Difelikefalin (Korsuva)

Difelikefalin is a hydrophilic synthetic D-amino-acid peptide developed as CR845/FE 202845 and marketed as Korsuva. Limited brain penetration favors peripheral rather than central action. US approval was in 2021 for persistent moderate-to-severe CKD-associated pruritus in adults on hemodialysis.

Kappa-receptor activation on peripheral sensory nerves dampens itch transmission; activation on immune cells may reduce inflammatory and itch-promoting mediators. Minimal central entry distinguishes it from classic mu-opioid analgesics and their euphoria, dependence and respiratory-depression profile.

The randomized KALM-1 and KALM-2 trials reported reductions in itch among adult hemodialysis patients. Over 12 weeks in KALM-1, significantly more difelikefalin recipients than placebo recipients achieved meaningful itch-intensity improvement, with better itch-related quality of life. Peripheral design does not eliminate every neurological adverse effect.

FDA approved the medicine in 2021 for moderate-to-severe itch associated with CKD in adults undergoing hemodialysis. An IVbolus is given through the dialysis circuit’s venous line at the end of each session, three times weekly. It is not a general anti-itch medicine for every cause or population.

Common effects include diarrhea, dizziness, nausea, hyperkalemia and headache. Drowsiness, altered mental status or gait changes can increase fall risk, especially with sedatives. Concomitant central nervous system depressants require caution despite the predominantly peripheral mechanism.