Difelikefalin
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From MedlinePlus, U.S. National Library of Medicine
Dosing in kidney impairment
2 DOSAGE AND ADMINISTRATION Recommended dosage is 0.5 mcg/kg. Administer by intravenous bolus injection into the venous line of the dialysis circuit at the end of each HD treatment. Do not mix or dilute KORSUVA prior to administration. Administer within 4 hours of syringe preparation. 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 0.5 mcg/kg administered by intravenous bolus injection into the venous line of the dialysis circuit at the end of each HD treatment [see Dosage and Administration ] .
Administer KORSUVA by intravenous bolus injection into the venous line of the dialysis circuit at the end of each HD session. The dose may be given either during or after rinse back of the dialysis circuit. If the dose is given after rinse back, administer KORSUVA into the venous line followed by at least 10 mL of normal saline flush.
Dosing in liver impairment
Hepatic Impairment The influence of mild-to-moderate hepatic impairment on the pharmacokinetics of KORSUVA was evaluated in a population pharmacokinetic analysis which concluded that no KORSUVA dosage adjustments are needed in these populations [see Clinical Pharmacology ] . The influence of severe hepatic impairment on the pharmacokinetics of KORSUVA in subjects undergoing HD has not been evaluated; therefore, use of KORSUVA in this population is not recommended.
Preparation and administration
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Preparation Instructions Do not mix or dilute KORSUVA prior to administration. Inspect KORSUVA for particulate matter and discoloration prior to administration. The solution should be clear and colorless. Do not use KORSUVA vials if particulate matter or discoloration is observed. KORSUVA is supplied in a single-dose vial.
Discard any unused product. Injection volume to be administered is determined by patient's target dry body weight in kilograms (one patient may use less than the full contents of the vial or use more than one vial). See Table 1 . [See table below.] 4 1.2 125 – 134 1.3 135 – 144 1.4 145 – 154 1.5 155 – 164 1.6 165 – 174 1.7 175 – 184 1.8 185 – 194 1.9 195 – 204 2
Administration Instructions KORSUVA is removed by the dialyzer membrane and must be administered after blood is no longer circulating through the dialyzer. Administer KORSUVA by intravenous bolus injection into the venous line of the dialysis circuit at the end of each HD session. The dose may be given either during or after rinse back of the dialysis circuit.
If the dose is given after rinse back, administer KORSUVA into the venous line followed by 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. The dose must be administered within 4 hours of the syringe preparation. Discard any unused product.
| Target Dry Body Weight Range (kg) | Injection Volume (mL)Total Injection Volume (mL) = Patient Target Dry Body Weight (kg) x 0.01, rounded to the nearest tenth (0.1 mL). For patient target dry body weight outside of the ranges in Table 1, use this formula. |
|---|---|
| 36 – 44 | 0.4 |
| 45 – 54 | 0.5 |
| 55 – 64 | 0.6 |
| 65 – 74 | 0.7 |
| 75 – 84 | 0.8 |
| 85 – 94 | 0.9 |
| 95 – 104 | 1 |
| 105 – 114 | 1.1 |
| 115 – 124 | 1.2 |
| 125 – 134 | 1.3 |
| 135 – 144 | 1.4 |
| 145 – 154 | 1.5 |
| 155 – 164 | 1.6 |
| 165 – 174 | 1.7 |
| 175 – 184 | 1.8 |
| 185 – 194 | 1.9 |
| 195 – 204 | 2 |
Contraindications
None None
Safety data
Reported adverse events (FAERS)
Liver injury (LiverTox)
ELikelihood score E: Unlikely cause of clinically apparent liver injury.
Difelikefalin is a synthetic tetrapeptide agonist of the kappa opioid receptor that is used to treat pruritus in adults with chronic kidney disease undergoing hemodialysis. Difelikefalin has not been associated with serum enzyme elevations during therapy or with episodes of clinically apparent liver injury.
ABCDEA: well known cause; E: unlikely cause. [HD]: high doses only.
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary The limited human data on use of KORSUVA in pregnant women are not sufficient to evaluate a drug-associated risk for major birth defects or miscarriage. In animal reproduction studies, intravenous injection 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 in either rats or rabbits (see Data ) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S.
general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data In an embryofetal development study, difelikefalin was administered by intravenous injection to pregnant rats at doses of 0.25, 2.5, and 25 mg/kg/day during the period of organogenesis. Difelikefalin was not associated with embryofetal lethality or fetal malformations. Difelikefalin increased the incidences of skeletal variations (wavy ribs and incompletely ossified ribs) at the dose of 25 mg/kg/day (711 times the MRHD based on AUC comparison).
In an embryofetal development study, difelikefalin was administered by intravenous injection to pregnant rabbits at doses of 0.025, 0.05, and 0.1 mg/kg/day during the period of organogenesis. Maternal toxicity evidenced by decreased maternal body weight gain was noted in all dose groups. Difelikefalin was not associated with embryofetal lethality or fetal malformations at doses up to 0.1 mg/kg/day (10 times the MRHD based on AUC comparison). In a prenatal and postnatal development study, difelikefalin was administered by intravenous injection to pregnant rats at doses of 0.6, 2.5, and 10 mg/kg/day beginning on gestation day 7 and continuing through lactation day 20.
Persisting effects on decreased maternal body weight and/or maternal body weight gain as well as food consumption were noted at doses greater than or equal to 2.5 mg/kg/day (68 times the MRHD based on AUC comparison). No maternal effects were observed at 0.6 mg/kg/day (14 times the MRHD based on AUC comparison). No difelikefalin-related effects on postnatal developmental, neurobehavioral, or reproductive performance of offspring were noted at doses up to 10 mg/kg/day (282 times the MRHD based on AUC comparison).
For breastfeeding, also see LactMed (National Library of Medicine), which summarizes milk levels and infant effects.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
Price ladder
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