Overview
11 DESCRIPTION KORSUVA (difelikefalin) is a kappa opioid receptor agonist. Difelikefalin is a synthetic peptide with a single stereoisomer and is present as an acetate salt. Difelikefalin acetate is a white to off-white powder with a molecular formula of C 36 H 53 N 7 O 6 ∙xAcOH (1.0≤ × ≤2.0) and a molecular weight of 679.4 g/mol (mono- isotopic; free base). It is soluble in water.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action KORSUVA is a kappa opioid receptor (KOR) agonist. The relevance of KOR activation to therapeutic effectiveness is not known. 12.2 Pharmacodynamics Difelikefalin exposure-response relationships and the time course of pharmacodynamic response are unknown. Cardiac Electrophysiology At a dose 6 times the recommended dosage, difelikefalin does not prolong the QTc interval to any clinically relevant extent. 12.3 Pharmacokinetics The pharmacokinetics of difelikefalin is dose proportional over a single dosage range from 1 to 3 mcg/kg (2 to 6 times the recommended dosage) and multiple intravenous dosage range from 0.5 to 2.5 mcg/kg (1 to 5 times the recommended dosage) in chronic kidney disease patients undergoing HD.
Indications
- 1 INDICATIONS AND USAGE KORSUVA is indicated for the treatment of moderate-to-severe pruritus associated with chronic kidney disease (CKD-aP) in adults undergoing hemodialysis (HD). KORSUVA is a kappa opioid receptor agonist indicated for the treatment of moderate-to-severe pruritus associated with chronic kidney disease (CKD-aP) in adults undergoing hemodialysis (HD). ( 1 ) Limitation of Use Korsuva has not been studied in patients on peritoneal dialysis and is not recommended for use in this population.
Common Doses
- 0.5 mcg
- 0.1 mL
- 10 mL
Dosage
2 DOSAGE AND ADMINISTRATION Recommended dosage is 0.5 mcg/kg. ( 2.1 ) Administer by intravenous bolus injection into the venous line of the dialysis circuit at the end of each HD treatment. ( 2.1 ) Do not mix or dilute KORSUVA prior to administration. ( 2.2 ) Administer within 4 hours of syringe preparation. ( 2.3 ) See full prescribing information for additional recommendations on preparation and administration of KORSUVA. ( 2.2 , 2.3 ) 2.1 Dosage The recommended dosage of KORSUVA is 0.
Contraindications
- 4 CONTRAINDICATIONS None None
Side Effects
- 6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Dizziness, Somnolence, Mental Status Changes, and Gait Disturbances [see Warnings and Precautions (5.1) ] The most common adverse reactions (incidence ≥2% and ≥1% higher than placebo) were diarrhea, dizziness, nausea, gait disturbances, including falls, hyperkalemia, headache, somnolence, and mental status change. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Vifor (International) Inc. at 1-844-835-8277 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.
Interactions
- No major interactions listed on the FDA label. Always consult a healthcare professional.