Stivarga Dosage/Direction for Use

Stivarga should be prescribed by physicians experienced in the administration of anticancer therapy.
Posology: The recommended dose of regorafenib is 160 mg (4 tablets of 40 mg) taken once daily for 3 weeks followed by 1 week off therapy. This 4-week period is considered a treatment cycle.
If a dose is missed, then it should be taken on the same day as soon as the patient remembers. The patient should not take two doses on the same day to make up for a missed dose. In case of vomiting after regorafenib administration, the patient should not take additional tablets.
Treatment should continue as long as benefit is observed or until unacceptable toxicity occurs (see Precautions).
Patients with performance status (PS) 2 or higher were excluded from clinical studies. There is limited data in patients with PS ≥2.
Posology adjustments: Dose interruptions and/or dose reductions may be required based on individual safety and tolerability. Dose modifications are to be applied in 40 mg (one tablet) steps. The lowest recommended daily dose is 80 mg. The maximum daily dose is 160 mg.
For recommended dose modifications and measures in case of hand-foot skin reaction (HFSR) / palmar-plantar erythrodysesthesia syndrome see Table 4. (See Table 4.)

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For recommended measures and dose modifications in case of worsening of liver function tests considered related to treatment with Stivarga see Table 5 (see also Precautions). (See Table 5.)

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Hepatic impairment: Regorafenib is eliminated mainly via the hepatic route.
In clinical studies, no relevant differences in exposure, safety or efficacy were observed between patients with mild hepatic impairment (Child-Pugh A) and normal hepatic function. No dose adjustment is required in patients with mild hepatic impairment. Since only limited data are available for patients with moderate hepatic impairment (Child Pugh B), no dose recommendation can be provided. Close monitoring of overall safety is recommended in these patients (see Precautions and Pharmacology: Pharmacokinetics under Actions).
Stivarga is not recommended for use in patients with severe hepatic impairment (Child-Pugh C) as Stivarga has not been studied in this population.
Renal impairment: Available clinical data indicate similar exposure of regorafenib and its metabolites M-2 and M-5 in patients with mild, moderate or severe renal impairment compared to patients with normal renal function. No dose adjustment is required in patients with mild, moderate or severe renal impairment (see also Pharmacology: Pharmacokinetics under Actions).
Elderly population: In clinical studies, no relevant differences in exposure, safety or efficacy were observed between elderly (aged 65 years and above) and younger patients (see also Pharmacology: Pharmacokinetics under Actions).
Gender: In clinical studies, no relevant differences in exposure, safety or efficacy were observed between male and female patients. No dose adjustment is necessary based on gender (see also Pharmacology: Pharmacokinetics under Actions).
Ethnic differences: In clinical studies, no relevant differences in exposure or efficacy were observed between patients of different ethnic groups. A higher incidence of hand foot skin reaction (HFSR)/palmar-plantar erythrodysesthesia syndrome, severe liver function test abnormalities and hepatic dysfunction was observed in Asian (in particular Japanese) patients treated with Stivarga compared with Caucasians. The Asian patients treated with Stivarga in clinical studies were primarily from East Asia (~90%).
There is limited data on regorafenib in the black patient population.
No dose adjustment is necessary based on ethnicity (see Pharmacology: Pharmacokinetics under Actions).
Paediatric population: There is no relevant use of Stivarga in the paediatric population in the indication of metastatic colorectal cancer.
The safety and efficacy of regorafenib in patients below 18 years of age in the indication gastrointestinal stromal tumours (GIST) have not been established. No data are available.
There is no relevant use of Stivarga in the paediatric population in the indication of hepatocellular carcinoma.
Method of administration: Stivarga is for oral use.
Stivarga should be taken at the same time each day. The tablets should be swallowed whole with water after a light meal that contains less than 30% fat. An example of a light (low-fat) meal would include 1 portion of cereal (about 30 g), 1 glass of skimmed milk, 1 slice of toast with jam, 1 glass of apple juice, and 1 cup of coffee or tea (520 calories, 2 g fat).