Free special edition 2023

MARKETING AUTHORISATIONS

NEW SUBSTANCE Difelikefalin ( kapruvia °) in pruritus associated with chronic kidney disease An option for patients experiencing major discomfort, despite the uncertainties

POSSIBLY HELPFUL In two double-blind randomised trials including about 850 patients with chronic kidney disease and on haemo dialysis, difelikefalin , a kappa opioid

● There is a risk of pharmacodynamic drug inter actions with difelikefalin , particularly when com binedwith drugs known to lead to somnolence and dizziness. KAPRUVIA° - difelikefalin solution for intravenous injection • 50microgram of difelikefalin per ml of solution (vials of 1 ml) Vifor ■ Kappa opioid receptor agonist ■ Indication: “ moderate-to-severe pruritus associated with chronic kidney disease in adult patients on haemodialysis ”. [EU centralised procedure] ■ Dosage: 0.5 microgram/kg of dry body weight (the target postdial ysis weight) three times per week, by intravenous bolus injection into the venous line of the dialysis circuit, at the end of the haemodialysis session, during or after rinse-back. If there are additional haemodialy sis sessions, a fourth dose perweek can be considered, but nomore. COMPARE BEFORE DECIDING Pruritus associated with chronic kidney disease, in brief 20% to 40% of chronic kidney disease patients on haemo dialysis report having pruritus graded as moderate to severe in intensity. It can be diffuse, or localisedmainly to the back, arms, head or abdomen. As for all types of pruritus, skin irritation due to scratching can lead to infection and thickening of the skin (lichenification). Pruritus sometimes has a marked impact on quality of life, particularly as a result of sleep disturbance and its consequences (1-5).

receptor agonist, was effective in reducing pruritus in the short-term in 15% to 20%more patients than in the placebo groups. Difelikefalin mainly carries a risk of gastrointestinal, neuropsychiatric, and per haps sometimes serious cardiac disorders. In prac tice, despite the uncertainties, difelikefalin is an option to consider, with care, in patientswho experi encemajordiscomfort despitenon-pharmacological measures. ● Patientswithchronickidneydiseasewhoareunder going haemodialysis sometimes experience major discomfort due to pruritus. One hypothesis put for wardtoexplainthemechanismforthispruritus is an imbalance of the endogenous opioid system, with overexpression of mu opioid receptors and a con comitant underexpressionof kappa receptors. ● Difelikefalin is a “selective” kappa opioid recep tor agonist. ● In this situation, two double-blind randomised trials including a total of 851 patients have evalu ated difelikefalin , administered for 12weeks via the venous access line at the end of each session of haemodialysis. It was effective in relieving pruritus in 15% to 20% more patients than in the placebo groups. These results are, however, weakened by missing data for a significant number of patients, especially in the difelikefalin groups. ● The main adverse effects of difelikefalin are gastrointestinal disorders, hyperkalaemia, andpos sibly cardiac disorders. Despite a supposedly limit ed ability to cross the blood-brain barrier, it also carries a risk of neuropsychiatric disorders.

Excerpt from Prescrire Int June 2023 Full article (4 pages) available to subscribers at english.prescrire.org

Prescrire International Special Edition 2023 • Page 3