Regorafenib
Regorafenib is a kinase inhibitor (a targeted cancer pill) used in adults with certain previously treated metastatic colorectal cancer, gastrointestinal stromal tumor (GIST), and hepatocellular carcinoma (liver cancer).
🧬 Where this information comes from Click to expand
The clinical label records used on this page are FDA-filed Structured Product Labeling (SPL) retrieved through openFDA. We identified 1 clinical label set within the page’s selected clinical scope after exact ingredient or ingredient-combination matching and applicable route/form matching. Forms, routes, brands, labelers, strengths, and NDC product-record counts are built separately from matching FDA National Drug Code Directory records. The linked DailyMed document is a representative official source for verification, not the page’s only clinical source. View the linked label on DailyMed →
Regorafenib (Stivarga) is a daily targeted cancer drug, on the market since about 2012, that blocks kinases (proteins driving tumor growth and the blood vessels tumors feed on); it is a later-line option for metastatic colorectal cancer, GIST and liver cancer once earlier treatments stop working. It is a demanding drug; hand-foot skin reaction (sore, peeling palms and soles), tiredness, diarrhea and rising blood pressure are common, so report them early. The boxed warning is severe, sometimes fatal liver damage, mostly in the first two months, so expect liver blood tests before and during treatment and call promptly about yellow skin or eyes or dark urine.
Clinical pearls
- Take it at the same time each day after a low-fat meal, swallowing the tablets whole with water.
- If you miss a day, skip it and never double up the next day to make up for it.
- Avoid grapefruit juice and St. John's Wort, and if you take warfarin, expect more frequent INR (clotting) checks.
- Tell your surgeon early, because treatment is held at least two weeks before planned surgery and until wounds heal afterward.
⚠️ FDA Boxed Warning — the FDA’s strongest safety alert ▾
Regorafenib can cause severe liver damage, and some cases have been fatal. This was seen in clinical trials, mostly within the first couple of months.
Your liver function will be checked with blood tests before you start and during treatment. If the tests show liver problems, your doctor may stop the medicine, lower the dose, or discontinue it. Tell your doctor right away about yellow skin or eyes, dark urine, or unusual tiredness or confusion.
Patient information guide A plain-language walkthrough of Regorafenib, written from its FDA label.
What Regorafenib is used for
▾
Regorafenib is a targeted cancer medicine for adults whose cancer has already been treated with other drugs. The Stivarga tablet is approved for:
- Metastatic colorectal cancer (CRC) previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if RAS wild-type, an anti-EGFR therapy
- Locally advanced, unresectable or metastatic gastrointestinal stromal tumor (GIST) previously treated with imatinib mesylate and sunitinib malate
- Hepatocellular carcinoma (HCC) previously treated with sorafenib
How Regorafenib works
▾
Regorafenib blocks multiple kinases, which are proteins that help cells grow and send signals. These include proteins involved in forming new tumor blood vessels, tumor growth, and spread.
In lab and animal studies, this slowed tumor growth and reduced spread of colorectal cancer models. Its main active byproducts (M-2 and M-5) have similar activity.
Regorafenib dosage
▾
Stivarga is a tablet taken by mouth once a day at the same time each day, for the first 21 days of each 28-day cycle. Treatment continues until the disease progresses or side effects become unacceptable.
- Swallow the tablets whole with water.
- Take them after a low-fat meal (under 600 calories and under 30% fat).
- Do not double up to make up for a missed dose from the previous day.
- Your doctor may lower the dose or pause treatment if side effects occur.
Dosing details from the FDA-approved label
From the Regorafenib prescribing information (“Dosage and Administration”). Doses are set by your prescriber for your product, condition, kidney function and age — never change a dose on your own.
- Recommended dose
- 160 mg (four 40 mg tablets) orally once daily for the first 21 days of each 28-day cycle
- Continue until disease progression or unacceptable toxicity
- Take at the same time each day, swallowed whole with water after a low-fat meal that contains less than 600 calories and less than 30% fat; do not take two doses on the same day to make up for a missed dose
- Dose modifications
- Reduce the dose in 40 mg (one tablet) increments
- Reduce to 120 mg for first occurrence of Grade 2 HFSR of any duration or after recovery of any Grade 3 or 4 adverse reaction except infection
- Reduce to 80 mg for re-occurrence of Grade 2 HFSR at the 120 mg dose or after recovery of any Grade 3 or 4 adverse reaction at the 120 mg dose (except hepatotoxicity o
- The lowest recommended daily dose is 80 mg daily
Read the label’s full dosing text
2 DOSAGE AND ADMINISTRATION • Recommended dose: 160 mg orally, once daily for the first 21 days of each 28-day cycle. ( 2.1 ) • Take STIVARGA after a low-fat meal. ( 2.1 , 12.3 ) 2.1 Recommended Dose The recommended dose is 160 mg STIVARGA (four 40 mg tablets) taken orally once daily for the first 21 days of each 28-day cycle. Continue treatment until disease progression or unacceptable toxicity. Take STIVARGA at the same time each day. Swallow tablet whole with water after a low-fat meal that contains less than 600 calories and less than 30% fat [see Clinical Pharmacology ( 12.3 )] . Do not take two doses of STIVARGA on the same day to make up for a missed dose from the previous day. 2.2 Dose Modifications If dose modifications are required, reduce the dose in 40 mg (one tablet) increments; the lowest recommended daily dose of STIVARGA is 80 mg daily. Interrupt STIVARGA for the following: • Grade 2 hand-foot skin reaction (HFSR) [palmar-plantar erythrodysesthesia syndrome (PPES)] that is recurrent or does not improve within 7 days despite dose reduction; interrupt therapy for a minimum of 7 days for Grade 3 HFSR • Symptomatic Grade 2 hypertension • Any Grade 3 or 4 adverse reaction • Worsening infection of any grade Reduce the dose of STIVARGA to 120 mg: • For the first occurrence of Grade 2 HFSR of any duration • After recovery of any Grade 3 or 4 adverse reaction except infection • For Grade 3 aspartate aminotransferase (AST)/alanine aminotransferase (ALT) elevation, only resume if the potential benefit outweighs the risk of hepatotoxicity Reduce the dose of STIVARGA to 80 mg: • For re-occurrence of Grade 2 HFSR at the 120 mg dose • After recovery of any Grade 3 or 4 adverse reaction at the 120 mg dose (except hepatotoxicity or infection) Discontinue STIVARGA permanently for the following: • Failure to tolerate 80 mg dose • Any occurrence of AST or ALT more than 20 times the upper limit of normal (ULN) • Any occurrence of AST or ALT more than 3 times ULN with concurrent bilirubin more than 2 times ULN • Re-occurrence of AST or ALT more than 5 times ULN despite dose reduction to 120 mg • For any Grade 4 adverse reaction; only resume if the potential benefit outweighs the risks
Read the full Dosage and Administration section on DailyMed →
Regorafenib side effects
▾
The most common side effects (in at least 1 in 5 people) include:
Common side effects
- Pain, including stomach and belly pain
- Hand-foot skin reaction (redness, soreness or peeling of palms and soles)
- Tiredness or weakness
- Diarrhea
- Decreased appetite
- High blood pressure
- Infection
- Mouth sores, rash, nausea, or weight loss
- Hoarse voice (dysphonia)
- High bilirubin in the blood
- Mouth sores or inflammation (mucositis)
When to get medical help
- Yellow skin or eyes, dark urine, or severe tiredness, which can signal liver injury
- Unexplained lethargy or confusion, which can signal a liver-related brain problem from high ammonia
- Signs of infection that are worsening or severe, such as fever or breathing problems
- Serious bleeding, including black stools, vomiting blood, or bleeding that will not stop
- Severe stomach pain, which may signal a tear (perforation) or abnormal connection (fistula) in the gut
- Severe or worsening skin reactions, especially on the hands and feet
- Severe or uncontrolled high blood pressure
- New chest pain or other signs of a heart attack or reduced blood flow to the heart
Call your doctor about signs of liver problems, serious infection, bleeding, severe stomach pain, severe skin reactions, very high blood pressure, chest pain, or sudden neurological symptoms.
Regorafenib warnings and precautions
▾
Liver damage is the biggest risk. It has been severe and sometimes fatal, usually within the first 2 months. Liver tests are done before treatment, at least every 2 weeks for the first 2 months, then monthly or as needed. Confusion or unusual lethargy may signal high ammonia levels affecting the brain, which has been reported after approval, especially in people with liver problems, liver metastases, or liver cancer.
- Infections: more common than with placebo, and some were fatal.
- Bleeding: more common, and some events were fatal.
- Gastrointestinal perforation or fistula: treatment should be stopped permanently.
- Skin reactions: very common, especially hand-foot skin reaction in the first cycle.
- High blood pressure and heart ischemia or heart attack.
- RPLS: treatment should be stopped.
- Impaired wound healing: stop at least 2 weeks before elective surgery.
- Harm to an unborn baby.
Asian patients had more hand-foot skin reactions and liver test abnormalities than White patients.
Regorafenib interactions
▾
Regorafenib is processed by the liver enzyme CYP3A4, so some other medicines change how much you get.
- Strong CYP3A4 inducers (rifampin, phenytoin, carbamazepine, phenobarbital, St. John's Wort): can lower levels and reduce effectiveness. Avoid.
- Strong CYP3A4 inhibitors (clarithromycin, grapefruit juice, itraconazole, ketoconazole, nefazodone, posaconazole, telithromycin, voriconazole): can raise levels and increase toxicity. Avoid.
- BCRP substrates (methotrexate, fluvastatin, atorvastatin): their levels can rise, so watch for side effects.
- Warfarin: bleeding risk is higher, so INR should be monitored more often.
Interactions listed in the FDA-approved label
From the Regorafenib prescribing information (“Drug Interactions”): what the manufacturer studied or reported to the FDA.
- Strong CYP3A4 inducers (e.g. rifampin, phenytoin, carbamazepine, phenobarbital, and St. John's Wort): Decreased the plasma concentrations of regorafenib, increased the plasma concentrations of the active metabolite M-5, and resulted in no change in the plasma concentrations of the active metabolite M-2, and may lead to decreased efficacy. Avoid concomitant use of STIVARGA with strong CYP3A4 inducers.
- Strong CYP3A4 inhibitors (e.g. clarithromycin, grapefruit juice, itraconazole, ketoconazole, nefazodone, posaconazole, telithromycin, and voriconazole): Increased the plasma concentrations of regorafenib and decreased the plasma concentrations of the active metabolites M-2 and M-5, and may lead to increased toxicity. Avoid concomitant use of STIVARGA with strong CYP3A4 inhibitors.
- BCRP substrates (e.g. methotrexate, fluvastatin, atorvastatin): Co-administration of STIVARGA with a BCRP substrate increased the plasma concentrations of the BCRP substrate. Monitor patients closely for signs and symptoms of exposure related toxicity to the BCRP substrate; consult the concomitant BCRP substrate product information when considering administration together with STIVARGA.
Read the label’s full interactions text
7 DRUG INTERACTIONS • Strong CYP3A4 inducers: Avoid strong CYP3A4 inducers. ( 7.1 ) • Strong CYP3A4 inhibitors: Avoid strong CYP3A4 inhibitors. ( 7.2 ) • BCRP substrates: Monitor patients closely for symptoms of increased exposure to BCRP substrates. ( 7.3 ) 7.1 Effect of Strong CYP3A4 Inducers on Regorafenib Co-administration of a strong CYP3A4 inducer with STIVARGA decreased the plasma concentrations of regorafenib, increased the plasma concentrations of the active metabolite M-5, and resulted in no change in the plasma concentrations of the active metabolite M-2 [see Clinical Pharmacology ( 12.3 )] , and may lead to decreased efficacy. Avoid concomitant use of STIVARGA with strong CYP3A4 inducers (e.g. rifampin, phenytoin, carbamazepine, phenobarbital, and St. John's Wort). 7.2 Effect of Strong CYP3A4 Inhibitors on Regorafenib Co-administration of a strong CYP3A4 inhibitor with STIVARGA increased the plasma concentrations of regorafenib and decreased the plasma concentrations of the active metabolites M-2 and M-5 [see Clinical Pharmacology ( 12.3 )] , and may lead to increased toxicity. Avoid concomitant use of STIVARGA with strong CYP3A4 inhibitors (e.g. clarithromycin, grapefruit juice, itraconazole, ketoconazole, nefazodone, posaconazole, telithromycin, and voriconazole). 7.3 Effect of Regorafenib on Breast Cancer Resistance Protein (BCRP) Substrates Co-administration of STIVARGA with a BCRP substrate increased the plasma concentrations of the BCRP substrate [see Clinical Pharmacology ( 12.3 )] . Monitor patients closely for signs and symptoms of exposure related toxicity to the BCRP substrate (e.g. methotrexate, fluvastatin, atorvastatin). Consult the concomitant BCRP substrate product information when considering administration of such products together with STIVARGA.
Not a complete list. The label covers the interactions the manufacturer studied or reported, and our own interaction database does not cover every medicine either. Bring your full medication list, including vitamins and herbal products, to your pharmacist.
Before taking Regorafenib
▾
- There are no listed contraindications.
- Tell your doctor about liver disease. It is not recommended in severe liver impairment (total bilirubin over 3 times the upper limit of normal) because it has not been studied.
- No dose change is recommended for mild or moderate liver impairment or for kidney impairment, but close monitoring is advised. There is no recommended dose for dialysis.
- Can cause fetal harm. Use effective contraception during treatment and for 2 months afterward (women and men).
- Do not breastfeed during treatment and for 2 weeks after the final dose.
- Not established for people under 18.
- Adults 65 and older had more severe high blood pressure.
- Plan ahead for surgery, since wound healing can be impaired.
Regorafenib overdose
▾
The highest dose studied was 220 mg per day. Side effects at that level included skin problems, hoarse voice, diarrhea, mouth inflammation, dry mouth, decreased appetite, high blood pressure, and fatigue. There is no known antidote. If an overdose is suspected, treatment is interrupted, supportive care is given, and you are observed until stable.
What Regorafenib does in the body
▾
In a study of 25 patients with advanced solid tumors, regorafenib at the usual daily dosing for 21 days did not cause large changes in the QTc interval (a measure of heart rhythm timing). No change over 20 milliseconds was seen on average.
How your body processes Regorafenib
▾
Regorafenib peaks in the blood about 4 hours after a dose. A low-fat meal increases how much is absorbed, and Stivarga was given after a low-fat meal in key studies. It is highly bound to proteins in the blood and recycles through the liver and gut.
It is broken down by CYP3A4 and UGT1A9 into active metabolites M-2 and M-5. Half-life is about 28 hours for regorafenib, and longer for M-5 at about 51 hours. Most of it leaves in the stool (about 71%), with some in urine (about 19%). Age, sex, race, and weight had no meaningful effect.
How to store Regorafenib
▾
Store STIVARGA at 25°C (77°F); excursions are permitted from 15 to 30°C (59 to 86°F) . Store tablets in the original bottle and do not remove the desiccant.
Written from the FDA-approved label with AI and reviewed by our pharmacy team. How we use AI →
Supplements & herbs that interact with Regorafenib
138 supplements and herbal products have documented interactions with Regorafenib in the licensed clinical database we use. Most are manageable — but your pharmacist should know about everything you take, including vitamins and herbals.
- Major · 3
- Moderate · 94
- Minor · 41
Educational information from a licensed clinical database (Natural Medicines) — see our data sources & update cadence. Not medical advice: an interaction being documented does not mean it will happen to you; do not start or stop medications or supplements without professional guidance.
Regorafenib: pharmacist answers to common questions
Quick, plain-English answers to the questions patients ask most about Regorafenib — the kind of thing our pharmacy team would talk through with you at the counter.
What is regorafenib for?
▾
How do I take it?
▾
What side effects should I expect?
▾
What should I call my doctor about right away?
▾
Do I need blood tests?
▾
Can I take other medicines or grapefruit juice with it?
▾
Is Regorafenib available over the counter?
▾
When was Regorafenib first available?
▾
Answers drafted from the FDA-approved label with AI and reviewed by our pharmacy team. How we use AI →
More about Regorafenib on HelloPharmacist
Regorafenib forms and strengths (how it comes)
Regorafenib is available in 1 form. Different forms and brands can have different approved uses, doses, schedules, and directions. Follow the instructions for your exact product, and do not switch forms without guidance from your prescriber or pharmacist.
Tablet
How this form is used
- Stivarga is used for previously treated metastatic colorectal cancer in adults.
- Stivarga is used for previously treated locally advanced, unresectable or metastatic GIST in adults.
- Stivarga is used for hepatocellular carcinoma previously treated with sorafenib in adults.
- Stivarga is taken by mouth once daily at the same time each day, for the first 21 days of each 28-day cycle.
- Swallow Stivarga tablets whole with water after a low-fat meal.
- Do not take two doses of Stivarga on the same day to make up for a missed dose.
- Treatment with Stivarga continues until the cancer progresses or side effects become unacceptable.
Regorafenib on the U.S. market: products, makers and brands
How Regorafenib appears in the FDA’s National Drug Code Directory — including its dosage forms, strengths, brand names, manufacturers, and FDA-listed product records. These are directory records, not sales or prescription volume.
1 company lists 1 Regorafenib product record with the FDA, mostly as tablet; the earliest marketing or approval year on record is 2012. Brand names on the directory include Stivarga; the rest are generics.
Also listed with the FDA, not a patient dose form: Powder (3) — bulk drug substance sold to compounders/manufacturers and multi-item kits. These aren’t counted in the dose-form total above.
How widely Regorafenib is used (Medicaid data)
A general measure of how commonly Regorafenib is prescribed, based on Medicaid — one of the largest public drug programs. The figure below is prescriptions filled in Q1–Q4 2025, summed across every form and brand of the drug.
Think of this as a proxy for how widely Regorafenib is used, drawn from freely available public data. Medicaid is just one program — these numbers don’t include Medicare, other government coverage, or commercial and cash-pay prescriptions, so real-world use is higher than what’s shown here.
How commonly is Regorafenib prescribed? Of the 1,601 medications we measure, Regorafenib ranks #1,337 by Medicaid prescriptions — more than 16% of them.
Utilization by Regorafenib product
Pick a product to see its own Medicaid numbers. Each chip is one clinical product — a specific strength & dosage form as defined by RxNorm — with brand-name and generic versions combined.
regorafenib 40 MG Oral Tablet
Summed across the 1 of 7 listed NDC products with Medicaid activity — every brand and generic of this exact strength & form. RxNorm 1312402
Shares are of the Medicaid prescriptions shown here. Product grouping follows RxNorm (the National Library of Medicine’s drug terminology), so “one product” means one strength & dosage form regardless of manufacturer. Dollar figures are gross Medicaid reimbursement before mandatory rebates — rebates (often large, especially for brand-name drugs) are confidential, so actual net cost to Medicaid is lower than shown.
Source: Medicaid State Drug Utilization Data (CMS), aggregated by generic ingredient — summed across every NDC (all brands, strengths, salt forms and dosage forms) of Regorafenib, and across all states and both fee-for-service and managed-care claims. A general popularity signal; it excludes Medicare, commercial insurance and cash prescriptions, so it is not total U.S. use. Based on the 1 of 7 listed Regorafenib NDCs with Medicaid activity.
Compare Regorafenib products
A representative set of FDA-listed product records for Regorafenib — across manufacturers, strengths, and dosage forms, grouped by form with each product’s manufacturer and how the FDA approved it. The same medicine may be made and packaged by different companies, so a single drug can have many directory entries. (It’s also why a refill can look different — a new shape, color, or box — even though it contains the same medication.)
| Strength | Route | Manufacturer / Labeler | Category ⓘ | Details |
|---|---|---|---|---|
| 💊Tablet | ||||
| 40 mg | Oral | Bayer HealthCare Pharmaceuticals Inc. | NDA | View NDC → |
Showing 1 of 1 products — FDA National Drug Code Directory. See every product, package size and price: browse all 1 Regorafenib NDCs →
Regorafenib side effects reported to the FDA (FAERS)
After a medicine reaches the market, patients, doctors and drugmakers can send the FDA reports of problems they think may be linked to it. Here’s what’s been reported for Regorafenib — a signal of what to watch for, not proof the drug caused it.
Source: openFDA, from the FDA Adverse Event Reporting System (FAERS). These are voluntary reports — they don’t prove the drug caused the effect, and counts reflect how often something was reported, not how often it actually happens. Reports also often name the very problem the medicine is taken for — a common reason to file one is that the drug didn’t help — so for a pain reliever you may see “pain” high on the list; that points to why the report was filed, not to the drug causing the symptom. This counts every report that lists Regorafenib in any role, so the total runs higher than the FDA’s official dashboard, which counts only cases where the drug is the suspect. For the authoritative figures, see the FDA FAERS Public Dashboard. Always talk to your pharmacist or doctor.
Regorafenib FDA approval history
How Regorafenib went from FDA review to the pharmacy shelf — the key milestones in its regulatory journey.
Source: Drugs@FDA.
Regorafenib recall history
A recall is when a specific batch of a medicine is pulled from the market — usually a manufacturing issue, not a problem with the drug itself. Class I is most serious, Class III least.
The FDA’s enforcement reports list no Regorafenib recalls since July 2021.
✅No Regorafenib recalls on record since July 2021Source: FDA enforcement (recall) reports, via openFDA; our copy was last updated Sep 24, 2026.
RxNorm Concept Web — From Ingredient to Every Form and Strength
This page starts with one ingredient concept (IN). The branches below show its dose-form concepts (SCDF), then the available clinical drug and strength concepts (SCD). Combination products remain separate concepts with their own pages.
RxCUI 1312397 1 dose form · 1 strength
-
Dose form (SCDF) Oral Tablet RxCUI 1312401In current FDA listingsClinical drug / strength (SCD) 40 MGRxCUI 1312402
Look up RxCUI 1312397 in the RxCUI Atlas →
RxNorm is the U.S. National Library of Medicine’s normalized drug vocabulary. Its concept hierarchy can include forms that are not currently marketed; the status on each branch compares that concept with current FDA listings. RxCUIs identify vocabulary concepts, not individual packages or manufacturers.
Regorafenib supply and shortage status
Whether Regorafenib is in short supply in the U.S. right now, plus any shortage history the FDA has on record. A shortage usually reflects a manufacturing or demand issue — not a safety problem with the drug.
Source: openFDA, from the FDA Drug Shortages database.
Regorafenib brand names
Regorafenib is sold under one brand name in the FDA directory — Stivarga. A brand and its generic contain the same active ingredient; the brand name belongs to one company's product.
Who makes Regorafenib: manufacturers and labelers
One company lists Regorafenib products with the FDA. By number of product records, the largest are Bayer HealthCare Pharmaceuticals Inc.. Labelers include manufacturers and repackagers; the product in your bottle depends on which one your pharmacy stocks.
Regorafenib drug class (RxNorm)
Regorafenib belongs to the Kinase Inhibitor class.
Classified by RxNorm RxClass — the U.S. National Library of Medicine's standardized drug-classification service (Established Pharmacologic Class from the FDA, the ATC drug family from the WHO, and mechanism of action). Reference only, not medical advice.
Sources for this Regorafenib page
Core label, product, RxNorm, safety, and utilization data on this page come from the sources identified below. AI-written, editorial, and licensed sections are labeled separately.
How this page is built
HelloPharmacist combines public FDA and NLM records and does not author the underlying clinical facts. The plain-language sections are written with AI from the FDA-approved label text and reviewed by our pharmacy team before publication. Bayer HealthCare Pharmaceuticals Inc. is the representative DailyMed label linked for verification and dates. This is general education, not medical advice: always talk to your doctor or pharmacist about your own medicines. How we build and review drug pages →