Regorafenib Dosage

Usual Adult Dose for Colorectal Cancer

160 mg orally once a day for the first 21 days of each 28-day cycle
-Lowest Dose: 80 mg per day
-Duration of Therapy: Until disease progression or unacceptable toxicity

Uses: Treatment of:
-Metastatic colorectal cancer 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 gastrointestinal stromal tumor previously treated with imatinib mesylate and sunitinib malate.
-Hepatocellular carcinoma 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
-Lowest Dose: 80 mg per day
-Duration of Therapy: Until disease progression or unacceptable toxicity

Uses: Treatment of:
-Metastatic colorectal cancer 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 gastrointestinal stromal tumor previously treated with imatinib mesylate and sunitinib malate.
-Hepatocellular carcinoma 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
-Lowest Dose: 80 mg per day
-Duration of Therapy: Until disease progression or unacceptable toxicity

Uses: Treatment of:
-Metastatic colorectal cancer 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 gastrointestinal stromal tumor previously treated with imatinib mesylate and sunitinib malate.
-Hepatocellular carcinoma previously treated with sorafenib.

Renal Dose Adjustments

Mild, Moderate, and Severe Renal Impairment: No adjustment recommended.

Liver Dose Adjustments

-MILD HEPATIC IMPAIRMENT (total bilirubin upper level of normal [ULN] or less AND AST greater than ULN, OR total bilirubin greater than ULN but no more than 1.5 x ULN): No adjustment recommended.
-MODERATE HEPATIC IMPAIRMENT (total bilirubin greater than 1.5 x ULN but no more than 3 x ULN AND any AST): No adjustment recommended.
-SEVERE HEPATIC IMPAIRMENT (total bilirubin greater than 3 x ULN): Not recommended.

IF HEPATOTOXICITY DEVELOPS DURING TREATMENT:
REDUCE DOSE to 120 mg for:
-Grade 3 AST/ALT elevation; only resume treatment if the potential benefit outweighs the risk of hepatotoxicity.
PERMANENTLY DISCONTINUE TREATMENT for:
-Any Occurrence of AST or ALT More Than 20 x ULN
-Any Occurrence of AST or ALT More Than 3 x ULN with Concurrent Bilirubin More Than 2 x ULN
-Recurrence of AST or ALT More Than 5 x ULN (despite dose reduction to 120 mg)

Comments: Closely monitor hepatically-impaired patients for adverse reactions.

Dose Adjustments

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 TREATMENT for:
-Failure to Tolerate 80 mg Dose
-Any Grade 4 Adverse Reaction; Only Resume Treatment if the Potential Benefit Outweighs the Risks

Comments: Dosing reductions should be made in 40 mg increments.

Precautions

US BOXED WARNING:
HEPATOTOXICITY: Severe and sometimes fatal hepatotoxicity has occurred in clinical trials. Monitor hepatic function prior to and during treatment. Hepatotoxicity manifests as elevated liver function tests or hepatocellular necrosis, depending upon severity and persistence. Interrupt and then reduce or discontinue this drug if hepatotoxicity occurs.

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:
-Advise patients to take this drug at the same time each day (ideally at breakfast), and to swallow tablets whole with water after a low-fat meal (less than 30% fat and less than 600 calories).
-Instruct patients not to take 2 doses on the same day to make up for a missed or vomited dose from the previous day.

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

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 treatment 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 treatment; 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).