SORAFENIB TOSYLATE
Clinical safety rating: avoid
Contraindicated (not allowed)
Sorafenib is a multikinase inhibitor that inhibits Raf serine/threonine kinases (C-Raf, B-Raf, and mutant B-Raf), vascular endothelial growth factor receptors (VEGFR-1, VEGFR-2, VEGFR-3), platelet-derived growth factor receptor (PDGFR-β), and other kinases, thereby inhibiting tumor cell proliferation and angiogenesis.
| Metabolism | Hepatic metabolism primarily via CYP3A4 and UGT1A9, with minor contributions from CYP2B6; sorafenib is a substrate of BCRP and P-glycoprotein. |
| Excretion | Fecal (77%) as unchanged drug and metabolites; renal (19%) as glucuronide conjugates; <1% excreted unchanged in urine. |
| Half-life | Terminal half-life of sorafenib is approximately 25-48 hours (mean ~37 hours); clinical steady-state achieved within 7 days. |
| Protein binding | 99.5% bound primarily to albumin; also binds to alpha-1-acid glycoprotein. |
| Volume of Distribution | Vd/F = 138-255 L (approx. 2-4 L/kg) indicating extensive extravascular distribution. |
| Bioavailability | Oral bioavailability is 38-49% when taken under fasting conditions; reduced by 29% with high-fat meal (AUC decreases ~29%). |
| Onset of Action | Oral: Clinical effect (e.g., tumor response) typically observed after 2-8 weeks of continuous dosing; trough concentrations reach steady-state by day 7. |
| Duration of Action | Dosing is continuous (twice daily) without drug-free intervals; effect persists as long as therapeutic plasma concentrations are maintained (approx. 12 hours post-dose). |
| Molecular Weight | 637 |
400 mg orally twice daily on an empty stomach (at least 1 hour before or 2 hours after a meal).
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Not recommended for patients with severe renal impairment (CrCl < 30 mL/min) due to lack of data. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: No established dose; use with caution. Child-Pugh C: Not recommended. |
| Pediatric use | Not approved for use in pediatric patients; safety and efficacy not established. |
| Geriatric use | No specific dose adjustments; monitor closely for adverse effects due to potential age-related comorbidities and reduced organ function. |
| 1st trimester | Contraindicated due to teratogenicity; potential for fetal harm based on animal studies and its mechanism of action (antiangiogenic). Alternative therapy should be considered. |
| 2nd trimester | Contraindicated due to risk of fetal vascular disruption, growth restriction, and potential for fetal death from antiangiogenic effects. |
| 3rd trimester | Contraindicated due to risk of fetal vascular disruption, growth restriction, and potential for fetal death from antiangiogenic effects. |
Clinical note
Strong CYP3A4 inducers may decrease efficacy Can cause hand-foot skin reaction and hypertension.
| Placental transfer | Sorafenib is known to cross the placenta in animal studies. In rats, placental transfer was confirmed with fetal plasma concentrations approximately 30-50% of maternal concentrations. Human data are lacking, but placental transfer is expected based on molecular weight (MW 637.0 Da) and lipophilicity. |
| Breastfeeding |
■ FDA Black Box Warning
No FDA Boxed Warning exists for Sorafenib Tosylate.
| Common Effects | hepatocellular carcinoma |
| Serious Effects |
PregnancyKnown hypersensitivity to sorafenib or any component of the formulation
| Precautions | Cardiac ischemia and myocardial infarction, Hemorrhage (including fatal bleeding), Hypertension (including hypertensive crisis), Dermatologic toxicity (hand-foot skin reaction), Gastrointestinal perforation, Wound healing complications, Hepatic impairment (increased risk of hepatotoxicity), QT interval prolongation, Thyroid dysfunction |
| Food/Dietary | Take sorafenib on an empty stomach (at least 1 hour before or 2 hours after a meal). Avoid grapefruit and grapefruit juice due to potential CYP3A4 inhibition. Avoid St. John's wort (CYP3A4 inducer) as it may decrease sorafenib efficacy. |
Loading safety data…
| It is unknown if sorafenib is excreted in human breast milk. Due to the potential for serious adverse reactions in nursing infants (e.g., antiangiogenic effects, gastrointestinal toxicity), breastfeeding should be avoided during treatment and for at least 2 weeks after the last dose. |
| Lactation Rating | L5 (Contraindicated) |
| Teratogenic Risk | Sorafenib is embryotoxic and teratogenic in animals. In humans, data are limited but it is contraindicated in pregnancy. First trimester exposure may cause major congenital malformations. Second and third trimester exposure risks fetal growth restriction, oligohydramnios, and potential fetal death due to anti-angiogenic effects. |
| Fetal Monitoring | Monitor maternal blood pressure (for hypertension), liver function (AST, ALT, bilirubin), renal function (serum creatinine), thyroid function (TSH), and electrolytes. Perform fetal ultrasound for growth and amniotic fluid volume during pregnancy. |
| Fertility Effects | Sorafenib may impair male and female fertility. In animal studies, it caused testicular degeneration and reduced spermatogenesis. Human data limited; patients should be counseled on potential reduced fertility. |
| Clinical Pearls | Sorafenib is a multikinase inhibitor (Raf, VEGFR, PDGFR) used in hepatocellular carcinoma (HCC), renal cell carcinoma (RCC), and differentiated thyroid carcinoma (DTC). Monitor for hand-foot skin reaction (HFSR), which may require dose interruption or reduction. Hypertension is common; monitor blood pressure weekly during the first 6 weeks. Sorafenib is a moderate CYP2C8 and CYP3A4 substrate; avoid strong CYP3A4 inducers (e.g., rifampin) and use caution with CYP2C8 inhibitors (e.g., gemfibrozil). Dose reduction is recommended in Child-Pugh B or C hepatic impairment. Administer on an empty stomach (at least 1 hour before or 2 hours after a meal) to improve absorption. |
| Patient Advice | Take sorafenib exactly as prescribed, usually 400 mg twice daily on an empty stomach (1 hour before or 2 hours after a meal). · Do not crush, break, or chew tablets; swallow whole with water. · Common side effects include diarrhea, fatigue, hand-foot skin reaction (redness, peeling, blisters on palms and soles), and high blood pressure. Report these to your doctor. · You may need regular blood pressure checks. If you develop severe skin reactions or bleeding, contact your healthcare provider immediately. · Avoid grapefruit and grapefruit juice while taking sorafenib. · Do not take St. John's wort, as it can reduce the effectiveness of sorafenib. · Tell your doctor about all medications, including over-the-counter drugs and supplements, especially blood thinners and antifungal medications. · Use effective contraception during treatment and for at least 2 weeks after the last dose. · Do not breastfeed while taking sorafenib and for 2 weeks after the last dose. |