Sorafenib

Sorafenib
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]; Associate Editor(s)-in-Chief: Alberto Plate [3]

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Overview

Sorafenib is a kinase inhibitor that is FDA approved for the treatment of unresectable hepatocellular carcinoma, advanced renal cell carcinoma, locally recurrent or metastatic, progressive, differentiated thyroid carcinoma refractory to radioactive iodine treatment. Common adverse reactions include hypertension, acral erythema, alopecia, Peeling of skin, rash, hypoalbuminemia, hypocalcemia, hypophosphatemia, raised TSH level, weight decreased, abdominal pain, decrease in appetite, diarrhea, Increased serum lipase level, Loss of appetite, nausea, serum amylase raised, lymphocytopenia, thrombocytopenia, ALT/SGPT level raised, Infectious diseases, fatigue and pain.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Recommended Dose for Hepatocellular Carcinoma, Renal Cell Carcinoma, and Differentiated Thyroid Carcinoma

• Dosage: 200 mg q12h, taken 1 hour before or 2 hours after a meal. Treatment should continue until the patient is no longer clinically benefiting from therapy or until unacceptable toxicity occurs. Temporary interruption of Sorafenib is recommended in patients undergoing major surgical procedures.
  • Temporary interruption or permanent discontinuation of Sorafenib may be required for the following:
    • Cardiac ischemia or infarction
    • Hemorrhage requiring medical intervention
    • Severe or persistent hypertension despite adequate anti-hypertensive therapy
    • Gastrointestinal perforation
    • QTc prolongation
    • Severe drug-induced liver injury

Dose modifications for Hepatocellular Carcinoma and Renal Cell Carcinoma

When dose reduction is necessary, the Sorafenib dose may be reduced to 400 mg once daily. If additional dose reduction is required, Sorafenib may be reduced to a single 400 mg dose every other day. If dermatological toxicity presented, the following scheme should be followed:

Dose Modifications for Differentiated Thyroid Carcinoma

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Sorafenib in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Sorafenib in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding Sorafenib FDA-Labeled Indications and Dosage (Pediatric) in the drug label.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Sorafenib in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Sorafenib in pediatric patients.

Contraindications

There is limited information regarding Sorafenib Contraindications in the drug label.

Warnings

There is limited information regarding Sorafenib Warnings' in the drug label.

Adverse Reactions

Clinical Trials Experience

There is limited information regarding Sorafenib Clinical Trials Experience in the drug label.

Postmarketing Experience

There is limited information regarding Sorafenib Postmarketing Experience in the drug label.

Drug Interactions

There is limited information regarding Sorafenib Drug Interactions in the drug label.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): There is no FDA guidance on usage of Sorafenib in women who are pregnant.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Sorafenib in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Sorafenib during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Sorafenib in women who are nursing.

Pediatric Use

There is no FDA guidance on the use of Sorafenib in pediatric settings.

Geriatic Use

There is no FDA guidance on the use of Sorafenib in geriatric settings.

Gender

There is no FDA guidance on the use of Sorafenib with respect to specific gender populations.

Race

There is no FDA guidance on the use of Sorafenib with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Sorafenib in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Sorafenib in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Sorafenib in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Sorafenib in patients who are immunocompromised.

Administration and Monitoring

Administration

There is limited information regarding Sorafenib Administration in the drug label.

Monitoring

There is limited information regarding Sorafenib Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Sorafenib and IV administrations.

Overdosage

There is limited information regarding Sorafenib overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

Pharmacology

There is limited information regarding Sorafenib Pharmacology in the drug label.

Mechanism of Action

There is limited information regarding Sorafenib Mechanism of Action in the drug label.

Structure

There is limited information regarding Sorafenib Structure in the drug label.

Pharmacodynamics

There is limited information regarding Sorafenib Pharmacodynamics in the drug label.

Pharmacokinetics

There is limited information regarding Sorafenib Pharmacokinetics in the drug label.

Nonclinical Toxicology

There is limited information regarding Sorafenib Nonclinical Toxicology in the drug label.

Clinical Studies

There is limited information regarding Sorafenib Clinical Studies in the drug label.

How Supplied

There is limited information regarding Sorafenib How Supplied in the drug label.

Storage

There is limited information regarding Sorafenib Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Sorafenib Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Sorafenib interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Sorafenib Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Sorafenib Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

Sorafenib

Clinical data
Synonyms	Nexavar Sorafenib tosylate
[[Regulation of therapeutic goods |Template:Engvar data]]	EU EMA: by INN US FDA: Sorafenib
Pregnancy category	AU: D US: D (Evidence of risk)
Routes of administration	Oral
ATC code	L01XE05 (WHO)
Legal status
Legal status	US: ℞-only
Pharmacokinetic data
Bioavailability	29-49%
Protein binding	99.5%
Metabolism	Hepatic oxidation and glucuronidation (CYP3A4-mediated)
Elimination half-life	25–48 hours
Excretion	Fecal (77%) and renal (19%)
Identifiers
IUPAC name 4-[4-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino] phenoxy]-N-methyl-pyridine-2-carboxamide
CAS Number	284461-73-0
PubChem CID	216239
DrugBank	APRD01304
E number	{{#property:P628}}
ECHA InfoCard	{{#property:P2566}}
Chemical and physical data
Formula	C21H16ClF3N4O3
Molar mass	464.825 g/mol
3D model (JSmol)	Interactive image
SMILES CNC(=O)C1=NC=CC(=C1)OC2=CC=C(C=C2)NC(=O)NC3=CC(=C(C=C3)Cl)C(F)(F)F

WikiDoc Resources for Sorafenib
Articles
Most recent articles on Sorafenib Most cited articles on Sorafenib Review articles on Sorafenib Articles on Sorafenib in N Eng J Med, Lancet, BMJ
Media
Powerpoint slides on Sorafenib Images of Sorafenib Photos of Sorafenib Podcasts & MP3s on Sorafenib Videos on Sorafenib
Evidence Based Medicine
Cochrane Collaboration on Sorafenib Bandolier on Sorafenib TRIP on Sorafenib
Clinical Trials
Ongoing Trials on Sorafenib at Clinical Trials.gov Trial results on Sorafenib Clinical Trials on Sorafenib at Google
Guidelines / Policies / Govt
US National Guidelines Clearinghouse on Sorafenib NICE Guidance on Sorafenib NHS PRODIGY Guidance FDA on Sorafenib CDC on Sorafenib
Books
Books on Sorafenib
News
Sorafenib in the news Be alerted to news on Sorafenib News trends on Sorafenib
Commentary
Blogs on Sorafenib
Definitions
Definitions of Sorafenib
Patient Resources / Community
Patient resources on Sorafenib Discussion groups on Sorafenib Patient Handouts on Sorafenib Directions to Hospitals Treating Sorafenib Risk calculators and risk factors for Sorafenib
Healthcare Provider Resources
Symptoms of Sorafenib Causes & Risk Factors for Sorafenib Diagnostic studies for Sorafenib Treatment of Sorafenib
Continuing Medical Education (CME)
CME Programs on Sorafenib
International
Sorafenib en Espanol Sorafenib en Francais
Business
Sorafenib in the Marketplace Patents on Sorafenib
Experimental / Informatics
List of terms related to Sorafenib

Overview

Sorafenib (rINN), marketed as Nexavar by Bayer, is a drug approved for the treatment of advanced renal cell carcinoma (primary kidney cancer). It has also received "Fast Track" designation by the FDA for the treatment of advanced hepatocellular carcinoma (primary liver cancer), and has since performed well in Phase III trials.

Pharmacology

It is a small molecular inhibitor of Raf kinase, PDGF (platelet-derived growth factor), VEGF receptor 2 & 3 kinases and c Kit the receptor for Stem cell factor. A growing number of drugs target most of these pathways. The originality of Sorafenib lays in its simultaneous targeting of the Raf/Mek/Erk pathway.

Approval

Sorafenib was approved by the U.S. Food and Drug Administration (FDA) on December 20, 2005 and received a E.U. marketing authorisation on July 19, 2006.

The European Commission has granted marketing authorization to Nexavar® (sorafenib) tablets for the treatment of patients with hepatocellular carcinoma (HCC), the most common form of liver cancer, on October 30, 2007. .

Studies

A New England Journal of Medicine article published in January 2007 showed compared with placebo, treatment with sorafenib prolongs progression-free survival in patients with advanced clear-cell renal-cell carcinoma in whom previous therapy has failed; the median progression-free survival was 5.5 months in the sorafenib group and 2.8 months in the placebo group (hazard ratio for disease progression in the sorafenib group, 0.44; 95% confidence interval [CI], 0.35 to 0.55; P<0.01). The first interim analysis of overall survival in May 2005 showed that sorafenib reduced the risk of death, as compared with placebo (hazard ratio, 0.72; 95% CI, 0.54 to 0.94; P=0.02), although this benefit was not statistically significant according to the O'Brien–Fleming threshold. Partial responses were reported as the best response in 10% of patients receiving sorafenib and in 2% of those receiving placebo (P<0.001).

At ASCO 2007, results from the SHARP trial were presented, which showed efficacy of sorafenib in hepatocellular carcinoma. The primary endpoint was overall survival, which showed a 44% improvement in patients who received sorafenib compared to placebo (hazard ratio 0.69; 95% CI, 0.55 to 0.87; p=0.0001). Both median survival and time to progression showed 3-month improvements.

Regulatory filing is planned.

Side effects

Side effects of sorafenib included skin rash, hand-foot skin reactions, diarrhea, and hypertension.

External links

• Nexavar.com – Manufacturer's website
• Prescribing Information – includes data from the key studies justifying the use of sorafenib for the treatment of kidney cancer (particularly clear cell renal cell carcinoma, which is associated with the von Hippel-Lindau gene)
• Patient Information from FDA
• Sorafenib in Treating Patients With Soft Tissue Sarcomas
• Clinical trial number NCT00217399 at ClinicalTrials.gov - Sorafenib and Anastrozole in Treating Postmenopausal Women With Metastatic Breast Cancer
• [http:/mpablog.typepad.com/david_foster] Two year experience blog on nexavar, sutent, side effects, etc.