[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [VEGFR multikinase inhibitors](https://durgical.com/en/pharmacology/classes/vegfr-multikinase-inhibitors/) › Regorafenib

# Regorafenib

## VEGFR multikinase inhibitors?

VEGFR multikinase inhibitors

## High 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.

Updated Nov 1, 2026

## Quick facts

**Group**
[VEGFR multikinase inhibitors](https://durgical.com/en/pharmacology/classes/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.

On this page

- The basics Mechanism of action
- Indications
- Adverse effects
- Pharmacokinetics
- Memory aid

- Clinical What the labels mean

- Safety Contraindications
- Key interactions
- What is monitored
- Administration and safety
- Pregnancy and breastfeeding
- Nursing care

- Study Test yourself

- Connections Connections

## Mechanism of action

✂**VEGFR1-3, TIE2, PDGFR, KIT, RET, RAF1 and other kinases**Regorafenib

ⓘ 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.

**Target in 3D:** VEGFR1-3, TIE2, PDGFR, KIT, RET, RAF1 and other kinases. PDB structure 4ASD (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/4ASD) · Drag to rotate · pinch to zoom

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 →](https://durgical.com/en/conditions/colorectal-cancer/)
- Advanced gastrointestinal stromal tumour after imatinib and sunitinib. [Gastrointestinal stromal tumour (GIST) →](https://durgical.com/en/conditions/gastrointestinal-stromal-tumour/)
- Hepatocellular carcinoma previously treated with sorafenib. [Hepatocellular carcinoma →](https://durgical.com/en/conditions/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

### Serious (rare, important)

- Severe hepatotoxicity (boxed warning)
- Bleeding
- Gastrointestinal perforation
- Impaired wound healing
- Chest pain (possible cardiac ischaemia); severe headache, confusion or seizures

## 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.

## Memory aid

«REGOrafenib = REGO, go again»: third line after sorafenib (liver), after imatinib + sunitinib (GIST) and after chemotherapy (colon).

## 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.

[Add to my cards (3)](https://durgical.app/estudiar/?add=/en/pharmacology/regorafenib/)

[More Pharmacology questions →](https://durgical.com/en/practice/?f=pharmacology)

## What the labels mean

**High 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…

## Connections

## Related drugs 3

- [Sorafenib](https://durgical.com/en/pharmacology/sorafenib/)
- [Sunitinib](https://durgical.com/en/pharmacology/sunitinib/)
- [Imatinib](https://durgical.com/en/pharmacology/imatinib/)

## Related conditions 3

- [Colorectal cancer](https://durgical.com/en/conditions/colorectal-cancer/)
- [Gastrointestinal stromal tumour (GIST)](https://durgical.com/en/conditions/gastrointestinal-stromal-tumour/)
- [Hepatocellular carcinoma](https://durgical.com/en/conditions/hepatocellular-carcinoma/)

[← Back to the class: VEGFR multikinase inhibitors](https://durgical.com/en/pharmacology/classes/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](https://medlineplus.gov/druginfo/meds/a613004.html) (MedlinePlus (U.S. National Library of Medicine), 2026); [Regorafenib - NCI](https://www.cancer.gov/about-cancer/treatment/drugs/regorafenib) (National Cancer Institute, 2023); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=L01EX05) (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake

Representative model, for educational purposes only.

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Source: https://durgical.com/en/pharmacology/regorafenib/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/regorafenib/