Defalix

• Approved Indications:
• Treatment of moderate to severe pruritus (itching) associated with chronic kidney disease (CKD) in adult patients undergoing hemodialysis (CKD-associated pruritus).
• Off-label/Investigational Uses:
• Potential treatment for other types of pruritus (e.g., cholestatic pruritus) under clinical investigation.
• Research ongoing for use in other neuropathic and inflammatory conditions involving pruritus.

• Route: Intravenous injection during hemodialysis session.
• Adult Dose:
• 0.5 micrograms/kg administered as an intravenous bolus injection at the end of each hemodialysis session, typically 3 times per week.
• Pediatrics:
• Safety and efficacy not established; not recommended.
• Elderly:
• No dose adjustment needed solely based on age.
• Renal/Hepatic Impairment:
• No adjustment required in patients on hemodialysis (primary population).
• Administration Notes:
• Inject slowly (over 1–2 minutes) at the end of dialysis to minimize injection-site reactions.

Difelikefalin acetate is a selective kappa-opioid receptor (KOR) agonist that acts peripherally on sensory neurons and immune cells, avoiding central nervous system penetration. By selectively activating peripheral KORs, it modulates the transmission of itch signals and reduces neuroinflammation associated with pruritus, thereby alleviating the sensation of itching in patients with CKD undergoing dialysis. This peripheral action minimizes the typical central opioid side effects such as sedation or addiction potential.

• Absorption: Administered intravenously; immediate systemic availability.
• Distribution: Moderate volume of distribution; limited CNS penetration due to poor blood-brain barrier permeability.
• Metabolism: Metabolized minimally; mainly eliminated unchanged.
• Half-life: Approximately 2.6 hours in hemodialysis patients.
• Elimination: Primarily renal elimination; removed during hemodialysis.
• Onset of Action: Symptom relief typically observed within hours after administration.

• Pregnancy:
• Data insufficient; no established safety profile in pregnancy. Use only if clearly needed.
• Lactation:
• Unknown if excreted in human milk. Caution advised. Breastfeeding not recommended during treatment until more data are available.

• Primary Class: Antipruritic agent
• Subclass: Peripheral kappa-opioid receptor agonist

• Known hypersensitivity to difelikefalin or any formulation excipients.
• Patients with known hypersensitivity to opioid agonists (caution due to class effects).

• Monitor for hypersensitivity reactions including rash, urticaria, or anaphylaxis.
• Use caution in patients with a history of seizures or neurological disorders; central nervous system effects are minimal but possible.
• Avoid abrupt discontinuation; monitor for potential withdrawal symptoms.
• Limited experience in patients with severe hepatic impairment; use with caution.
• Injection-site reactions may occur; rotate injection sites when possible.

Common:

• Diarrhea
• Dizziness
• Gait disturbances or falls
• Nausea
• Fatigue
• Headache

Less Common/Rare:

• Hypersensitivity reactions including rash and pruritus worsening
• Injection site reactions such as pain or erythema
• Possible dizziness leading to fall risk, especially in elderly

• No significant CYP450 enzyme interactions identified.
• Potential additive sedative effects if combined with CNS depressants.
• No known interactions with commonly used dialysis medications.
• Avoid concomitant use with other opioids unless carefully monitored.

• FDA approval granted for treatment of moderate-to-severe CKD-associated pruritus in hemodialysis patients, reflecting unmet clinical need.
• Ongoing studies evaluating broader antipruritic indications and long-term safety.
• Recent guidelines for CKD-associated pruritus incorporate difelikefalin as a therapeutic option following failure of conventional therapies.

• Store refrigerated at 2°C to 8°C (36°F to 46°F).
• Protect from light.
• Do not freeze.
• Use immediately after opening; discard unused portions.
• Keep out of reach of children.