REGONOL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for REGONOL (REGONOL).
Regorafenib is a multikinase inhibitor that targets various receptor tyrosine kinases involved in angiogenesis, oncogenesis, and tumor microenvironment, including VEGFR1-3, TIE2, PDGFR-β, FGFR1, KIT, RET, RAF-1, and BRAF.
| Metabolism | Primarily metabolized by CYP3A4 and UGT1A9, with minor contributions from CYP2C8. |
| Excretion | Approximately 70% renal (unchanged) and 30% biliary/fecal as glucuronide conjugates. |
| Half-life | Terminal half-life of 2–4 hours; clinically relevant for dosing every 6–8 hours in renal impairment. |
| Protein binding | 92% bound primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 1.2 L/kg (0.8–1.6 L/kg); indicates extensive tissue distribution. |
| Bioavailability | Oral: 85% (range 75–95%); rectal: 50%; IM: 100%. |
| Onset of Action | Oral: 30–60 minutes; IV: 5–15 minutes. |
| Duration of Action | 4–6 hours; may be prolonged in hepatic impairment. |
Intravenous: 400 mg every 12 hours for 60 doses. Maintenance: 400 mg twice daily for 180 days (6 months).
| Dosage form | INJECTABLE |
| Renal impairment | CrCl >50 mL/min: no adjustment. CrCl 30-50 mL/min: 400 mg every 24 hours. CrCl <30 mL/min: not recommended. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: 200 mg every 12 hours. Child-Pugh C: not recommended. |
| Pediatric use | Not established for children under 18 years; safety and efficacy not studied. |
| Geriatric use | No specific dose adjustment; monitor renal function due to age-related decline. Use with caution due to potential for increased adverse effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for REGONOL (REGONOL).
| Breastfeeding | Excreted into human breast milk with an M/P ratio of 0.8. Limited data; use only if benefit outweighs risk. Monitor infant for bradycardia and hypotension. |
| Teratogenic Risk | First trimester: Animal studies show increased risk of cardiac malformations and neural tube defects at doses equivalent to human exposure. Second/third trimester: Potential for fetal growth restriction and oligohydramnios due to placental hypoperfusion. |
| Fetal Monitoring |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["None known"]
| Precautions | ["Hepatotoxicity: Severe and sometimes fatal hepatic injury; monitor liver function tests.","Hemorrhage: Increased risk of bleeding events; discontinue if severe hemorrhage occurs.","Cardiac ischemia: Increased incidence of myocardial ischemia.","Gastrointestinal perforation: Discontinue if gastrointestinal perforation occurs.","Dermatologic toxicity: Hand-foot skin reaction, severe rash; manage with supportive care and dose modifications.","Hypertension: Monitor blood pressure; manage with antihypertensives.","Wound healing complications: Discontinue at least 2 weeks before elective surgery.","Reversible posterior leukoencephalopathy syndrome (RPLS): Discontinue if RPLS occurs.","Thyroid dysfunction: Monitor thyroid function.","Infection: Increased risk of infections, including fatal infections.","Arterial thrombotic events: Increased risk including stroke and myocardial infarction."] |
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| Regular fetal ultrasound for growth and amniotic fluid index. Maternal blood pressure and heart rate monitoring. Assess fetal heart rate patterns after maternal dosing. |
| Fertility Effects | Reversible impairment of spermatogenesis in males (oligospermia, reduced motility). Limited human data; advise contraception during treatment. |