Stivarga 40 mg (Regorafenib)

Adult dose

The recommended daily dose is 160 mg of regorafenib (equivalent to four 40 mg tablets of this medicine), taken orally once daily. The treatment cycle is 4 weeks: 3 weeks of treatment followed by 1 week without treatment. Take this medicine after a light meal at the same time each day. Swallow the tablets whole with water. If you forget a dose, take it as soon as you remember; do not take 2 doses in one day to make up for the dose missed the previous day. Continue treatment with this medicine until disease progression or unacceptable toxicity occurs. Depending on each patient's safety and tolerability, temporary treatment interruption and/or dose reduction may be necessary. Dose changes are made in increments of one 40 mg tablet. The minimum recommended daily dose is 80 mg. The maximum daily dose is 160 mg. Dose adjustments should follow the recommendations below. Temporarily interrupt treatment with this medicine in the following cases: - Recurrent Grade 2 hand-foot skin reaction (HFSR), or a reaction that does not improve within 7 days despite dose reduction; for Grade 3 HFSR, interrupt treatment for at least 7 days. - Grade 2 symptomatic hypertension - Grade 3 or 4 adverse reactions - Worsening infection of any Grade Reduce the dose of this medicine to 120 mg in the following cases: - First occurrence of Grade 2 HFSR - After recovery from a Grade 3 or 4 adverse reaction (excluding infection) - Grade 3 aspartate aminotransferase or alanine aminotransferase (AST or ALT) elevation; restart treatment with this medicine if the potential benefit outweighs the risk of hepatotoxicity. Reduce the dose of this medicine to 80 mg in the following cases: - Recurrence of Grade 2 HFSR at a dose of 120 mg - After recovery from a Grade 3 or 4 adverse reaction at a dose of 120 mg (for hepatotoxicity of the same Grade, see the permanent discontinuation section; for infection, see the temporary interruption section) Permanently discontinue this medicine in the following cases: - The patient cannot tolerate a dose of 80 mg - Aspartate aminotransferase or alanine aminotransferase (AST or ALT) levels exceed 20 times the upper limit of normal (ULN) - Abnormal aspartate aminotransferase or alanine aminotransferase (AST or ALT) levels (greater than 3 times the upper limit of normal) accompanied by abnormal bilirubin levels (greater than 2 times the upper limit of normal) - Recurrence of aspartate aminotransferase or alanine aminotransferase (AST or ALT) levels greater than 5 times the upper limit of normal at a dose of 120 mg - Occurrence of a Grade 4 adverse reaction; restart treatment with this medicine only if the potential benefit outweighs the risk. Adverse reactions are graded according to the NCI CTCAE Version 3.0 criteria. Patients with hepatic impairment No clinically significant difference in exposure was observed between patients with normal hepatic function and patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment. No dose adjustment is necessary for patients with mild or moderate hepatic impairment. Close monitoring of overall safety is recommended for these patients. This medicine has not been studied in patients with severe hepatic impairment (Child-Pugh C); therefore, its use in these patients is not recommended. Patients with renal impairment Based on the available clinical data, no difference in exposure related to this medicine was observed between patients with mild renal impairment and those with normal renal function. No dose adjustment is necessary for patients with mild or moderate renal impairment.

This medication can cause severe liver damage, so liver function tests are required before starting treatment, and liver function should be regularly monitored every two weeks during the first two months of treatment. If liver function abnormalities are detected, more frequent tests may be needed, and the medication may be temporarily suspended or the dose reduced or completely stopped depending on the condition. Pregnant women should not use this medication as it may harm the fetus, and women and men who are capable of pregnancy should use effective contraception during treatment and for 8 weeks afterward. It should not be administered to patients who are allergic to this medication or any of its components. Caution is advised in patients with impaired liver function, and close monitoring should be conducted. This drug can increase the risk of infection and bleeding, so patients with symptoms of infection or at risk of bleeding should be monitored carefully, and treatment should be discontinued in severe cases. Patients with a history of cardiac ischemia or myocardial infarction should be closely observed for cardiac status, and if cardiac issues arise, medication may be temporarily or permanently stopped. Common side effects include skin reactions on hands and feet, fatigue, diarrhea, decreased appetite, and high blood pressure, whereas severe skin reactions, liver damage, gastrointestinal perforation, and infections may occur as serious adverse reactions. This drug may cause an increase in blood pressure, and blood pressure should be measured frequently before and during treatment, and adjusted if necessary. Patients scheduled for surgery are advised to stop this medication at least 2 weeks prior and resuming only after confirming wound recovery. Reducing pressure on hands and feet and using moisturizing cream may help diminish skin toxicity. This drug may interact with several medications, so patients taking other medications should consult their doctor or pharmacist. Women who are pregnant or breastfeeding should not use this medication and should stop breastfeeding as well. This drug may impair the ability to drive or operate machinery, so caution is necessary. In case of overdose, medication should be stopped immediately and medical staff should monitor and treat the condition. This medication should be kept out of reach of children, used within 7 weeks after opening, and stored away from moisture and direct sunlight.

Fatal drug-induced liver damage, liver failure, hepatocellular injury, abnormal liver function tests, severe liver function abnormalities, liver failure, mild indirect hyperbilirubinemia, infections, bleeding, cardiac ischemia, myocardial infarction, pain, skin reactions on hands and feet, asthenia, fatigue, diarrhea, decreased appetite and food intake, hypertension, headache, tremors, peripheral neuropathy, reversible posterior leukoencephalopathy syndrome, hyperammonemic encephalopathy, speech disorders, stomatitis, vomiting, nausea, dysgeusia, dry mouth, gastroesophageal reflux disease, gastroenteritis, gastrointestinal perforation, gastrointestinal fistula, pancreatitis, hyperbilirubinemia, transaminase elevation, severe liver injury, rash, hair loss, dry skin, exfoliative rash, nail abnormalities, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, muscle cramps, proteinuria, hypersensitivity reactions, high fever, myositis, weight loss, amylase elevation, lipase elevation, abnormal INR, thrombocytopenia, anemia, leukopenia, thrombotic microangiopathy, hypothyroidism, hypokalemia, hypophosphatemia, hypocalcemia, hyponatremia, hypomagnesemia, hyperuricemia, dehydration, myocardial ischemia, hypertensive crisis, erythema and sensory disturbance on palms and soles, epistaxis, cerebral hemorrhage, respiratory bleeding, gastrointestinal bleeding, urogenital bleeding, urinary tract infection, nasopharyngitis, mucocutaneous and systemic fungal infections, pneumonia, aneurysm, arterial dissection, pneumonia, abdominal pain, abdominal distension, vomiting, sepsis, soft tissue infection, device-related infections, perirenal abscess, perirectal abscess, fever, peripheral edema, hepatitis, jaundice, toxic hepatitis, hepatorenal syndrome, hydronephrosis, acute kidney injury, azotemia, hematuria, ureteral stones, cough, pleural effusion, pneumothorax, rash, maculopapular rash, alanine aminotransferase elevation, conjugated bilirubin elevation, myopathy, pathological fractures, febrile neutropenia, acidosis, hepatic encephalopathy, drowsiness, vaginal-rectal fistula, vaginal bleeding, hypertension, hypovolemic shock, insomnia, anxiety, vesicles, pruritus, peripheral edema, confused state, depressed mood, depression, chronic cholecystitis, cholestatic jaundice, dizziness, inability to stabilize posture, cerebellar infarction, sensory abnormalities, radiculopathy, vocal cord paralysis, arthralgia, alkaline phosphatase elevation, increased serum adrenocorticotropic hormone, increased serum creatinine, C-reactive protein elevation, deep vein thrombosis, hypotension, appendiceal abscess, inguinal abscess, perirenal abscess, atrial fibrillation, supraventricular tachycardia, dry eyes, xerophthalmia, vulvar discomfort

This medication should be stored in a tightly sealed container to prevent exposure to air or moisture. The appropriate storage temperature is room temperature between 1 and 30 degrees Celsius, avoiding excessively hot or cold places.

Appearance

Light pink oval film-coated tablet

Package unit

28 tablets/bottle