower limit of normal (LLN) following 24 weeks of burosumab therapy in 50% and 69% of adult patients with TIO. The safety and efficacy of burosumab in pediatric patients 2 years and older with TIO were extrapolated from adult TIO study data and study and pharmacokinetic data in adults and pediatric patients with XLH. The use of oral phosphate and active vitamin D analogs is contraindicated during burosumab treatment; discontinue these products 1 week prior to the initiation of burosumab. Ensure serum phosphorous concentrations are below the reference range for age prior to treatment initiation; monitor serum phosphorus monthly for the first 3 months of treatment and periodically thereafter.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
-If a dose is missed, resume treatment as soon as possible; treatments may be given 3 days on either side of the scheduled treatment date.
Route-Specific Administration
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Burosumab is clear to slightly opalescent and colorless to pale brown-yellow.
Subcutaneous Administration
-Administer burosumab by subcutaneous injection only. Do not administer intravenously or intramuscularly.
-If the dose requires using multiple burosumab vials, contents from 2 vials can be combined in the same syringe.
-Inject the burosumab dose subcutaneously into the abdomen, buttocks, upper thigh, or the upper arms; rotate administration sites with each injection.
-Do not inject into moles, scars, or areas where the skin is tender, bruised, red, hard, or not intact.
-Do not administer more than 1.5 mL per injection site. If more than 1.5 mL is required on a given dosing day, the total volume of burosumab must be split and administered at 2 different injection sites.
-Discard any unused portion in the vial.
Mild or moderate hypersensitivity reactions were reported in 6% to 22% of adult patients who received burosumab therapy in clinical trials. If serious hypersensitivity reactions occur, discontinue burosumab and initiate appropriate medical treatment. In pediatric patients, rash (10% to 23%), injection site rash (6% to 10%), and urticaria (5% to 7%) were the most frequent potential hypersensitivity reactions. The term rash included pruritic rash, maculopapular rash, erythematous rash, and pustular rash. In a pooled analysis of 2 studies (n = 27), the most common hypersensitivity reactions were eczema (11%) and rash (11%) in adult patients with tumor-induced osteomalacia; rash including papular rash occurred in 15% of patients.
Subcutaneous administration of burosumab can cause an injection site reaction. If severe injection site reactions occur, discontinue burosumab and administer appropriate medical treatment. Symptoms of a reaction may include erythema, pruritus, swelling, pain, rash, bruising, discoloration, discomfort, hematoma, hemorrhage, induration, macule, and urticaria. During clinical trials, injection site reactions occurred in 52% to 59% of pediatric patients and approximately 12% to 15% of adult patients who received burosumab. Injection site reactions were generally mild in severity, occurred within 1 day of injection, lasted approximately 1 to 3 days, required no treatment, and resolved in almost all instances.
Headache (pediatric patients, 34% to 60%; adults, 11% to 13%) and dizziness (pediatric patients, 12%; adults, 10% to 15%) were reported during burosumab clinical trials.
Gastrointestinal adverse reactions, such as vomiting (41% to 48%), diarrhea (24%), constipation (17%), and nausea (10%), were reported in pediatric patients during burosumab clinical trials. Constipation was reported in 9% to 15% of adult patients during burosumab clinical trials.
During burosumab clinical trials, pain in extremity (38% to 42%) and myalgia (15%) were reported in pediatric patients. Back pain (15%) and muscle cramps/spasms (7% to 19%) were reported in adults.
Approximately 12% of adult patients reported worsening of baseline restless legs syndrome (RLS) or new onset RLS of mild to moderate severity during a burosumab clinical trial. These events did not usually lead to drug discontinuation, however, during other studies, there was a case of worsening baseline RLS that led to drug discontinuation with subsequent resolution of the event. In a pooled analysis of 2 studies (n = 27), mild RLS was reported in 7% of adult patients with tumor-induced osteomalacia.
Dental caries (31%), toothache or dental pain (22%), and tooth abscess or infection (17% to 34%) were reported in pediatric patients during burosumab clinical trials. Tooth abscess or infection was reported in 13% to 19% of adult patients. Fever (44% to 55%) and cough (52%) were also reported in pediatric patients.
Spinal stenosis is prevalent in adults with X-linked hypophosphatemia (XLH) and spinal cord compression has been reported. In clinical trials of adult patients with XLH receiving burosumab (n = 176), a total of 6 patients underwent spinal surgery. Most of these cases appeared to be progression of a pre-existing spinal stenosis. It is unknown if burosumab exacerbates spinal stenosis or spinal cord compression.
Hyperphosphatemia was reported in 6% to 7% of adult patients and 0% of pediatric patients during burosumab clinical trials. Hyperphosphatemia was managed with dose reduction. Increased blood phosphorus level was reported in pediatric patients with X-linked hypophosphatemia in postmarketing surveillance of burosumab. Vitamin D decreases, including vitamin D deficiency, were reported in 24% to 32% of pediatric patients and 7% to 12% of adult patients.
Antibody formation has been reported in 19% or less of adult and pediatric patients who received burosumab therapy; antibody formation was not associated with clinically relevant changes in pharmacokinetics, pharmacodynamics, efficacy, or safety of burosumab in patients with X-linked hypophosphatemia. Neutralizing antibodies developed in 3 pediatric patients (aged 5 to 12 years).
Due to the risk of hyperphosphatemia, use of burosumab is contraindicated in patients who have a serum phosphorus concentration within or above the normal range for age. Coadministration of burosumab with oral phosphate and/or active vitamin D analogs (i.e., calcitriol, paricalcitol, doxercalciferol, calcifediol) is also contraindicated due to the risk of hyperphosphatemia. Measure fasting serum phosphorus concentrations at baseline, monthly for the first 3 months of treatment, and then periodically thereafter as appropriate to maintain phosphorus concentrations within the normal range based on age. A temporary interruption of therapy and/or dose reduction may be required based on serum phosphorus concentrations. The risk of nephrocalcinosis is increased when serum phosphorus increases to above the upper limit of normal.
Burosumab is contraindicated in patients with severe renal impairment (adults, CrCl 15 to 29 mL/minute; pediatrics, eGFR 15 to 29 mL/minute/1.73 m2), renal failure, and end-stage renal disease (adults, CrCl less than 15 mL/minute; pediatrics, eGFR less than 15 mL/minute/1.73 m2) since these conditions are associated with abnormal mineral metabolism.
Hold burosumab therapy if a patient with tumor-induced osteomalacia undergoes treatment of the underlying tumor (i.e., excision by surgery or radiation therapy), check phosphorus levels after treatment. Restart therapy at the initiation dosage if phosphorus levels remain below the lower limit of normal; titrate dosage based on subsequent fasting serum phosphorus levels.
There are no available data regarding burosumab use during human pregnancy to inform a drug-associated risk. Animal data (monkeys) did not reveal evidence of teratogenic effects. Adverse effects such as late fetal loss and preterm birth were observed in pregnant cynomolgus monkeys; however, these effects occurred at a drug exposure with an AUC 15-fold higher than the maximum human exposure at 2 mg/kg/dose every 2 weeks and are unlikely to indicate human risk. Maternal hyperphosphatemia and placental mineralization occurred concomitantly. If burosumab is used during pregnancy, monitor serum phosphorus concentrations throughout the pregnancy. Report pregnancies to the Ultragenyx Adverse Event reporting line at 1-888-756-8657.
There are no data on the presence of burosumab in human milk, the effects on breast-feeding infants, or the effects on milk production. Maternal IgG is present in breast milk; however, the effects of local gastrointestinal exposure and limited systemic exposure to burosumab in the breast-feeding infant are unknown. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.
General dosing information:
-Discontinue oral phosphate and/or active vitamin D analogs (i.e., calcitriol, paricalcitol, doxercalciferol, calcifediol) 1 week prior to initiation of treatment and ensure fasting serum phosphorus concentrations are below the reference range for age.
For the treatment of X-linked hypophosphatemia (XLH):
Subcutaneous dosage:
Adults: 1 mg/kg/dose administered subcutaneously every 4 weeks; round to the nearest 10 mg (Max: 90 mg/dose). Measure fasting serum phosphorus (2 weeks post-dose) monthly for the first 3 months of treatment and periodically thereafter. Continue current dose if phosphorus is within the normal range. Do not adjust the dosage more frequently than every 4 weeks; reassess phosphorus concentration 2 weeks after a dosage adjustment. To avoid missed doses, treatments may be given 3 days on either side of the scheduled treatment date.
Adolescents: 0.8 mg/kg/dose administered subcutaneously every 2 weeks; round to the nearest 10 mg. Measure fasting serum phosphorus monthly for the first 3 months of treatment and periodically thereafter. Continue current dose if phosphorus is above the lower limit of the reference range for age and below 5 mg/dL. If phosphorus is below the reference range for age, the dose may be increased stepwise up to the maximum dose of 2 mg/kg/dose (Max: 90 mg/dose), administered every 2 weeks. Do not adjust the dosage more frequently than every 4 weeks; reassess phosphorus concentration 4 weeks after a dosage adjustment. To avoid missed doses, treatments may be given 3 days on either side of the scheduled treatment date.
Infants and Children 6 months to 12 years weighing more than 10 kg: 0.8 mg/kg/dose administered subcutaneously every 2 weeks; round to the nearest 10 mg. Measure fasting serum phosphorus monthly for the first 3 months of treatment and periodically thereafter. Continue current dose if phosphorus is above the lower limit of the reference range for age and below 5 mg/dL. If phosphorus is below the reference range for age, the dose may be increased stepwise up to the maximum dose of 2 mg/kg/dose (Max: 90 mg/dose), administered every 2 weeks. Do not adjust the dosage more frequently than every 4 weeks; reassess phosphorus concentration 4 weeks after a dosage adjustment. To avoid missed doses, treatments may be given 3 days on either side of the scheduled treatment date.
Infants and Children 6 months to 12 years weighing less than 10 kg: 1 mg/kg/dose administered subcutaneously every 2 weeks; round to the nearest 1 mg. Measure fasting serum phosphorus monthly for the first 3 months of treatment and periodically thereafter. Continue current dose if phosphorus is above the lower limit of the reference range for age and below 5 mg/dL. If phosphorus is below the reference range for age, the dose may be increased stepwise up to the maximum dose of 2 mg/kg/dose, administered every 2 weeks. Do not adjust the dosage more frequently than every 4 weeks; reassess phosphorus concentration 4 weeks after a dosage adjustment. To avoid missed doses, treatments may be given 3 days on either side of the scheduled treatment date.
For the treatment of FGF23-related hypophosphatemia in tumor-induced osteomalacia (TIO) associated with phosphaturic mesenchymal tumors that cannot be curatively resected or localized:
NOTE: Burosumab has been designated as an orphan drug for the treatment of TIO syndrome.
Subcutaneous dosage:
Adults: 0.5 mg/kg/dose administered subcutaneously every 4 weeks; round to the nearest 10 mg. Measure fasting serum phosphorus (2 weeks post-dose) monthly for the first 3 months of treatment and periodically thereafter. Continue current dose if phosphorus is above the lower limit of the reference range for age. If phosphorus is below the reference range for age, the dose may be increased stepwise up to the maximum dose of 2 mg/kg/dose (Max: 180 mg/dose), administered every 2 weeks. Do not adjust the dosage more frequently than every 4 weeks; reassess phosphorus concentration 2 weeks after a dosage adjustment. To avoid missed doses, treatments may be given 3 days on either side of the scheduled treatment date. Hold burosumab if a patient undergoes treatment of the underlying tumor (i.e., surgical excision or radiation therapy). In a single-arm, phase 2 trial, the mean serum phosphorus concentrations increased to above the LLN after 24 weeks of burosumab therapy in 50% of adult patients (n = 14; median age, 59.5 years; range, 33 to 68 years) with FGF23-related hypophosphatemia due to an underlying tumor (including TIO) that was not amenable to surgical excision or could not be located. Patients had increased fasting mean serum phosphorus concentrations from 1.6 +/- 0.47 mg/dL at baseline to 2.64 +/- 0.76 mg/dL at week 24. The increased mean serum phosphorus concentrations were sustained near or above the LLN through week 144 of treatment. The mean serum phosphorus concentrations increased to above the LLN after 24 weeks of burosumab therapy in 69% of adult patients (n = 13; median age, 58 years; range, 41 to 73 years) with TIO in another single-arm, phase 2 trial. Patients had increased fasting mean serum phosphorus concentrations from 1.62 +/- 0.49 mg/dL at baseline to 2.63 +/- 0.87 mg/dL at week 24. The increased mean serum phosphorus concentrations were sustained above the LLN through week 88 of treatment. The target range was 2.5 to 4 mg/dL for fasting serum phosphorus concentrations in these trials.
Children and Adolescents 2 to 17 years: 0.4 mg/kg/dose administered subcutaneously every 2 weeks; round to the nearest 10 mg. Measure fasting serum phosphorus (2 weeks post-dose) monthly for the first 3 months of treatment and periodically thereafter. Continue current dose if phosphorus is above the lower limit of the reference range for age. If phosphorus is below the reference range for age, the dose may be increased stepwise up to the maximum dose of 2 mg/kg/dose (Max: 180 mg/dose), administered every 2 weeks. Do not adjust the dosage more frequently than every 4 weeks; reassess phosphorus concentration 4 weeks after a dosage adjustment. To avoid missed doses, treatments may be given 3 days on either side of the scheduled treatment date. Hold burosumab if a patient undergoes treatment of the underlying tumor (i.e., surgical excision or radiation therapy).
Therapeutic Drug Monitoring:
Dosage Adjustments Based on Serum Phosphorus Concentrations
X-Linked Hypophosphatemia
Adults
-For serum phosphorus concentration above the reference range, hold therapy and reassess phosphorus concentration in 4 weeks. When the phosphorus concentration is below the reference range, resume therapy at approximately half the initial starting dose, up to a maximum of 40 mg every 4 weeks. For a previous dose of 40 or 50 mg, reinitiate dose at 20 mg; for a previous dose of 60 or 70 mg, reinitiate dose at 30 mg; and for a previous dose of 80 or 90 mg, reinitiate dose at 40 mg. Reassess the phosphorus concentration 2 weeks after any change in dose.
Pediatric Patients
-For serum phosphorus concentration below the reference range for age, the dose may be increased stepwise up to approximately 2 mg/kg/dose administered every 2 weeks (Max: 90 mg/dose) according to the dosing schedule below:
--weight less than 10 kg: first increase, 1.5 mg/kg/dose; second increase, 2 mg/kg/dose (round dose to nearest 1 mg)
-weight 10 to 14 kg: first increase, 15 mg; second increase, 20 mg
-weight 15 to 18 kg: first increase, 20 mg; second increase, 30 mg
-weight 19 to 31 kg: first increase, 30 mg; second increase, 40 mg
-weight 32 to 43 kg: first increase, 40 mg; second increase, 60 mg
-weight 44 to 56 kg: first increase, 60 mg; second increase, 80 mg
-weight 57 to 68 kg: first increase, 70 mg; second increase, 90 mg
-weight 69 kg or more: first increase, 90 mg; second increase, 90 mg
-For serum phosphorus concentration above 5 mg/dL, hold therapy and reassess phosphorus in 4 weeks; resume therapy at approximately half the initial starting dose when the phosphorus concentration is below the reference range for age.
--weight less than 10 kg: Restart treatment at 0.5 mg/kg/dose administered subcutaneously every 2 weeks; round to the nearest 1 mg. If the phosphorous concentration remains below the reference range for age 4 weeks after the reinitiation dose, the dose can be retitrated in a stepwise manner to the maximum dose of 2 mg/kg/dose. Reassess the phosphorus concentration in 4 weeks; titrate the dosage as appropriate.
-weight 10 kg or more: For a previous dose of 10 mg, reinitiate dose at 5 mg; for a previous dose of 15, 20, or 30 mg, reinitiate dose at 10 mg; for a previous dose of 40 or 50 mg, reinitiate dose at 20 mg; for a previous dose of 60 or 70 mg, reinitiate dose at 30 mg; and for a previous dose of 80 or 90 mg, reinitiate dose at 40 mg. If the phosphorous concentration remains below the reference range for age 4 weeks after the reinitiation dose, the dose can be retitrated in a stepwise manner to the maximum dose of 90 mg. Reassess the phosphorus concentration in 4 weeks; titrate the dosage as appropriate.
Tumor-Induced Osteomalacia
Adults
Note: Round dose to the nearest 10 mg.
-For serum phosphorus concentration below the lower limit of normal (LLN) at 2 weeks post-dose adjustment:
--First dosage increase: 1 mg/kg/dose every 4 weeks OR 0.5 mg/kg/dose every 2 weeks.
-Second dosage increase: 1.5 mg/kg/dose* every 4 weeks OR 0.75 mg/kg/dose every 2 weeks.
-Third dosage increase: 2 mg/kg/dose* every 4 weeks OR 1 mg/kg/dose every 2 weeks.
-Fourth dosage increase: 1.5 mg/kg/dose every 2 weeks (Max: 180 mg/dose).
-Fifth dosage increase: 2 mg/kg/dose every 2 weeks (Max: 180 mg/dose).
*If the calculated dose is more than 180 mg every 4 weeks, use the 2-week dosing option.
-For serum phosphorus concentration above the normal range:
--Hold therapy and reassess phosphorus in 4 weeks; resume therapy at approximately half the initial starting dose (up to a maximum dosage of 180 mg every 2 weeks) when the phosphorus concentration is below the reference range. Reassess the phosphorus concentration in 2 weeks; titrate the dosage as appropriate.
Pediatric Patients
-For serum phosphorus concentration below the reference range for age, the dose may be increased stepwise up to approximately 2 mg/kg/dose administered every 2 weeks (Max: 180 mg/dose) according to the dosing schedule below:
--weight 10 to 14 kg: first increase, 10 mg; second increase, 15 mg; third increase,* 20 mg
-weight 15 to 18 kg: first increase, 10 mg; second increase, 20 mg; third increase,* 25 mg
-weight 19 to 31 kg: first increase, 20 mg; second increase, 25 mg; third increase,* 30 mg
-weight 32 to 43 kg: first increase, 30 mg; second increase, 40 mg; third increase,* 50 mg
-weight 44 to 56 kg: first increase, 40 mg; second increase, 50 mg; third increase,* 70 mg
-weight 57 to 68 kg: first increase, 50 mg; second increase, 70 mg; third increase,* 90 mg
-weight 69 to 80 kg: first increase, 60 mg; second increase, 80 mg; third increase,* 100 mg
-weight 81 to 93 kg: first increase, 70 mg; second increase, 100 mg; third increase,* 120 mg
-weight 94 to 105 kg: first increase, 80 mg; second increase, 110 mg; third increase,* 140 mg
-weight 106 kg or more: first increase, 90 mg; second increase, 130 mg; third increase,* 160 mg
*Further dose increases to a maximum of 2 mg/kg/dose given every 2 weeks (Max: 180 mg/dose) should be calculated by the physician.
-For serum phosphorus concentration above the reference range for age:
--Hold therapy and reassess phosphorus in 4 weeks; resume therapy at approximately half the initial starting dose (up to a maximum dosage of 180 mg every 2 weeks) when the phosphorus concentration is below the reference range for age. Reassess the phosphorus concentration in 4 weeks; titrate the dosage as appropriate.
Maximum Dosage Limits:
-Adults
X-linked hypophosphatemia: 1 mg/kg/dose subcutaneously every 4 weeks (Max: 90 mg/dose).
Tumor-induced osteomalacia: 2 mg/kg/dose subcutaneously every 2 weeks (Max: 180 mg/dose).
-Geriatric
X-linked hypophosphatemia: 1 mg/kg/dose subcutaneously every 4 weeks (Max: 90 mg/dose).
Tumor-induced osteomalacia: 2 mg/kg/dose subcutaneously every 2 weeks (Max: 180 mg/dose).
-Adolescents
X-linked hypophosphatemia: 2 mg/kg/dose subcutaneously every 2 weeks (Max: 90 mg/dose).
Tumor-induced osteomalacia: 2 mg/kg/dose subcutaneously every 2 weeks (Max: 180 mg/dose).
-Children
2 to 12 years: X-linked hypophosphatemia: 2 mg/kg/dose subcutaneously every 2 weeks (Max: 90 mg/dose).
Tumor-induced osteomalacia: 2 mg/kg/dose subcutaneously every 2 weeks (Max: 180 mg/dose).
1 year:
X-linked hypophosphatemia: 2 mg/kg/dose subcutaneously every 2 weeks.
Tumor-induced osteomalacia: Safety and efficacy have not been established.
-Infants
6 to 11 months:
X-linked hypophosphatemia: 2 mg/kg/dose subcutaneously every 2 weeks.
Tumor-induced osteomalacia: Safety and efficacy have not been established.
1 to 5 months:
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; however, burosumab is contraindicated in patients with severe renal impairment (adults, CrCl 15 to 29 mL/minute; pediatrics, eGFR 15 to 29 mL/minute/1.73 m2) or end-stage renal disease (adults, CrCl less than 15 mL/minute; pediatrics, eGFR less than 15 mL/minute/1.73 m2).
*non-FDA-approved indication
Calcifediol: (Contraindicated) Vitamin D analogs are contraindicated in patients receiving burosumab; discontinue vitamin D analogs 1 week prior to initiation of burosumab.
Calcitriol: (Contraindicated) Vitamin D analogs are contraindicated in patients receiving burosumab; discontinue vitamin D analogs 1 week prior to initiation of burosumab.
Calcium Phosphate, Supersaturated: (Contraindicated) Oral phosphates are contraindicated in patients receiving burosumab; discontinue sodium phosphate, disbasic, sodium phosphate, monobasic 1 week prior to initiation of burosumab.
Doxercalciferol: (Contraindicated) Vitamin D analogs are contraindicated in patients receiving burosumab; discontinue vitamin D analogs 1 week prior to initiation of burosumab.
Erdafitinib: (Major) Avoid coadministration of burosumab with erdafitinib before the initial dose increase period (days 14 to 21) which is based on serum phosphate levels. Burosumab increases serum phosphate levels. Erdafitinib causes hyperphosphatemia as a consequence of FGFR inhibition. Changes in serum phosphate levels by burosumab may interfere with the determination of this initial dose increase and may cause additive hyperphosphatemia.
Ibritumomab Tiuxetan: (Contraindicated) Oral phosphates are contraindicated in patients receiving burosumab; discontinue potassium phosphate 1 week prior to initiation of burosumab.
Paricalcitol: (Contraindicated) Vitamin D analogs are contraindicated in patients receiving burosumab; discontinue vitamin D analogs 1 week prior to initiation of burosumab.
Potassium Phosphate: (Contraindicated) Oral phosphates are contraindicated in patients receiving burosumab; discontinue potassium phosphate 1 week prior to initiation of burosumab.
Potassium Phosphate; Sodium Phosphate: (Contraindicated) Oral phosphates are contraindicated in patients receiving burosumab; discontinue potassium phosphate 1 week prior to initiation of burosumab.
Sodium Phosphate Monobasic Monohydrate; Sodium Phosphate Dibasic Anhydrous: (Contraindicated) Oral phosphates are contraindicated in patients receiving burosumab; discontinue sodium phosphate, disbasic, sodium phosphate, monobasic 1 week prior to initiation of burosumab.
Vitamin D analogs: (Contraindicated) Vitamin D analogs are contraindicated in patients receiving burosumab; discontinue vitamin D analogs 1 week prior to initiation of burosumab.
X-linked hypophosphatemia (XLH) 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, a human monoclonal immunoglobulin G1 antibody, binds to and inhibits the biological activity of FGF23 restoring renal phosphate reabsorption and increasing the serum concentration of 1,25 dihydroxy vitamin D.
Burosumab is administered as a subcutaneous injection. It exhibits linear pharmacokinetics across the dose range of 0.1 to 1 mg/kg. The elimination half-life after subcutaneous administration is approximately 19 days and the apparent clearance is 0.29 L/day. The apparent volume of distribution is 8 liters. Clearance and volume of distribution of burosumab increases with body weight. No significant difference in burosumab pharmacokinetics has been observed based on age. The exact pathway for burosumab metabolism has not been characterized, but it is expected to be degraded into small peptides and amino acids via catabolic pathways.
-Route-Specific Pharmacokinetics
Subcutaneous Route
Burosumab exhibits linear pharmacokinetics across the dose range of 0.1 to 1 mg/kg subcutaneously. The mean steady state trough concentration is 5.8 (+/- 3.4) mcg/mL in adult patients with X-linked hypophosphatemia (XLH). The mean Tmax values range from 8 to 11 days. Based on a population pharmacokinetic analysis (PK), the PK parameters of burosumab were similar between patients with XLH and tumor-induced osteomalacia.
-Special Populations
Hepatic Impairment
The effect of hepatic impairment on burosumab pharmacokinetics is unknown.
Renal Impairment
The 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 alone. This increase may result in hyperphosphatemia which can induce nephrocalcinosis.
Pediatrics
The burosumab steady state trough concentration is 15.8 (+/- 0.4) mcg/mL and 11.2 (+/- 4.6) mcg/mL in pediatric patients with X-linked hypophosphatemia aged 5 to 12 years and 1 to 4 years, respectively.