Gefitinib

Oral
EGFR positive locally advanced non-small cell lung cancer, EGFR positive metastatic non-small cell lung cancer

Patients taking strong CYP3A inducers (e.g. rifampicin, phenytoin, TCAs): 500 mg once daily, if tolerated. May reduce dose to 250 mg once daily after 7 days of discontinuing the potent CYP3A4 inducer. Dosage recommendations may vary between countries (refer to local guidelines).

Pharmacogenomics:

Gefitinib is metabolised by CYP2D6 enzyme to its metabolite, O-desmethyl gefitinib. Individuals with reduced CYD2D6 enzyme activity, known as CYP2D6 poor metabolisers, may have increased gefitinib exposure.

Individuals who are CYP2D6 poor metabolisers may have an increased exposure to gefitinib which could be clinically significant as some adverse effects (e.g. severe hepatotoxicity) are associated with higher gefitinib exposure. While no specific dosage adjustment is recommended for CYP2D6 poor metabolisers, these individuals should be carefully monitored for potential adverse reactions.

Gefitinib May be taken with or without food. May disperse tab & administer soln/susp orally or via feeding tubes. Take immediately.

Lactation.

Patient with risk factors for gastrointestinal perforation (e.g. history of gastrointestinal ulceration, bowel metastases at the site of perforation, receiving steroids or NSAIDs, increasing age, smoking). Patient taking strong CYP3A inducers (e.g. rifampicin, phenytoin, TCAs). CYP2D6 poor metabolisers. Renal (CrCl ≤20 mL/min) and moderate to severe hepatic (Child-Pugh B or C) impairment. Pregnancy.

Significant: Dermatologic toxicity (e.g. toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, dermatitis bullous); severe or persistent diarrhoea, nausea, vomiting or anorexia leading to dehydration; increased ALT, AST and bilirubin; ocular toxicity (e.g. keratitis, ulcerative keratitis, corneal erosion, abnormal eyelash growth, conjunctivitis, blepharitis, dry eye, blindness). Rarely, gastrointestinal perforation.
Gastrointestinal disorders: Stomatitis, dry mouth.
General disorders and administration site conditions: Asthenia, pyrexia.
Immune system disorders: Allergic reactions, including urticaria and angioedema.
Infections and infestations: Cystitis.
Investigations: Increased serum creatinine.
Renal and urinary disorders: Proteinuria, haematuria.
Respiratory, thoracic and mediastinal disorders: Epistaxis.
Skin and subcutaneous tissue disorders: Pustular rash, skin fissures, alopecia, dry skin, nail disorders.
Potentially Fatal: Hepatic failure, interstitial lung disease (ILD) or ILD-like reactions (e.g. acute respiratory distress syndrome, lung infiltration, pneumonitis, pulmonary fibrosis).

This drug may cause asthenia, if affected, do not drive or operate machinery. Women of childbearing potential must use effective contraception during and for at least 2 weeks after stopping the treatment. Do not breastfeed during therapy.

Confirm the presence of EGFR mutations in tumour or plasma specimen prior to treatment initiation. Perform HBV screening, including HBsAg, hepatitis B core antibody, total Ig or IgG, and antibody to HBsAg before or at the beginning of systemic anticancer therapy. Monitor LFTs (e.g. ALT, AST, bilirubin) at baseline and periodically thereafter; INR or prothrombin time (in patients receiving warfarin). Assess for signs and symptoms of gastrointestinal perforation, hepatotoxicity, and dermatologic, ocular or pulmonary toxicity.

Symptoms: Diarrhoea, skin rash. Management: Symptomatic and supportive treatment.

Decreased serum concentration and therapeutic effect with CYP3A4 inducers (e.g. phenytoin, carbamazepine, rifampicin, barbiturates, TCAs). Increased risk of bleeding events or elevated INR with warfarin. Reduced bioavailability, plasma concentrations, and therapeutic effect with agents that elevate gastric pH (e.g. proton pump inhibitors, H₂-antagonists, antacids). Increased serum concentration and risk of adverse effects with strong CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, posaconazole, voriconazole, clarithromycin, telithromycin) and strong CYP2D6 inhibitors. May increase exposure of CYP2D6 substrates with narrow therapeutic index (e.g. metoprolol). May exacerbate the neutropenic effect of vinorelbine.

Decreased serum concentration and therapeutic effect with St. John's wort.

Description:
Mechanism of Action: Gefitinib is a tyrosine kinase inhibitor which reversibly inhibits the kinase activity of wild-type and select activation mutations of epidermal growth factor receptor (EGFR), which is expressed on the cell surface of normal and cancer cells and is involved in cell growth and proliferation. Inhibition of EGFR prevents the autophosphorylation of tyrosine residues associated with the receptor, thereby blocking further downstream signalling and EGFR-dependent proliferation. It also exhibits a higher binding affinity for EGFR exon 19 deletion and exon 21 (L858R) substitution mutations than wild-type EGFR.
Pharmacokinetics:
Absorption: Slowly absorbed from the gastrointestinal tract. Bioavailability: Approx 60%. Time to peak plasma concentration: 3-7 hours.
Distribution: Extensively distributed throughout the body. Plasma protein binding: Approx 90%, to albumin and α₁-acid glycoprotein.
Metabolism: Extensively metabolised in the liver mainly by CYP3A4 and to a lesser extent by CYP2D6 to form the less potent major metabolite, O-desmethyl gefitinib.
Excretion: Mainly via faeces (86%); urine (<4%). Elimination half-life: 41-48 hours.

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 123631, Gefitinib. https://pubchem.ncbi.nlm.nih.gov/compound/Gefitinib. Accessed Apr. 29, 2025.

Store between 20-25°C. This is a cytotoxic drug. Follow applicable procedures for receiving, handling, administration, and disposal.

Targeted Cancer Therapy

L01EB01 - gefitinib ; Belongs to the class of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. Used in the treatment of cancer.

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