difelikefalin acetate: clinical use

Prescribing considerations

• Exclude causes of pruritus other than chronic kidney disease before treatment.
• Restrict use to in-centre haemodialysis under clinicians experienced in the condition.
• Review concurrent sedatives and assess risks from dizziness, somnolence and falls.
• Use caution if the blood–brain barrier is clinically disrupted because central nervous system exposure may increase.
• Severe hepatic impairment has not been studied; use is not recommended.

Contraindications and cautions

• Hypersensitivity to difelikefalin or any excipient.

Monitoring

• Monitor serum potassium frequently; trials found a numerical imbalance in hyperkalaemia without an established causal relationship.
• Record itch severity and response using a consistent assessment method.
• Observe for drowsiness, dizziness, confusion and falls, particularly in older adults or with concurrent sedatives.
• Remain alert to cardiac failure or atrial fibrillation events, particularly with relevant history or interrupted cardiac treatment.

Clinical pharmacology

Difelikefalin is a hydrophilic synthetic peptide and selective kappa-opioid receptor agonist with low central nervous system penetration. Clearance is markedly reduced in haemodialysis patients, and dialysis removes a substantial proportion of circulating medicine. CYP-mediated and transporter-mediated pharmacokinetic interactions are unlikely.

Formulation and product differences

• Clear, colourless, particle-free intravenous solution in a single-use glass vial.
• Essentially sodium-free; contains acetic acid, sodium acetate, sodium chloride and water for injections.
• Must not be diluted or mixed with other medicinal products.