Drugs List

Therapeutic Indications

Uses

Locally advanced/metastatic Non-Small Cell Lung Cancer (NSCLC)

Epidermal Growth Factor Receptor (EGFR) TKI-naive patients with locally advanced or metastatic non-small lung cell cancer (NSCLC) with activating EGFR mutations.
Locally advanced or metastatic non-small cell lung cancer (NSCLC) of squamous histology progressing on or after platinum-based chemotherapy.

Contraindications

Children under 18 years
Breastfeeding
Galactosaemia
Pregnancy
Renal impairment - eGFR below 15ml/minute/1.73m sq
Severe hepatic impairment - Child-Pugh score greater than or equal to 10

Precautions and Warnings

Females
Underweight patients
Wearing of contact lenses
Glucose-galactose malabsorption syndrome
History of keratitis
Keratitis
Lactose intolerance
Left ventricular dysfunction
Renal impairment - eGFR below 30ml/minute/1.73m sq
Severe dry eyes

Refer patients with symptoms of keratitis to an ophthalmology specialist
Advise ability to drive/operate machinery may be affected by side effects
Anti-diarrhoeals may be required during treatment
Confirm EGFR mutation status of tumour prior to treatment
Treatment to be initiated and supervised by a specialist
Contains lactose
Advise no food for at least 3 hours pre- and 1 hour post dose
Consult local policy on the safe use of anti-cancer drugs
Staff: Not to be handled by pregnant staff
Evaluate benefit of continued therapy if LVEF has decreased from baseline
Monitor closely patient at risk of cardiovascular disorders
Monitor closely patient with pre-existing hepatic impairment
Monitor closely patient with pre-existing renal impairment
Monitor females & underweight patients as increased risk of adverse effects
Monitor for signs and symptoms of interstitial lung disease
Monitor patients with cardiac disorders
Advise patient to report any symptoms of interstitial lung disease
Consider dose reduction for subsequent doses if severe diarrhoea occurs
Discontinue / interrupt treatment if ulcerative keratitis develops
Discontinue treatment if interstitial lung disease develops
Suspend treatment if grade 3 or worse skin reaction occurs
Advise patient to seek advice at first indications of pregnancy
Discontinue if severe hepatic changes occur
Discontinue if severe skin reaction occurs
Suspend treatment if grade 2 intolerable or 48 hour plus duration diarrhoea
Suspend treatment if grade 2 intolerable or 7 day plus duration rash occurs
Suspend treatment if grade 3 or greater diarrhoea occurs
Advise patient not to take St John's wort concurrently
Female: Contraception required during and for 1 month after treatment
Advise patient on appropriate sun protection methods
Advise patient to avoid exposure to sunlight and UV rays during treatment

Higher exposure to afatinib has been observed in female patients, patients with lower body weight and those with underlying renal impairment. Close monitoring is recommended in patients with these risk factors.

Symptoms such as acute or worsening eye inflammation, lacrimation, light sensitivity, blurred vision, eye pain, and/or red eye should be referred promptly to an ophthalmology specialist.

In patients who develop relevant cardiac signs/symptoms during treatment, cardiac monitoring including LVEF assessment should be considered.

Early intervention (such as emollients, antibiotics) of dermatologic reactions can facilitate continuous afatinib treatment.

Pregnancy and Lactation

Pregnancy

Afatinib is contraindicated during pregnancy.

The manufacturer advises use of afatinib during pregnancy or if the patient becomes pregnant while or after receiving afatinib, she should be informed of the potential hazard to the foetus. At the time of writing there is limited amount of data from the use of this medicinal product in pregnant women. The risk for humans is unknown.

Animal studies did not indicate direct or indirect harmful effects with respect to reproductive toxicity. Studies in animals have shown no signs of teratogenicity up to and including maternally lethal dose levels.

Lactation

Afatinib is contraindicated during breastfeeding.

The manufacturer does not recommend breastfeeding whilst receiving this medicinal product. Available pharmacokinetic data in animals have shown excretion of afatinib in milk. Based on this, it is likely that afatinib is excreted in human milk. A risk to the breastfeeding child cannot be excluded.

Side Effects

Acne-like eruptions
Alanine aminotransferase increased
Allergic alveolitis
Aspartate aminotransferase increased
Bullous reactions
Cheilitis
Conjunctivitis
Cystitis
Decreased appetite
Dehydration
Diarrhoea
Dry eyes
Dry skin
Dysgeusia
Dyspepsia
Epistaxis
Hypokalaemia
Interstitial lung disease
Keratitis
Muscle spasm
Nausea
Palmar-Plantar Erythrodysaesthesia syndrome
Pancreatitis
Paronychia
Pneumonitis
Pruritus
Pulmonary infiltration
Pyrexia
Rash
Renal failure
Renal impairment
Respiratory distress syndrome
Rhinorrhoea
Skin reactions
Stevens-Johnson syndrome
Stomatitis
Toxic epidermal necrolysis
Vomiting
Weight loss

Presentation

Oral formulations of afatinib.

Drugs List

Therapeutic Indications

Uses

Locally advanced/metastatic Non-Small Cell Lung Cancer (NSCLC)

Epidermal Growth Factor Receptor (EGFR) TKI-naive patients with locally advanced or metastatic non-small lung cell cancer (NSCLC) with activating EGFR mutations.
Locally advanced or metastatic non-small cell lung cancer (NSCLC) of squamous histology progressing on or after platinum-based chemotherapy.

Dosage

Adults

Additional Dosage Information

Contraindications

Children under 18 years
Breastfeeding
Galactosaemia
Pregnancy
Renal impairment - eGFR below 15ml/minute/1.73m sq
Severe hepatic impairment - Child-Pugh score greater than or equal to 10

Precautions and Warnings

Females
Underweight patients
Wearing of contact lenses
Glucose-galactose malabsorption syndrome
History of keratitis
Keratitis
Lactose intolerance
Left ventricular dysfunction
Renal impairment - eGFR below 30ml/minute/1.73m sq
Severe dry eyes

Refer patients with symptoms of keratitis to an ophthalmology specialist
Advise ability to drive/operate machinery may be affected by side effects
Anti-diarrhoeals may be required during treatment
Confirm EGFR mutation status of tumour prior to treatment
Treatment to be initiated and supervised by a specialist
Contains lactose
Advise no food for at least 3 hours pre- and 1 hour post dose
Consult local policy on the safe use of anti-cancer drugs
Staff: Not to be handled by pregnant staff
Evaluate benefit of continued therapy if LVEF has decreased from baseline
Monitor closely patient at risk of cardiovascular disorders
Monitor closely patient with pre-existing hepatic impairment
Monitor closely patient with pre-existing renal impairment
Monitor females & underweight patients as increased risk of adverse effects
Monitor for signs and symptoms of interstitial lung disease
Monitor patients with cardiac disorders
Advise patient to report any symptoms of interstitial lung disease
Consider dose reduction for subsequent doses if severe diarrhoea occurs
Discontinue / interrupt treatment if ulcerative keratitis develops
Discontinue treatment if interstitial lung disease develops
Suspend treatment if grade 3 or worse skin reaction occurs
Advise patient to seek advice at first indications of pregnancy
Discontinue if severe hepatic changes occur
Discontinue if severe skin reaction occurs
Suspend treatment if grade 2 intolerable or 48 hour plus duration diarrhoea
Suspend treatment if grade 2 intolerable or 7 day plus duration rash occurs
Suspend treatment if grade 3 or greater diarrhoea occurs
Advise patient not to take St John's wort concurrently
Female: Contraception required during and for 1 month after treatment
Advise patient on appropriate sun protection methods
Advise patient to avoid exposure to sunlight and UV rays during treatment

Higher exposure to afatinib has been observed in female patients, patients with lower body weight and those with underlying renal impairment. Close monitoring is recommended in patients with these risk factors.

Symptoms such as acute or worsening eye inflammation, lacrimation, light sensitivity, blurred vision, eye pain, and/or red eye should be referred promptly to an ophthalmology specialist.

In patients who develop relevant cardiac signs/symptoms during treatment, cardiac monitoring including LVEF assessment should be considered.

Early intervention (such as emollients, antibiotics) of dermatologic reactions can facilitate continuous afatinib treatment.

Pregnancy and Lactation

Pregnancy

Afatinib is contraindicated during pregnancy.

The manufacturer advises use of afatinib during pregnancy or if the patient becomes pregnant while or after receiving afatinib, she should be informed of the potential hazard to the foetus. At the time of writing there is limited amount of data from the use of this medicinal product in pregnant women. The risk for humans is unknown.

Animal studies did not indicate direct or indirect harmful effects with respect to reproductive toxicity. Studies in animals have shown no signs of teratogenicity up to and including maternally lethal dose levels.

Lactation

Afatinib is contraindicated during breastfeeding.

The manufacturer does not recommend breastfeeding whilst receiving this medicinal product. Available pharmacokinetic data in animals have shown excretion of afatinib in milk. Based on this, it is likely that afatinib is excreted in human milk. A risk to the breastfeeding child cannot be excluded.

Side Effects

Acne-like eruptions
Alanine aminotransferase increased
Allergic alveolitis
Aspartate aminotransferase increased
Bullous reactions
Cheilitis
Conjunctivitis
Cystitis
Decreased appetite
Dehydration
Diarrhoea
Dry eyes
Dry skin
Dysgeusia
Dyspepsia
Epistaxis
Hypokalaemia
Interstitial lung disease
Keratitis
Muscle spasm
Nausea
Palmar-Plantar Erythrodysaesthesia syndrome
Pancreatitis
Paronychia
Pneumonitis
Pruritus
Pulmonary infiltration
Pyrexia
Rash
Renal failure
Renal impairment
Respiratory distress syndrome
Rhinorrhoea
Skin reactions
Stevens-Johnson syndrome
Stomatitis
Toxic epidermal necrolysis
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: July 2019

Reference Sources

Summary of Product Characteristics: Giotrif 20mg, 30mg, 40mg, 50mg film-coated tablets. Boehringer Ingelheim Ltd. Revised June 2018.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 22 July 2019