Indications
Difelikefalin is approved for use in adults with moderate-to-severe pruritus linked to chronic kidney disease-associated pruritus (CKD-aP or uremic pruritus). This treatment is specifically recommended for patients undergoing hemodialysis.
Pharmacodynamics
Difelikefalin functions by targeting opioid receptors to alleviate the pruritus often experienced by patients with chronic kidney disease undergoing hemodialysis. It is administered at the conclusion of each hemodialysis session through a bolus intravenous injection. Due to its action on opioid receptors, patients may experience side effects such as dizziness and somnolence, which could impair mental and physical abilities. Therefore, it is essential that patients refrain from operating heavy machinery or engaging in activities that require full mental alertness until their individual response to the medication is ascertained.
Absorption
Difelikefalin is introduced into the patient's system via bolus intravenous injection in conjunction with hemodialysis treatments, achieving nearly complete bioavailability with each dose.
Metabolism
Difelikefalin undergoes minimal metabolic processing, as it is not significantly metabolized and does not interact with cytochrome P450 enzymes. This characteristic simplifies its metabolic profile and reduces the risk of interactions with drugs that are metabolized by this enzyme system.
Mechanism of Action
Difelikefalin is a synthetic peptide that functions as an agonist of kappa opioid receptors (KORs), which are recognized for their role in modulating the itching sensation. Endogenous KOR agonists, known as dynorphins, exert a neuroinhibitory effect on itch perception at the spinal cord level. Studies utilizing mouse models have demonstrated the antipruritic effects of KOR agonists when addressing itchiness caused by various pruritogens. While the precise mechanism remains to be fully understood, the use of KOR agonists like difelikefalin has been shown to effectively reduce itching and improve the quality of life for patients experiencing uremic pruritus.
