Regorafenib (Stivarga)

Medicine at a glance

Regorafenib is an oral targeted cancer treatment, also called Stivarga. It blocks several proteins involved in cancer growth and the development of blood vessels. Tablets are usually taken once daily for three weeks, followed by one week without tablets. Food instructions matter: take your prescribed dose after a light, low-fat meal.

Monitoring is especially important early in treatment. Liver blood tests, blood-pressure checks and examination of painful skin changes help the team recognise problems before they become severe. A treatment break or lower dose can be part of safe treatment. Your prescription and the instructions from your oncology pharmacist take priority over the usual examples here.

What regorafenib is and how it works

Regorafenib is a multikinase inhibitor. Kinases are proteins that help pass instructions inside cells. Regorafenib blocks several of these signals, including signals involved in making new blood vessels that support tumour growth. These effects can slow cancer growth, but they also affect healthy tissues. This explains why a targeted tablet can cause significant side effects.

Treatment aims are individual. Your team will explain what benefit they hope for and how they will judge whether continuing is worthwhile. Feeling side effects does not prove the medicine is working; having few side effects does not mean it is ineffective.

How the team decides whether it is suitable

The decision depends on your diagnosis, previous treatment and its tolerability, test results, daily activity, liver function and other health conditions. There is no single universal genetic test that everyone must have solely to take regorafenib. Your team may use tumour tests relevant to your diagnosis and treatment choices.

Significant liver disease, uncontrolled blood pressure, recent heart problems, active bleeding or an unhealed wound can affect the decision. US and European labels use different descriptions of liver impairment, so do not interpret a blood result yourself to choose a dose. Severe liver impairment is not a recommended setting for treatment. Dialysis requires specialist consideration because there is no established recommended dose for that situation in the US label. Safety and effectiveness in children are not established.

Before treatment starts

Give the team a complete medicine list, including non-prescription painkillers, traditional remedies, supplements and products bought online. Mention liver disease, hepatitis, kidney problems, high blood pressure, angina, heart attacks, bleeding, bowel problems, infections and previous drug allergies. Tell them about aneurysms, which are abnormal bulges in blood vessels.

Baseline checks normally include blood pressure, blood counts, liver and kidney blood tests, and other tests appropriate to your health. The team may check thyroid function, blood salts and urine protein. A pregnancy assessment or test may be arranged when pregnancy is possible. Infection screening depends on your history and local policy; regorafenib does not impose one identical screening schedule for everyone.

Show the team existing sores, calluses, blisters or cracked skin on your feet and hands. Foot care before treatment can reduce avoidable pressure and friction. Report recent operations, dental extractions and any planned procedure. People with cirrhosis may need assessment and treatment of enlarged veins in the food pipe, called oesophageal varices, because these can bleed.

Before leaving, know how to contact your hospital's urgent oncology service, where to obtain blood tests, and when the first tablets and next cycle are due.

How to take regorafenib

The usual calendar

The labelled dose is 160 mg once daily, taken as four 40 mg tablets, on days 1–21 of a 28-day cycle. Days 22–28 are usually a planned break. Your oncologist may prescribe a different dose because of tolerability or your circumstances. Use your written calendar rather than copying another patient's prescription.

Do not extend the treatment week to compensate for missed tablets. Before a new cycle, check that the team has approved restarting, particularly if tests or side effects caused a delay.

Food and swallowing

Take the tablets at approximately the same time each treatment day, after a light, low-fat meal, with water. The US label specifies a meal containing less than 600 calories and less than 30% fat; this means less than 30% of its energy comes from fat. The European label describes a light meal with less than 30% fat. This is not a requirement to avoid all fat throughout the day. Ask the dietitian or pharmacist to help you choose a suitable familiar meal.

Swallow the tablets whole. Do not crush, chew or break them, and do not improvise a feeding-tube mixture. Contact the pharmacist before the next dose if swallowing becomes difficult. Avoid grapefruit and grapefruit juice.

A missed dose, vomiting or too many tablets

If you remember a missed dose on the same day, take it then, following the food instructions. If that day has passed, skip it and resume your calendar. Never take two doses on the same day to replace a missed dose. If you vomit after taking regorafenib, do not take replacement tablets; take the next scheduled dose as instructed. Report repeated vomiting or difficulty keeping fluids down.

If you take too much, contact the oncology team or emergency department immediately. Bring the packaging and details of what you took.

Storage and handling

Keep tablets in their original, tightly closed bottle, protected from moisture and out of children's reach. Keep the drying material inside the bottle, but never swallow it. Do not transfer tablets into a daily or weekly pill organiser; ask the pharmacist about a reminder system that keeps them in their bottle. Stivarga bottle instructions specify use within seven weeks after opening; write the opening date on the bottle and follow the supplied storage label. Return unwanted or expired tablets through your pharmacy's medicine-disposal service.

Monitoring and checking whether treatment is working

Liver tests include ALT, AST and bilirubin. They are checked before treatment, at least every two weeks during the first two months, then at least monthly or more often when needed. Abnormal results may require weekly checks. Serious liver injury often starts during the first two months, sometimes before obvious symptoms.

Blood pressure must be controlled before treatment. The US label specifies weekly checks during the first six weeks, then every cycle, with additional checks when needed. If you monitor at home, ask for a written reporting threshold and keep a record. Do not change blood-pressure tablets yourself.

Blood counts, kidney function, urine protein, thyroid function and blood salts may also be checked. Skin symptoms, appetite, weight and hydration matter alongside laboratory results. Extra tests depend on symptoms; for example, unexplained confusion or marked sleepiness can require an ammonia blood test.

Scans and clinical reviews assess cancer control. There is no single scan timetable suitable for everybody. A dose reduction does not by itself mean treatment has failed. The team balances benefit against the risks of continuing, pausing, reducing or stopping.

Common side effects and practical management

Hand–foot skin reaction

Regorafenib can cause tender, thickened, red or darker skin, particularly on pressure points of the palms and soles. Tingling, cracking, blisters or pain when walking may follow. This is often an early problem, so report symptoms promptly rather than waiting until the next cycle.

Use a bland moisturiser, comfortable shoes and cushioned socks. Reduce repetitive friction and pressure, and protect your hands during chores. Avoid very hot water. Ask for advice about calluses rather than cutting them yourself or using strong acid treatments. The team may prescribe specific creams, pain relief or a treatment break. Broken skin or pain affecting walking needs prompt assessment.

Diarrhoea, nausea and appetite changes

Record changes from your usual bowel pattern, including increased stoma output. Use anti-diarrhoea medicine only according to the plan your team provides. Sip fluids regularly and follow any individual fluid restriction. Dizziness, reduced urine, persistent vomiting, bloody stools or inability to drink need urgent advice; severe abdominal pain needs emergency assessment.

Small, frequent meals may be easier when appetite is poor. Take prescribed anti-sickness medicine as directed. Report ongoing weight loss early so nutritional support can be arranged. The low-fat dosing meal should not become an unnecessarily restrictive all-day diet.

Mouth, skin, hair and voice changes

A sore mouth, altered taste, dry skin, rash or hoarse voice can occur. Use gentle mouth care and a soft toothbrush. Avoid foods that sting sore areas. Report ulcers, white patches or pain that interferes with eating or drinking. Moisturise dry skin and report worsening rash. Hair thinning can occur, although complete hair loss is not typical.

Tiredness and blood-count changes

Pace activity and allow short rests. Gentle movement can help when you feel able. New or worsening exhaustion should be assessed because anaemia, infection, dehydration, thyroid changes or liver problems may contribute. Low platelets can increase bruising or bleeding; changes in infection-fighting blood cells can increase infection risk.

Less common but important side effects

Liver injury and raised ammonia

Regorafenib can cause severe, sometimes fatal liver injury. Contact the team immediately for yellow eyes or skin, dark urine, right-sided upper abdominal pain, unexplained bruising or unusual drowsiness. Do not dismiss symptoms because the last blood test was normal.

A separate warning concerns raised ammonia affecting the brain, called hyperammonaemic encephalopathy. New confusion, disorientation, trembling, major changes in alertness or difficulty waking need urgent assessment. Caregivers may notice these changes first. Risk appears greater with some underlying liver problems, but a person should not wait to establish the cause at home. If confirmed, treatment is withheld and permanent discontinuation is considered by the team.

High blood pressure, heart and blood-vessel problems

Blood pressure can rise without symptoms. Severe headache, visual disturbance, chest pain or severe breathlessness needs immediate assessment. Regorafenib can reduce blood supply to the heart and cause a heart attack. European information also warns about weakening or tearing of artery walls; sudden severe chest, back or abdominal pain warrants emergency help.

Bleeding and bowel damage

Bleeding may occur even without a low platelet count. Report new nosebleeds, unexplained bruises or blood in urine. Vomiting blood, coughing blood, black tar-like stools, uncontrolled bleeding or collapse requires emergency care.

A hole in the bowel, called perforation, or an abnormal connection between organs, called a fistula, can occur. Severe or persistent abdominal pain, particularly with fever, vomiting or a swollen abdomen, needs urgent hospital assessment. Do not treat severe new abdominal pain simply as routine indigestion.

Serious infection, skin and neurological reactions

Infections can become serious. Fever, shaking chills, worsening cough, painful urination or feeling suddenly very unwell requires urgent oncology advice, even without a high temperature. Severe breathing difficulty or collapse is an emergency.

A rapidly spreading rash with blisters, peeling skin or sores around the mouth or eyes may be a severe skin reaction. Stop taking further tablets and obtain urgent medical assessment. Seizures, severe headache, confusion or vision changes can signal a brain condition called posterior reversible encephalopathy syndrome, or PRES. Seek emergency help and do not drive yourself.

Kidney and small-vessel problems

Report foamy urine, swelling or less urine. European information and a 2026 Canadian safety communication describe thrombotic microangiopathy: injury and tiny clots in small blood vessels that can damage kidneys and blood cells. Unusual bruising together with marked weakness, fever, confusion or reduced urine needs urgent assessment. If TMA is diagnosed, regorafenib should be discontinued and prompt treatment is required. Its frequency cannot be reliably estimated from post-marketing reports.

Other changes worth reporting

Tell the team about a new skin lump, a changing skin lesion or a sore that does not heal; certain skin cancers have been reported. Severe upper abdominal pain with vomiting can also indicate inflammation of the pancreas. Sudden swelling of the lips, tongue or throat, or difficulty breathing, may be an allergic reaction and needs emergency care.

Wound healing and procedures

Regorafenib can slow wound healing. Tell every surgeon and dentist you take it. US instructions require withholding it for at least two weeks before elective surgery, and for at least two weeks after major surgery and until adequate healing. European information requires interruption for major procedures and bases restarting on healing without specifying the same fixed intervals. Your oncology and surgical teams must agree your actual stop and restart dates. Do not restart simply because two weeks have elapsed.

Other medicines, supplements and vaccinations

Regorafenib interacts with medicines that change liver enzymes, especially CYP3A4. Examples include some antibiotics such as clarithromycin or rifampicin, some antifungals, and epilepsy medicines such as carbamazepine or phenytoin. St John's wort and grapefruit should be avoided. European information also identifies interactions with certain anti-inflammatory medicines, including mefenamic acid. Strong CYP3A4 inhibitors and inducers should be avoided; the pharmacist should arrange a suitable alternative or treatment plan. Do not independently stop an essential prescribed medicine.

Regorafenib can increase exposure to medicines transported by a protein called BCRP, including rosuvastatin. Give the pharmacist your exact cholesterol-medicine name. Warfarin needs closer INR monitoring because bleeding risk can increase. Other blood thinners and non-prescription painkillers also need review. Simply separating tablets by a few hours does not reliably prevent these interactions.

Discuss vaccinations with the oncology team. The appropriate timing and choice depend on your treatment, blood counts and other medicines. Check before a live vaccine. Do not assume supplements or herbal products are safe because they are described as natural.

Everyday life during treatment

Plan meals and tablet reminders around your treatment calendar. Keep appointments even if you feel well. For work or travel, consider access to monitoring, urgent care, suitable food and safe medicine storage. Carry tablets in their labelled container and keep your treatment summary available.

Adjust activity if your feet are sore; forcing yourself through painful walking can worsen skin damage. Avoid driving when sleepy, confused, dizzy or unable to concentrate. Sudden neurological symptoms need assessment rather than simply resting until they pass.

Discuss alcohol with the team because liver health matters. Tell your dentist about treatment before invasive dental work. Ask about comfort and protection during sex if skin soreness, fatigue or bleeding affects intimacy. Emotional strain and practical worries deserve attention too; your nurse can help arrange counselling, dietetic or social support.

Fertility, contraception, pregnancy and breastfeeding

Regorafenib may harm an unborn baby. Discuss reliable contraception before treatment, including what to do if vomiting or diarrhoea could affect an oral contraceptive. Contact the team immediately if pregnancy occurs or is suspected in you or your partner.

US instructions require effective contraception during treatment and for two months after the final dose for patients who can become pregnant and for male patients with partners who can become pregnant. European instructions specify eight weeks after treatment for women of childbearing potential and men. These intervals are expressed differently; have your team give you a clear end date and follow any longer restriction required by another medicine.

Do not breastfeed during regorafenib treatment. The US label also specifies two weeks after the final dose. The European label prohibits breastfeeding during treatment without giving a fixed restart interval. Arrange feeding support and confirm when restarting is safe rather than assuming it is immediate.

Animal studies suggest fertility may be affected in both sexes, but the effect in people is not established. Discuss sperm or egg preservation before treatment when relevant. Possible reduced fertility does not mean contraception is unnecessary.

After treatment finishes

Continue the team's monitoring plan until side effects and abnormal tests have settled. Keep reporting new confusion, jaundice, bleeding, infection symptoms or problems with wound healing after the last dose. Do not restart leftover tablets yourself.

Maintain the agreed contraception and breastfeeding precautions. Ask which supportive medicines should continue, when blood-pressure treatment will be reviewed, and who will manage ongoing fatigue, nutritional or skin problems. Return unused tablets safely. Your team will discuss the next treatment or follow-up plan according to your situation.

Frequently asked questions