Generic
Regorafenib Monohydrate
1 brands available in the market
At a glance
Regorafenib is a multi-kinase inhibitor used for metastatic colorectal cancer (CRC), locally advanced unresectable or metastatic gastrointestinal stromal tumor (GIST), and hepatocellular carcinoma (HCC) after prior therapy failure.
Description
Regorafenib is a small molecule inhibitor of multiple membrane-bound and intracellular kinases involved in oncogenesis, tumor angiogenesis, metastasis, and tumor immunity. It inhibits RET, VEGFR1/2/3, KIT, PDGFR-α/β, FGFR1/2, TIE2, RAF-1, BRAF, BRAF V600E, and other kinases.
Indications
- Metastatic colorectal cancer (after fluoropyrimidine, oxaliplatin, irinotecan-based chemotherapy, anti-VEGF therapy, and anti-EGFR therapy for RAS wild-type)
- Locally advanced unresectable or metastatic GIST (after imatinib and sunitinib)
- Hepatocellular carcinoma (after sorafenib)
Therapeutic class
Targeted Cancer Therapy
Pharmacological class
Multi-kinase Inhibitor (TKI)
Pharmacology
Regorafenib inhibits multiple kinases involved in tumor growth, angiogenesis, and metastasis. It inhibits RET, VEGFR1/2/3, KIT, PDGFR, FGFR, RAF-1, BRAF, and other kinases. It demonstrates anti-angiogenic and anti-metastatic activity in animal models.
Mechanism of action
Prevents tumor growth and angiogenesis by inhibiting multiple tyrosine kinases.
Dosage
Adult Dose (Oral):
- Recommended dose: 160 mg (four 40 mg tablets) once daily for the first 21 days of each 28-day cycle
- Take with a low-fat meal (<600 calories, <30% fat) and swallow whole with water
- Dose modifications: Reduce in 40 mg increments; lowest recommended dose 80 mg daily
Administration
- Take at the same time each day
- Take with a low-fat meal
- Swallow tablet whole
- Do not take two doses on the same day to make up for a missed dose from the previous day
Missed dose
If you miss a dose, take it as soon as you remember; skip if it's almost time for next dose; do not double the dose.
Side effects
Side Effects:
- Hepatotoxicity
- Infections
- Hemorrhage
- Gastrointestinal perforation or fistula
- Hand-foot skin reaction (HFSR)
- Hypertension
- Cardiac ischemia and infarction
- Reversible Posterior Leukoencephalopathy Syndrome (RPLS)
Precautions & warnings
- Hepatotoxicity: Monitor LFT every 2 weeks during first 2 months; withhold, reduce, or discontinue for severe toxicity
- Hemorrhage: Permanently discontinue for severe or life-threatening hemorrhage; monitor INR in patients on warfarin
- GI perforation/fistula: Permanently discontinue
- Hypertension: Control blood pressure; monitor weekly for first 6 weeks
- Wound healing: Discontinue at least 2 weeks before surgery
- Embryo-fetal toxicity: Use effective contraception
Contraindications
- Hypersensitivity to regorafenib or any component
Drug interactions
- Strong CYP3A4 inducers (rifampin, phenytoin, carbamazepine, phenobarbital, St. John's Wort): Avoid
- Strong CYP3A4 inhibitors (clarithromycin, grapefruit juice, itraconazole, ketoconazole): Avoid
- BCRP substrates (methotrexate, fluvastatin, atorvastatin): Increased plasma concentrations; monitor for toxicity
Food interactions
Take with a low-fat meal for better absorption; it is not known whether it is safe to consume alcohol.
Use in pregnancy
Use in Pregnancy: No data on use in pregnant women; advise of potential risk to the fetus.
Pregnancy Category: D — always consult a doctor before taking during pregnancy.
Use in lactation
Use in Lactation: No data on presence in human milk; due to potential serious adverse reactions, do not breastfeed during treatment and for 2 weeks after the final dose.
Pediatric use
Safety and efficacy not established in pediatric patients under 18 years.
Geriatric use
Caution required in elderly patients; dose adjustment may be needed.
Renal / hepatic impairment
Renal Impairment: Caution in kidney disease; dose adjustment may be needed; consult your doctor.
Hepatic Impairment: Caution in liver disease; risk of hepatotoxicity; dose adjustment may be needed; consult your doctor.
Overdose effects
Overdose (highest studied 220 mg/day): Dermatological events, dysphonia, diarrhea, mucosal inflammation, dry mouth, decreased appetite, hypertension, fatigue; no specific antidote; discontinue, supportive care, observe.
Storage conditions
Store below 30°C in a cool and dry place, away from sunlight; keep out of reach of children.
Chemical structure
Regorafenib Monohydrate