Regonat 40mg Tablet

Regorafenib is a kinase inhibitor indicated for the treatment of adult patients with: - Metastatic colorectal cancer (CRC) who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if RAS wild-type, an anti-EGFR therapy. - Locally advanced, unresectable or metastatic gastrointestinal stromal tumor (GIST) who have been previously treated with imatinib mesylate and sunitinib malate. - Hepatocellular carcinoma (HCC) who have been previously treated with sorafenib Colorectal Cancer Regorafenib is indicated for the treatment of adult patients with metastatic colorectal cancer (CRC) who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if RAS wild-type, an anti-EGFR therapy. Gastrointestinal Stromal Tumors Regorafenib is indicated for the treatment of adult patients with locally advanced, unresectable or metastatic gastrointestinal stromal tumor (GIST) who have been previously treated with imatinib mesylate and sunitinib malate. Hepatocellular Carcinoma Regorafenib is indicated for the treatment of adult patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib.

---

Source: US FDA prescribing information, via openFDA. Provided for general information only — it is not a substitute for your doctor's or pharmacist's advice. Always follow your prescriber's instructions.

Boxed warning. HEPATOTOXICITY - Severe and sometimes fatal hepatotoxicity has occurred in clinical trials. - Monitor hepatic function prior to and during treatment. - Interrupt and then reduce or discontinue Regorafenib for hepatotoxicity as manifested by elevated liver function tests or hepatocellular necrosis, depending upon severity and persistence. WARNING: HEPATOTOXICITY See full prescribing information for complete boxed warning. - Severe and sometimes fatal hepatotoxicity has occurred in clinical trials. - Hepatotoxicity: Monitor liver function tests. Withhold and then reduce or discontinue Regorafenib based on severity and duration. - Infections: Withhold Regorafenib in patients with worsening or severe infections. - Hemorrhage: Permanently discontinue Regorafenib for severe or life-threatening hemorrhage. - Gastrointestinal perforation or fistula: Discontinue Regorafenib. - Dermatologic toxicity: Withhold and then reduce or discontinue Regorafenib depending on severity and persistence of dermatologic toxicity. - Hypertension: Temporarily or permanently withhold Regorafenib for severe or uncontrolled hypertension. - Cardiac ischemia and infarction: Withhold Regorafenib for new or acute cardiac ischemia/infarction and resume only after resolution of acute ischemic events. - Reversible posterior leukoencephalopathy syndrome (RPLS): Discontinue Regorafenib. - Risk of impaired wound healing: Withhold for at least 2 weeks prior to elective surgery. Do not administer for at least 2 weeks after major surgery and until adequate wound healing. The safety of resumption of Regorafenib after resolution of wound healing complications has not been established. - Embryo-fetal toxicity: Can cause fetal harm. Advise women of potential risk to a fetus and to use effective contraception during treatment and for 2 months after the final dose. Advise males to use effective contraception for 2 months after the final dose. Hepatotoxicity Severe drug-induced liver injury with fatal outcome occurred in Regorafenib-treated patients in clinical trials. In most cases, liver dysfunction occurred within the first 2 months of therapy and was characterized by a hepatocellular pattern of injury. Additionally, hyperammonemic encephalopathy, including fatal cases, have been reported in the postmarketing setting in patients treated with Regorafenib. The risk of hyperammonemic encephalopathy appears increased in patients with liver dysfunction, liver metastases, or primary liver cancer. In the CORRECT study, fatal hepatic failure occurred in 1.6% of patients in the regorafenib arm and in 0.4% of patients in the placebo arm. In the GRID study, fatal hepatic failure occurred in 0.8% of patients in the regorafenib arm. Abridged from the full prescribing information.

---

Source: US FDA prescribing information, via openFDA. Provided for general information only — it is not a substitute for your doctor's or pharmacist's advice. Always follow your prescriber's instructions.

The following serious adverse reactions are discussed elsewhere in the labeling: - Hepatotoxicity - Infections - Hemorrhage - Gastrointestinal Perforation or Fistula - Dermatological Toxicity - Hypertension - Cardiac Ischemia and Infarction - Reversible Posterior Leukoencephalopathy Syndrome (RPLS) The most common adverse reactions (≥20%) are pain (including gastrointestinal and abdominal pain), HFSR, asthenia/fatigue, diarrhea, decreased appetite/food intake, hypertension, infection, dysphonia, hyperbilirubinemia, fever, mucositis, weight loss, rash, and nausea. Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rate observed in practice. The data described in the WARNINGS AND PRECAUTIONS section reflect exposure to Regorafenib in more than 4800 patients who were enrolled in four randomized, placebo-controlled trials (n=1142), an expanded access program (CONSIGN, n=2864), or single arm clinical trials (single agent or in combination with other agents). There were 4518 patients who received Regorafenib as a single agent; the distribution of underlying malignancies was 80% CRC, 4% GIST, 10% HCC, 6% other solid tumors; and 74% were White, 11% Asian, and 15% race not known. Among these 4518 patients, 83% received Regorafenib for at least 21 days and 20% received Regorafenib for 6 months or longer. In randomized placebo-controlled trials (CORRECT, GRID, RESORCE and CONCUR), the most frequently observed adverse drug reactions (≥20%) in patients receiving Regorafenib are pain (including gastrointestinal and abdominal pain), HFSR, asthenia/fatigue, diarrhea, decreased appetite/food intake, hypertension, infection, dysphonia, hyperbilirubinemia, fever, mucositis, weight loss, rash, and nausea. Colorectal Cancer The safety data described below, except where noted, are derived from a randomized (2:1), double-blind, placebo-controlled trial (CORRECT) in which 500 patients (median age 61 years; 61% men) with previously-treated metastatic colorectal cancer (CRC) received Regorafenib as a single agent at the dose of 160 mg daily for the first 3 weeks of each 4 week treatment cycle and 253 patients (median age 61 years; 60% men) received placebo. The median duration of therapy was 1.7 months (range 2 days, 10.8 months) for patients receiving Regorafenib. Abridged from the full prescribing information.

---

Source: US FDA prescribing information, via openFDA. Provided for general information only — it is not a substitute for your doctor's or pharmacist's advice. Always follow your prescriber's instructions.