Korsuva (difelikefalin acetate)
Analgesic Opioid Agonists - Antipruritic Intravenous Vial (Ml)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Difelikefalin acetate is a kappa opioid receptor agonist.
Difelikefalin is a kappa opioid receptor (KOR) agonist. It is a selective, full agonist of KOR with significantly greater affinity for KORs than mu opioid receptors. Alleviation of itching is postulated to occur through activation of KOR on peripheral sensory neurons and immune cells as well as through a reduction in inflammatory markers.
Due to the hydrophilicity of difelikefalin, there is minimal penetration across the blood-brain barrier. The mechanism of action of difelikefalin is not fully understood.
The pharmacokinetics of difelikefalin are dose proportional over single and multiple IV dosages in patients with chronic kidney disease undergoing hemodialysis (HD). Steady-state was reached after the second administered dose. Difelikefalin is 23 to 28% protein bound in patients undergoing dialysis .
The half-life in HD subjects prior to dialysis ranged between 23 and 31 hours. Following administration of radiolabeled difelikefalin, >99% of circulating radioactivity was present in plasma as parent drug. Hemodialysis reduced difelikefalin plasma concentrations by 70 to 80% and difelikefalin was not detectable in plasma after 2 dialysis cycles.
Difelikefalin is not metabolized by cytochrome P-450 (CYP) isoenzymes 1A2, 2C19, 2C8, 2C9, 2D6 or 3A. Following administration to patients on HD, 11% of the dosage was excreted in urine, 59% in feces, and 20% in dialysate fluid. No clinically significant differences in pharmacokinetics of difelikefalin were observed based on age (25-80 years), sex, race/ethnicity, or mild to moderate hepatic impairment.
Generic name: difelikefalin acetate
Drug class: Analgesic Opioid Agonists - Antipruritic
Therapeutic class: Analgesic, Anti-inflammatory or Antipyretic
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Korsuva
Indications
The following indications are listed for Korsuva:
- Pruritus In Hemodialysis-Dependent Chronic Kidney Disease
Also known as: Chronic Kidney Disease Associated Pruritus In Hemodialysis-Dependent Person, Ckd-Ap In Hdd Patient.
Dosing
No dosing information is available for this tab.
Difelikefalin is administered by IV bolus injection into the venous line of the dialysis circuit at the end of each hemodialysis (HD) treatment. The drug is removed by the dialyzer and must be administered after blood is no longer circulating through the dialyzer.
Administer the dose of difelikefalin either during or after rinse back of the dialysis circuit. If the dose is given after rinse back, follow the injection of difelikefalin with at least 10 mL of normal saline flush. If the dose is given during rinse back, no additional normal saline is needed to flush the line.
Difelikefalin is available as a single-dose solution. Do not mix or dilute the solution. Administer the dose within 60 minutes of completion of the syringe preparation. Discard any unused product.
If a HD treatment is missed, resume difelikefalin at the end of the next HD treatment.
Store vials of difelikefalin at 20-25degreesC (excursions permitted between 15-30degreesC). Do not freeze. Prepared injection syringes can be stored at 20-25degreesC until dosing.
| Drug label | Dosing type | Instructions |
|---|---|---|
| Korsuva 65 Mcg/1.3 Ml Vial | Maintenance | Inject 0.5 mcg/kg via venous line of dialysis circuit by intravenous route 3 times per week at the end of dialysis during rinse back. |
No dosing information is available for this tab.
Drug interactions
No clinical studies evaluating the drug interaction potential of difelikefalin have been conducted.
In vitro studies indicate that difelikefalin does not inhibit cytochrome P-450 (CYP) isoenzymes 1A2, 2B6, 2C8, 2C9, 2C19, 3A, or 2D6 or induce CYP1A2, CYP2B6, or CYP3A. Difelikefalin is not a substrate of CYP450 enzymes (CYP1A2, CYP2C19, CYP2C8, CYP2C9, CYP2D6, or CYP3A).
Difelikefalin is not an inhibitor of uridine diphosphate (UDP)-glucuronosyl transferase (UGT) enzymes 1A3, 1A9, or 2B7.
Difelikefalin does not inhibit the following transporters: breast cancer resistance protein (BCRP), P-glycoprotein (P-gp), organic anion transporter (OAT)1, OAT3, organic cation transporter (OCT)1, OCT2, OAT polypeptide (OATP)1B1, OATP1B3, multidrug and toxic compound extrusion (MATE)1, or MATE2-K. Difelikefalin is not a substrate of OAT1, OAT2, OAT3, OATP1A2, OCT2, OCT3, L-type amino acid transporter (LAT)1, peptide transporter (PEPT)1, PEPT2, apical sodium-dependent bile acid transporter (ASBT), bile salt export pump (BSEP), multidrug resistance protein (MRP)2, OATP1B1, OATP1B3, OATP2B1, OCT1, novel OCT (OCTN)1, OCTN2, P-gp, BCRP, organic solute transporter (OST)alpha/beta, MATE1, or MATE2-K.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*None
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
- No disease contraindications
Adverse reactions
The most common adverse reactions associated with difelikefalin in clinical trials with an incidence of >=2% and >=1% higher than placebo were diarrhea, dizziness, nausea, gait disturbances (including falls), hyperkalemia, headache, somnolence, and mental status changes.
More Frequent
- Hyperkalemia
Less Frequent
- Accidental fall
More Frequent
- Altered mental status
- Dizziness
- Drowsy
- Gait abnormality
- Headache disorder
- Nausea
Precautions
No enhanced messaging available.
The safety and effectiveness of difelikefalin in pediatric patients have not been established.
There are limited human data on use of difelikefalin in pregnancy to evaluate a drug-associated risk for major birth defects or miscarriage. In animal reproduction studies, administration of difelikefalin to pregnant rats and rabbits during the period of organogenesis at doses 711 and 10 times the maximum recommended human dose (MRHD), respectively, resulted in no adverse effects.
There are no data regarding the presence of difelikefalin in human milk, effects on the breast-fed infant, or effects on milk production. In animal studies, difelikefalin was transferred into the milk of lactating rats. When a drug is present in animal milk, it is likely that the drug will be present in human milk.
Consider the developmental and health benefits of breastfeeding along with the mother's clinical need for difelikefalin and any potential adverse effects on the breast-fed child or from the underlying maternal condition.
The manufacturer makes no specific dosage recommendations for geriatric patients.
Of the 848 patients who received difelikefalin in clinical trials, 32.8% were >=65 years of age and 11.6% were >=75 years of age. No overall differences in safety or effectiveness have been observed between patients >=65 years of age and younger patients, with the exception of a higher incidence of somnolence (7 versus 2.8%). Placebo-treated patients in these age groups experienced comparable incidences of somnolence. No differences in plasma concentration of difelikefalin were observed based on age.
ICD codes
| Code | Type | Description |
|---|---|---|
| Pruritus in hemodialysis-dependent chronic kidney disease | ||
| N18.6 | ICD10CM | End stage renal disease |
ICD code information from First Databank (FDB).
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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