The FDA has approved Difelikefalin injection (Korsuva; Cara Therapeutics and Vifor Pharma) for the treatment of moderate-to-severe chronic kidney disease–associated pruritus in adults undergoing hemodialysis.
The FDA has approved Difelikefalin injection (Korsuva; Cara Therapeutics and Vifor Pharma) for the treatment of moderate-to-severe chronic kidney disease–associated pruritus (CKD-aP) in adults undergoing hemodialysis (HD). The approval carries the limitation that Korsuva has not been studied in patients on peritoneal dialysis and is not recommended for use in this population.1
CKD-aP is an intractable systemic itch condition that occurs in patients with CKD who are undergoing dialysis. An estimated 60% to 70% of dialysis patients report pruritus, with 30% to 40% describing the pruritus as moderate or severe. Most patients with CKD-aP will experience symptoms for months or years, resulting in an association with depression and decreased quality of life. Because of an increased risk of infections and inflammation, CKD-aP is also an independent predictor of mortality.2
Pharmacology and Pharmacokinetics
Korsuva is a κ-opioid receptor agonist. It achieves steady state plasma concentration after the second dose and has an elimination half-life of 23 to 31 hours. Korsuva is not metabolized by cytochrome P450 enzymes CYP1A2, CYP2C19, CYP2C8, CYP2C9, CYP2D6, or CYP3A. No clinically significant pharmacokinetic differences were observed based on age, ethnicity, gender, mild-to-moderate hepatic impairment, or race.1
Dosage and Administration
The recommended dose of Korsuva is 0.5 mcg/kg administered by intravenous (IV) bolus injection into the venous line of the dialysis circuit at the end of each HD treatment. Korsuva is supplied as a single-dose vial that should not be diluted or mixed prior to administration. It must be given within 60 minutes of syringe preparation.1
Korsuva was evaluated for efficacy in 2 double-blind, multicenter, placebo-controlled, randomized trials of 851 adults who were undergoing HD and experiencing moderate-to-severe pruritus. All participants received IV bolus injections of either Korsuva 0.5 mcg/kg or a placebo into the venous line of the HD circuit at the end of each HD session 3 times per week for 12 weeks. In both trials, a 7-day run-in period before randomization was used to confirm each participant had moderate-to-severe pruritus. The run-in period also established a baseline itch intensity, which was measured by the daily, patient-reported 24-hour Worst Itch Numeric Rating Scale (WI-NRS) scores, with 0 representing no itch and 10 representing the worst itch imaginable.
Efficacy in each trial was based on the proportion of participants who demonstrated a 4-point or greater improvement from baseline in the weekly mean of the daily 24-hour WI-NRS score at week 12. Both trials found improvement in the groups that were using Korsuva compared with those using the placebo. In trial one, 40% of the Korsuva group and 21% of the placebo group experienced itch reduction. In trial 2, itch reduction was reported in 37% of the Korsuva group and 26% of the placebo group. Additionally, itch reduction was observed at week 4 and sustained through week 12 in both trials.1
Contraindictions, Warnings, and Precautions
There are no contraindications to treatment with Korsuva. Dizziness; gait disturbances, including falls; mental status changes; and somnolence have occurred in patients using Korsuva. The incidence of somnolence was higher in patients who were 65 years and older. The concurrent use of centrally acting depressant medications, opioid analgesics, and sedating antihistamines may increase the likelihood of these adverse reactions and should be used cautiously during treatment with Korsuva. Korsuva may impair the mental or physical abilities needed to perform potentially hazardous activities, such as driving a car and operating machinery. Advise patients not to drive or operate dangerous machinery until the effect of the medication on the patient’s ability to drive or operate machinery is known. The use of Korsuva in patients with severe hepatic impairment is not recommended. The most common adverse reactions are diarrhea; dizziness; gait disturbances, including falls; headaches; hyperkalemia; mental status change; nausea; and somnolence.1
Monica Holmberg, PharmD, BCPS is a pharmacist and Pharmacy Times® contributor.
1. Korsuva. Prescribing information. Cara Therapeutics Inc and Vifor (International) Inc; 2021. Accessed December 1, 2021. https://korsuva.com/sites/g/files/brlbcj1286/files/2021-08/ korsuva-prescribing-information.pdf
2. Cara Therapeutics and Vifor Pharma announce U.S. FDA approval of Korsuva (difelikefalin) injection for the treatment of moderate-to-severe pruritus in hemodialysis patients. News release. Cara Therapeutics and Vifor Pharma; August 23, 2021. Accessed December 1, 2021. https://ir.caratherapeutics.com/news-releases/ news-release-details/cara-therapeutics-and-vifor-pharma-announce-us-fda-approval