Gefitinib

Gefitinib is a prescription medication used to treat a certain type of lung cancer (non-small cell lung cancer or NSCLC) that has not responded to chemotherapy.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

You should not use gefitinib if you are allergic to it.

To make sure gefitinib is safe for you, tell your doctor if you have:

• liver disease;

• kidney disease;

• vision problems;

• breathing problems, lung disease other than lung cancer; or

• if you take a blood thinner (warfarin, Coumadin, Jantoven).

Do not use gefitinib if you are pregnant. It could harm the unborn baby. Use effective birth control to prevent pregnancy while you are using this medicine and for at least 2 weeks after your treatment ends.

This medicine may affect fertility (the ability to have children) in women. Tell your doctor if you plan to become pregnant.

It is not known whether gefitinib passes into breast milk or if it could harm a nursing baby. Do not breast-feed while taking gefitinib.

Avoid taking an antacid or stomach acid reducer (Nexium, Pepcid, Prevacid, Prilosec, Zantac, and others) within 6 hours before or 6 hours after you take gefitinib. These other medicines can make gefitinib much less effective when taken at the same time.

Contraindications

• Known severe hypersensitivity to gefitinib or any ingredient in the formulation.1

Warnings/Precautions

Warnings

Interstitial lung disease, sometimes fatal, reported; described as interstitial pneumonia, pneumonitis, or alveolitis.1 7 Manifestations often include acute onset of dyspnea, sometimes associated with cough or low-grade fever, usually becoming severe within a short time and requiring hospitalization.1 8

Risk of increased mortality in patients with concurrent idiopathic pulmonary fibrosis whose condition worsens while receiving gefitinib.1

If acute onset or worsening of pulmonary symptoms (dyspnea, cough, fever) occurs, interrupt therapy, promptly evaluate patient, and institute appropriate therapy.1 If diagnosis of interstitial lung disease is confirmed, discontinue gefitinib and provide appropriate treatment.1

May cause fetal harm; neonatal mortality soon after parturition, reduction in number of offspring born alive, and reduced fetal weight demonstrated in animals.1

Avoid pregnancy during therapy; if pregnancy occurs, apprise of potential fetal hazard or risk of pregnancy loss.1

Sensitivity Reactions

Allergic reactions, including angioedema and urticaria, reported.1

Major Toxicities

Diarrhea, nausea, vomiting, anorexia, and weight loss reported.1

Rash, acne, and dry skin reported.1 Toxic epidermal necrolysis and erythema multiforme reported rarely.1

Ocular pain and corneal erosion or ulcer, sometimes in association with aberrant eyelash growth, reported.1 Corneal membrane sloughing, ocular ischemia, or ocular hemorrhage reported rarely.1

Hemorrhage (e.g., epistaxis, hematuria) reported.1 Pancreatitis reported rarely.1

General Precautions

Asymptomatic elevations of hepatic aminotransferase concentrations reported.1

Consider periodic monitoring of liver function (aminotransferase, bilirubin, alkaline phosphatase concentrations); if severe elevations of test results occur, consider discontinuance.1

Specific Populations

Category D.1 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Gefitinib and its metabolites are distributed into milk in rats; not known whether distributed into human milk.1 Women receiving gefitinib should not breast-feed.1

Safety and efficacy not established in children <18 years of age; therefore, not indicated for use in pediatric patients.1 9 CNS hemorrhage and death reported in pediatric patients receiving gefitinib alone or with radiation for primary CNS tumors.1

No substantial differences in safety and efficacy relative to younger adults.1

Possible increased exposure.1 (See Special Populations under Pharmacokinetics.)

Not studied in patients with severe renal impairment; use with caution.1

Common Adverse Effects

Diarrhea, rash, acne, dry skin, nausea, vomiting, pruritus, anorexia, asthenia.1

Metabolized principally by CYP3A4.1 Does not inhibit CYP isoenzymes 1A2, 2C9, or 3A4 in vitro, but may inhibit 2C19 and 2D6 at high drug concentrations.1

Drugs Affecting Hepatic Microsomal Enzymes

CYP3A4 inhibitors: Potential pharmacokinetic interaction (decreased gefitinib metabolism, increased plasma gefitinib concentrations).1 2 3 Possible increased risk of adverse effects.1 Use with caution.1

CYP3A4 inducers: Potential pharmacokinetic interaction (increased gefitinib metabolism, decreased plasma gefitinib concentrations).1 If used concomitantly with potent CYP3A4 inducer, consider increasing gefitinib dosage to 500 mg daily in the absence of severe adverse effects.1

Drugs Affecting Gastric Acidity

Possible pharmacokinetic interaction (decreased plasma gefitinib concentrations, possible reduction in gefitinib efficacy) with drugs that cause substantial, sustained gastric pH elevation.1 10

Specific Drugs

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Throwing up.
• Loose stools (diarrhea).
• Skin irritation.
• Pimples (acne).
• Dry skin.
• Change in nails.
• Not hungry.
• Dry eyes.
• Eye irritation.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Iressa: 250 mg

• Iressa

Non-small cell lung cancer:

US labeling: First-line treatment of metastatic non-small cell lung cancer (NSCLC) in tumors with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an approved test.

Limitation of use: Safety and efficacy have not been established in patients with metastatic NSCLC whose tumors have EGFR mutations other than exon 19 deletions or exon 21 (L858R) substitution mutations

Canadian labeling: First-line treatment of locally advanced (nonresponsive to curative therapy) or metastatic NSCLC with activating mutations of the epidermal growth factor receptor tyrosine kinase (EGFR-TK).

Refer to adult dosing.

Dermatologic toxicity:

Skin reactions (grade 3 or higher): Withhold treatment for up to 14 days; may resume treatment when fully resolved or improved to grade 1. Canadian labeling: Discontinue if unable to tolerate rechallenge following treatment interruption.

Severe bullous, blistering or exfoliating dermatologic conditions: Interrupt or discontinue treatment.

Gastrointestinal toxicity:

Diarrhea (grade 3 or higher): Withhold treatment for up to 14 days; may resume treatment when fully resolved or improved to grade 1. Canadian labeling: Discontinue if unable to tolerate rechallenge following treatment interruption.

Gastrointestinal perforation: Permanently discontinue.

Ocular toxicity:

Signs/symptoms of severe or worsening disorders, including keratitis: Withhold treatment for up to 14 days; may resume treatment when fully resolved or improved to grade 1. Canadian labeling: Discontinue if unable to tolerate rechallenge following treatment interruption.

Persistent ulcerative keratitis: Permanently discontinue.

Pulmonary toxicity:

Acute onset or worsening symptoms (dyspnea, cough, fever): Withhold treatment for up to 14 days; may resume treatment when fully resolved or improved to grade 1.

Interstitial lung disease (ILD), confirmed: Permanently discontinue.

Applies to gefitinib: oral tablet

Respiratory

Common (1% to 10%): Interstitial lung disease or ILD-like adverse reactions[Ref]

Hepatic

Very common (10% or more): Increased AST (up to 40%), increased ALT (up to 38%)
Common (1% to 10%): Increased bilirubin
Uncommon (0.1% to 1%): Hepatitis/hepatic failure
Rare (less than 0.1%): Fatal hepatotoxicity[Ref]

Gastrointestinal

Very common (10% or more): Diarrhea (up to 29%), nausea (up to 18%), vomiting (up to 14%)
Common (1% to 10%): Stomatitis, dry mouth, pancreatitis, dehydration (secondary to diarrhea, nausea, vomiting, or anorexia)
Uncommon (0.1% to 1%): GI perforation[Ref]

Ocular

Common (1% to 10%): Keratitis, conjunctivitis, blepharitis, dry eye
Uncommon (0.1% to 1%): Corneal erosion/aberrant eyelash growth[Ref]

Nervous system

Rare (less than 0.1%): CNS hemorrhage
Frequency not reported: Cerebrovascular events[Ref]

Dermatologic

Reported skin reactions: acne/acne pustular, dermatitis (acneiform and exfoliative), drug eruption, dry skin, erythema, folliculitis, pruritus, rash (erythematous, exfoliative, generalized, macular, maculo-papular, papular, pruritic, pustular, vesicular), skin exfoliation, skin toxicity, and xeroderma.[Ref]

Very common (10% or more): Skin reactions (up to 47%)
Common (1% to 10%): Nail disorder, alopecia
Rare (less than 0.1%): Bullous conditions (including toxic epidermal necrolysis, Stevens Johnson syndrome, erythema multiforme), cutaneous vasculitis[Ref]

Renal

Very common (10% or more): Proteinuria (up to 35%)
Common (1% to 10%): Elevated blood creatinine, cystitis
Rare (less than 0.1%): Hemorrhagic cystitis
Frequency not reported: Renal failure[Ref]

Metabolic

Very common (10% or more): Decreased appetite (up to 17%), anorexia (10%)[Ref]

Other

Very common (10% or more): Asthenia (up to 17%)
Common (1% to 10%): Pyrexia[Ref]

Hematologic

Common (1% to 10%): Hemorrhage (including epistaxis and hematuria)[Ref]

Immunologic

Common (1% to 10%): Allergic reactions (including angioedema and urticaria)[Ref]

Some side effects of gefitinib may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Data not available.