Difelikefalin
Also known as: Korsuva, Kapruvia, CR845
A peripherally acting kappa-opioid receptor agonist peptide, FDA-approved in 2021 as Korsuva for itch in adults on hemodialysis. Prescription medication.
Last updated
Mechanism of Action
Difelikefalin is a synthetic peptide built from D-amino acids that selectively activates kappa-opioid receptors. Its hydrophilic structure keeps it largely outside the central nervous system, so it acts on kappa receptors on peripheral sensory neurons and immune cells, reducing itch signaling and inflammation. Because it does not meaningfully activate mu-opioid receptors, it lacks the typical mu-opioid effects such as euphoria and respiratory depression.
- Half-life
- ~23-31 hours in hemodialysis patients
- Administration Routes
- Intravenous
- Research Status
- Clinical
Reported Benefits
- FDA-approved for moderate to severe pruritus linked to chronic kidney disease in adults on hemodialysis
- Reduced itch intensity versus placebo in the phase 3 KALM-1 trial
- Improved itch-related quality of life scores in phase 3 trials
Potential Side Effects
- Diarrhea
- Dizziness and somnolence
- Nausea
- Gait disturbances, including falls
- Hyperkalemia and headache
Common Dosing
Given as an intravenous bolus into the dialysis line at the end of each hemodialysis session (usually three times weekly), dosed by target dry body weight. It is given by dialysis staff, not at home. Dosing is set and supervised by the prescribing clinician.
The dosing information above is aggregated from research literature and anecdotal community reports for educational purposes only. It is not a recommendation, prescription, or medical advice. Peptides are sold as research chemicals only and are not intended for human use.
Contraindications
- No absolute contraindications on the US label
- Use caution with other centrally acting depressants because of dizziness and somnolence
- Not studied in peritoneal dialysis and not recommended there
No documented stacking partners for Difelikefalin yet.