Drugs List

Therapeutic Indications

Uses

Advanced/metastatic non-small cell lung cancer with EGFR-TK mutations
Metastatic pancreatic cancer in combination with gemcitabine

Locally advanced or metastatic non-small cell lung cancer with EGFR activating mutations:
- First line Treatment
- Treatment after failure of at least one other chemotherapy regimen
- Maintenance treatment as a monotherapy with stable disease after 4 cycles of standard platinum-based first-line chemotherapy

Treatment of metastatic pancreatic cancer in combination with gemcitabine.

Administration

Tablets should be taken at least one hour before or two hours after food.

Contraindications

Children under 18 years
Elevated serum transaminases - greater than 5 times upper limit of normal
Breastfeeding
Galactosaemia
Pregnancy
Severe renal impairment

Precautions and Warnings

Tobacco smoking
Wearing of contact lenses
Diverticulitis
Glucose-galactose malabsorption syndrome
Hepatic impairment
History of keratitis
History of peptic ulcer
Lactose intolerance
Renal impairment
Severe dry eyes

Refer patients with symptoms of keratitis to an ophthalmology specialist
Confirm EGFR mutation status of tumour prior to treatment
Treatment to be prescribed under the supervision of 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 in patients with hepatic impairment
Monitor pulmonary function regularly
Monitor renal function in patients with dehydration or severe diarrhoea
Monitor serum electrolytes in patients with dehydration or severe diarrhoea
Patients with new pulmonary symptoms should be investigated
Persistent diarrhoea - monitor patient; reduce dose or discontinue therapy
Advise patient to report any blurred vision or any other eye symptoms
Discontinue / interrupt treatment if ulcerative keratitis develops
Discontinue treatment if interstitial lung disease develops
Discontinue if severe skin reaction occurs
Discontinue if significant/persistent hepatic function abnormalities occur
Discontinue or interrupt treatment with acute/worsening ocular disorders
Discontinue treatment if gastrointestinal perforation occurs
If dehydration occurs, discontinue treatment until patient has recovered
Dose adjustment required if patient starts/stops smoking during therapy
Advise patient not to self medicate with antacids or acid suppressants
Advise patient not to take St John's wort concurrently
Advise patients to avoid aspirin and NSAID use
Avoid antacids 4 hours before or 2 hours after dose
Female: Contraception required during and for 2 weeks after treatment
Breastfeeding: Do not breastfeed during & for 2 weeks after treatment
Advise patient on appropriate sun protection methods
Advise patient on giving up smoking

Cigarette smoking has been shown to reduce erlotinib exposure by 50-60%. The 300mg dose did not show improved efficacy in patients who smoke cigarettes when compared to the 150mg dose. Efficacy and long term safety of a dose higher than the recommended starting doses have not been established in patients who continue to smoke cigarettes. Therefore, current smokers should be advised to stop smoking, as plasma concentrations of erlotinib in smokers as compared to non-smokers are reduced.

Rare cases of hepatic failure have been reported during erlotinib treatment. Hepatic function testing should be considered in patients with pre-existing hepatic disease or concomitant hepatotoxic medications.

In cases of moderate or severe diarrhoea, patients should be treated with loperamide or other antidiarrhoeal agents. In some cases, dose reduction may be necessary. In the event of severe or persistent diarrhoea, nausea, anorexia, or vomiting associated with dehydration, erlotinib should be interrupted and appropriate measures should be taken to treat the dehydration.

There have been reports of hypokalaemia and renal failure secondary to severe dehydration mainly in patients receiving concomitant chemotherapy. In patients with aggravating risk factors (concomitant medications, symptoms or diseases or other predisposing factors such as advanced age) therapy should be interrupted and steps taken to intensively rehydrate patients intravenously. Renal function and serum electrolytes including potassium should be monitored in patients at risk of dehydration.

Pregnancy and Lactation

Pregnancy

Erlotinib is contraindicated during pregnancy.

The manufacturer does not recommend using erlotinib during pregnancy.

There are no studies in pregnant women using erlotinib and the potential risk for humans is unknown, but animal studies in rabbits and rats have shown some reproductive toxicity.

Lactation

Erlotinib is contraindicated during breastfeeding.

The manufacturer does not recommend breastfeeding whilst taking erlotinib and for at least two weeks after treatment.

There is limited information on the use of erlotinib during breastfeeding. It is not known whether the drug passes into breast milk but the long elimination half life and the molecular weight suggest this is likely. The effects on the nursing infant are unknown, but because of the potential for serious adverse reactions, breastfeeding should be stopped if treatment with erlotinib is necessary.

Side Effects

Abdominal pain
Acne-like rash
Alopecia
Anorexia
Blindness
Blistering
Brittle nails
Bullous reactions
Cellulitis
Conjunctivitis
Corneal perforation
Corneal ulcer
Cough
Dehydration
Depression
Diarrhoea
Dry skin
Dyspepsia
Dyspnoea
Epistaxis
Exfoliative dermatitis
Exfoliative rash
Eyelash/eyebrow changes
Fatigue
Flatulence
Folliculitis
Gastro-intestinal perforation
Gastrointestinal bleeding
Headache
Hepatic failure
Hirsutism
Hyperpigmentation of skin
Hypokalaemia
Increase in serum ALT/AST
Infections
Interstitial lung disease
Keratitis
Keratoconjunctivitis
Mucositis
Nausea
Nephritis
Neuropathy
Neutropenia
Palmar-Plantar Erythrodysaesthesia syndrome
Paronychia
Pneumonia
Proteinuria
Pruritus
Pyrexia
Rash
Renal failure
Rigors
Sepsis
Serum bilirubin increased
Skin fissures
Stevens-Johnson syndrome
Stomatitis
Toxic epidermal necrolysis
Ulcerative keratitis
Uveitis
Vomiting
Weight loss

Presentation

Oral formulations of erlotinib.

Drugs List

Therapeutic Indications

Uses

Advanced/metastatic non-small cell lung cancer with EGFR-TK mutations
Metastatic pancreatic cancer in combination with gemcitabine

Locally advanced or metastatic non-small cell lung cancer with EGFR activating mutations:
- First line Treatment
- Treatment after failure of at least one other chemotherapy regimen
- Maintenance treatment as a monotherapy with stable disease after 4 cycles of standard platinum-based first-line chemotherapy

Treatment of metastatic pancreatic cancer in combination with gemcitabine.

Dosage

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

Adults

Administration

Tablets should be taken at least one hour before or two hours after food.

Contraindications

Children under 18 years
Elevated serum transaminases - greater than 5 times upper limit of normal
Breastfeeding
Galactosaemia
Pregnancy
Severe renal impairment

Precautions and Warnings

Tobacco smoking
Wearing of contact lenses
Diverticulitis
Glucose-galactose malabsorption syndrome
Hepatic impairment
History of keratitis
History of peptic ulcer
Lactose intolerance
Renal impairment
Severe dry eyes

Refer patients with symptoms of keratitis to an ophthalmology specialist
Confirm EGFR mutation status of tumour prior to treatment
Treatment to be prescribed under the supervision of 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 in patients with hepatic impairment
Monitor pulmonary function regularly
Monitor renal function in patients with dehydration or severe diarrhoea
Monitor serum electrolytes in patients with dehydration or severe diarrhoea
Patients with new pulmonary symptoms should be investigated
Persistent diarrhoea - monitor patient; reduce dose or discontinue therapy
Advise patient to report any blurred vision or any other eye symptoms
Discontinue / interrupt treatment if ulcerative keratitis develops
Discontinue treatment if interstitial lung disease develops
Discontinue if severe skin reaction occurs
Discontinue if significant/persistent hepatic function abnormalities occur
Discontinue or interrupt treatment with acute/worsening ocular disorders
Discontinue treatment if gastrointestinal perforation occurs
If dehydration occurs, discontinue treatment until patient has recovered
Dose adjustment required if patient starts/stops smoking during therapy
Advise patient not to self medicate with antacids or acid suppressants
Advise patient not to take St John's wort concurrently
Advise patients to avoid aspirin and NSAID use
Avoid antacids 4 hours before or 2 hours after dose
Female: Contraception required during and for 2 weeks after treatment
Breastfeeding: Do not breastfeed during & for 2 weeks after treatment
Advise patient on appropriate sun protection methods
Advise patient on giving up smoking

Cigarette smoking has been shown to reduce erlotinib exposure by 50-60%. The 300mg dose did not show improved efficacy in patients who smoke cigarettes when compared to the 150mg dose. Efficacy and long term safety of a dose higher than the recommended starting doses have not been established in patients who continue to smoke cigarettes. Therefore, current smokers should be advised to stop smoking, as plasma concentrations of erlotinib in smokers as compared to non-smokers are reduced.

Rare cases of hepatic failure have been reported during erlotinib treatment. Hepatic function testing should be considered in patients with pre-existing hepatic disease or concomitant hepatotoxic medications.

In cases of moderate or severe diarrhoea, patients should be treated with loperamide or other antidiarrhoeal agents. In some cases, dose reduction may be necessary. In the event of severe or persistent diarrhoea, nausea, anorexia, or vomiting associated with dehydration, erlotinib should be interrupted and appropriate measures should be taken to treat the dehydration.

There have been reports of hypokalaemia and renal failure secondary to severe dehydration mainly in patients receiving concomitant chemotherapy. In patients with aggravating risk factors (concomitant medications, symptoms or diseases or other predisposing factors such as advanced age) therapy should be interrupted and steps taken to intensively rehydrate patients intravenously. Renal function and serum electrolytes including potassium should be monitored in patients at risk of dehydration.

Pregnancy and Lactation

Pregnancy

Erlotinib is contraindicated during pregnancy.

The manufacturer does not recommend using erlotinib during pregnancy.

There are no studies in pregnant women using erlotinib and the potential risk for humans is unknown, but animal studies in rabbits and rats have shown some reproductive toxicity.

Lactation

Erlotinib is contraindicated during breastfeeding.

The manufacturer does not recommend breastfeeding whilst taking erlotinib and for at least two weeks after treatment.

There is limited information on the use of erlotinib during breastfeeding. It is not known whether the drug passes into breast milk but the long elimination half life and the molecular weight suggest this is likely. The effects on the nursing infant are unknown, but because of the potential for serious adverse reactions, breastfeeding should be stopped if treatment with erlotinib is necessary.

Side Effects

Abdominal pain
Acne-like rash
Alopecia
Anorexia
Blindness
Blistering
Brittle nails
Bullous reactions
Cellulitis
Conjunctivitis
Corneal perforation
Corneal ulcer
Cough
Dehydration
Depression
Diarrhoea
Dry skin
Dyspepsia
Dyspnoea
Epistaxis
Exfoliative dermatitis
Exfoliative rash
Eyelash/eyebrow changes
Fatigue
Flatulence
Folliculitis
Gastro-intestinal perforation
Gastrointestinal bleeding
Headache
Hepatic failure
Hirsutism
Hyperpigmentation of skin
Hypokalaemia
Increase in serum ALT/AST
Infections
Interstitial lung disease
Keratitis
Keratoconjunctivitis
Mucositis
Nausea
Nephritis
Neuropathy
Neutropenia
Palmar-Plantar Erythrodysaesthesia syndrome
Paronychia
Pneumonia
Proteinuria
Pruritus
Pyrexia
Rash
Renal failure
Rigors
Sepsis
Serum bilirubin increased
Skin fissures
Stevens-Johnson syndrome
Stomatitis
Toxic epidermal necrolysis
Ulcerative keratitis
Uveitis
Vomiting
Weight loss

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: October 2019

Reference Sources

British National Formulary, 63rd Edition (2012) Pharmaceutical Press, London.

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.

Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.

Summary of Product Characteristics: Tarceva 25mg, 100mg and 150mg Film-Coated Tablets. Roche Products Ltd. Revised December 2018.

The Renal Drug Handbook. 3rd edition. (2009) ed. Ashley, C and Currie, Radcliffe Publishing Ltd, Abingdon.