KORSUVA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for KORSUVA (KORSUVA).
Selective kappa opioid receptor (KOR) agonist; modulates pruritus via peripheral and central mechanisms.
| Metabolism | Metabolized by peptidases to active metabolite; not significantly metabolized by CYP450 enzymes. |
| Excretion | Primarily eliminated via biliary excretion into feces (approximately 70%), with renal excretion accounting for about 30% (mostly as unchanged drug and metabolites). |
| Half-life | Terminal elimination half-life approximately 24-36 hours in healthy subjects; prolonged to 40-60 hours in patients with moderate to severe hepatic impairment, requiring dose adjustment. |
| Protein binding | Approximately 99% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution approximately 0.1-0.3 L/kg (total body weight), indicating limited extravascular distribution and largely confined to plasma compartment. |
| Bioavailability | Subcutaneous administration: absolute bioavailability approximately 80%. |
| Onset of Action | Subcutaneous administration: onset of itch reduction observed within 1-2 weeks, with maximal effect by 12-24 weeks. |
| Duration of Action | Following single subcutaneous dose, pharmacodynamic effect (pruritus reduction) persists for approximately 2-4 weeks, supporting once-monthly dosing interval. |
0.5 mcg/kg IV bolus three times per week post-hemodialysis.
| Dosage form | SOLUTION |
| Renal impairment | No adjustment required for any degree of renal impairment as drug is only indicated in dialysis patients. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose to 0.25 mcg/kg; Child-Pugh C: not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment recommended; monitor for adverse effects due to potential age-related changes. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for KORSUVA (KORSUVA).
| Breastfeeding | It is unknown if difelikefalin is excreted in human milk. No data on M/P ratio. Due to potential for adverse reactions in breastfed infants, breastfeeding is not recommended during treatment and for 24 hours after the last dose. |
| Teratogenic Risk | Korsuva (difelikefalin) is not recommended during pregnancy due to lack of adequate human data. Animal studies show no evidence of fetal harm at doses up to 10 times the maximum recommended human dose. However, exposure in first trimester is not recommended. In second and third trimesters, use only if potential benefit justifies risk. |
■ FDA Black Box Warning
No FDA boxed warning exists for Korsuva (difelikefalin).
| Serious Effects |
None known.
| Precautions | ["May cause dizziness, somnolence, or gait disturbances; monitor for falls.","Avoid use with other CNS depressants.","Potential for abuse or dependence; limited data in patients with history of substance abuse."] |
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| Fetal Monitoring | Monitor maternal blood pressure and heart rate due to potential for dizziness or hypotension. Fetal monitoring not specifically required but standard obstetric monitoring recommended. Assess for signs of addiction or misuse in mother. |
| Fertility Effects | No human data on fertility effects. In animal studies, no adverse effects on male or female fertility were observed at doses up to 10 times the MRHD. |