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Tyrosine Kinase Inhibitor (HCC) Pregnancy: Contraindicated — embryotoxic and teratogenic in animal studies. Highly effective contraception required for women of childbearing potential and male patients with female partners during treatment and for 6 months after stopping.

Sorafenib

Brand names: Nexavar

Adult dose

Dose: 400 mg twice daily
Route: Oral
Frequency: Twice daily (on empty stomach or with low-fat meal)
Max: 800 mg/day
Unresectable hepatocellular carcinoma (HCC). Take on empty stomach or with a low-fat, low-calorie meal. Hold for 2 hours before or 1 hour after food if possible. Common dose reduction pattern: 400 mg once daily, then 400 mg every other day for toxicity. Source: BNF 90; EASL-EORTC HCC Guidelines 2022.

Paediatric dose

Dose: Not licensed in paediatric HCC N/A/kg
Route: N/A
Frequency: N/A
Max: N/A
Sorafenib is not approved for paediatric use in HCC.

Dose adjustments

Renal

Mild-moderate renal impairment: no dose adjustment. Severe renal impairment (eGFR <30 mL/min, dialysis): limited data — use with caution.

Hepatic

Child-Pugh A: no adjustment. Child-Pugh B: caution — higher toxicity risk. Child-Pugh C: avoid — inadequate data and increased toxicity.

Paediatric weight-based calculator

Sorafenib is not approved for paediatric use in HCC.

Clinical pearls

  • SHARP trial (NEJM 2008): landmark trial establishing sorafenib as standard of care for unresectable HCC. Median OS 10.7 months vs 7.9 months placebo (HR 0.69). First systemic therapy shown to improve survival in HCC.
  • Now second-line in many patients: atezolizumab + bevacizumab (IMbrave150 trial NEJM 2020) and tremelimumab + durvalumab (HIMALAYA trial) now preferred first-line for preserved liver function Child-Pugh A patients. Sorafenib remains an option when immunotherapy is contraindicated (autoimmune disease, oesophageal varices — bevacizumab CI).
  • Hand-foot skin reaction management: grade 1 (mild) — emollients, cushioned insoles, reduce walking. Grade 2 (blistering, pain, affects ADLs) — dose reduce 400 mg once daily, urea cream 40%, clobetasol 0.05%. Grade 3 — stop temporarily, restart at 400 mg once daily. Dose reduction preserves disease control while managing toxicity.
  • Hypertension management: start antihypertensive before sorafenib if BP borderline. Amlodipine and ACE inhibitors preferred. Avoid beta-blockers if variceal bleeding risk (portal hypertension context). Check BP weekly for first 6 weeks.
  • Performance status and Child-Pugh: sorafenib only benefits patients with Child-Pugh A (well-compensated cirrhosis) and ECOG performance status 0–2. Child-Pugh B/C patients derive no benefit and have excessive toxicity — select patients carefully. Source: BNF 90; EASL-EORTC HCC Guidelines 2022; Llovet et al. NEJM 2008 (SHARP).

Contraindications

  • Hypersensitivity to sorafenib
  • Squamous cell lung carcinoma (increased bleeding and toxicity risk)
  • Pregnancy and breastfeeding

Side effects

  • Hand-foot skin reaction (palmar-plantar erythrodysaesthesia, PPES): most common dose-limiting toxicity — pain, blistering, desquamation of palms and soles
  • Diarrhoea (common — often dose-limiting)
  • Hypertension (VEGFR inhibition — systolic often increases 10–15 mmHg)
  • Fatigue, alopecia, weight loss
  • Haemorrhage (VEGFR inhibition reduces vascular integrity — nasal, GI)
  • Cardiac toxicity: QTc prolongation, reduced LVEF (rare)
  • Thyroid dysfunction (hypothyroidism — monitor TSH)

Interactions

  • Strong CYP3A4 inducers (rifampicin, phenytoin, carbamazepine): reduce sorafenib exposure — avoid or increase sorafenib dose
  • Warfarin: sorafenib inhibits CYP2C9 — INR increases. Monitor INR more frequently
  • Docetaxel: sorafenib increases docetaxel AUC — avoid combination or reduce docetaxel
  • UGT1A1 substrates (irinotecan): sorafenib inhibits UGT1A1 — increased irinotecan toxicity
  • QTc-prolonging drugs: additive risk — avoid combination or monitor ECG

Monitoring

  • Blood pressure (weekly for first 6 weeks, then monthly)
  • LFTs, bilirubin (every 4–6 weeks — hepatotoxicity and liver function deterioration)
  • INR (if on warfarin — weekly initially)
  • TSH every 3 months (hypothyroidism)
  • Hand-foot skin reaction grading at every appointment
  • Imaging (CT/MRI) every 8–12 weeks for disease response assessment

Reference: BNFc; BNF 90; Llovet et al. NEJM 2008 (SHARP trial); EASL-EORTC Clinical Practice Guidelines HCC 2022; MHRA SPC Nexavar. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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