What Is Sorafenib?
Sorafenib is an oral receptor multikinase inhibitor recently used in targeted cancer cell therapy. Sorafenib is a synthetic compound that blocks growth signals in cancer cells. Sorafenib belongs to the class of phenyl ureas (urea containing nitrogen substituted by the 4-chloro-3-trifluorophenyl group). It is a pyridine carboxamide (a member of monochlorobenzenes), which is an aromatic ether. It acts as a potent antineoplastic agent and a tyrosine kinase inhibitor. Sorafenib induces ferroptosis and inhibits angiogenesis. It is also effective as an anti-coronaviral agent.
Is Sorafenib FDA-Approved?
Yes, the Food and Drug Administration (FDA) approved Sorafenib on 20th December 2005 and has listed it in the FDA Orange Book (Approved Drug Products with Therapeutic Equivalence Evaluations).
Indications
Advanced renal cell carcinoma.
In cases of untreatable end-stage renal cell carcinoma, such as failure or unresponsiveness to anticancer cytokines (interferon-alpha, interleukin-2) therapy.
In advanced renal cell carcinoma patients for whom surgeries or anticancer cytokine therapy are contraindicated.
Unresectable (surgery contraindicated) hepatocellular carcinoma (liver cancer).
In differentiated (follicular, papillary, Hurthle cell) thyroid carcinoma.
To treat various stages of thyroid carcinoma (progressive, locally invasive, and metastatic).
It is indicated in thyroid cancers that are refractory to radioactive iodine.
To treat colon, metastatic pancreatic, and lung cancers.
Malignant melanoma.
Prostate cancers that are refractory to steroids.
Contraindications
In known cases of severe hypersensitivity to Sorafenib.
In combination, cancer therapy with Paclitaxel and Carboplatin to treat squamous cell lung carcinoma.
Dosage Forms and Strengths
Sorafenib is available as 200 mg tablets coated with a film (a thin, uniform layer of polymer). Tablet film coating is done to increase drug availability and achieve therapeutic efficacy.
Dosage and Administration
Route of Administration - oral intake.
Recommended Dose - 400 mg (2 x 200 mg tablet).
Two tablets of Sorafenib are taken twice daily on an empty stomach, without food (one hour before the meal or two hours after it.
An interrupted treatment regimen or dosage reduction is adopted to manage reported adverse drug side effects.
In dose reduction, 400 mg of Sorafenib is recommended once daily.
If an additional dose reduction is required, a single dose of 400 mg every other alternate day is advised.
Treatment with the prescribed dosage must continue until no clinical improvement in the patient’s condition from the therapy or until severe toxic side effects occur.
For Patients
What Is Sorafenib?
Sorafenib is a man-made cancer medicine that helps slow down cancer growth. It works in two main ways:
It blocks signals that tell cancer cells to grow and divide.
It stops the cancer from forming new blood vessels, which cuts off the supply of oxygen and nutrients the tumor needs to grow.
Sorafenib is used to treat advanced renal cell carcinoma, especially when the cancer comes back after surgery or does not respond to other cancer treatments. Studies show that patients taking Sorafenib have a longer time before the cancer worsens, with an average progression-free survival of about 5.5 months.
Because Sorafenib can cause side effects, it is given only on a doctor’s prescription, and patients are closely monitored during treatment.
How Is Sorafenib Taken?
Take Sorafenib exactly the way your doctor has prescribed.
The usual dose is 2 tablets twice a day, for a total of 4 tablets each day.
Your doctor may change the dose depending on how well the medicine is working and if you have any side effects.
Swallow the tablets with water. Take them on an empty stomach, either 1 hour before a meal or 2 hours after a meal.
If you miss a dose, skip it and take your next dose at the usual time. Do not take two doses together.
If you accidentally take more than the prescribed amount, contact your doctor right away.
How Should Sorafenib Be Stored?
Store Sorafenib at room temperature, between 15 and 30 degrees Celsius.
Keep it out of reach of children.
Store the tablets in a cool, dry place, away from direct sunlight.
What Are the Side Effects of Sorafenib?
Side effects can vary from person to person and may be affected by other treatments, such as radiation therapy. Skin problems are the most common side effects.
Possible side effects include:
Hand-foot syndrome causes redness, pain, peeling, or rashes on the palms and soles.
Skin rash and itching.
Diarrhea or constipation.
Feeling very tired or weak.
Weight loss.
Loss of appetite.
Fever with chills.
Nosebleeds or other bleeding.
Dry skin.
Thinning of hair.
Pain in the joints or abdomen.
Headaches.
Low phosphate levels in the blood.
Increased pancreatic enzyme levels.
Heart-related problems.
What Precautions Should Be Taken While Using Sorafenib?
Sorafenib should be taken on an empty stomach because food can reduce its effectiveness.
Tell the doctor right away if there are signs of an allergic reaction.
Pregnant and breastfeeding women should not take Sorafenib, as it can harm the baby.
Women who think they may be pregnant should inform their doctor immediately.
Inform the doctor before any surgery or dental procedure, as Sorafenib can increase the risk of bleeding.
Avoid vitamin supplements and herbal medicines unless approved by the doctor.
Live vaccines should not be taken during treatment.
Patients with liver problems should tell their doctor before starting Sorafenib.
Any side effects should be reported to the doctor. Do not stop the medicine on your own.
Taking too much Sorafenib should be treated as an emergency and reported immediately.
For Doctors
Pharmacodynamics
Sorafenib is a medicine used to treat cancer. It helps slow down or stop the growth of cancer cells. Cancer cells grow because of certain signals in the body. Sorafenib blocks these signals, making it harder for cancer cells to grow and multiply.
This medicine blocks proteins called tyrosine kinase and RAF kinase. These proteins normally tell cancer cells to grow and divide quickly. When Sorafenib blocks them, cancer growth slows down.
Sorafenib also stops tumors from making new blood vessels. Tumors need blood vessels to get oxygen and nutrients. Sorafenib blocks signals like VEGFR-2 and PDGFR that help form these blood vessels.
When fewer blood vessels form, the tumor cannot grow as easily. By blocking cancer growth signals and blood vessel formation, Sorafenib helps control cancer in the body.
Pharmacokinetics
Sorafenib is taken by mouth and absorbed into the bloodstream. Food, especially high-fat meals, can reduce the amount of the drug absorbed, so it is usually taken on an empty stomach. In the blood, sorafenib binds strongly to proteins. It is mainly broken down in the liver by enzymes, especially CYP3A4. The drug and its breakdown products are removed from the body mostly through the stool and a small amount through urine.
Bioavailability
Upon oral administration, Sorafenib has an average bioavailability of 38% to 49% and a mean half-life of 25 to 48 hours.
Continuous dosing of Sorafenib for 7 consecutive days results in a 2.5- to 7-fold accumulation in plasma compared with a single dose.
Steady-state serum Sorafenib concentrations are reached within seven days.
Absorption and Distribution
Following oral administration in a fasting state, Sorafenib is readily absorbed and reaches peak plasma levels within 3 hours.
The bioavailability of Sorafenib is reduced by 29% when taken with a high-fat meal.
It is recommended that Sorafexib be administered without food to increase its absorption.
99.5% of Sorafenib binds to plasma proteins in humans.
Metabolism and Elimination
Sorafenib is mainly broken down in the liver.
The liver uses an enzyme called CYP3A4 to change the drug first.
After that, another enzyme called UGT1A9 further processes it.
The body forms about eight breakdown products (metabolites) of Sorafenib.
These metabolites make up around 70% to 85% of what is found in the blood.
The main metabolite in the blood is called pyridine N-oxide.
This main metabolite accounts for about 9% to 16% of Sorafenib in the blood at steady levels.
After taking the medicine by mouth, about 96% of the dose is removed from the body within 14 days.
Route of Elimination - 77 % in feces and 19 % in urine in glucuronidated metabolites. Unchanged Sorafenib is also eliminated through feces but is not found in urine.
Toxicity in Sorafenib Therapy
Despite the effective outcome of Sorafenib therapy in advanced renal cell carcinoma, its use is associated with various toxic effects. Its use is associated with several toxic effects, such as cardiovascular, gastrointestinal, and dermatologic complications.
The following are the toxicities related to Sorafenib.
Cardiac ischemia and myocardial infarction.
Congestive heart failure.
Higher risk for bleeding and hemorrhage.
Esophageal varices.
Severe hypertension.
Dermatologic toxicities causing desquamation of hand-foot skin (Palmar-plantar erythrodysesthesia).
Gastrointestinal perforation.
Delayed or impaired wound healing, particularly after major surgeries.
Liver injury.
Arthralgia and myalgia.
Transient ischemic attack.
Arrhythmia.
Thromboembolism.
Hypersensitivity reactions and urticaria.
Dyspnea.
Leukopenia and lymphopenia.
Erectile dysfunction.
Birth defects and fetal loss are reported when administered during pregnancy.
Dose Modifications According to the Severity of Skin Toxicity
In Grade 1 Toxicity - Numbness, paresthesia, tingling, erythema, and tolerable discomfort in hands and feet, no change in Sorafenib dosage. Topical symptomatic relief therapy is recommended.
In Grade 2 Toxicity - Painful erythema and swelling of the hands or feet, Sorafenib dosage is decreased by a single dose level (400 mg per day or 400 mg every alternate day).
In Grade 3 Toxicity - Wet desquamation along with ulceration and blistering of the hands or feet, the dosage is reduced to below 400 mg per day or 400 mg every alternate day. If the condition worsens, the use of Sorafenib is discontinued.
Drug Interactions
Increased bleeding tendencies with Warfarin co-administration.
Increased mortality rate when used with Carboplatin and Paclitaxel.
Sorafenib increases the drug bioavailability of Docetaxel and Doxorubicin.
Sorafenib inhibits the metabolism of Irinotecan (blocks glucuronidation).
Concomitant use of Sorafenib and Rifampicin reduces the bioavailability of Sorafenib.
Anti-epileptic drugs such as Phenytoin, Phenobarbital, and Carbamazepine increase the metabolism of Sorafenib.
Neomycin decreases the plasma levels of Sorafenib.
Sorafenib interferes with antibody production when live vaccines are administered.
Use of Sorafenib in Special Considerations
Pregnancy - Toxic effects on the fetus occur when administered to pregnant mothers. The reduction in dose below 400 mg twice daily could prevent toxicity in the fetus.
Nursing Mothers - No documented evidence on the excretion of Sorafenib in milk. Due to the potential toxicity of Sorafenib, the drug can be discontinued during nursing, or the drug is usually recommended.
Pediatric Use - The safety of Sorafenib in the pediatric population has not yet been studied. Hypocellularity in bone marrow is observed in animal models.
Patients with Hepatic Dysfunction - Since Sorafenib is metabolized in the liver, the dosage should be reduced in mild to moderate liver impairment.
Geriatric Use - No significant dose change related to adverse reactions is reported.
Patients With Renal Dysfunction - Fluid and electrolyte balance should be monitored in individuals susceptible to renal impairment.
Conclusion:
Sorafenib is a targeted cancer medicine that slows tumor growth. It works by blocking signals that help cancer cells multiply and form new blood vessels. This helps control cancer progression and improve treatment outcomes. Talk to our cancer specialist before taking this drug.
