DIFELIKEFALIN INJ,SOLN

Clinical Criteria Summary

Pruritus attributed to cause other than end-stage kidney disease
Severe hepatic impairment
Inclusion Criteria (All of the following must be met)
Care provided by a VA / VA Community Care nephrologist
End-stage kidney disease receiving hemodialysis three times per week
Moderate-to-severe pruritus associated with chronic kidney disease despite optimized management of condition
Inadequate benefit from trial of topical emollients and/or topical analgesic agents (e.g., capsaicin, pramoxine)
Inadequate benefit from trial of gabapentin (or pregabalin, if gabapentin not tolerated)
Weekly mean score of more than 4 points on the 24-hour Worst Itching Intensity Numerical Rating Scale (WI-NRS)
Optimization of dialysis, management of hyperparathyroidism and hyperphosphatemia
Trial of oral antihistamines, and/or alternate agents (e.g., montelukast, sertraline) or phototherapy may also be useful in managing symptoms and considered on an individual basis

Indicated for the treatment of moderate-to-severe pruritus associated with chronic kidney disease in adults undergoing hemodialysis.
Clinical trial population included patients with end-stage kidney disease receiving hemodialysis at least three times per week for at least 3 months, with moderate-to-severe pruritus defined as a weekly mean score >4 points on the WI-NRS.

Recommended dose is 0.5 mcg/kg by intravenous (IV) bolus injection into the venous line of the dialysis circuit at the end of each hemodialysis treatment.
Available as a 65 mcg/1.3 mL (50 mcg/mL) solution for injection.

Primary efficacy outcome defined as ≥3-point decrease from baseline in weekly mean WI-NRS score; FDA-recommended primary outcome is ≥4-point decrease.
Treatment effect noted by week 1 and persists throughout the 12 weeks of treatment.
Patient should be reassessed for response to treatment; therapy should be discontinued if there is not a clinically meaningful reduction in itch intensity (e.g., at least a 3 to 4-point reduction on the WI-NRS) or improvement in itch-related sleep disturbance, mood, or quality of life, or if treatment is not tolerated.

Recommended for refractory uremic pruritus.
May be considered after attempts to reduce symptoms through optimization of dialysis, management of hyperparathyroidism and hyperphosphatemia, use of topical emollients and/or analgesic agents (e.g., capsaicin, pramoxine), a trial of oral antihistamines (e.g., diphenhydramine, hydroxyzine, loratadine), and gabapentin (pregabalin if gabapentin not tolerated).
Alternate agents (e.g., montelukast, sertraline) may be considered prior to difelikefalin on an individual basis. Phototherapy may also be considered as a treatment option.

No boxed warning or contraindications.
Dizziness, somnolence, mental status changes, and gait disturbances, including falls, have occurred. Centrally-acting depressant medications, sedating antihistamines, and opioid analgesics should be used with caution.
May impair mental or physical abilities; advise patients not to drive or operate dangerous machinery until the effect on the patient’s ability is known.

Not recommended for patients with severe hepatic impairment (not evaluated).
No clinically significant difference in pharmacokinetics noted in patients with mild to moderate hepatic impairment.
Higher incidence of somnolence in patients 65 years of age and older compared to patients <65 years.
Abuse potential: Peripherally restricted, selective kappa opioid receptor agonist; no indication of abuse or physical dependence, and no reported adverse events related to withdrawal upon discontinuation.