All about Sorafenib Tosylate

Sorafenib is a kinase inhibitor (substance that blocks a type of enzyme called kinase) drug. Sorafenib is co-developed and co-marketed by Bayer and Onyx Pharmaceuticals. This drug is sold under the trade name Nexavar.
Sorafenib is recommended for patients with unresectable hepatocellular carcinoma (HCC), advanced renal cell carcinoma(RCC), differentiated thyroid carcinoma(DTC), which is refractory to radioactive iodine treatment.

Sorafenib usage:

Sorafenib tablets have two functions: it blocks tumors from forming new blood vessels, which tumors need to grow; moreover, it also targets some proteins on cancer cells that fuel growth. Sorafenib comes in the form of pills. It is used chiefly in the treatment of the following:
Hepatocellular carcinoma
Hepatocellular carcinoma is a type of liver cancer that cannot be removed by surgery. At ASCO 2007, results from the SHARP trial were presented, which showed the efficacy of Sorafenib in hepatocellular carcinoma.
Renal Cell Carcinoma
Renal cell carcinoma is a type of kidney cancer. Clinical trial results, published January 2007, showed that, 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.
Differentiated Thyroid Carcinoma
A kind of thyroid cancer, also known as differentiated thyroid carcinoma, cannot be treated with radioactive iodine any longer. On November 22, 2013, Sorafenib was approved by the FDA for the treatment of locally recurrent or metastatic, progressively differentiated thyroid carcinoma (DTC) refractory to radioactive iodine treatment.

Sorafenib Dosage

Sorafenib dosage depends upon several factors, and treatment will be according to the prescription which the doctor will prescribe to the patient.
Generally, the recommended dosage of Sorafenib for patients with hepatocellular carcinoma, renal cell carcinoma, and differentiated thyroid carcinoma is 400mg(2X200mg) taken twice daily without food, at least one hour before or two hours after a meal.
If dose reduction is necessary, sorafenib dose may be reduced to 400mg once daily, and if more reduction of the amount is required, it may be reduced to 400mg dose once every other day.

Sorafenib comes in one strength, i.e., 200 mg.

Overdosage

There is no specific treatment for overdosage of Sorafenib, the adverse reactions observed at this dose were primarily diarrhea and dermatologic. In cases of a suspected overdose, It should be withheld and supportive care instituted.

Sorafenib side effects

Common side effects

• Weight loss
• Nausea
• Vomiting
• Diarrhea
• Loss of appetite
• Changes in taste
• Dry skin
• Mouth sores
• Hair loss
• Voice changes
• Tiredness

Severe side effects

• Cardiovascular Events
  The incidence of cardiac ischemia/infarction was observed in sorafenib-treated patients.
• Hemorrhage
  The risk of increased bleeding may occur after Sorafenib administration. According to the SHARP (HCC) study, an excess of bleeding regardless of causality was not apparent, and the rate of bleeding from esophageal varices was 2.4% in sorafenib-treated patients because of the potential risk of bleeding, tracheal, bronchial, and esophageal infiltration should be treated with local therapy before administering Sorafenib in patients with DTC.
• Hypertension
  On the basis of the DECISION (DTC) study, hypertension was reported in 40.6% of sorafenib-treated patients. Hypertension was usually mild or moderate, occurred early in the course of treatment, and was managed with standard antihypertensive therapy.
• Dermatologic Toxicities
  There are some cases of severe dermatologic toxicities reported, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). These cases may be life-threatening. Discontinue Sorafenib if any such toxicities are observed.
• Gastrointestinal Perforation
  It is an uncommon adverse reaction and has been reported in less than 1% of patients taking Sorafenib.
• Wound Healing Complications
  Temporary interruption of Sorafenib is recommended in patients undergoing major surgical procedures.
• Embryo-Fetal Toxicity
  Based on research and findings, Sorafenib caused embryo-fetal toxicities in animals at maternal exposures that were significantly lower than the human exposures at the recommended dose of 400 mg twice daily. Therefore, it is advised to the female of reproductive potential to verify the potential risk to a fetus before taking sorafenib medication.

Preparation and administration

The dosage is based on patients’ medical history and response to treatment. Do not increase your dose or use this drug more often or for longer than prescribed. Increased dosage of Sorafenib by oneself needs to be strictly restricted, it will not improve patients’ condition rapidly, but it will lead to worse or even fatal outcomes.
The daily recommended dose of Sorafenib is 400 mg (2 x 200 mg tablets) taken twice daily without food. Treatment should continue till any kind of unacceptable toxicity happens.

Warnings and precautions

• In many clinical trials, congestive heart failure has been reported in 1.9% of Sorafenib-treated patients. There are some cases of cardiac ischemia/infarction of 2.7% in Sorafenib tosylate-treated patients. Discontinuation of Sorafenib should be considered in patients who develop cardiovascular events.

• In the SHARP (HCC) study, an excess of bleeding regardless of causality was not apparent, and the rate of bleeding from esophageal varices was 2.4% in patients who received Sorafenib medication. In the TARGET (RCC) study, bleeding regardless of causality was reported in 15.3% of patients in the Sorafenib-treated group. Based on the DECISION (DTC) study, bleeding was reported in 17.4% of Sorafenib-treated patients. If any bleeding incident happens, permanent discontinuation of Sorafenib should be considered.

• While taking Sorafenib, monitor blood pressure weekly during the first 6 weeks. After that, monitor blood pressure and treat hypertension if required. In the SHARP (HCC) study, hypertension was reported in 9.4% of Sorafenib-treated patients.

• In case of severe or persistent hypertension, despite the institution of antihypertensive therapy, consider temporary or permanent discontinuation of Sorafenib.

• Embryo-fetal toxicities may occur when Sorafenib is administered to any pregnant female. Based on research, Sorafenib caused embryo-fetal toxicities in animals at maternal exposures that were significantly lower than the human exposures at the recommended dose of 400 mg twice daily.

• It is advised to females having the reproductive potential to use effective contraception during treatment and for 6 months following the last dose of Sorafenib. It is also recommended to the male who has a female partner with reproductive potential to use effective contraception during treatment and for 3 months following the last dose of Sorafenib.