PARSABIV Solution for injection Ref.[9571] Active ingredients: Etelcalcetide

Posology

The recommended initial dose of etelcalcetide is 5 mg administered by bolus injection 3 times per week. Corrected serum calcium should be at or above the lower limit of the normal range prior to administration of first dose of Parsabiv, a dose increase, or reinitiation after a dose stop (see also dose adjustments based on serum calcium levels). Parsabiv should not be administered more frequently than 3 times per week.

Dose titration

Parsabiv should be titrated so that doses are individualised between 2.5 mg and 15 mg. The dose may be increased in 2.5 mg or 5 mg increments no more frequently than every 4 weeks to a maximum dose of 15 mg 3 times per week to achieve the desired parathyroid hormone (PTH) target.

Dose adjustments based on PTH levels

PTH should be measured after 4 weeks from initiation or dose adjustment of Parsabiv, and approximately every 1-3 months during maintenance. Dose adjustment may be necessary at any time during treatment including the maintenance phase.

If PTH is below 100 pg/mL (10.6 pmol/L), the dose should be reduced or temporarily stopped. If PTH does not return to >100 pg/mL following dose reduction, the dose should be stopped. For patients in whom the dose is stopped, Parsabiv should be reinitiated at a lower dose once PTH returns to >150 pg/mL (15.9 pmol/L) and pre-dialysis serum corrected calcium (cCa) ≥8.3 mg/dL (2.08 mmol/L). If the patient’s last administered dose was 2.5 mg, Parsabiv may be reinitiated at the 2.5 mg dose level if PTH is >300 pg/mL (31.8 pmol/L), and the most recent pre-dialysis serum cCa ≥8.3 mg/dL (2.08 mmol/L).

Additional recommendations related to the management of low calcium are provided in the table below.

Parsabiv may be used as part of a therapeutic regimen including phosphate binders and/or vitamin D sterols, as appropriate (see section 5.1).

Missed doses

If a regularly scheduled haemodialysis treatment is missed, do not administer any missed doses. Parsabiv should be administered at the next haemodialysis treatment at the same dose. If doses are missed for more than 2 weeks, then Parsabiv should be administered at 5 mg, (or 2.5 mg if that was the patient’s last administered dose), and titrated to achieve the desired PTH.

Dose adjustments based on serum calcium levels

Serum calcium should be measured within 1 week of initiation or dose adjustment of Parsabiv. Once the maintenance phase has been established for a patient, corrected serum calcium should be measured approximately every 4 weeks. In the studies total serum calcium was measured using Roche modular analysers. The lower limit of the normal range for corrected serum calcium was 8.3 mg/dL (2.08 mmol/L). Other laboratory assays may have different cut-offs for the lower limit of the normal range.

In the event that clinically meaningful decreases in corrected serum calcium levels below the lower limit of the normal range occur and/or symptoms of hypocalcaemia occur, the following management is recommended:

Switch from cinacalcet to Parsabiv

Parsabiv should not be initiated in patients until 7 days after the last dose of cinacalcet and the corrected serum calcium is at or above the lower limit of the normal range (see section 5.1).

Paediatric population

The safety and efficacy of etelcalcetide in children and adolescents less than 18 years has not yet been established. No data are available.

Elderly

Dosing recommendations for elderly patients are the same as for adult patients.

Method of administration

Parsabiv should not be diluted.

Parenteral medicinal products should be inspected visually for particulate matter and change in colour prior to administration.

Parsabiv is administered into the venous line of the dialysis circuit at the end of the haemodialysis treatment during rinse-back or intravenously after rinse-back. When given during rinse-back at least 150 mL of rinse-back volume should be administered after injection. If rinse-back is completed and Parsabiv was not administered, then it may be administered intravenously followed by at least 10 mL saline flush volume.

Overdose of etelcalcetide may lead to hypocalcaemia with or without clinical symptoms and may require treatment. In the event of overdose, serum calcium should be checked and patients should be monitored for symptoms of hypocalcaemia (see section 4.4) and appropriate measures should be taken (see section 4.2). Although Parsabiv is cleared by dialysis, haemodialysis has not been studied as a treatment for overdose. Single doses up to 60 mg and multiple doses up to 22.5 mg 3 times a week at the end of dialysis in patients receiving haemodialysis were safely administered in clinical trials.

Shelf life: 4 years.

Once removed from the refrigerator:

• Parsabiv is stable for a maximum of 7 cumulative days if stored in the original carton. No special temperature storage requirements are needed.
• If removed from the original carton Parsabiv is stable for a maximum of 4 hours if protected from direct sunlight.

Store in a refrigerator (2°C–8°C).

Keep the vial in the outer carton in order to protect from light.

Parsabiv 2.5 mg solution for injection: Single use vial (type I glass) with stopper (fluoropolymer laminated elastomeric) and an aluminium seal with flip-off dust cover. Each vial contains 0.5 mL solution for injection.

Parsabiv 5 mg solution for injection: Single use vial (type I glass) with stopper (fluoropolymer laminated elastomeric) and an aluminium seal with flip-off dust cover. Each vial contains 1 mL solution for injection.

Parsabiv 10 mg solution for injection: Single use vial (type I glass) with stopper (fluoropolymer laminated elastomeric) and an aluminium seal with flip-off dust cover. Each vial contains 2 mL solution for injection.

Pack sizes of 1, 6, 12 and 42 vials.

Not all pack sizes may be marketed.

For single use only.

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