CRYSVITA Solution for injection Ref.[7654] Active ingredients: Burosumab

Treatment should be initiated by a physician experienced in the management of patients with metabolic bone diseases.

Posology

Oral phosphate and vitamin D analogues should be discontinued 1 week prior to initiation of treatment. At initiation, fasting serum phosphate concentration should be below the reference range for age (see section 4.3).

The recommended starting dose is 0.4 mg/kg of body weight and the normal maintenance dose is 0.8 mg/kg burosumab given every two weeks. The maximum dose is 90 mg. All doses should be rounded to the nearest 10 mg.

After initiation of treatment with burosumab, fasting serum phosphate should be measured every 2 weeks for the first month of treatment, every 4 weeks for the following 2 months and thereafter as appropriate. Fasting serum phosphate should also be measured 4 weeks after any dose adjustment. If fasting serum phosphate is within the reference range for age, the same dose should be maintained.

To decrease the risk for ectopic mineralisation, it is recommended that fasting serum phosphate is targeted in the lower end of the normal reference range for age (see section 4.4).

Dose increase

If fasting serum phosphate is below the reference range for age, the dose may be increased stepwise by 0.4 mg/kg up to a maximum dose of 2.0 mg/kg (maximum dose of 90 mg). Fasting serum phosphate should be measured 4 weeks after dose adjustment. Burosumab should not be adjusted more frequently than every 4 weeks.

Dose decrease

If fasting serum phosphate is above the reference range for age, the next dose should be withheld and the fasting serum phosphate reassessed within 4 weeks. The patient must have fasting serum phosphate below the reference range for age to restart burosumab at approximately half of the previous dose.

Missed dose

If a patient misses a dose, burosumab should be resumed as soon as possible at previously prescribed dose.

Special populations

Renal impairment

Burosumab has not been studied in patients with renal impairment. Burosumab must not be given to patients with severe or end stage renal disease (see section 4.3).

Paediatric population

The safety and efficacy of burosumab in children aged less than one year have not been established. No data are available.

Method of administration

For subcutaneous use.

Burosumab should be injected in the arm, abdomen, buttock or thigh. The maximum volume of medicinal product per injection site is 1.5 ml. If more than 1.5 ml is required on a given dosing day, the total volume of medicinal product should be split and should be administered at two different injection sites. Injections sites should be rotated and carefully monitored for signs of potential reactions (see section 4.4).

For handling of burosumab before administration, see section 6.6.

There is no experience with overdose of burosumab. Burosumab has been administered in paediatric clinical trials without dose limiting toxicity using doses up to 2.0 mg/kg body weight with a maximal dose of 90 mg every two weeks. In adult clinical trials no dose limiting toxicity has been observed using doses up to 1.0 mg/kg or a maximal total dose of 128 mg every 4 weeks.

Management

In case of overdose, it is recommended to stop burosumab and to monitor biochemical response.

2 years.

Store in a refrigerator (2°C to 8°C). Do not freeze.

Store in the original package in order to protect from light.

Clear glass vial with butyl rubber stopper, and aluminium seal.

Pack size of one vial.

Each vial is for single use only.

o not shake the vial before use.

Burosumab should be administered using aseptic technique and sterile disposable syringes and injection needles.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.