Sorafenib Tosilate 200mg (56 tablets) - Bayer anticancer and antitumor drug.

Sorafenib is a multi-target tyrosine kinase inhibitor, primarily used for the treatment of malignant tumors.

I. Basic Drug Information

1. Generic Name : Sorafenib Tosylate Tablets
2. English name : Sorafenib Tosilate Tablets
3. Product name : Nexavar tablets 200mg (Nexavar tablets 200mg)
4. Dosage form : Film-coated tablets
5. Indications :
   • Radical resection of unresectable or metastatic renal cell carcinoma
   • Unresectable hepatocellular carcinoma
   • Radical cure of thyroid cancer that cannot be removed
6. Element :
   • Active ingredient : Each tablet contains 200mg of sorafenib (274.0mg as sorafenib tosylate).
   • Additives : croscarmellose sodium cellulose, crystalline cellulose, hydroxypropyl methylcellulose, sodium lauryl sulfate, magnesium stearate, polyethylene glycol 4000, titanium dioxide, ferric oxide
7. Characteristics :
   • Color tone: Red
   • Diameter: 10mm
   • Thickness: 4.5mm
   • Weight: 349.85mg
   • Identification code: 200

II. Usage and Dosage

1. The usual dosage for adults is 400 mg (calculated as sorafenib) twice daily orally, which may be adjusted according to the patient's condition.
2. Dosage adjustment plan
   • Radical cure of unresectable or metastatic renal cell carcinoma and unresectable hepatocellular carcinoma

• Radical cure of thyroid cancer that cannot be removed

3. Usage-related precautions
   • The efficacy and safety of combining sirolimus with other anti-cancer drugs containing sirolimus have not been established.
   • A high-fat diet can lower blood drug concentrations, so medication should be avoided between 1 hour before and 2 hours after meals.
   • When dosage adjustments are necessary due to side effects, specific standards must be followed according to the toxicity classification (dermal toxicity, hematological toxicity, non-hematological toxicity) (see "Precautions" for details).

III. Taboos

1. Those with a history of severe allergies to any of the ingredients in this medicine.
2. Pregnant women or women who may become pregnant (animal studies have shown embryotoxicity and teratogenicity).

IV. Precautions

1. Precautions for medication use in special populations
   • For patients with hypertension : This may worsen hypertension, so blood pressure needs to be monitored regularly, and medication may need to be discontinued if necessary.
   • Patients with liver dysfunction : Contraindicated in patients with severe liver dysfunction (Child-Pugh C) (excluded from clinical trials).
   • Breastfeeding women : It is recommended to stop breastfeeding during the period of discontinuation of medication (the medication can enter breast milk).
   • Children : No clinical trials have been conducted, but animal studies have shown effects on bones and teeth.
   • Elderly individuals : Due to decreased physiological function, medication should be administered with caution and close monitoring is necessary.
2. Medication monitoring and management
   • It should be used under the guidance of a physician with experience in cancer chemotherapy in a medical facility capable of handling emergencies.
   • Before treatment, the risks and benefits should be fully explained to the patient and their family, and medication should be administered only after obtaining their consent.
   • Regular check-up items include: liver function, complete blood count (including white blood cell differential), pancreatic enzymes, serum electrolytes, kidney function, and blood pressure.
   • Severe skin reactions may occur (such as hand-foot syndrome, toxic epidermal necrolysis), requiring prompt dermatological consultation.
   • It may cause acute lung injury and interstitial pneumonia, and symptoms such as difficulty breathing and fever need to be monitored.
   • Medication should be suspended during surgery (which may delay wound healing), and the patient's condition should be assessed before resuming medication after surgery.
3. Drug Preservation
   • Storage: Store at room temperature
   • Validity period: 36 months
   • Once opened, the aluminum bag should be stored in a moisture-proof environment (to avoid reducing its leaching properties).

V. Adverse Reactions

1. Serious adverse reactions (requiring immediate treatment)
   • Skin: Hand-foot syndrome (46.7%), exfoliative dermatitis, toxic epidermal necrolysis (TEN), etc.
   • Digestive diseases: gastrointestinal bleeding (7.5%), gastrointestinal perforation (potentially fatal), pancreatitis (0.3%).
   • Blood: Leukopenia (1.5%), thrombocytopenia (2.1%), anemia (3.4%).
   • Other: acute lung injury, hypertensive crisis, tumor lysis syndrome, liver failure, etc.
2. Common adverse reactions
   • Digestive system: diarrhea, nausea, loss of appetite (occurrence rate over 10%).
   • Skin: hair loss, rash, itching (occurrence rate over 10%).
   • Systemic symptoms: fatigue, weight loss (occurrence rate over 10%).
3. Adverse reaction management
   • Mild reactions (such as Grade 1 skin toxicity) can be treated with continued medication and symptomatic treatment.
   • For moderate to severe reactions (such as grade 3 hematologic toxicity), the medication should be discontinued until symptoms subside, and then the dosage should be gradually reduced before resuming administration.
   • Life-threatening reactions (such as grade 4 non-hematologic toxicity) require permanent discontinuation of the drug.

VI. Drug Interactions

VII. Pharmacological effects

1. Mechanism of action : It inhibits tumor cell proliferation-related C-Raf and B-Raf kinases, as well as tumor angiogenesis-related VEGF receptors and PDGF receptors, thereby inhibiting tumor growth and angiogenesis.
2. Anti-tumor effect : It can inhibit tumor proliferation in animal models such as renal cell carcinoma and hepatocellular carcinoma.

VIII. Pharmacokinetics

1. Absorption : Peak plasma concentration (Cmax) is reached 8 hours after oral administration. Absorption is reduced by a high-fat diet (AUC decreases by 29%).
2. Distribution : 99.5% of plasma proteins are bound, mainly to albumin.
3. Metabolism : Metabolized by CYP3A4 and UGT1A9, with metabolites accounting for 6-12% of the total AUC.
4. Excretion : 77% is excreted in feces within 14 days, and 19% is excreted in urine.

IX. Clinical Research

1. Renal cell carcinoma : Phase III trials showed a significant increase in progression-free survival (PFS) compared to placebo (168 days vs 84 days, p<0.000001).
2. Hepatocellular carcinoma : Phase III trials showed a significant increase in overall survival (OS) (324 days vs 241 days, p=0.000583).
3. Thyroid cancer : Phase III trials showed significantly prolonged progression-free survival (PFS) (329 days vs 175 days, p<0.0001).

10. Packaging Specifications

XI. Production Information

Manufacturer : バイエル薬品 Co., Ltd.