Afatinib

Introduction

Afatinib is an oral, irreversible tyrosine kinase inhibitor used in the treatment of various types of cancer. It is specifically designed to target and inhibit the epidermal growth factor receptor (EGFR) and other related receptors, which play a critical role in the growth and spread of cancer cells.

Uses

Afatinib is primarily used for:

• Treatment of non-small cell lung cancer (NSCLC) that is positive for EGFR mutations, particularly in patients with advanced or metastatic disease.
• Treatment of head and neck squamous cell carcinoma (HNSCC) in combination with chemotherapy or as a second-line treatment.

Brand Name	Afatinib
Type
Weight
Generic	Afatinib
Manufacturer
Available in	English বাংলা

Mechanism of Action

Afatinib works by irreversibly binding to and inhibiting the tyrosine kinase activity of the EGFR family of receptors, including EGFR (HER1), HER2, and HER4. This inhibition disrupts the signaling pathways involved in tumor cell proliferation, survival, and metastasis, thereby slowing down or halting tumor growth.

How Long Does It Take to Work?

The clinical effects of Afatinib can be observed within a few weeks of starting treatment. However, the time to response can vary based on the individual patient's condition and the type of cancer being treated. Most patients may start to see clinical improvement within 1-2 months.

Absorption

Afatinib is well absorbed after oral administration, with peak plasma concentrations typically reached within 2-4 hours. The bioavailability of Afatinib is about 90%, and food intake does not significantly affect its absorption.

Route of Elimination

Afatinib is primarily metabolized by the liver through oxidative processes. It is excreted mainly in the feces (approximately 87% of the dose) and to a lesser extent in the urine (approximately 4%).

Dosage

The recommended dosage of Afatinib is usually:

• Initial dose: 40 mg once daily.
• Adjustment: The dose can be adjusted based on tolerance and adverse effects. The maximum recommended dose is 50 mg once daily.

Dosage adjustments are required for patients with severe adverse effects or those with hepatic impairment.

Administration

Afatinib is administered orally in the form of tablets. It should be taken on an empty stomach, ideally 1 hour before or 2 hours after a meal, to ensure optimal absorption. Tablets should be swallowed whole and not chewed or crushed.

Side Effects

Common side effects of Afatinib include:

• Diarrhea
• Rash
• Stomatitis (mouth sores)
• Fatigue
• Loss of appetite

Serious side effects may include:

• Pulmonary toxicity
• Severe skin reactions
• Liver function abnormalities

Toxicity

Signs of Afatinib toxicity include severe diarrhea, rash, and liver enzyme abnormalities. Management involves dose reduction or interruption, supportive care, and symptomatic treatment. Regular monitoring of liver function and gastrointestinal symptoms is essential.

Precautions

• Monitor liver function regularly due to potential hepatotoxicity.
• Monitor for pulmonary symptoms as Afatinib can cause interstitial lung disease.
• Be cautious in patients with a history of severe gastrointestinal conditions.

Interaction

Afatinib may interact with other medications, including:

• CYP3A4 inhibitors: May increase Afatinib levels.
• CYP3A4 inducers: May decrease Afatinib levels.
• Other drugs affecting gastric pH: May affect Afatinib absorption.

Disease Interaction

Afatinib should be used with caution in patients with:

• Pre-existing liver disease or hepatic impairment.
• History of severe gastrointestinal disorders.
• Pulmonary disease or symptoms indicative of lung problems.

Drug Interaction

Afatinib interacts with:

• CYP3A4 substrates: Care should be taken with drugs that are metabolized by CYP3A4, as they may affect Afatinib levels.
• Antacids and H2-receptor antagonists: These can affect the absorption of Afatinib . It is advisable to avoid taking them simultaneously.

Food Interactions

Food intake does not significantly affect the absorption of Afatinib . However, it is generally recommended to take Afatinib on an empty stomach to maintain consistent drug levels.

Pregnancy Use

Afatinib is categorized as a pregnancy category D drug, indicating that it should be avoided during pregnancy due to potential harm to the fetus. Women of childbearing age should use effective contraception while taking Afatinib .

Lactation Use

It is not known whether Afatinib is excreted in breast milk. Due to the potential for serious adverse effects in a breastfeeding infant, breastfeeding should be discontinued during Afatinib therapy.

Acute Overdose

In case of acute overdose, treatment includes symptomatic and supportive care. There is no specific antidote for Afatinib . Patients should be monitored closely, and treatment should focus on managing symptoms and supportive measures.

Contraindication

Afatinib is contraindicated in:

• Patients with known hypersensitivity to Afatinib or any of its components.
• Pregnant women due to potential fetal harm.

Use Direction

Afatinib should be taken once daily, ideally at the same time each day. It should be swallowed whole with water, ideally on an empty stomach, and should not be chewed, crushed, or broken.

Storage Conditions

Store Afatinib at room temperature, away from moisture and heat. Keep out of reach of children.

Volume of Distribution

The volume of distribution of Afatinib is approximately 1000 L, indicating extensive distribution throughout the body, including tissues.

Half Life

The elimination half-life of Afatinib is about 37 hours, which allows for once-daily dosing.

Clearance

Afatinib is primarily cleared by hepatic metabolism. The clearance rate can be affected by liver function, with a decrease in clearance in patients with hepatic impairment.

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Some Frequently Asked Questions About Afatinib