Sorafenib

NEXAVAR

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Pronunciation: soe-RAF-e-nib

Sorafenib ballicule: receptor binding, kinetics and half-life diagram — Mechanism of action: Sorafenib ballicule

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.

Sorafenib molecular structure (skeletal formula) — Molecular structure: Sorafenib

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

Available strengths

tab 200 mg

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

Cost

Sorafenib (NEXAVAR)

Strength		#/mo	generic $/mo	CostPlus
200 mg	tab	60 BID		offered

NADAC is a voluntary CMS survey of what retail community pharmacies pay for the drugs they stock. Sorafenib is dispensed outside retail pharmacies, so it rarely appears on surveyed invoices.

Generic entry2020

NO BOXED WARNINGS

Principal riskNo FDA boxed warning.

Classes and tags

QT-prolonging medications

Clinical profile

Therapeutic safety burden3 / 4

Overdose danger2 / 4

Weight-gain liability0 / 4

Sedation liability0 / 4

QT / Torsades2 / 4

Direct muscarinic antagonism0 / 4

Embryofetal risk3 / 4

Legacy pregnancy categoryD

Defining liabilityMyelosuppression and agent-specific hepatic, cardiac, pulmonary, neurologic or reproductive toxicity require oncology monitoring.

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