Usual Adult Dose for Familial Hypophosphatemia

Initial dose: 1 mg/kg (rounded to nearest 10 mg) subcutaneously every 4 weeks
Maximum dose: 90 mg

Measure serum phosphorus 2 weeks post-dose for the first 3 months, then as clinically indicated
Maintenance dose: For serum phosphorus levels within the normal range, continue with same dose

For serum phosphorus levels ABOVE the normal range: Withhold next dose and reassess serum phosphorus level in 4 weeks; when serum phosphorus level drops below the normal range, reinitiate therapy at approximately one-half the initial starting dose as follows:

• Previous dose: 40 or 50 mg; Re-initiation dose: 20 mg
• Previous dose: 60 or 70 mg; Re-initiation dose: 30 mg
• Previous dose: 80 or 90 mg; Re-initiation dose: 40 mg

Comments:

• Discontinue oral phosphate and active vitamin D analogs 1 week prior to treatment initiation; fasting serum phosphorus concentrations should be below the reference range for age prior to initiation of therapy.
• Doses are administered subcutaneously by a healthcare provider; maximum volume per injection is 1.5 mL; if multiple injections are required, administer at different injection sites; may administer 3 days either side of scheduled treatment date.
• Monitor 25-hydroxy vitamin D levels; supplement with cholecalciferol or ergocalciferol to maintain 25 hydroxy vitamin D levels in the normal range for age; do not administer active Vitamin D analogs during treatment.

Use: For the treatment of X-linked hypophosphatemia.

Usual Adult Dose for Osteomalacia

Initial dose: 0.5 mg/kg (rounded up to nearest 10 mg) subcutaneously every 4 weeks

• Measure serum phosphorus 2 weeks post-dose for the first 3 months, then as clinically indicated

Maintenance dose: For serum phosphorus levels within the normal range, continue with same dose
Maximum dose: 2 mg/kg, not to exceed 180 mg every 2 weeks

DOSE ADJUSTMENTS: Reassess fasting serum phosphorus level 2 weeks after dose adjustment; do not adjust more frequently than every 4 weeks (round to nearest 10 mg):

• Dose INCREASES: If serum phosphorus is below the normal range, titrate dose stepwise:
• First dose increase: 1 mg/kg every 4 weeks OR 0.5 mg/kg every 2 weeks
• Second dose increase: 1.5 mg/kg every 4 weeks OR 0.75 mg/kg every 2 weeks
• Third dose increase: 2 mg/kg every 4 weeks OR 1 mg/kg every 2 weeks
• Fourth dose increase: 1.5 mg/kg (not to exceed 180 mg) every 2 weeks
• Fifth dose increase: 2 mg/kg (not to exceed 180 mg) every 2 weeks
• Dose DECREASES: If serum phosphorus is above the normal range, withhold the next dose and reassess the serum

phosphorus level in 4 weeks

• Restart at approximately one-half initial starting dose; reassess serum phosphorus level 2 weeks after dose adjustment and if level remains below reference range, adjust dose as above

DOSE INTERRUPTION: If a patient undergoes treatment of the underlying tumor (i.e., surgical excision or radiation therapy), treatment should be interrupted and serum phosphorus reassessed after treatment has been completed; dose should be restarted at the patient's initiation dose if serum phosphorus remains below the lower limit of normal, follow dose adjustments to maintain serum phosphorus within the reference range

Comments:

• Discontinue oral phosphate and active vitamin D analogs 1 week prior to treatment initiation; fasting serum phosphorus concentrations should be below the reference range for age prior to initiation of therapy.
• Doses are administered subcutaneously by a healthcare provider; maximum volume per injection is 1.5 mL; if multiple injections are required, administer at different injection sites; may administer 3 days either side of scheduled treatment date.
• Monitor 25-hydroxy vitamin D levels; supplement with cholecalciferol or ergocalciferol to maintain 25 hydroxy vitamin D levels in the normal range for age; do not administer active Vitamin D analogs during treatment.

Use: For the treatment of FGF23-related hypophosphatemia in tumor-induced osteomalacia (TIO) associated with phosphaturic mesenchymal tumors that cannot be curatively resected or localized.

Usual Pediatric Dose for Familial Hypophosphatemia

6 months or older:
INITIAL DOSES:

• Weight less than 10 kg: 1 mg/kg (rounded to nearest 1 mg) subcutaneously every 2 weeks
• Weight 10 kg or greater: 0.8 mg/kg (rounded to nearest 10 mg) subcutaneously every 2 weeks; minimum dose 10 mg; maximum dose: 90 mg

DOSE ADJUSTMENTS: Measure serum phosphorus every 4 weeks for the first 3 months, then as clinically indicated; do not dose adjust more frequently than every 4 weeks
Dose INCREASES: If serum phosphorus is below reference range for age:

• Weight less than 10 kg: Increase to 1.5 mg/kg, then 2 mg/kg (all doses are founded to the nearest 1 mg); Maximum dose: 2 mg/kg
• Weight 10 kg or greater: Increase stepwise up to approximately 2 mg/kg (see product labeling for stepwise dose increases); Maximum dose 2 mg/kg

Dose DECREASES: If serum phosphorus is above 5 mg/kg, hold next dose and reassess serum phosphorus in 4 weeks; treatment may restart when serum phosphorus is below reference range for age

• Weight less than 10 kg: Restart at 0.5 mg/kg (all doses are founded to the nearest 1 mg)
• Weight 10 kg or greater: See product labeling for re-initiation dose which is based on previous dose

MAINTENANCE DOSE: Maintain serum phosphorus within the reference range for age without exceeding maximum doses

Comments:

• Discontinue oral phosphate and active vitamin D analogs 1 week prior to treatment initiation; fasting serum phosphorus concentrations should be below the reference range for age prior to initiation of therapy.
• Doses are administered subcutaneously by a healthcare provider; maximum volume per injection is 1.5 mL; if multiple injections are required, administer at different injection sites; may administer 3 days either side of scheduled treatment date.
• Monitor 25-hydroxy vitamin D levels; supplement with cholecalciferol or ergocalciferol to maintain 25 hydroxy vitamin D levels in the normal range for age; do not administer active Vitamin D analogs during treatment.

Use: For the treatment of X-linked hypophosphatemia in pediatric patients 6 months or older.

Usual Pediatric Dose for Osteomalacia

2 years or older:
Initial dose: 0.4 mg/kg (rounded up to nearest 10 mg) subcutaneously every 2 weeks

• Measure serum phosphorus 2 weeks post-dose for the first 3 months, then as clinically indicated

Maintenance dose: For serum phosphorus levels within the normal range, continue with same dose
Maximum dose: 2 mg/kg, not to exceed 180 mg every 2 weeks

DOSE ADJUSTMENTS: Reassess fasting serum phosphorus level 4 weeks after dose adjustment; do not adjust more frequently than every 4 weeks (round to nearest 10 mg):

• Dose INCREASES: If serum phosphorus is below the normal range, titrate doses in accordance table in package labeling; dose should not exceed maximum dose of 2 mg/kg every 2 weeks; single maximum dose should not exceed 180 mg
• Dose DECREASES: If serum phosphorus is above the normal range, withhold the next dose and reassess the serum

phosphorus level in 4 weeks

• Restart at approximately one-half initial starting dose; reassess serum phosphorus level 4 weeks after dose adjustment and if level remains below reference range, adjust dose as above

DOSE INTERRUPTION: If a patient undergoes treatment of the underlying tumor (i.e., surgical excision or radiation therapy), treatment should be interrupted and serum phosphorus reassessed after treatment has been completed; dose should be restarted at the patient's initiation dose if serum phosphorus remains below the lower limit of normal, follow dose adjustments to maintain serum phosphorus within the reference range

Maximum dose: 2 mg/kg, not to exceed 180 mg every 2 weeks

Comments:

• Discontinue oral phosphate and active vitamin D analogs 1 week prior to treatment initiation; fasting serum phosphorus concentrations should be below the reference range for age prior to initiation of therapy.
• Doses are administered subcutaneously by a healthcare provider; maximum volume per injection is 1.5 mL; if multiple injections are required, administer at different injection sites; may administer 3 days either side of scheduled treatment date.
• Monitor 25-hydroxy vitamin D levels; supplement with cholecalciferol or ergocalciferol to maintain 25 hydroxy vitamin D levels in the normal range for age; do not administer active Vitamin D analogs during treatment.

Use: For the treatment of pediatric patients 2 years or older with FGF23-related hypophosphatemia in tumor-induced osteomalacia (TIO) associated with phosphaturic mesenchymal tumors that cannot be curatively resected or localized.

Renal Dose Adjustments

Severe renal impairment (eGFR less than 30 mL/min/1.73 m2 or CrCl less than 30 mL/min): Contraindicated

Liver Dose Adjustments

No adjustment recommended

Dose Adjustments

Fasting serum phosphorus levels should be assessed and doses adjusted to maintain serum phosphorus levels; package labeling should be consulted for dose adjustment tables. Doses should not be adjusted more frequently than every 4 weeks

Precautions

CONTRAINDICATIONS:

• Concomitant use with oral phosphate and/or active vitamin D analogs (e.g. calcitriol, paricalcitol, doxercalciferol, calcifediol) due to the risk of hyperphosphatemia
• Treatment initiation when serum phosphorus is within or above the normal range for age
• Severe renal impairment or ESRD as these conditions are associated with abnormal mineral metabolism

Safety and efficacy have not been established in patients younger than 6 months for the treatment of X-linked hypophosphatemia (XLH) and in patients younger than 2 years for the treatment of FGF23-related hypophosphatemia in tumor induced osteomalacia (TIO) associated with phosphaturic mesenchymal tumors that cannot be curatively resected or localized.

Consult WARNINGS section for additional precautions.

Dialysis

Contraindicated in severe renal impairment and ESRD because these conditions are associated with abnormal mineral metabolism

Other Comments

Administration advice:

• To be administered subcutaneously by a healthcare provider
• Rotate injection sites (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
• Maximum volume per injection site is 1.5 mL; if greater volume is needed, split dose and administer into 2 different sites

Missed dose: If a dose is missed, resume as soon as possible at the prescribed dose; treatments may be administered 3 days either side of the scheduled treatment date

Storage requirements:

• Store refrigerated (36F to 46F [2C to 8C]) in original carton until time of use
• Do not freeze or shake vials
• Single-dose vials; discard unused product

General:

• Oral phosphate and active vitamin D analogs should be discontinued 1 week prior to therapy initiation.
• Cholecalciferol or ergocalciferol supplementation may be necessary to maintain 25-hydroxy vitamin D levels in the normal range for age.

Monitoring:

• Pediatric patients with X-linked hypophosphatemia: Measure fasting serum phosphorus levels at baseline, every 4 weeks for the first 3 months, 4 weeks after dose adjustments, and as clinically indicated
• Pediatric patients with tumor-induced osteomalacia: Measure fasting serum phosphorus levels at baseline, monthly for the first 3 months measured 2 weeks post-dose, 4 weeks after dose adjustments, and as clinically indicated
• Adults: Measure fasting serum phosphorus levels at baseline, monthly for the first 3 months measured 2 weeks post-dose, 2 weeks after dose adjustments, and as clinically indicated
• Monitor 25-hydroxy vitamin D levels
• Monitor for injection site reactions

Patient advice:

• Patients should be instructed to read the US FDA-approved patient labeling (Patient Information).
• Patients should be instructed to contact their healthcare provider if they develop hypersensitivity or injection site reactions; or new or worsening symptoms of restless leg syndrome.
• Patients should be instructed not to use any oral phosphate and/or active vitamin D analog products.
• Patients should speak to their healthcare provider if they are pregnant, or considering pregnancy; pregnancy should be reported to the manufacturer's adverse event reporting line at 1-888-756-8657.

Frequently asked questions

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