Regora40 mg

Regora is an oral multikinase inhibitor used to treat certain advanced cancers after prior standard therapies have failed. It is prescribed and monitored by an oncologist and is not used as a first-line cancer treatment.

FDA-Approved (Established) Indications

• Metastatic colorectal cancer (mCRC): in patients previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF therapy, and (if RAS wild-type) an anti-EGFR therapy.
• Advanced gastrointestinal stromal tumor (GIST): in patients previously treated with imatinib and sunitinib.
• Hepatocellular carcinoma (HCC): in patients previously treated with sorafenib.

Regora is given as monotherapy in each of these settings; it is not combined with other anticancer agents as part of its approved use, and it should only be used after the specified prior treatments have been given and have failed or are no longer tolerated.

Each film-coated tablet of Regorafenib contains 40 mg of regorafenib (as regorafenib monohydrate) as the active ingredient, together with standard pharmaceutically inert excipients used in tablet manufacturing.

Regora is an orally administered small-molecule anticancer medicine belonging to the multikinase inhibitor class. It works by blocking several enzymes (kinases) that tumor cells use to grow, form new blood vessels, and spread. Regora is used only for specific advanced-stage cancers that have already been treated with other standard anticancer therapies, and treatment must be supervised by a cancer specialist because of its significant safety monitoring requirements.

Regora belongs to the therapeutic class of antineoplastic agents, specifically the oral multikinase (multi-target tyrosine kinase) inhibitor class of targeted anticancer drugs.

Regorafenib is a small-molecule inhibitor that blocks the activity of multiple protein kinases involved in tumor growth, tumor blood vessel formation (angiogenesis), and the tumor microenvironment.

• Angiogenic kinases: VEGFR1, VEGFR2, VEGFR3, and TIE2.
• Stromal/oncogenic kinases: KIT, RET, RAF-1, wild-type BRAF, mutant BRAF (including BRAF V600E), PDGFR, and FGFR.

By inhibiting these targets, Regorafenib reduces tumor angiogenesis, slows tumor cell proliferation, and interferes with the tumor microenvironment, which together contribute to its anticancer effect in colorectal cancer, GIST, and hepatocellular carcinoma.

Regora should be taken by mouth at approximately the same time every day, after a low-fat meal (less than 30% fat and under 600 calories), to ensure consistent absorption. Tablets should be swallowed whole with a glass of water and must not be crushed, chewed, or split. Do not take a missed dose if it is within 12 hours of the next dose. See Dosage and Administration for the complete dosing schedule.

Regora is metabolized mainly by the liver enzyme CYP3A4 and undergoes UGT1A9-mediated glucuronidation, making it prone to clinically significant drug interactions.

• Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, grapefruit juice): increase Regora exposure; avoid concomitant use if possible.
• Strong CYP3A4 inducers (e.g., rifampin, phenytoin, carbamazepine, phenobarbital, St. John's Wort): reduce Regora exposure and may decrease efficacy; avoid concomitant use.
• Warfarin and other vitamin K antagonists: Regora can increase exposure to warfarin and raise bleeding risk; monitor INR closely and watch for bleeding (see Contraindications/Precautions for bleeding risk).
• UGT1A1 substrates (e.g., irinotecan): Regora can increase exposure to irinotecan and its active metabolite; use with caution.
• BCRP substrates: Regora is a BCRP inhibitor and may raise levels of drugs transported by this pathway.

Patients should inform their oncologist of all prescription drugs, over-the-counter medicines, and herbal products before starting Regora.

Side effects of Regora are common and can be serious; regular monitoring by the treating oncologist is essential.

Very Common Side Effects

• Hand-foot skin reaction (palmar-plantar erythrodysesthesia)
• Fatigue and weakness (asthenia)
• Hypertension (high blood pressure)
• Diarrhea
• Decreased appetite and weight loss
• Nausea, vomiting, and mouth sores (mucositis)
• Voice changes (dysphonia)
• Rash and dry skin
• Infection

Serious Side Effects

These require urgent medical attention and are described in detail under Precautions and Warnings: severe or fatal liver injury (hepatotoxicity), serious or fatal bleeding, gastrointestinal perforation or fistula, hypertensive crisis, cardiac ischemia/infarction, reversible posterior leukoencephalopathy syndrome (RPLS), and wound-healing complications.

Pregnancy: Regora can cause fetal harm based on its mechanism of action (inhibition of angiogenesis) and animal reproduction studies showing teratogenicity and embryo-fetal toxicity. Regora should not be used during pregnancy; it should be used only if a physician determines there is no safer alternative and the potential benefit clearly justifies the potential risk to the fetus. Women of reproductive potential should use effective contraception during treatment and for at least a specified period after the final dose, as advised by their oncologist; male patients with female partners of reproductive potential should also use effective contraception.

Lactation: It is not known whether Regora passes into human breast milk. Because of the potential for serious adverse effects in a breastfed infant, women should not breastfeed during treatment with Regora and for a period after the last dose as advised by their physician.

Regora carries a boxed warning for severe and sometimes fatal hepatotoxicity. Treatment must be managed by an oncologist with close clinical and laboratory monitoring.

• Hepatotoxicity: Obtain liver function tests before starting Regora, every 2 weeks for the first 2 months, then monthly (or more frequently as clinically indicated). Interrupt, reduce, or permanently discontinue based on severity of liver enzyme elevation.
• Hemorrhage: Bleeding, including severe and fatal cases, has occurred. Permanently discontinue in patients with severe or life-threatening bleeding.
• Gastrointestinal perforation or fistula: Discontinue Regora if this occurs.
• Hypertension: Blood pressure should be well-controlled before starting; monitor weekly during the first cycle and regularly thereafter; treat hypertension per standard guidelines and interrupt/reduce dose or discontinue for severe or uncontrolled hypertension.
• Dermatologic toxicity: Hand-foot skin reaction and severe skin reactions can occur; manage with supportive care, dose interruption, or dose reduction.
• Wound-healing complications: Interrupt Regora at least 2 weeks before scheduled surgery and resume only after adequate wound healing.
• Cardiac ischemia and infarction: Withhold Regora for new or acute cardiac ischemia; resume only after resolution if benefit outweighs risk.
• Reversible posterior leukoencephalopathy syndrome (RPLS): Discontinue permanently if RPLS is diagnosed.
• Proteinuria: Monitor periodically; manage per severity.

Because of these risks, Regora should only be prescribed and monitored by physicians experienced in cancer chemotherapy.

There is no specific antidote for Regora overdose. The highest dose studied clinically was 220 mg per day; effects observed with higher-than-recommended doses included increased skin, gastrointestinal (diarrhea), voice (dysphonia), and liver-related adverse reactions, and elevated blood pressure. In case of a suspected overdose of Regora, seek immediate medical attention or contact a poison control center/emergency services right away. Management is supportive, based on the patient's clinical signs and symptoms, under medical supervision; do not attempt specific home treatment.

Store Regora tablets at room temperature, between 15°C and 30°C, in the original container, away from excess heat, light, and moisture. Keep the bottle tightly closed. Once opened, discard any unused tablets after 7 weeks (49 days). Keep out of reach and sight of children.

• Pediatric patients: Safety and efficacy of Regora have not been established in patients under 18 years of age; it is not recommended for use in children.
• Elderly patients: No overall differences in effectiveness were observed between elderly and younger adult patients, but elderly patients may be more susceptible to certain adverse reactions; monitor closely.
• Renal impairment: No dose adjustment is required for mild-to-moderate renal impairment; data in severe renal impairment are limited, so use with caution.
• Hepatic impairment: No dose adjustment is needed for mild-to-moderate (Child-Pugh A/B) hepatic impairment; Regora is not recommended in severe (Child-Pugh C) hepatic impairment.
• Pregnancy and lactation: See Pregnancy and Lactation section above.

Regora is given in repeated 28-day cycles (160 mg once daily for 21 days, followed by 7 days off treatment). Treatment with Regora is continued for as long as the patient continues to derive clinical benefit and tolerates the medicine, and is stopped if the disease progresses or if toxicity becomes unacceptable, as determined by the treating oncologist.

Regorafenib belongs to the drug classes: multikinase inhibitors, antineoplastic (anticancer) agents, and angiogenesis inhibitors.

Regorafenib acts by inhibiting multiple membrane-bound and intracellular kinases involved in normal cellular function and pathologic processes such as tumor angiogenesis, oncogenesis, and maintenance of the tumor microenvironment. Its molecular targets include VEGFR1, VEGFR2, VEGFR3, TIE2, KIT, RET, RAF-1, BRAF (wild-type and V600E mutant), PDGFR, and FGFR. By blocking these targets simultaneously, Regorafenib deprives tumors of their blood supply and directly inhibits tumor cell growth signaling, producing its anticancer effect.

The safety and efficacy of Regora have not been established in pediatric patients. Regora is not recommended for use in children or adolescents outside of a clinical trial setting, and no pediatric dosing has been established.