1. Ingredients

Each LegaRego 40mg tablet contains:

• Regorafenib 40mg.
• Excipients: sufficient quantity for one tablet.
  Dosage form: Tablets.

2. Effects and Indications of LegaRego 40mg

LegaRego 40mg is used in the treatment of metastatic colorectal cancer in patients who have previously been treated with or are not suitable for therapies involving fluoropyrimidine-based chemotherapy, anti-VEGF therapy, or anti-EGFR therapy.

3. Dosage and Administration of LegaRego 40mg

3.1 Recommended Dosage

• The recommended dose of LegaRego 40mg is 160mg once daily for 3 consecutive weeks followed by a 1-week break, forming a 4-week treatment cycle.
• Dosage may be adjusted based on patient response.
• Minimum dose: 80mg/day.
• Maximum dose: 160mg/day.

3.2 Administration Instructions

• LegaRego 40mg should be taken orally, after a light meal, and at the same time each day.
• Swallow the tablet whole; do not chew or break it.

4. Contraindications

Do not use LegaRego 40mg in patients who are hypersensitive to any component of the product, including excipients.

5. Side Effects

Possible side effects during treatment may include:

• Infections.
• Cutaneous squamous cell carcinoma, keratoacanthoma.
• Anemia, leukopenia, thrombocytopenia.
• Hypothyroidism.
• Decreased appetite and food intake.
• Hypocalcemia, hypokalemia, hyponatremia, hypomagnesemia, hypophosphatemia, hyperuricemia.
• Headache, reversible posterior leukoencephalopathy syndrome (RPLS), tremor.
• Ischemia, myocardial infarction.
• Hypertension, bleeding.
• Hoarseness.
• Nausea, vomiting, diarrhea, stomatitis, dry mouth, gastroenteritis, dysgeusia, gastrointestinal perforation/fistula, gastroesophageal reflux disease.
• Severe liver damage, hepatic dysfunction.
• Alopecia, hand-foot skin reaction, dry skin, skin peeling, erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome, nail disorders.
• Proteinuria.
• Muscle stiffness.
• Fever, weakness, fatigue, mucosal inflammation.
• Weight loss, increased lipase, increased amylase, abnormal INR.

6. Drug Interactions

• Strong CYP3A4 inhibitors may affect exposure and steady-state levels of LegaRego 40mg and should be avoided.
• Strong CYP3A4 inducers may decrease LegaRego plasma concentrations, reducing its efficacy.
• LegaRego 40mg may increase systemic exposure to UGT1A1 and UGT1A9 substrates.
• LegaRego 40mg may also increase plasma concentrations of BCRP substrates.

7. Warnings, Precautions, and Storage

7.1 Warnings and Precautions

• Regular monitoring of liver function is necessary during treatment.
• Carefully weigh benefits versus risks in patients with KRAS-mutated tumors.
• Monitor blood cell counts in patients at risk for bleeding or using anticoagulants.
• Patients with a history of ischemic heart disease should be monitored for related symptoms during treatment.
• Discontinue use if symptoms of reversible posterior leukoencephalopathy syndrome (RPLS) appear.
• Discontinue if gastrointestinal perforation/fistula occurs.
• Immediately stop treatment and consult a doctor if adverse reactions occur.
• Caution is advised for pregnant or breastfeeding women.

7.2 Use in Pregnancy and Breastfeeding

• Both women of childbearing potential and men should use effective contraception during treatment and for at least 8 weeks after the final dose of LegaRego 40mg.
• Do not use LegaRego 40mg during pregnancy.
• Breastfeeding should be discontinued during treatment with LegaRego 40mg.

7.3 Overdose Management

Symptoms of overdose may include hoarseness, diarrhea, severe skin reactions, dry mouth, loss of appetite, mucosal inflammation, hypertension, and fatigue.

• No specific antidote for LegaRego 40mg overdose exists; supportive treatment should be provided.

7.4 Storage

• Store LegaRego 40mg in a dry, cool place below 30°C.

8. Alternative Products

• Oxitan 100mg/20ml (Fresenius Kabi Deutschland GmbH): Contains Oxaliplatin 100mg/20ml, indicated for metastatic colorectal cancer or post-tumor resection.
• Oxaliplatin Ebewe 50mg/10ml: Used for stage III colorectal cancer after primary tumor surgery or metastatic colorectal cancer, manufactured by Oncotec Pharma Produktion GmbH.

9. Mechanism of Action

9.1 Pharmacodynamics

Regorafenib is an orally administered multi-kinase inhibitor targeting proteins involved in tumor angiogenesis and oncogenesis. It has demonstrated strong anti-cancer effects in various cancer cell types, including colorectal cancer, through anti-angiogenic, anti-proliferative, and anti-metastatic mechanisms.

9.2 Pharmacokinetics

• Absorption: Oral bioavailability of approximately 69–83%. Peak plasma concentration occurs within 3–4 hours after administration.
• Distribution: About 99.5% bound to plasma proteins.
• Metabolism: Metabolized primarily by liver enzyme CYP3A4.
• Elimination: Half-life of 20–30 hours. About 71% excreted in feces, 19% in urine.

10. Advantages

• LegaRego 40mg has been clinically proven to be effective in treating metastatic colorectal cancer.
• Convenient tablet form allows patients to take the medication at home.
• Regorafenib is considered a third-line therapy for metastatic colorectal cancer patients who have progressed after two prior chemotherapies and targeted therapies. [1]

11. Disadvantages

• LegaRego 40mg may cause some adverse effects during treatment.