A brief overview on sorafenib which is used for treatment of Hepatocellular Carcinoma,Renal Cell Carcinoma and Differentiated Thyroid Carcinoma including some indications, side effects, overdose, contraindications and using during pregnancy.

1. Sorafenib (NEXAVAR)®

2. Sorafenib

3. NEXAVAR (sorafenib) tablets, oral
Initial U.S. Approval: 2005.
Manufactured by: Bayer
HealthCare Pharmaceuticals Inc.

4. Storage : Store at 25°C (77°F);
excursions permitted to 15–30°C
(59–86°F). Store in a dry place.
Shelf life: 3 years.

5. Indications and Usage:
1. Hepatocellular Carcinoma:
For the treatment of patients with unresectable hepatocellular
carcinoma (HCC).
2. Renal Cell Carcinoma:
For treatment of locally advanced/metastatic clear cell renal cell
carcinoma (RCC) in patients who have failed or are intolerant of
prior systemic therapy.
3. Differentiated Thyroid Carcinoma:
For the treatment of patients with locally recurrent or metastatic,
progressive, differentiated thyroid carcinoma (DTC) that is
refractory to radioactive iodine treatment.

6. Mechanism of Action:
Sorafenib is a kinase inhibitor that decreases tumor cell proliferation in vitro.
Sorafenib was shown to inhibit multiple intracellular (c-CRAF, BRAF and mutant
BRAF) and cell surface kinases (KIT, FLT- 3, RET, RET/PTC, VEGFR-1, VEGFR- 2,
VEGFR- 3, and PDGFR-ß).
Several of these kinases are thought to be involved in tumor cell signaling,
angiogenesis and apoptosis. Sorafenib inhibited tumor growth of human
hepatocellular carcinoma( HCC), renal cell carcinoma( RCC), and Differentiated
thyroid carcinoma (DTC) human tumor xenografts in immunocompromised mice.
Reductions in tumor angiogenesis were seen in models of HCC and RCC upon
sorafenib treatment, and increases in tumor apoptosis were observed in models
of HCC, RCC, and DTC.

7. Dosage and Administration:
The recommended daily dose of NEXAVAR is 400 mg (2 x 200 mg tablets) taken
twice daily without food (at least 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.
No dose adjustment is required on the basis of patient age, gender, or body weight.

8. Overdosage:
There is no specific treatment for NEXAVAR overdose.
In cases of suspected overdose, NEXAVAR should be withheld
and supportive care instituted.
The highest dose of NEXAVAR studied clinically is 800 mg twice
daily.
The adverse reactions observed at this dose were primarily
diarrhea and dermatologic.

9. The most common side effects of NEXAVAR include:
• diarrhea (frequent or loose bowel movements).
• tiredness. • infection. • rash.
• hair thinning or patchy hair loss. • weight loss.
• loss of appetite.• nausea. • stomach (abdominal) pain.
• low blood calcium levels in people with differentiated thyroid cancer.

10. ADVERSE REACTIONS:
• Cardiac ischemia, infarction. • Hemorrhage. • Hypertension.
• Hand-foot skin reaction and rash. • Gastrointestinal perforation.
• Wound healing complications. • QT Interval Prolongation.
• Drug-Induced Hepatitis.
• Impairment of TSH suppression in DTC.

11. CONTRAINDICATIONS :
• NEXAVAR is contraindicated in patients with known severe
hypersensitivity to sorafenib or any other component of
NEXAVAR.
• NEXAVAR in combination with carboplatin and paclitaxel is
contraindicated in patients with squamous cell lung cancer.

12.  Effects of Age, Gender and Race: Gender and age do not
have a clinically meaningful effect on the pharmacokinetics
of sorafenib. A study of the pharmacokinetics of sorafenib
indicated that the mean AUC of sorafenib in Asians was 30%
lower than in Caucasians .
 Renal Impairment: No dose adjustment is necessary.
 Mild (CLcr 50-80 mL/min), moderate (CLcr 30 - <50
mL/min), and severe (CLcr <30 mL/min) renal impairment
do not affect the pharmacokinetics of sorafenib.
 Hepatic Impairment: No dose adjustment is necessary.
 Mild and moderate hepatic impairment do not affect the
pharmacokinetics of sorafenib.

13.  Use in Pregnancy:
Category D
 Based on its mechanism of action and findings in animals,
NEXAVAR may cause fetal harm when administered to a
pregnant woman.
 There are no adequate and well-controlled studies in
pregnant women using NEXAVAR.
 If this drug is used during pregnancy, or if the patient
becomes pregnant while taking this drug, the patient should
be apprised of the potential hazard to the fetus .

14. Missed Doses:
If a dose of NEXAVAR is missed, the next dose should be taken
at the regularly scheduled time, and not double the dose.

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