Sorafenib Tosylate

Introduction

Sorafenib Tosylate is an oral multikinase inhibitor primarily used in the treatment of certain cancers, including advanced renal cell carcinoma (RCC), unresectable hepatocellular carcinoma (HCC), and differentiated thyroid carcinoma (DTC). By inhibiting tumor cell proliferation and angiogenesis, it helps to slow cancer progression.

Uses

Sorafenib Tosylate is used for the treatment of:

Advanced renal cell carcinoma (RCC)
Unresectable hepatocellular carcinoma (HCC)
Locally recurrent or metastatic, progressive differentiated thyroid carcinoma (DTC) that is refractory to radioactive iodine treatment

Brand Name	Sorafenib Tosylate
Type
Weight
Generic	Sorafenib Tosylate
Manufacturer
Available in	English বাংলা

Mechanism of Action

Sorafenib inhibits multiple intracellular and cell surface kinases, including RAF kinases, VEGFR (vascular endothelial growth factor receptor), PDGFR (platelet-derived growth factor receptor), and RET (rearranged during transfection). This results in reduced tumor cell proliferation, tumor angiogenesis, and an overall slowing of cancer growth.

How Long Does It Take to Work?

The effects of Sorafenib in slowing cancer progression may take several weeks to be noticeable. Patients are generally evaluated periodically for clinical responses, but measurable benefits can be observed within 12-16 weeks of treatment.

Absorption

Sorafenib is rapidly absorbed after oral administration. However, bioavailability can be reduced by high-fat meals. Peak plasma concentrations are reached within 3 hours of ingestion.

Route of Elimination

Sorafenib is primarily eliminated via the liver through metabolism by cytochrome P450 enzymes, particularly CYP3A4. The majority is excreted in feces, with a smaller portion eliminated in urine.

Dosage

The recommended daily dose of Sorafenib is 400 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.

Management of suspected adverse drug reactions may require temporary interruption and/or dose reduction of Sorafenib therapy. When dose reduction is necessary, the Sorafenib dose may be
reduced to 400 mg once daily. If additional dose reduction is required, Sorafenib may be reduced to a single 400 mg dose every other day.

Recommended regimens and treatment duration for Sorafenib therapy.

Grade 1: Numbness, dysesthesia, paresthesia, tingling, painless swelling, erythema or discomfort of the hands or feet which does not disrupt the patient's:

Any occurrence: Continue treatment with Sorafenib and consider topical therapy for symptomatic relief.

Grade 2: Painful erythema and swelling of the hands or feet and/ or discomfort affecting the patient’s normal activities

1st occurrence: Continue treatment with Sorafenib and consider topical therapy for symptomatic relief. If no improvement within 7 days, see below.
No improvement within 7 days or 2nd or 3rd occurrence: Interrupt Sorafenib treatment until toxicity resolves to Grade 0-1 When resuming treatment, decrease Sorafenib dose by one dose level (400 mg daily or 400 mg every other day).
4th occurrence: Discontinue Sorafenib treatment.

Grade 3: Moist desquamation, ulceration, blistering or severe pain of the hands or feet, or severe discomfort that causes the patient to be unable to work or perform activities of daily living:

1st or 2nd occurrence: Interrupt Sorafenib treatment until toxicity resolves to Grade 0-1 When resuming treatment, decrease Sorafenib dose by one dose level (400 mg daily or 400 mg every other day).
3rd occurrence: Discontinue Sorafenib treatment.

No dose adjustment is required on the basis of patient age, gender, or body weight.

Missed doses: If a dose of Sorafenib is missed, skip the missed dose, and take next dose at regular time. Do not double your dose of Sorafenib.

The standard dosage for adults is 400 mg (two 200 mg tablets) taken twice daily. The dose may be adjusted based on individual tolerance, response, or the development of adverse effects.

Administration

Sorafenib should be taken without food, or with a low-fat meal, as high-fat meals can reduce absorption.
Tablets should be swallowed whole with water and should not be chewed or crushed.
Adherence to a regular dosing schedule is important to maintain therapeutic drug levels.

Side Effects

Fatigue
Hand-foot skin reaction (palmar-plantar erythrodysesthesia)
Rash
Diarrhea
Hypertension (high blood pressure)
Nausea and vomiting
Weight loss
Hair thinning or loss

Toxicity

In cases of overdose, symptoms may include severe diarrhea, skin reactions, and hypertension. Supportive care and close monitoring of vital signs are recommended. Dialysis is not effective due to Sorafenib’s high plasma protein binding.

Precautions

Patients with cardiovascular diseases should use Sorafenib cautiously, as it may increase the risk of hypertension and heart failure.
Patients with liver or renal impairments require close monitoring for potential dose adjustments.
Not recommended for use during pregnancy due to potential harm to the fetus.
Risk of gastrointestinal perforation in patients with a history of gastrointestinal issues.

Interaction

Concomitant use with strong CYP3A4 inhibitors (e.g., ketoconazole) can increase Sorafenib plasma concentrations.
Co-administration with CYP3A4 inducers (e.g., rifampin) may reduce Sorafenib levels and efficacy.
Anti-hypertensive medications may require dose adjustment due to Sorafenib’s potential to increase blood pressure.

Disease Interaction

Cardiovascular disease (increased risk of heart failure and hypertension)
Hepatic impairment (altered drug metabolism)
Renal impairment (potential accumulation of the drug)
Bleeding disorders (increased risk of bleeding)

Drug Interaction

Warfarin: May increase the risk of bleeding.
Ketoconazole: Can increase Sorafenib levels and side effects.
Rifampin: May decrease Sorafenib’s efficacy by enhancing its metabolism.
Doxorubicin: May increase Sorafenib toxicity when used together.

Food Interactions

High-fat meals reduce the bioavailability of Sorafenib and should be avoided.
It is recommended to take Sorafenib at least 1 hour before or 2 hours after a meal.

Pregnancy Use

Sorafenib is contraindicated during pregnancy (Category D) due to the potential for fetal harm. Women of childbearing age should use effective contraception during treatment and for some time after the last dose.

Lactation Use

It is not recommended to breastfeed while taking Sorafenib, as it is unknown whether the drug passes into breast milk. The potential for serious adverse effects in nursing infants cannot be ruled out.

Acute Overdose

In the case of an overdose, symptoms can include severe gastrointestinal reactions (such as diarrhea) and skin toxicities. Medical intervention should focus on supportive care, as there is no specific antidote.

Contraindication

Hypersensitivity to Sorafenib or any of its components
Pregnancy (due to potential fetal harm)
Severe hepatic or renal impairment
Uncontrolled hypertension

Use Direction

Take 400 mg orally twice daily, on an empty stomach (either 1 hour before or 2 hours after a meal).
In case of missed doses, skip the dose and continue with the next scheduled dose. Do not double the dose.

Storage Conditions

Store at room temperature (20-25°C or 68-77°F).
Protect from moisture and light.
Keep out of reach of children.

Volume of Distribution

The volume of distribution of Sorafenib is approximately 20-30 L. This indicates extensive tissue distribution.

Half-Life

The half-life of Sorafenib is approximately 25 to 48 hours, allowing for twice-daily dosing.

Clearance

Sorafenib has a clearance rate of around 0.7 L/h, primarily through hepatic metabolism. The drug is mainly excreted in feces, with a small portion excreted in urine.

See in details version Sorafenib Tosylate also Sorafenib Tosylate in bangla