Regorafenib

When should one not use Regorafenib

Common side effects of this drug are:

• Diarrhoea
• Stomatitis
• Vomiting
• Nausea
• Constipation
• Thrombocytopenia
• Anaemia
• Decreased appetite and food intake
• Haemorrhage
• Hypertension
• Dysphonia
• Hyperbilirubinaemia
• Increase in transaminases
• Rash
• Weight loss

Other General Warnings

• You have liver disease or a history of liver problems.
• You have a history of Gilbert's syndrome.
• You have an active infection or develop signs of an infection that worsen.
• You have a condition that predisposes you to bleeding.
• You are taking blood thinners (anticoagulants) like warfarin or phenprocoumon.
• You have liver cirrhosis.
• You develop severe abdominal pain.
• You have unstable angina, new-onset angina (within the last 3 months), or a recent heart attack (within the last 6 months).
• You have heart failure (NYHA Class 2 or higher).
• You have a history of ischemic heart disease and experience new or worsening chest pain or other signs of reduced blood flow to the heart.
• You experience seizures, severe headaches, altered mental status, vision changes, or cortical blindness, possibly with high blood pressure.
• You have high blood pressure that is not well controlled.
• You have risk factors for aneurysms or artery dissections, such as high blood pressure or a history of aneurysm.
• You develop signs of Thrombotic Microangiopathy (TMA) such as fatigue, fever, confusion, decreased urination, or bruising easily.
• You are scheduled for major surgery.
• You develop a severe or persistent skin rash, especially on your hands and feet (Hand-Foot Skin Reaction).
• You experience persistent or recurrent significant changes in your blood electrolyte levels (e.g., low phosphate, calcium, sodium, or potassium).
• You experience persistent or recurrent significant changes in thyroid-stimulating hormone, lipase, or amylase levels.
• You are on a low-sodium diet.
• You have a known allergy to soya or lecithin derived from soya.

How Does It Work?

Interactions with other medicines

• CYP3A4 Inhibitors: Strong inhibitors (e.g., ketoconazole, clarithromycin, grapefruit juice) can increase regorafenib exposure and decrease active metabolite exposure. Avoid concomitant use.
• UGT1A9 Inhibitors: Strong inhibitors (e.g., mefenamic acid, diflunisal) should be avoided due to potential unknown effects on regorafenib and metabolite levels.
• CYP3A4 Inducers: Strong inducers (e.g., rifampicin, phenytoin, St. John's Wort) can decrease regorafenib exposure and increase one active metabolite. Avoid or consider alternative medications.
• UGT1A1/9 Substrates: Regorafenib can increase the exposure of drugs metabolized by these enzymes (e.g., irinotecan's active metabolite SN-38).
• BCRP Substrates: Regorafenib can significantly increase the plasma concentrations of BCRP substrates (e.g., rosuvastatin, methotrexate). Monitor for increased side effects.
• P-glycoprotein Substrates: No clinically significant interaction observed with digoxin.
• P-glycoprotein and BCRP Inhibitors/Inducers: May affect the exposure of regorafenib's active metabolites (M-2 and M-5); clinical significance is unknown.
• CYP2C8, CYP2C9, CYP2B6, CYP3A4, CYP2C19 Substrates: No clinically meaningful drug interaction expected.
• Antibiotics (Neomycin): Can significantly decrease the exposure of active metabolites M-2 and M-5, potentially reducing regorafenib efficacy.
• Bile Salt-Sequestering Agents: May decrease regorafenib absorption, potentially reducing efficacy.

Overdose

Missed a Dose