Sorafenib
NEXAVAR
What it isSorafenib is an oral small-molecule multikinase inhibitor that blocks RAF serine/threonine kinases along with VEGFR, PDGFR-beta, and KIT to suppress tumor proliferation and angiogenesis.
Why this oneIt is approved for advanced hepatocellular carcinoma, advanced renal cell carcinoma, and radioactive iodine-refractory differentiated thyroid carcinoma.
What limits itDose-limiting toxicities include hand-foot skin reaction, hypertension, diarrhea, bleeding, and QT-interval prolongation.
FDA label
Read the full label on DailyMed ↗
| FDA dosing | Population | Start | Target | Max |
|---|---|---|---|---|
| Hepatocellular carcinoma (unresectable) | Adults | 400 mg BID without food | 400 mg BID | 400 mg BID |
| Advanced renal cell carcinoma | Adults | 400 mg BID without food | 400 mg BID | 400 mg BID |
| Differentiated thyroid carcinoma | Adults | 400 mg BID without food | 400 mg BID | 400 mg BID |
Renal No adjustment needed (mild-severe, not on dialysis); dialysis not studied
Hepatic No adjustment needed (mild-moderate); severe (Child-Pugh C) not studied
Per-toxicity dose-reduction schema differs by indication: HCC/RCC reduce 400 mg QD then 200 mg QD (or 400 mg QOD); DTC reduces to 600 mg/day split, then 200 mg BID, then 200 mg QD
Instructions
- Take without food (at least 1 h before or 2 h after a meal)
- Continue until no clinical benefit or unacceptable toxicity
- Withhold at least 10 days before elective surgery; do not give for at least 2 weeks after major surgery and until adequate wound healing
Contraindications
- With carboplatin/paclitaxel in patients with squamous cell lung cancer (increased mortality)
Cautions
- Cardiac ischemia/infarction and CHF — consider interruption or discontinuation
- Hemorrhage — permanently discontinue if bleeding requires medical intervention
- Hypertension — monitor BP weekly for first 6 weeks, then periodically
- Dermatologic toxicity incl. hand-foot skin reaction; discontinue if SJS/TEN suspected
- GI perforation — permanently discontinue
- Impaired wound healing (VEGF-pathway inhibitor)
- QT prolongation — avoid in congenital long QT; monitor ECG/electrolytes in at-risk patients; interrupt if QTc >500 ms or increase >=60 ms
- Drug-induced liver injury — monitor LFTs regularly; discontinue for unexplained transaminase elevations
- Embryo-fetal toxicity — effective contraception required
- Impairs TSH suppression in DTC — monitor TSH monthly
- Warfarin — monitor PT/INR and for bleeding
Adverse reactions
- Diarrhea
- Fatigue
- Infection
- Alopecia
- Hand-foot skin reaction
- Rash
- Weight loss
- Decreased appetite
- Nausea
- GI/abdominal pain
- Hypertension
- Hemorrhage
Pregnancy May cause fetal harm (embryotoxic/teratogenic in animals at sub-clinical exposures); contraception during and 6 months after (females) / 3 months after (males)
Lactation Do not breastfeed during treatment and for 2 weeks after last dose
NO BOXED WARNINGS
Principal riskNo FDA boxed warning.
Cost, est. cash$5,000–$30,000+/month or cycle
Generic entry2020
Classes and tags
Clinical profile
Legacy pregnancy categoryD
Defining liabilityMyelosuppression and agent-specific hepatic, cardiac, pulmonary, neurologic or reproductive toxicity require oncology monitoring.
Mechanism of action: Sorafenib ballicule
