Regorafenib Dosage

Medically reviewed by Drugs.com. Last updated on Mar 3, 2023.

Applies to the following strengths: 40 mg

Usual Adult Dose for:

Colorectal Cancer
Gastrointestinal Stromal Tumor
Hepatocellular Carcinoma

Additional dosage information:

Renal Dose Adjustments
Liver Dose Adjustments
Dose Adjustments
Precautions
Dialysis
Other Comments

Usual Adult Dose for Colorectal Cancer

160 mg orally once a day for the first 21 days of each 28-day cycle until disease progression or unacceptable toxicity

Uses:

Metastatic colorectal cancer (CRC) previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF therapy, and an anti-EGFR therapy if RAS wild-type
Locally advanced, unresectable or metastatic GI stromal tumor (GIST) previously treated with imatinib mesylate and sunitinib malate
Hepatocellular carcinoma (HCC) previously treated with sorafenib

Usual Adult Dose for Gastrointestinal Stromal Tumor

160 mg orally once a day for the first 21 days of each 28-day cycle until disease progression or unacceptable toxicity

Uses:

Metastatic colorectal cancer (CRC) previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF therapy, and an anti-EGFR therapy if RAS wild-type
Locally advanced, unresectable or metastatic GI stromal tumor (GIST) previously treated with imatinib mesylate and sunitinib malate
Hepatocellular carcinoma (HCC) previously treated with sorafenib

Usual Adult Dose for Hepatocellular Carcinoma

160 mg orally once a day for the first 21 days of each 28-day cycle until disease progression or unacceptable toxicity

Uses:

Metastatic colorectal cancer (CRC) previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF therapy, and an anti-EGFR therapy if RAS wild-type
Locally advanced, unresectable or metastatic GI stromal tumor (GIST) previously treated with imatinib mesylate and sunitinib malate
Hepatocellular carcinoma (HCC) previously treated with sorafenib

Renal Dose Adjustments

No adjustment recommended.

Liver Dose Adjustments

Mild (Child-Pugh A) hepatic impairment: No adjustment recommended.
Moderate (Child-Pugh B) hepatic impairment: Dose adjustment(s) may be required; however, no specific guidelines have been suggested. Caution recommended.
Severe (Child-Pugh C) hepatic impairment: Not recommended.

DOSE MODIFICATIONS FOR HEPATIC IMPAIRMENT:
ALT AND/OR AST:
GREATER than or equal to 5 times upper limit of normal (ULN) (maximum Grade 2):

Any occurrence: Continue therapy; monitor liver function weekly until transaminases return to less than 3 x ULN (Grade 1) or baseline

GREATER than 5 x ULN to less than or equal to 20 x ULN (Grade 3):

First occurrence: Interrupt therapy; monitor transaminases weekly until return to less than 3 times ULN or baseline.
Restart: If the potential benefit outweighs the risk of hepatotoxicity, restart therapy, reduce dose by 40 mg, and monitor liver function weekly for at least 4 weeks
Reoccurrence: Permanently discontinue therapy.

GREATER than 20 times ULN (Grade 4):

Any occurrence: Permanently discontinue therapy.

GREATER than 3 times ULN (Grade 2 or higher) with concurrent bilirubin greater than 2 x ULN:

Any occurrence: Permanently discontinue therapy; Monitor liver function weekly until resolution or return to baseline.
Exception: Patients with Gilbert's syndrome who develop elevated transaminases should be managed as per the above outlined recommendations for the respective observed elevation of ALT and/or AST.

Dose Adjustments

If dose modifications are required, reduce the dose in 40 mg increments; the lowest recommended daily dose is 80 mg daily.

INTERRUPT DOSING FOR:

Grade 2 hand-foot skin reaction (HFSR; palmar-plantar erythrodysesthesia syndrome) that is recurrent or does not improve within 7 days despite dose reduction; interrupt dosing for at least 7 days for Grade 3 HFSR.
Symptomatic Grade 2 hypertension
Any Grade 3 or 4 adverse reaction
Worsening infection of any Grade

REDUCE DOSE to 120 mg for:

First occurrence of Grade 2 HFSR of any duration
After recovery of any Grade 3 or 4 adverse reaction (except infection)

REDUCE DOSE to 80 mg for:

Recurrence 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)

PERMANENTLY DISCONTINUE THERAPY for:

Failure to tolerate 80 mg dose
Any Grade 4 adverse reaction; only resume therapy if the potential benefit outweighs the risks

Precautions

US BOXED WARNINGS:
HEPATOTOXICITY:

Severe, sometimes fatal, hepatotoxicity has been reported.

Recommendations:

Monitor hepatic function prior to and during therapy.
Interrupt and then reduce the dose or discontinue this drug for hepatotoxicity as manifested by elevated liver function tests or hepatocellular necrosis, depending upon severity and persistence.

CONTRAINDICATIONS:

None

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

Take this drug 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.
Do not take 2 doses of this drug on the same day to make up for a missed dose from the previous day.

Storage requirements:

Store at 25C (77F); excursions are permitted from 15C to 30C (59F to 86).
To protect from moisture, keep tablets in the original bottle and do not remove the desiccant.
Keep the bottle tightly closed after opening; discard any unused tablets 7 weeks after opening the bottle.

Reconstitution/preparation techniques:

The manufacturer product information should be consulted.

General:

Overdose: There is no known antidote; in the event of suspected overdose: immediately interrupt dosing, institute supportive care, and observe until clinical stabilization.

Monitoring:

Cardiovascular: Blood pressure (weekly for the first 6 weeks of therapy and then every cycle or more frequently, as clinically indicated)
Hepatic: ALT, AST, bilirubin (at least every 2 weeks during the first 2 months of therapy; thereafter, monitor monthly or more frequently as clinically indicated)
Metabolism: Biochemical and metabolic parameters (periodically during treatment)

Patient advice:

Avoid drinking grapefruit juice and taking St. John's Wort during treatment.
Take this drug after eating a low-fat meal that contains less than 30% fat and less than 600 calories. An example: 1 cup of cereal (about 30 g), 1 glass (about 250 mL) of skim milk, 1 slice of toast with jam, 1 glass of apple juice, and 1 cup of coffee or tea (2 g fat, 520 calories).