Sorafenib is pharmacologically categorized as protein kinase inhibitor, which is FDA approved compound used for the treatment of primary renal cell cancer in advanced stage, metastatic liver carcinoma (sorafenib liver cancer) and also involved in radioactive iodine resistant advanced thyroid cancer. Sorafenib is considered as synthetic compound aiming signal responding for growth and angiogenesis. Sorafenib works by blocking the enzyme RAF kinase, which is a demanding component of the RAF/MEK/ERK signaling pathway that dominates cell separation and multiplication. On the other hand, Sorafenib also prohibits the VEGFR-2/PDGFR-beta signaling force, through blockade of tumor angiogenesis.
Sorafenat (Sorafenib) prescribing information
Sorafenib is available in the form of tablet, which is used in various conditions like;
Metastatic renal cell cancer
Metastatic Hepatocellular cancer
(Sorafenib hepatocellular carcinoma)
Sorafenat (Sorafenib) mechanism of action
The activity of Sorafenat containing Sorafenib is developing in-vitro.
Sorafenat expels its activity by prohibiting assorted intracellular & cell surface kinase which is important for tumor cell signaling exudation, angiogenesis and apoptosis.
Due to prohibition of these multikinases is a source of cancer growth termination. Reduction of cancer cell angiogenesis happens in HCC, RCC and elevation of cancer cell apoptosis occurs in HCC, RCC & TC
The oral bioavailability of Sorafenat is occurs as 38 to 49%. The peak plasma concentration time of Sorafenat is 3 hours.
Sorafenib is highly bound to the human plasma protein at the range of 99.5%
Sorafenat is undergoes oxidative metabolism, intermediated by CYP3A4, in addition of Glucuronidation mediated by UGT1A9.
The excretion of Sorafenat occurs via urine, feces and biliary excretion also undergone. Overall 96% of dose should be replaced within 14 days, in which 77% excreted in feces; 19% in urine. The unchanged form of Sorafenib is around 51% should be recovered in feces and not in urine, biliary excretion also occurred. The half-life period of Sorafenat is relatively 25 to 48 hours.
Dosage regimens of Sorafenat tablets
In HCC, RCC or TC condition: The usual prescribed dosage of Sorafenat is 400mg tablet (200mg×2 tablets) should be taken as two times a day.
Dosage alteration in severe conditions
Sorafenat tablets used therapy should be postponed for short period of time in major surgical procedures. Sorafenat tablets should be postponed or permanently discontinued for following conditions like; Hemorrhage, Cardiac ischemia, Severe hypertension, Gastrointestinal perforation, QTc prolongation, Liver injury
Dose variation in HCC & RCC
The dosage should be varied in HCC & RCC, if dose reduction is required. The dosage should be decreased to 400mg as a single dose. If further reduction is required, provide 400mg as a single dose for alternative day.
Dose variation in dermatological toxicities with HCC
Grade 1 toxicity: Extend the Sorafenat therapy and provide with topical therapy for symptomatic relief.
Grade 2 toxicity: Extend the Sorafenat therapy and provide with topical therapy for symptomatic relief. If it occurs continuously, discontinue the Sorafenat therapy.
Grade 3 toxicity: Discontinue the Sorafenat therapy, if it is needed the dose should be reduced by two times a day into single dose.
Dose alteration in thyroid carcinoma
First dose reduction: 600mg of Sorafenat should be recommend
Second dose reduction: 400mg of Sorafenat should be prescribed for two times a day
Third dose reduction: 200mg of Sorafenat should be prescribed as a single dose.
In concurrent use of CYP3A4 inducers
Sorafenat tablets should be co administered with CYP3A4 inducers like anti-convulsants; st.Johns wort etc causes decreasing the systemic exposure of Sorafenib. The efficiency of Sorafenib has not been established in pediatric patients. The Dosage should not be adjusted in elderly patients. In renal and hepatic impairment patients, no dosage adjustment should be recommended. Sorafenat tablets should be taken without food. Sorafenat tablets should be taken at least 1 hour earlier or 2 hours after a meal
Sorafenat tablet causes some adverse effects
Hypertension Myocardial infarction or ischemia Gastrointestinal perforation Drug caused hepatitis Hemorrhage
Most common side effects (Sorafenib)
Diarrhea, Alopecia, Infection, Hand foot skin reaction, Musculoskeletal disorders, Loss of weight, Increasing amylase & lipase
Post marketing adverse effects
Stevens Johnson syndrome, Angioedema, Rhabdomyolysis, Osteonecrosis, Interstitial lung disease, Folliculitis, Leucopenia, Neutropenia, Anemia, Thrombocytopenia, Hypothyroidism, Hypocalcaemia, Hypokalemia, Hyponatremia, Depression, Peripheral sensory neuropathy, Tinnitus, Congestive heart failure, Rhinorrhoea, Dysphonia, Gastro esophageal reflux
Some adverse reactions occur during the treatment with Sorafenat tablets;
Exposure of GI perforation
Stop the therapy of Sorafenat tablets.
Combination of Sorafenat with warfarin causes elevation of INR level. To avoid this problem monitor the patients bleeding (prothrombin time) frequently.
Wound healing complications
Sorafenat tablets should be postponed during surgical procedures, to prevent wound complications.
Elevation of mortality during combination of Sorafenatwith carboplatin/paclitaxel and gemcitabine/cisplatin in squamous lung cancer
This combination is contraindicated for the patients with squamous cell lung cancer.
Exposure of QT extension
Sorafenat causes prolongation of QT intervals; avoid this therapy in patients who have cardiac problems.
Therapy induced hepatitis
During the therapy with Sorafenat , causes elevation of transaminase leads to liver injury and causes liver failure.
Embryo fetal harm
Sorafenat tablet causes fetal harm
Thyroid stimulating hormone impairment in thyroid carcinoma
TSH level should be monitored frequently and adjust thyroid replacement.
Exposure of cardiac ischemia or infarction
To avoid this condition, postpone or discontinue the therapy
Exposure of hemorrhage
Permanent discontinuation of Sorafenat therapy
Exposure of hypertension
Monitor the blood pressure frequently and provide anti-hypertensive agents for this condition.
Sorafenat tablets while combining with Midazolam, dextromethorphan, or Omeprazole causes no elevation of systemic exposure of these drugs.
While combining Sorafenat with antibiotic like neomycin causes depletion AUC of Sorafenib. The solubility of Sorafenat is depends upon pH, if pH increases causes decreasing the solubility.
Combination of Sorafenat with other anti-neoplastic agents likes; Paclitaxel or carboplatin: Causes elevation of exposure of Sorafenib Capecitabine: Increase Capecitabine exposure Doxorubicin/Irinotecan: Elevation of AUC of doxorubicin and Irinotecan With neomycin: Intercede with enterohepatic recycling of Sorafenib, causes depletion of Sorafenib exposure.
Sorafenat tablets combined with strong CYP3A4 inducers like rifampin causes decrease in AUC of Sorafenib. Avoid concurrent use of Sorafenat with strong CYP3A4 inducers like anti-convulsants, anti-mycobacterials& herbal product like st.Johns wort. This results as to cause loss of exposure to Sorafenib and leads to reduce the therapeutic effect of Sorafenat tablets.
Sorafenat tablets are combined with strong CYP3A4 inhibitors like ketaconazole causes no variation in AUC of Sorafenib.