KOROSTATIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for KOROSTATIN (KOROSTATIN).
KOROSTATIN is a direct thrombin inhibitor that binds reversibly to the active site of thrombin, blocking its interaction with substrates and thereby inhibiting fibrin formation, platelet activation, and coagulation cascade amplification.
| Metabolism | Metabolized via hydrolysis to an inactive metabolite; minimal hepatic cytochrome P450 involvement. |
| Excretion | Renal: 70% unchanged; biliary/fecal: 20% as metabolites; 10% other |
| Half-life | 8-12 hours in normal renal function; prolonged to 24-36 hours in severe renal impairment (CrCl <30 mL/min) |
| Protein binding | 99% bound to albumin |
| Volume of Distribution | 0.3-0.5 L/kg, indicating distribution primarily in extracellular fluid |
| Bioavailability | Oral: 70-80% |
| Onset of Action | Oral: 30-60 minutes; IV: 5-10 minutes |
| Duration of Action | Oral: 8-12 hours; IV: 6-8 hours |
50 mg orally twice daily
| Dosage form | TABLET |
| Renal impairment | GFR ≥60 mL/min: No adjustment. GFR 30-59 mL/min: 25 mg twice daily. GFR 15-29 mL/min: 25 mg once daily. GFR <15 mL/min: Not recommended. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: 25 mg once daily. Child-Pugh C: Not recommended. |
| Pediatric use | Weight ≥20 kg: 1.25 mg/kg twice daily; maximum 50 mg twice daily. Weight <20 kg: Not established. |
| Geriatric use | No specific dose adjustment; monitor renal function and consider age-related decline in GFR. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for KOROSTATIN (KOROSTATIN).
| Breastfeeding | Present in breast milk; M/P ratio 0.8. Avoid use due to potential neonatal renal toxicity. |
| Teratogenic Risk | First trimester: No human data; animal studies show skeletal malformations at 5x MRHD. Second/third trimester: Risk of fetal renal impairment and oligohydramnios, especially with prolonged use. |
| Fetal Monitoring | Monitor fetal renal function via ultrasound (amniotic fluid index) and Doppler. Evaluate maternal renal function (serum creatinine, BUN) and blood pressure. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Active pathological bleeding (e.g., intracranial hemorrhage, gastrointestinal bleeding).","History of hypersensitivity to KOROSTATIN or any of its excipients.","Severe renal impairment (creatinine clearance <30 mL/min) due to increased bleeding risk.","Concurrent use of other anticoagulants (e.g., warfarin, heparin, LMWH) unless specifically indicated."]
| Precautions | ["Increased risk of bleeding, especially in patients with renal impairment, concomitant use of antiplatelet agents or anticoagulants, and in elderly patients.","Spinal/epidural hematomas may occur with neuraxial anesthesia or spinal puncture, leading to long-term or permanent paralysis.","Discontinue KOROSTATIN prior to invasive procedures; monitor for signs of bleeding.","Hepatic toxicity: monitor liver enzymes; discontinue if significant elevation occurs."] |
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| Fertility Effects | Reversible reduction in spermatogenesis in males; ovarian suppression in females with return to baseline after discontinuation. |