Fenitab

• Advanced Hepatocellular Carcinoma (HCC):
  Indicated for the treatment of patients with unresectable or metastatic hepatocellular carcinoma, especially those with preserved liver function (Child-Pugh Class A).
• Advanced Renal Cell Carcinoma (RCC):
  Approved for patients with advanced or metastatic renal cell carcinoma after prior systemic therapy (such as cytokines).
• Differentiated Thyroid Carcinoma (DTC):
  Used in patients with locally advanced or metastatic, radioactive iodine-refractory differentiated thyroid carcinoma.
• Off-label/Investigational Uses:
  Includes treatment of some sarcomas, non-small cell lung cancer, and other malignancies under clinical trials.

• Adults:
  The recommended dose is 400 mg orally twice daily (total 800 mg/day), administered approximately 12 hours apart. It should be taken on an empty stomach — either at least 1 hour before or 2 hours after a meal.
• Administration:
  Tablets should be swallowed whole with water and not crushed or chewed.
• Dose Adjustments:
  Dose modifications are recommended in response to adverse effects, such as hand-foot skin reaction or hypertension. Dose reductions are typically in increments of 200 mg/day. Temporary interruption or discontinuation may be necessary depending on severity.
• Special Populations:
• Hepatic impairment: Use with caution in mild to moderate impairment (Child-Pugh A and B). Avoid use in severe hepatic impairment (Child-Pugh C).
• Renal impairment: No dose adjustment necessary in mild to moderate renal impairment; limited data in severe impairment—use cautiously.
• Elderly: No initial dose adjustments; monitor closely for tolerability.

Sorafenib is an oral multikinase inhibitor that targets both tumor cell proliferation and angiogenesis pathways. It inhibits the serine/threonine kinases RAF-1 and BRAF, blocking the RAF/MEK/ERK signaling cascade that promotes tumor cell growth. It also inhibits receptor tyrosine kinases involved in angiogenesis, including vascular endothelial growth factor receptors (VEGFR-2, VEGFR-3), platelet-derived growth factor receptor beta (PDGFR-β), KIT, and FLT-3. This dual inhibition reduces tumor vascularization and proliferation, thereby limiting tumor growth and metastasis.

• Absorption: Peak plasma concentrations occur approximately 3 hours after oral administration.
• Bioavailability: Absolute bioavailability is approximately 38–49%. Food delays absorption but does not significantly affect total exposure.
• Distribution: Highly protein bound (~99.5%).
• Metabolism: Extensively metabolized in the liver primarily via CYP3A4 and UGT1A9 enzymes.
• Half-life: Terminal elimination half-life ranges from 25 to 48 hours, allowing twice-daily dosing.
• Excretion: Mainly eliminated via feces (~77%) and to a lesser extent via urine (~19%).

• Pregnancy: Classified as FDA Pregnancy Category D. There is positive evidence of human fetal risk; sorafenib is contraindicated during pregnancy unless the potential benefits outweigh the risks.
• Lactation: It is unknown whether sorafenib is excreted in human breast milk; breastfeeding is not recommended during treatment and for at least two weeks after the last dose.

• Primary Therapeutic Class: Antineoplastic agent
• Subclass: Multikinase inhibitor (targeted cancer therapy)

• Known hypersensitivity to sorafenib or any of its excipients
• Pregnancy and breastfeeding
• Severe hepatic impairment (Child-Pugh Class C)

• Hemorrhage: Increased risk of bleeding; monitor carefully especially in patients with recent surgery or bleeding disorders.
• Hypertension: Monitor blood pressure regularly and manage hypertension aggressively.
• Cardiac Ischemia and Infarction: Discontinue if severe cardiac events occur.
• Wound Healing: Interrupt therapy prior to planned surgery; impaired wound healing reported.
• Hand-Foot Skin Reaction: May require dose modification.
• Hepatotoxicity: Monitor liver function tests regularly due to risk of severe liver injury.
• Gastrointestinal Perforation: Report immediately if suspected; may be life-threatening.
• Dermatologic Toxicities: Monitor for skin malignancies and severe skin reactions.

• Common (>20%):
• Diarrhea
• Fatigue
• Hand-foot skin reaction (palmar-plantar erythrodysesthesia)
• Rash and desquamation
• Hypertension
• Alopecia
• Nausea, vomiting
• Anorexia
• Serious but rare:
• Hepatotoxicity and liver failure
• Myocardial ischemia or infarction
• Gastrointestinal perforation
• Severe hypertension and hypertensive crisis
• Severe dermatologic reactions
• Most adverse effects occur within the first 6 weeks and may be dose-related.

• CYP3A4 Inducers (e.g., rifampicin, carbamazepine): May reduce sorafenib plasma concentration, lowering efficacy.
• CYP3A4 Inhibitors (e.g., ketoconazole): May increase sorafenib levels, increasing toxicity risk.
• Anticoagulants (e.g., warfarin): Increased bleeding risk; close monitoring required.
• P-glycoprotein substrates: Sorafenib weakly inhibits P-gp; monitor co-administered drugs accordingly.
• Avoid grapefruit juice due to CYP3A4 interaction.

• Current guidelines from NCCN and ESMO confirm sorafenib as a first-line therapy for advanced HCC and selected RCC patients.
• New safety communications emphasize early monitoring of cardiac function and blood pressure.
• EMA updated safety labeling with emphasis on rare but serious liver toxicity risk.
• Included in WHO Essential Medicines List for advanced liver cancer.

• Store tablets at controlled room temperature: 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep tablets in original container until use.
• Do not freeze.