KAPRUVIA Solution for injection Ref.[49880] Active ingredients: Difelikefalin

Kapruvia should be restricted for in-centre haemodialysis use only.

Kapruvia is intended for use by healthcare professionals experienced in the diagnosis and treatment of conditions for which difelikefalin is indicated. Causes of pruritus other than chronic kidney disease should be excluded before initiating treatment with difelikefalin.

Posology

Difelikefalin is administered 3 times per week by intravenous bolus injection into the venous line of the dialysis circuit at the end of the haemodialysis treatment during rinse-back or after rinse-back.

The recommended dose of difelikefalin is 0.5 micrograms/kg dry body weight (i.e., the target postdialysis weight). The total dose volume (mL) required from the vial should be calculated as follows: 0.01 × dry body weight (kg), rounded to the nearest tenth (0.1 mL). For patients with a dry body weight equal to or above 195 kg the recommended dose is 100 micrograms (2 mL).

Injection volumes are detailed in the table below:

¹ More than 1 vial may be necessary if an injection volume of more than 1 mL is required.

An effect of difelikefalin in reducing pruritus is expected after 2-3 weeks of treatment.

Missed doses

If a regularly scheduled haemodialysis treatment is missed, Kapruvia should be administered at the next haemodialysis treatment at the same dose.

Extra treatment

If a 4th haemodialysis treatment is performed in a week, Kapruvia should be administered at the end of the haemodialysis per the recommended dose. No more than 4 doses per week should be administered even if the number of haemodialysis treatments in a week exceeds 4. A 4th dose of Kapruvia is unlikely to lead to accumulation of difelikefalin that would be of concern for safety, as the majority of remaining difelikefalin from the previous treatment will be cleared by haemodialysis (see sections 4.9 and 5.2). However, safety and efficacy of a 4th dose has not been fully established due to insufficient data.

Patients with incomplete haemodialysis treatment

For haemodialysis treatments less than 1 hour, administration of difelikefalin should be withheld until the next haemodialysis session.

Following administration of difelikefalin in haemodialysis subjects, up to 70% is eliminated from the body prior to the next haemodialysis session (see sections 4.9 and 5.2). Difelikefalin plasma level remaining at the time of the next haemodialysis is reduced by about 40-50% within one hour of haemodialysis.

Patients with hepatic impairment

No dose adjustment is required for patients with mild or moderate hepatic impairment (see section 5.2). Difelikefalin has not been studied in subjects with severe hepatic impairment (National Cancer Institute (NCI) Organ Dysfunction Working Group (ODWG)) and is therefore not recommended for use in this patient population.

Elderly population (≥65 years of age)

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

Paediatric population

The safety and efficacy of difelikefalin in children aged 0-17 years has not yet been established.

No data are available.

Method of administration

Kapruvia should not be diluted and should not be mixed with other medicinal products.

Difelikefalin is removed by the dialyzer membrane and must be administered after blood is no longer circulating through the dialyzer. Difelikefalin is administered 3 times per week by intravenous bolus injection into the venous line of the dialysis circuit at the end of the haemodialysis treatment during rinse-back or after rinse-back.

When given after rinse-back, at least 10 mL of sodium chloride 9 mg/mL (0.9%) solution for injection rinse-back volume should be administered after injection of Kapruvia. If the dose is given during rinse-back, no additional sodium chloride 9 mg/mL (0.9%) solution for injection is needed to flush the line.

Single dose of difelikefalin up to 12 times and multiple doses of difelikefalin up to 5 times the clinical dose of 0.5 micrograms/kg were administered in clinical studies in patients undergoing haemodialysis. A dose-dependent increase in adverse events including dizziness, somnolence, mental status changes, paraesthesia, fatigue, hypertension and vomiting, was observed.

In the event of overdose, the appropriate medical attention based on patient’s clinical status should be provided. Haemodialysis for 4 hours using a high-flux dialyzer effectively cleared approximately 70-80% of difelikefalin from plasma, and difelikefalin was not detectable in plasma at the end of the second of two dialysis cycles (see section 5.2).

2 years.

This medicinal product does not require any special storage conditions.

Kapruvia is supplied in a single use 2 mL glass vial (type I), with a bromobutyl rubber stopper, an aluminium seal and a blue flip-off plastic cap.

Pack sizes of 3 and 12 vials containing 1 mL of solution for injection.

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.