Medicine > All about Sorafina (Sorafenib) tablet

All about Sorafina (Sorafenib) tablet

Name of Medicine - Sorafina 

Product Ingredient - Sorafenib 

Chemical Formula - C21H16ClF3N4O3 

Description - Sorafenib is marketed by Arechar Healthcare under the brand name Sorafina. It is an approved drug for the treatment of advanced cell carcinoma (Kidney cancer), Liver cancer, and Thyroid cancer. 

What is Sorafina?

Sorafina (Sorafenib) is a cancer medication that stops the growth and spread of cancer cells in the body. This medication is used to treat certain types of cancers (kidney cancer, liver cancer, and thyroid cancer). Sorafenib is a synthetic compound and small molecular inhibitor of RAF kinase, PDGF (platelet-derived growth factor), and VEGF (Vascular endothelial growth factor) receptor 2 & 3 kinases. This medication works by blocking tumor angiogenesis (formation of new blood vessels). 

Clinical Relevance

Clinical relevance or indication refers to the use of a drug treating a particular disease or more than one disease. A patient should be aware of the indication of the medicine used for the treatment. It is advised to not use any medicine without a prescription by a qualified physician or healthcare professional. Indications of Sorafina (Sorafenib) are mentioned below:- 

  • Renal cell carcinoma:- This medication is approved and indicated for use in the treatment of advanced renal cell carcinoma (kidney cancer).  

  • Hepatocellular carcinoma:- Sorafina (Sorafenib) is indicated for use in patients suffering from advanced Hepatocellular carcinoma (liver cancer). 

  • Thyroid carcinoma:- This tablet is used to treat patients with metastatic (spread of cancer cells from one part to another) thyroid carcinoma. 

Clinical Pharmacology 

It defines how the body responds after the administration of the drug. The pharmacology of the drug covers the various aspects of the medicine. It includes the therapeutic result of the drugs that explains some factors like - chemical processes involved in metabolism and the drug absorption time. These factors are required to check the efficacy of the drug. Therapeutic results are proportional to the concentration of the drug at the site of action and it usually depends upon the reactions that occur in the body. 

Pharmacodynamics 

Sorafina is a kinase inhibitor that is responsible for the decrease in tumor cell proliferation in vitro. The compound tends to inhibit HCC and RCC tumor growth and DTC human tumor xenografts in immunocompromised mice. Decreases in tumor angiogenesis were noted in HCC and RCC models during treatment with Sorafina, and increases in tumor apoptosis were seen in models of HCC, RCC, and DTC.

Pharmacokinetics 

The concentrations of this compound after the administration of Sorafenib 400 mg twice a day were calculated in patients of DTC, RCC, and HCC. Patients with DTC have average steady-state concentrations that are 1.8-fold greater than patients with HCC and 2.3-fold greater than those with RCC patients. The reason for this increase in Sorafenib concentrations in DTC patients is not known.

Absorption

After administering Sorafenib tablets, the average relative bioavailability was observed to be 38–49% in comparison to an oral solution. Following oral administration, Sorafenib reached peak plasma levels in about 3 hours. With a moderate-fat meal, bioavailability was the same as that in the fasted state. With a high-fat meal, bioavailability was decreased by 29% in comparison to that in the fasted state. It is preferred that Sorafenib be administered without food. Sorafenib to human plasma proteins binding in vitro was 99.5%.

Metabolism

The compound is metabolized initially in the liver, undergoing oxidative metabolism, mediated by CYP3A4, and glucuronidation mediated by UGT1A9. It accounts for about 70-80% of the circulating analytes in plasma at steady-state. The metabolites of Sorafenib have been identified, five out of which have been detected in plasma. The main circulating metabolite of the compound in plasma shows in vitro potency same as that of Sorafenib. This metabolite comprises about 9-16% of circulating analytes at steady-state. 

Mechanism of action 

Sorafenib tends to interact with CRAF, BRAF, mutant BRAF, KIT, FLT-3, VEGFR-2, VEGFR-3, and PDGFR-ß. Many of such kinases are involved in angiogenesis, therefore this compound decreases blood flow to the tumor. It is unique in targeting the Raf/Mek/Erk pathway. By doing so, genetic transcription including cell proliferation and angiogenesis is inhibited.

Clinical Trials

Sorafenib is an oral multikinase inhibitor with activity against Raf-1, B-Raf, c-Kit receptors, VEGFR2, PDGFR. It has a potent antiangiogenic and proapoptotic activity. The compound thus presents a marked antitumoral effect. In patients who have Child-Pugh A-class (a well-preserved liver function) and advanced-stage HCC (BCLC-C) or in patients suffering from HCC progressing specifically after locoregional therapies, with a high grade of recommendation, it is considered to be the standard HCC systemic therapy. The exploratory subgroup analyses demonstrated that the compound, Sorafenib, consistently improved median OS and DCR in comparison with placebo in patients suffering from advanced HCC, irrespective of factors like disease etiology, baseline tumor burden, prior therapy, performance status, and tumor stage.

 

SHARP, the Sorafenib Hepatocellular Carcinoma (HCC) Assessment Randomized Protocol trial, demonstrated that the compound improves overall survival. It is safe for patients suffering from advanced HCC. In the clinical trial, 602 patients with well-preserved liver function (greater than 95% Child-Pugh A) were randomized to administer Sorafenib 400 mg on a continuous basis. Baseline patient characteristics may affect individual responses to the therapy since HCC is a heterogeneous disease.

Interactions

Drug-Drug Interactions

Amiodarone:- Administration of Sorafenib with other drugs can prolong the QT intervals and it may result in adverse side effects and increases the risk of various other diseases. Amiodarone is an antiarrhythmic drug that can cause dose-related prolongation of the QT interval. This drug Generates the QT Prolongation and it may increase certain underlying risk factors. 

 

Fingolimod:- This medication can increase the risk of irregular heartbeat that may be life-threatening. Use of fingolimod with Sorafenib may interact if you have a previous history of heart diseases. Seek immediate medical attention if you experience side effects like fainting, shortness of breath, lightheadedness, dizziness, and heart palpitations. 

 

Leflunomide:- This drug may cause some serious liver damage and interact vigorously with Sorafenib. Avoid the consumption of alcohol during the treatment with this medication. If you experience any side effects like bleeding, swelling, joint pain, loss of appetite, unusual bruising, and pale skin. Do not take medicines without a proper prescription by your physician. 

 

Ventoclax:- use of this medication with sorafenib increases blood levels in your body and also increases the risk of developing tumor lysis syndrome. Avoiding side effects like nausea, vomiting, diarrhea, and low blood levels can also increase the risk of anemia. Dose alteration is required during treatment with this medication. 

Drug-Disease Interaction

Lung toxicity:- This medication can cause lung toxicity in patients. If you have a history of interstitial pneumonitis or pulmonary fibrosis discuss with your healthcare professional. Your physician may suggest or change your dosage according to your health conditions. 

Dosage and Administration

Recommended Dose:- The recommended dose of Sorafina is 400 mg (2 tablets of 200mg each) administered orally twice daily. The treatment with Sorafina should be continued in patients till unacceptable toxicity occurs. Severe adverse reactions (if any) should be managed by either interrupting the therapy or dose adjustments. The safety and efficacy of this medicine for Pediatric use have not been studied yet.

 

Dose Adjustments:- In the case of patients suffering from Child-Pugh A and B hepatic impairment, no dose adjustments are needed. However, to manage severe adverse reactions, dose adjustments may be needed. 

 

Overdosage:- There is no proven treatment for overdose of Sorafina. The symptoms of overdose primarily include diarrhea and dermatologic events. In case of an overdose, it is advised to consult a qualified medical practitioner or an emergency medical helpline immediately. The patients will be given supportive care with proper monitoring. 

Adverse Reactions 

It is important to consult a qualified medical practitioner to know about the reactions and other related consequences before starting treatment with Sorafina. The following are the drug-related adverse reactions observed during the clinical trials. 

 

Several cardiovascular effects such as hypertensive crisis ( increase in blood pressure), infarction (tissue death), and myocardial ischemia (damage in the heart’s major blood vessels). These reactions may lead to severe heart attack and stroke. 

 

Digestive disorders may also occur after the administration of this medication including increased lipase, increased amylase, mucositis (painful inflammation of mucous membranes), stomatitis (including dry mouth and glossodynia), dyspepsia (indigestion), dysphagia (difficulty in swallowing), pancreatitis (inflammation of the pancreas),  gastrointestinal reflux, and gastritis (inflammation of stomach lining).

 

Dermatologic reactions like erythema (redness of the skin), exfoliative dermatitis (peeling of the skin), acne, flushing, folliculitis (bacterial or fungal infection), eczema (itchiness, inflammation, swelling, and cracked skin), and erythema multiforme (rash on the skin) may occur. 

 

Other general disorders like asthenia (weakness or lack of energy), pain (mouth pain, muscle pain, bone pain), loss of appetite, influenza-like symptoms (fever, muscle ache, chills, sweating, headache, shortness of breath, tiredness, runny nose, cough, and congestion), leukopenia (low white blood cell count), anemia (low red blood cell count), neutropenia (low neutrophils count), and thrombocytopenia (low platelets count).

 

Respiratory tract diseases may be experienced by some patients including hoarseness (breathy, raspy, or strained voice),  cerebral hemorrhage (bleeding in the brain), transient ischemic attack (stroke-like attack), cardiac failure (congestive heart failure), arrhythmia (irregular heartbeat), thromboembolism (obstruction of a blood vessel by a blood clot), and acute renal failure. 

 

In some patients, reproductive reactions like erectile dysfunction (inability to get or keep an erection for sexual intercourse) and gynecomastia (swollen male breast tissue) may occur during the course of this medication. 

 

Administration of Sorafina may also lead to certain metabolic and nutritional effects like hypophosphatemia (low level of phosphate in the blood), dehydration, hyponatremia (low level of sodium in the blood), and hypothyroidism (decrease in the production of thyroid hormone).

Warnings and Precautions

Reactions that may occur

  • Dermatologic Toxicities
    Hand-foot skin reaction and rash are the most common adverse effects observed in patients administering Sorafenib. Such severe effects can be managed by dose adjustments in most patients. 

  • Hypertension
    In about 16.9% of Sorafenib-treated patients, hypertension was noted. Regular monitoring of blood pressure should be done (almost every week) during the first 6 weeks of treatment with Sorafenib. 

  • Hemorrhage
    Hemorrhage (bleeding) is also one of the most common reactions of Sorafenib tablets. The patients should be made aware of such effects before starting Sorafina therapy. 

Special Population

  • Pregnant Women
    In rats and rabbits, Sorafenib has been proved to be teratogenic and to induce embryo-fetal toxicity. Sorafina, being a formulation of Sorafenib, may lead to fetal harm when administered to a pregnant female. If this medicine is administered during pregnancy, or if the individual becomes pregnant while receiving treatment with this drug, the individual should be made aware of the potential hazard to the fetus. 

  • Nursing Mothers
    It is not known whether Sorafina is excreted in human milk or not. Since many medicines are excreted in human milk and Sorafenib has not been studied in such patients, it is advised to discontinue breastfeeding while administering Sorafina.

  • Pediatric Use
    The safety and efficacy of this medicine for Pediatric use have not been studied yet. 

  • Geriatric Use
    During the clinical trials, no differences in the efficacy and safety of Sorafenib between younger and older patients were reported. However, approximately 30% of RCC patients treated with Sorafenib were aged 65 years and above. 

  • Hepatic Impairment
    In the case of patients suffering from Child-Pugh A and B hepatic impairment, no dose adjustments are needed.

  • Renal Impairment
    The safety and efficacy of this medicine have not been studied in patients suffering from severe renal impairment. 

Packaging and Storage

Sorafina tablets are packed in bottles. Each bottle contains 120 tablets. The tablets should be stored in the same container. Note that Sorafina tablets are for oral use only. Store this medicine at room temperature not exceeding 30ºC. Protect the tablets from direct light, heat, and moisture. Keep Sorafina and all other medicines away from the reach of children and