SORAFENIB TOSYLATE

Clinical safety rating: avoid

Contraindicated (not allowed)

How it works

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.

What the body does with it

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).

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Strong CYP3A4 inducers may decrease efficacy Can cause hand-foot skin reaction and hypertension.

Breastfeeding	No human data on excretion in breast milk; M/P ratio unknown. Due to potential for serious adverse reactions in nursing infants, breastfeeding is not recommended during therapy and for at least 2 weeks after last dose.
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.

Warnings & precautions

■ FDA Black Box Warning

No FDA Boxed Warning exists for Sorafenib Tosylate.

Side Effect Profile

Common Effects	hepatocellular carcinoma
Serious Effects

Absolute Contraindications

["Hypersensitivity to sorafenib or any excipients","Severe hepatic impairment (Child-Pugh C) in patients with hepatocellular carcinoma"]

Clinical Precautions

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"]

Clinical Tips & Counseling

Drug interactions

Loading safety data…