Drug Interaction:
Anticoagulants, rifampicin, phenytoin, phenobarbitone, cabamazpine, phenobarbitone St Johns wort, irinotecam, substates of CYP2B6 or 2C8, Digoxin, doxorubicin, docetaxel, neomycin
Indication:
U.S.FDA APPROVED DRUGS FROM 01-01-08 TO 31-12-08
Drug name Indication Date of Approval
22.Sorafenib tablets 200mg 22-01-08
(Addl.Indication)
For hepatocellular Carcinoma
U.S.FDA APPROVED DURING 2007
120. Sorafenib (as Tosylate) 200mg 31-07-07
tablet
For advanced renal cell carcinoma
Approved by U.S.FDA on 30-12-2008 (Ref- FDA approved List- 2008)
NEXAVAR (sorafenib) tablets, oral
Initial U.S. Approval: 2005
Sorafenib tosylate tablet 200mg (Additional Strength)
Indication-
For treatment of patients with locally advanced or metastatic
differentiated thyroid carcinoma refractory to radioactive iodine
Approved by FDA on 25-09-2014 (Ref- FDA approved List- 2014)
Proprietary Name- NEXAVAR TABLETS
Established Name- Sorafenib
Applicant- BAYER HEALTHCARE PHARMACEUTICALS INC.
Indication- For the treatment of Locally Recurring Metastatic.Progressive,
Differentiated Thyroid Carcinoma(DTC) refractory to radioactive
treatment.
Sorafenib was previously approved for the treatment of Renal
Cell Carcinoma (2005) and Hepatocellular Carcinoma(2007)
Approval Date- November, 22,2013
Approved by US FDA (Ref- FDA approved list- 2013)
New Drugs Approved by (DCI) Drug Controller GENERAL - India For Marketing
(Ref- IDMA Publication)
Name of Drug Indication Date of Approval
1.Sorafenib Tosylate 200mg tablet 31-07-2007
For Advanced renal Cell Carcinoma
2.Sorafenib Tosylate tablet 200mg 25-09-2014
Addl.Indcn
For the treatment of Patients with Locally advanced or Metastatic differentiated
thyroid Carcinoma Refractory to Radioactive Iodine
3.Sorafenib Tablets 200mg 22-01-2008
Addl.Indcn
For Hepatacelluar Carconoma
Hepatocelular carcinoma
Adverse Reaction:
GI upset, skin disorders, flushing, alopecia, hand foot reactions, anemia, lymphopaenia, leucopenia, neutropenia, thrombocytopenia, hypophosphotaemia, anorexia, weight loss,
Depression, neuropathy, dyspnoea, cough, haemorrhage, hypertension, arthalgia,myalgia, erectile dysfunction, fatigue, tinnitus, hoarseness, asthenia,
Weight loss, pain, fever, nfluenza like illness, renal dysfuction, congestive heart failure, increased lipase and transaminase. Pulmonary effects.
Contra-Indications:
Pregnancy, lactation
Special Precautions -
Discontinue treatment if severe or persistent dermatological toxicities, hypertension haemorrhage, or GI perforation, cardiac ischema, or MI occur.
Withdraw before elective surgery Hepatic impairment. Monitor blood pressure and renal function
Dosages/ Overdosage Etc:
Indication-
For treatment of patients with locally advanced or metastatic
differentiated thyroid carcinoma refractory to radioactive iodine
Indication-
Hepatocelular carcinoma
Dosage-
400mg twice daily at least 1 hr before or 2 hr after a meal.
Patient under 18 years not recommended
INDICATIONS AND USAGE
1. Hepatocellular Carcinoma
NEXAVAR® is indicated for the treatment of patients with unresectable hepatocellular
carcinoma (HCC).
2. Renal Cell Carcinoma
NEXAVAR is indicated for the treatment of patients with advanced renal cell
carcinoma (RCC).
3. Differentiated Thyroid Carcinoma
NEXAVAR is indicated for the treatment of patients with locally recurrent or
metastatic, progressive,differentiated thyroid carcinoma (DTC) that is refractory
to radioactive iodine treatment.
DOSAGE AND ADMINISTRATION
1. Recommended Dose for Hepatocellular Carcinoma, Renal Cell Carcinoma,
and Differentiated Thyroid Carcinoma
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.
Patient Information:
Sorafenib tosylate-
1, inform women patients that sorafenib may cause birth defects or fetal loss and that they
should not become pregnant during treatment
2. Caution men and women to use effective birth control measures during treatment with
sorafenib and for at least 2 weeks after stopping treatment
3. Advice patients of the possible occurence of of hand-foot skin reactin and rash during the
first 6 weeks of therapy and to monitor blood pressure
4, Inform patients that sorafenib may increae the risk of bleeding and they promptly
report episodes of bleeding
5. Advice patients that GI peforation have been reported n patients taking sorafenib
6. Discuss with patients that cardiac ischema and/or infractin has been reported during
sorfenib treatmentand they immediately report any episodes of chest pain or other
symptoms of cardiac ischemia and/or infarction
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1. Mechanism of Action
Sorafenib is a kinase inhibitor that decreases tumor cell proliferation in vitro.
Sorafenib was shown to inhibit multiple intracellular (CRAF, BRAF and mutant
BRAF) and cell surface kinases (KIT, FLT-3, RET, 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 and angiogenesis of human
hepatocellular carcinoma and renal cell carcinoma, and several other human tumor
xenografts in immunocompromised mice.
2.Pharmacokinetics
After administration of NEXAVAR tablets, the mean relative bioavailability was
38 to49% when compared to an oral solution. The mean elimination half-life of
sorafenib was approximately 25 to 48 hours.
Multiple doses of NEXAVAR for 7 days resulted in a 2.5- to 7-fold accumulation
compared to a single dose.
Steady-state plasma sorafenib concentrations were achieved within 7 days,
with a peak-to-trough ratio of mean concentrations of less than 2.
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy
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. Inform patients of childbearing potential that NEXAVAR
can cause birth defects or fetal loss.
Instruct both men and women of childbearing potential to use effective birth control
during treatment with NEXAVAR and for at least 2 weeks after stopping
treatment.
Counsel female patients to contact their healthcare provider if they become
pregnant while taking NEXAVAR.
2. Nursing Mothers
It is not known whether sorafenib is excreted in human milk. Because many drugs
are excreted in human milk and because of the potential for serious adverse
reactions in nursing infants from NEXAVAR, a decision should be made whether
to discontinue nursing or to discontinue the drug, taking into account the
importance of the drug to the mother.
.
3. Pediatric Use
The safety and effectiveness of NEXAVAR in pediatric patients have not been studied.
4. Geriatric Use
In total, 59% of HCC patients treated with NEXAVAR were age 65 years or older,
and 19% were 75 and older. In total, 32% of RCC patients treated with NEXAVAR
were age 65 years or older, and 4% were 75 and older.
No differences in safety or efficacy were observed between older and younger
patients, and other reported clinical experience has not identified differences
in responses between the elderly and younger patients, but greater sensitivity
of some older individuals cannot be ruled out.
Manufacturer Details