Drugs List

Therapeutic Indications

Uses

Advanced/metastatic non-small cell lung cancer with EGFR-TK mutations

Monotherapy for the treatment of adults with locally advanced or metastatic non-small cell lung cancer with activating mutations of EGFR-TK.

Contraindications

Children under 18 years
Breastfeeding
Galactosaemia
Pregnancy

Precautions and Warnings

CYP2D6 poor metaboliser genotype
Glucose-galactose malabsorption syndrome
Lactose intolerance
Moderate hepatic impairment
Renal impairment - creatinine clearance below 20ml/minute

Refer patients with symptoms of keratitis to an ophthalmology specialist
Advise ability to drive/operate machinery may be affected by side effects
Confirm EGFR mutation status of tumour prior to treatment
Treatment to be initiated and supervised by a specialist
Contains lactose
Consult local policy on the safe use of oral anti-cancer drugs
Staff: Not to be handled by pregnant staff
Monitor hepatic function periodically
Advise patient to report any blurred vision or any other eye symptoms
Advise patient to report any new or worsening respiratory symptoms
Advise pt to seek medical advice for severe/persistent GI disturbances
Discontinue / interrupt treatment if ulcerative keratitis develops
Discontinue treatment if interstitial lung disease develops
Consider discontinuing treatment if severe hepatic changes occur
Interrupt treatment if adverse skin reactions occur
Interrupt treatment if poorly tolerated diarrhoea occurs
Suspend treatment if patients experience worsening of respiratory symptoms
Advise patient not to self medicate with antacids or acid suppressants
Advise patient not to take St John's wort concurrently
Female: Ensure adequate contraception during treatment

Patients should be advised to report worsening of respiratory symptoms such as dyspnoea, cough and fever. If these occur, treatment should be interrupted and the patient should be investigated. If interstitial lung disease (ILD) is confirmed, gefitinib should be discontinued and the patient treated appropriately. An increased risk of ILD was observed during the first 4 weeks of treatment, with the relative risk being lower thereafter.

Gastrointestinal perforation has been reported in patients taking gefitinib. In most cases this is associated with other known risk factors including, concomitant steroids or NSAIDs, underlying history of gastrointestinal ulceration, age, smoking or bowel metastases at sites of perforation.

Patients with a CYP2D6 poor metaboliser genotype are predisposed to elevated plasma levels of gefitinib if also treated with a potent CYP3A4 inhibitor. At initiation of treatment with a CYP3A4 inhibitor patients should be closely monitored for adverse reactions.

Pregnancy and Lactation

Pregnancy

Gefitinib is contraindicated during pregnancy.

The manufacturer states that gefitinib should not be used during pregnancy unless clearly necessary. Studies in animals have shown reproductive toxicity. There are no data, at the time of writing, on the use of gefitinib during human pregnancy. It is not known if gefitinib crosses the human placenta. However, its molecular weight and long elimination half-life suggest it is likely to cross the human placenta.

Lactation

Gefitinib is contraindicated during breastfeeding.

The manufacturer states that gefitinib is contraindicated during breastfeeding. Animal data reports gefitinib is expressed in breast milk however it is unknown whether gefitinib is secreted in human milk. Its molecular weight and long elimination half-life suggest it is likely to be excreted into human milk. Briggs suggests the effect of gefitinib on a nursing infant could be serious.

Side Effects

Acne
Allergic reaction
Alopecia
Angioedema
Anorexia
Asthenia
Blepharitis
Blindness
Conjunctivitis
Corneal erosion
Corneal perforation
Cutaneous vasculitis
Cystitis
Dehydration
Diarrhoea
Dry eyes
Dry mouth
Dry skin
Epistaxis
Erythema multiforme
Gastro-intestinal perforation
Haematuria
Haemorrhage
Haemorrhagic cystitis
Hepatitis
Increase in serum ALT/AST
Interstitial lung disease
Keratitis
Misdirected eyelash growth
Nail disorders
Nausea
Pancreatitis
Proteinuria
Pruritus
Pustular rash
Pyrexia
Serum bilirubin increased
Serum creatinine increased
Skin fissures
Skin reactions
Stevens-Johnson syndrome
Stomatitis
Toxic epidermal necrolysis
Ulcerative keratitis
Urticaria
Vomiting

Presentation

Oral formulations of gefitinib

Drugs List

Therapeutic Indications

Uses

Advanced/metastatic non-small cell lung cancer with EGFR-TK mutations

Monotherapy for the treatment of adults with locally advanced or metastatic non-small cell lung cancer with activating mutations of EGFR-TK.

Dosage

Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.

Adults

Additional Dosage Information

Contraindications

Children under 18 years
Breastfeeding
Galactosaemia
Pregnancy

Precautions and Warnings

CYP2D6 poor metaboliser genotype
Glucose-galactose malabsorption syndrome
Lactose intolerance
Moderate hepatic impairment
Renal impairment - creatinine clearance below 20ml/minute

Refer patients with symptoms of keratitis to an ophthalmology specialist
Advise ability to drive/operate machinery may be affected by side effects
Confirm EGFR mutation status of tumour prior to treatment
Treatment to be initiated and supervised by a specialist
Contains lactose
Consult local policy on the safe use of oral anti-cancer drugs
Staff: Not to be handled by pregnant staff
Monitor hepatic function periodically
Advise patient to report any blurred vision or any other eye symptoms
Advise patient to report any new or worsening respiratory symptoms
Advise pt to seek medical advice for severe/persistent GI disturbances
Discontinue / interrupt treatment if ulcerative keratitis develops
Discontinue treatment if interstitial lung disease develops
Consider discontinuing treatment if severe hepatic changes occur
Interrupt treatment if adverse skin reactions occur
Interrupt treatment if poorly tolerated diarrhoea occurs
Suspend treatment if patients experience worsening of respiratory symptoms
Advise patient not to self medicate with antacids or acid suppressants
Advise patient not to take St John's wort concurrently
Female: Ensure adequate contraception during treatment

Patients should be advised to report worsening of respiratory symptoms such as dyspnoea, cough and fever. If these occur, treatment should be interrupted and the patient should be investigated. If interstitial lung disease (ILD) is confirmed, gefitinib should be discontinued and the patient treated appropriately. An increased risk of ILD was observed during the first 4 weeks of treatment, with the relative risk being lower thereafter.

Gastrointestinal perforation has been reported in patients taking gefitinib. In most cases this is associated with other known risk factors including, concomitant steroids or NSAIDs, underlying history of gastrointestinal ulceration, age, smoking or bowel metastases at sites of perforation.

Patients with a CYP2D6 poor metaboliser genotype are predisposed to elevated plasma levels of gefitinib if also treated with a potent CYP3A4 inhibitor. At initiation of treatment with a CYP3A4 inhibitor patients should be closely monitored for adverse reactions.

Pregnancy and Lactation

Pregnancy

Gefitinib is contraindicated during pregnancy.

The manufacturer states that gefitinib should not be used during pregnancy unless clearly necessary. Studies in animals have shown reproductive toxicity. There are no data, at the time of writing, on the use of gefitinib during human pregnancy. It is not known if gefitinib crosses the human placenta. However, its molecular weight and long elimination half-life suggest it is likely to cross the human placenta.

Lactation

Gefitinib is contraindicated during breastfeeding.

The manufacturer states that gefitinib is contraindicated during breastfeeding. Animal data reports gefitinib is expressed in breast milk however it is unknown whether gefitinib is secreted in human milk. Its molecular weight and long elimination half-life suggest it is likely to be excreted into human milk. Briggs suggests the effect of gefitinib on a nursing infant could be serious.

Counselling

If the patient is unable to swallow whole tablets, it may be administered as a dispersion in water. Without crushing it, the tablet should be dropped in half a glass of drinking water and swirled occasionally until the tablet is dispersed (this may take up to 20 minutes). The dispersion should be drunk immediately after dispersion is complete (within 60 minutes) and the glass should be rinsed with half a glass of water, which should also be drunk. The dispersion can also be administered through a naso-gastric or gastrostomy tube.

Patients should be advised to avoid concurrent St John's Wort during treatment with gefitinib.

Patients should be advised to avoid concurrent H2 antagonists and proton pump inhibitors during treatment with gefitinib.

Patients should be advised to avoid taking antacids within 2 hours of each dose of gefitinib.

Patients should be advised to seek medical advice immediately if they experience any eye symptoms.

Patients should be advised to seek medical advice if they experience severe or persistent diarrhoea, nausea, vomiting or anorexia as these may indirectly lead to dehydration.

Patients should be advised to report worsening of respiratory symptoms such as dyspnoea, cough and fever.

Advise women of childbearing potential to use adequate contraception during therapy.

Advise patients that some side effects may affect their ability to drive and operate machinery.

Side Effects

Acne
Allergic reaction
Alopecia
Angioedema
Anorexia
Asthenia
Blepharitis
Blindness
Conjunctivitis
Corneal erosion
Corneal perforation
Cutaneous vasculitis
Cystitis
Dehydration
Diarrhoea
Dry eyes
Dry mouth
Dry skin
Epistaxis
Erythema multiforme
Gastro-intestinal perforation
Haematuria
Haemorrhage
Haemorrhagic cystitis
Hepatitis
Increase in serum ALT/AST
Interstitial lung disease
Keratitis
Misdirected eyelash growth
Nail disorders
Nausea
Pancreatitis
Proteinuria
Pruritus
Pustular rash
Pyrexia
Serum bilirubin increased
Serum creatinine increased
Skin fissures
Skin reactions
Stevens-Johnson syndrome
Stomatitis
Toxic epidermal necrolysis
Ulcerative keratitis
Urticaria
Vomiting

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: April 2021

Reference Sources

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Summary of Product Characteristics: Iressa 250mg film-coated tablets. AstraZeneca UK Ltd. Revised January 2021.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 27 April 2021