Gefitinib - Uses, Dosage, Side Effects, Interaction - Rxharun

Gefitinib – Uses, Dosage, Side Effects, Interaction

Mechanism of Action

Gefitinib is an inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase that binds to the adenosine triphosphate (ATP)-the binding site of the enzyme. EGFR is often shown to be overexpressed in certain human carcinoma cells, such as lung and breast cancer cells. Overexpression leads to enhanced activation of the anti-apoptotic Ras signal transduction cascades, subsequently resulting in increased survival of cancer cells and uncontrolled cell proliferation. Gefitinib is the first selective inhibitor of the EGFR tyrosine kinase which is also referred to as Her1 or ErbB-1. By inhibiting EGFR tyrosine kinase, the downstream signaling cascades are also inhibited, resulting in inhibited malignant cell proliferation.

Gefitinib inhibits the intracellular phosphorylation of numerous tyrosine kinases associated with transmembrane cell surface receptors, including the tyrosine kinases associated with the epidermal growth factor receptor (EGFR-TK). EGFR is expressed on the cell surface of many normal cells and cancer cells.


Gefitinib is the first selective inhibitor of epidermal growth factor receptor’s (EGFR) tyrosine kinase domain. Thus gefitinib is an EGFR inhibitor. The target protein (EGFR) is a member of a family of receptors (ErbB) which includes Her1(EGFR), Her2(Erb-B2), Her3(Erb-B3), and Her4 (Erb-B4). EGFR is overexpressed in the cells of certain types of human carcinomas – for example in lung and breast cancers. This leads to inappropriate activation of the anti-apoptotic Ras signaling cascade, eventually leading to uncontrolled cell proliferation. Research on gefitinib-sensitive non-small cell lung cancers has shown that a mutation in the EGFR tyrosine kinase domain is responsible for activating anti-apoptotic pathways.[rx][rx] These mutations tend to confer increased sensitivity to tyrosine kinase inhibitors such as gefitinib and erlotinib. Of the types of non-small cell lung cancer histologies, adenocarcinoma is the type that most often harbors these mutations. These mutations are more commonly seen in Asians, women, and non-smokers (who also tend to more often have adenocarcinoma). Gefitinib inhibits EGFR tyrosine kinase by binding to the adenosine triphosphate (ATP)-the binding site of the enzyme.[rx] Thus the function of the EGFR tyrosine kinase in activating the anti-apoptotic Ras signal transduction cascade is inhibited, and malignant cells are inhibited.[rx]


  • For the continued treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of either platinum-based or docetaxel chemotherapies.
  • Iressa is indicated for the treatment of adult patients with locally advanced or metastatic non-small-cell lung cancer with activating mutations of epidermal-growth-factor-receptor tyrosine kinase.
  • Gefitinib is a selective tyrosine kinase receptor inhibitor used in the therapy of non-small cell lung cancer.
  • Gefitinib is used to treat non-small cell lung cancer that has spread to other parts of the body in people with certain types of tumors. Gefitinib is in a class of medications called kinase inhibitors.
  • In Europe, gefitinib is indicated since 2009 in advanced NSCLC in all lines of treatment for patients harboring EGFR mutations. This label was granted after gefitinib was demonstrated as a first-line treatment to significantly improve progression-free survival vs. a platinum doublet regime in patients harboring such mutations. IPASS has been the first of four phases III trials to have confirmed gefitinib superiority in this patient population.
  • IRESSA is contraindicated in patients with severe hypersensitivity to gefitinib or to any other component of IRESSA.

Use in Cancer

Gefitinib is approved to treat:

Gefitinib is also being studied in the treatment of other types of cancer.


  • a type of inflammation of the lung called interstitial pneumonitis
  • a condition where there is a formation of fibrous tissue in the lung called pulmonary fibrosis
  • liver problems
  • severe renal impairment
  • pregnancy
  • a patient who is producing milk and breastfeeding


Strengths: 250 mg

Non-Small Cell Lung Cancer

  • 250 mg orally once a day until disease progression or unacceptable toxicity
  • Select patients for the first-line treatment of metastatic NSCLC with this drug based on the presence of EGFR exon 19 deletions or exon 21 L858R mutations in their tumor or plasma specimens.

    NOTE: For patients who have difficulty swallowing tablets immerse the tablet in 4 to 8 ounces of water (noncarbonated) and stir until dispersed (about 15 minutes). Drink the liquid or administer through a nasogastric tube. Rinse the container with 4 to 8 ounces of water and drink or administer through nasogastric tube.

Dose Adjustments

Withhold therapy for up to 14 days for the following adverse drug reactions and resume when fully resolved to Grade 1:

  • Acute onset or worsening of pulmonary symptoms (e.g., dyspnea, cough, fever)
  • Grade 2 or higher in alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) elevations
  • Grade 3 or higher diarrhea
  • Severe or worsening ocular disorders including keratitis
  • Grade 3 or higher skin reactions

Permanently discontinue therapy for:

  • Confirmed interstitial lung disease (ILD)
  • Severe hepatic impairment
  • GI perforation
  • Persistent ulcerative keratitis

Concomitant use with strong CYP450 3A4 inducers:

  • Avoid concomitant use if possible.
  • If concomitant use is required, increase dose to 500 mg orally once a day (in the absence of severe adverse drug reaction); resume at 250 mg dose 7 days after discontinuation of the strong CYP450 3A4 inducer.

Concomitant use with proton-pump inhibitor/H2 receptor antagonist/antacid:

  • Avoid concomitant use if possible.
  • If concomitant use is required, take this drug 12 hours after the last dose of the proton-pump inhibitor or 12 hours before the next dose of the proton-pump inhibitor.
  • Take this drug 6 hours after the last dose of the H2-receptor antagonist or antacid, or 6 hours before the next dose of the H2-receptor antagonist or antacid.

Administration Advice:

  • Therapy should be initiated and supervised by a physician experienced in the use of anticancer therapies.
  • This drug should be taken at about the same time each day, with or without food.
  • A missed dose should not be taken within 12 hours of the next dose.

Side Effects

The Most Common

  • dry skin
  • itching
  • rash
  • acne
  • mouth sores
  • weakness
  • new or worsening shortness of breath, cough, or fever
  • severe or ongoing diarrhea
  • severe abdominal pain
  • loss of appetite
  • eye pain, redness, or irritation
  • vision changes
  • watery eyes
  • eye sensitivity to light
  • hives
  • blisters or peeling skin
  • swelling of the eyes, face, lips, tongue, throat, hands, arms, feet, ankles or lower legs
  • nausea
  • vomiting
  • yellowing of the skin or eyes
  • dark urine
  • pale stools
  • pain or discomfort in the right upper stomach area

More common

  • Abdominal or stomach pain or tenderness
  • clay-colored stools
  • dark urine
  • decreased appetite
  • diarrhea, severe
  • fever
  • headache
  • itching or skin rash
  • loss of appetite
  • nausea and vomiting
  • swelling of the feet or lower legs
  • unusual tiredness or weakness
  • yellow eyes or skin
  • Burning, dry, or itching eyes
  • chest pain
  • chills
  • cough
  • difficult breathing
  • discharge or excessive tearing
  • dry eyes
  • a general feeling of discomfort or illness
  • redness, pain, or swelling of the eye, eyelid, or inner lining of the eyelid
  • thickening of bronchial secretions
  • troubled breathing
  • troubled or quick, shallow breathing


  • severe or ongoing diarrhea;
  • sudden chest pain or discomfort, new or worsening cough with fever, trouble breathing;
  • blurred vision, watery eyes, eye pain or redness, eyes being more sensitive to light;
  • liver problems–nausea, upper stomach pain, itching, tired feeling, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);
  • signs of stomach bleeding–severe stomach pain, bloody or tarry stools, coughing up blood or vomit that looks like coffee grounds; or
  • severe skin reaction–fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.
  • Blistering, peeling, or loosening of the skin
  • bloody, black, or tarry stools
  • eye redness, irritation, or pain
  • heartburn
  • indigestion
  • joint or muscle pain
  • red skin lesions, often with a purple center
  • severe abdominal or stomach pain, cramping, or burning
  • sore throat
  • sores, ulcers, or white spots in the mouth or on the lips
  • vomiting of material that looks like coffee grounds, severe and continuing

Drug Interactions

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Pregnancy and Lactation

AU TGA pregnancy category: C
US FDA pregnancy category: Not assigned.


Based on its mechanism of action and animal data, IRESSA can cause fetal harm when administered to a pregnant
woman. In animal reproductive studies, oral administration of gefitinib from organogenesis through weaning resulted in fetotoxicity and neonatal death at doses below the recommended human dose (see Animal Data). Advise pregnant women of the potential hazard to a fetus or potential risk for loss of the pregnancy. The background risk of major birth defects and miscarriage for the indicated population is unknown; however, the background risk in the U.S. general population of major birth defects is 2-4% and miscarriage is 15-20% of clinically
recognized pregnancies


No information is available on the clinical use of gefitinib during breastfeeding. Because gefitinib is 90% bound to plasma proteins, the amount in milk is likely to be low. However, its half-life is about 48 hours and it might accumulate in the infant. The manufacturer recommends that breastfeeding be discontinued during gefitinib therapy.

How should this medicine be used?

Gefitinib comes as a tablet to take by mouth. It is usually taken with or without food once a day. Take gefitinib at around the same time every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take gefitinib exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

If you are unable to swallow the tablets, you may dissolve them in water. Place one tablet in 4 to 8 ounces (120 to 240 mL) of plain, noncarbonated drinking water. Stir with a spoon for about 15 minutes until the tablet is dissolved. Drink the mixture right away. Rinse the glass with another 4 to 8 ounces (120 to 240 mL) of water and drink the rinse water right away to be sure that you swallow all of the medication.

Your doctor may delay or permanently stop your treatment if you experience certain side effects. Be sure to tell your doctor how you are feeling during your treatment with gefitinib.

What special precautions should I follow?

Before taking gefitinib,

  • tell your doctor and pharmacist if you are allergic to gefitinib, any other medications, or any of the ingredients in gefitinib tablets. Ask your pharmacist for a list of the ingredients.
  • tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, and nutritional supplements you are taking or plan to take. Be sure to mention any of the following: anticoagulants (‘blood thinners) such as warfarin (Coumadin, Jantoven); antifungals such as itraconazole (Onmel, Sporanox) and ketoconazole (Nizoral); metoprolol (Lopressor, Toprol XL, in Dutoprol); phenytoin (Dilantin, Phenytek); and tricyclic antidepressants such as imipramine (Tofranil) and amitriptyline. Many other medications may interact with gefitinib, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
  • if you are taking an antacid or an H2 blocker medication for indigestion, heartburn, or ulcers such as cimetidine (Tagamet), famotidine (Pepcid), nizatidine (Axid), or ranitidine (Zantac), take them at least 6 hours before or 6 hours after taking gefitinib.
  • if you are taking a proton pump inhibitor medication for indigestion, heartburn, or ulcers such as esomeprazole (Nexium), lansoprazole (Prevacid), omeprazole (Prilosec), pantoprazole (Protonix), or rabeprazole (AcipHex), take it at least 12 hours before or at least 12 hours after taking gefitinib.
  • tell your doctor if you have or have ever had pulmonary fibrosis (scarring of the lungs) or other lung or breathing problems, eye or vision problems, or liver disease.
  • tell your doctor if you are pregnant or plan to become pregnant. Gefitinib may cause infertility (difficulty becoming pregnant) in females. However, you should use birth control to prevent pregnancy during your treatment with gefitinib and for at least 2 weeks after you stop taking the medication. If you become pregnant while taking gefitinib, call your doctor. Gefitinib may harm the fetus and increase the risk of pregnancy loss.
  • tell your doctor if you are breastfeeding. You should not breastfeed while you are taking gefitinib.


  12. NCI Thesaurus Tree
  13. gefitinib
    NORMAN Suspect List Exchange Classification
  14. PubChem
  15. Therapeutic category of drugs in Japan
    Anatomical Therapeutic Chemical (ATC) classification
    Target-based classification of drugs
    Drugs listed in the Japanese Pharmacopoeia
  16. NCBI

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