Regorafenib
VEGFR multikinase inhibitors
VEGFR multikinase inhibitorsHigh alert
An error with this medicine can cause serious harm: double checks and protocols are used.Pregnancy: avoid
Avoid in pregnancy. Can harm the fetus: a pregnancy test is done before starting, effective contraception is used during treatment and for a time afterwards (by women and by men…
A later-line multikinase inhibitor for colorectal cancer, GIST and liver cancer after earlier drugs. Boxed warning: liver; hand-foot skin reaction.
Quick facts
- Group
- VEGFR multikinase inhibitors
- Target
- VEGFR1-3, TIE2, PDGFR, KIT, RET, RAF1 and other kinases
- Key effects
- Fatigue and weakness · Hand-foot skin reaction
- Monitor
- Liver tests before and during treatment
- ATC
- L01EX05
No doses: the clinician sets them by the current guideline.
Mechanism of action
No regorafenib structure with VEGFR2 was used: the figure shows sorafenib, which differs from regorafenib by one fluorine atom and occupies the same ATP pocket of human VEGFR2.
Regorafenib, a close chemical relative of sorafenib, inhibits many kinases: VEGFR1-3 and TIE2 in the vessels, and KIT, RET, RAF1, PDGFR, FGFR and others in the tumour and its stroma. It is used after standard treatments have failed.
- Blocks VEGFR1-3 and TIE2: angiogenesis stops
- Blocks KIT, RET, RAF1 and PDGFR in tumour and stroma
- Used after standard drugs have failed
Indications
- Metastatic colorectal cancer after previous chemotherapy and anti-VEGF or anti-EGFR therapy. Colorectal cancer →
- Advanced gastrointestinal stromal tumour after imatinib and sunitinib. Gastrointestinal stromal tumour (GIST) →
- Hepatocellular carcinoma previously treated with sorafenib. Hepatocellular carcinoma →
Adverse effects
Common
- Fatigue and weakness
- Hand-foot skin reaction (red, painful, peeling palms and soles)
- Diarrhoea, decreased appetite, weight loss
- Hypertension
- Sore mouth and throat; hoarseness
Contraindications
- No absolute contraindications in the label apart from hypersensitivity; see the warnings
Key interactions
- Strong CYP3A4 inhibitors (clarithromycin, itraconazole, ketoconazole, ritonavir) and grapefruit
- Raise its levels and its toxicity.
- Strong CYP3A4 inducers (rifampicin, carbamazepine, phenytoin, St John's wort)
- Lower its levels and can make it fail.
- Anticoagulants and antiplatelet drugs
- Add to its bleeding risk.
What is monitored
- Liver tests before and during treatment
- Blood pressure before starting and regularly
- Skin of the hands and feet
- Signs of bleeding or infection
Administration and safety
- Oral tablets once daily with a low-fat meal, swallowed whole.
- Grapefruit, its juice and St John's wort are avoided because they change its levels.
- Stopped before planned surgery or dental surgery and restarted only when the wound has healed, as the doctor directs.
Pregnancy and breastfeeding
Avoid in pregnancy. Can harm the fetus: a pregnancy test is done before starting, effective contraception is used during treatment and for a time afterwards (by women and by men with partners who could conceive), and breastfeeding is avoided.
Nursing care
- Teach to report jaundice, dark urine, right upper abdominal pain or unusual tiredness at once.
- Measure blood pressure at every visit and teach home monitoring if ordered.
- Inspect palms and soles; teach to report painful, blistered or swollen skin.
- Teach to report bleeding, black stools, vomiting blood, severe abdominal pain, chest pain or stroke symptoms at once.
- Confirm a negative pregnancy test before the first dose and teach contraception during treatment and afterwards.
Pharmacokinetics
- Absorption
- Oral tablets, once daily, with a low-fat meal.
- Metabolism
- Liver, mostly CYP3A.
- Half-life
- About 28 hours.
Test yourself
Think of the answer, then tap the question to see it.
After which two drugs is regorafenib used in GIST?
Imatinib and sunitinib.
How is regorafenib taken with respect to meals?
Once daily with a low-fat meal.
What are regorafenib's boxed warning and its typical skin effect?
Severe hepatotoxicity; hand-foot skin reaction.
Connections
← Back to the class: VEGFR multikinase inhibitors
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Regorafenib: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); Regorafenib - NCI (National Cancer Institute, 2023); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.