Product Information
Registration Status: ActiveSTIVARGA TABLET 40MG is approved to be sold in Singapore with effective from 2013-07-06. It is marketed by BAYER (SOUTH EAST ASIA) PTE LTD, with the registration number of SIN14360P.
This product contains Regorafenib 40mg in the form of TABLET, FILM-COATED. It is approved for ORAL use.
This product is manufactured by Bayer Pharma AG in GERMANY.
It is a Prescription Only Medicine that can only be obtained from a doctor or a dentist, or a pharmacist with a prescription from a Singapore-registered doctor or dentist.
Description
Regorafenib is an orally-administered inhibitor of multiple kinases. It is used for the treatment of metastatic colorectal cancer and advanced gastrointestinal stromal tumours. FDA approved on September 27, 2012. Approved use of Regorafenib was expanded to treat Hepatocellular Carcinoma in April, 2017.
Indication
Regorafenib is indicated for the treatment of patients with metastatic colorectal cancer (CRC) who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if KRAS wild type, an anti-EGFR therapy. Regorafenib is also indicated for the treatment of patients with locally advanced, unresectable or metastatic gastrointestinal stromal tumor (GIST) who have been previously treated with imatinib mesylate and sunitinib malate.
Mechanism of Action
Regorafenib is a small molecule inhibitor of multiple membrane-bound and intracellular kinases involved in normal cellular functions and in pathologic processes such as oncogenesis, tumor angiogenesis, and maintenance of the tumor microenvironment. In in vitro biochemical or cellular assays, regorafenib or its major human active metabolites M-2 and M-5 inhibited the activity of RET, VEGFR1, VEGFR2, VEGFR3, KIT, PDGFR-alpha, PDGFR-beta, FGFR1, FGFR2, TIE2, DDR2, TrkA, Eph2A, RAF-1, BRAF, BRAFV600E , SAPK2, PTK5, and Abl at concentrations of regorafenib that have been achieved clinically. In in vivo models, regorafenib demonstrated anti-angiogenic activity in a rat tumor model, and inhibition of tumor growth as well as anti-metastatic activity in several mouse xenograft models including some for human colorectal carcinoma.
Pharmacokinetics
- Absorption
- Cmax = 2.5 μg/mL; Tmax = 4 hours; AUC = 70.4 μg*h/mL; Cmax, steady-state = 3.9 μg/mL; AUC, steady-state = 58.3 μg*h/mL; The mean relative bioavailability of tablets compared to an oral solution is 69% to 83%.
- Distribution
- Regorafenib undergoes enterohepatic circulation with multiple plasma concentration peaks observed across the 24-hour dosing interval.
- Metabolism
- Regorafenib is metabolized by CYP3A4 and UGT1A9. The main circulating metabolites of regorafenib measured at steady-state in human plasma are M-2 (N-oxide) and M-5 (N-oxide and N-desmethyl), both of them having similar in vitro pharmacological activity and steady-state concentrations as regorafenib. M-2 and M-5 are highly protein bound (99.8% and 99.95%, respectively).
- Elimination
Toxicity
The most common adverse reactions (≥20%) are asthenia/fatigue, HFSR, diarrhea, decreased appetite/food intake, hypertension, mucositis, dysphonia, and infection, pain (not otherwise specified), decreased weight, gastrointestinal and abdominal pain, rash, fever, and nausea
Active Ingredient/Synonyms
Regorafenib | Régorafénib | Regorafenibum | Regorafenib |
Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.