Neratinib tablets
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of neratinib.
Drugs List
Therapeutic Indications
Uses
HER2 +ve early breast cancer
Indicated for the extended adjuvant treatment of adult patients with early stage hormone receptor positive HER2 overexpressed or amplified breast cancer and who completed adjuvant trastuzumab-based therapy less than a year ago.
Dosage
Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.
Adults
Initial dose: 240mg daily, continuously for one year
First dose reduction: 200mg daily
Second dose reduction: 160mg daily
Third dose reduction: 120mg daily
Discontinue neratinib for patients who:
Fail to recover to grade 1 or less from treatment-related toxicity,
Toxicities that result in a treatment delay of more than 3 weeks,
Unable to tolerate a dose of 120mg daily.
Additional Dosage Information
If concurrent use of a moderate CYP3A4/P-pg inhibitor is necessary, reduce dose to 40mg once daily. If tolerated, increase dose by 40mg at least every 7 days. Maximum dose 160mg daily. If concurrent use of a potent CYP3A4/P-gp inhibitor is necessary, reduce dose to 40mg daily.
Missed dose
Missed doses should not be replaced and treatment should resume with the next scheduled daily dose.
Severity of toxicity
Grade 3: Stop neratinib treatment until recovery to less than or equal to grade 1 or baseline toxicity within 3 weeks of stopping treatment. Resume neratinib at the next lowest dose.
Severity of diarrhoea
Grade 1 (increase of more than 4 stools per day over baseline), Grade 2 (increase of 4-6 stools per day over baseline) lasting more than 5 days or Grade 3 (increase of 7 or more stools per day over baseline) lasting 2 or more days:
Adjust anti-diarrhoeal treatment
Modify diet
Intake of 2 litres of fluid to avoid dehydration
Once event resolves to Grade 1 or baseline, consider restarting anti-diarrhoea prophylaxis if appropriate with each neratinib administration.
Any grade with complicated features, Grade 2 lasting 5 days or longer or Grade 3 lasting between 2 days and 3 weeks:
Interrupt treatment
Modify diet
Intake of 2 litres of fluid to avoid dehydration
If resolved to Grade 1 or less in one week, then resume treatment at the same dose
If resolved to Grade 1 or less in longer than one week, then resume treatment at reduced dose
Once event resolves to Grade 1 or baseline, consider restarting anti-diarrhoea prophylaxis if appropriate with each neratinib administration.
If Grade 3 diarrhoea persists longer than 3 weeks, discontinue neratinib permanently.
Diarrhoea recurs to Grade 2 or higher at 120mg per day: Discontinue neratinib.
Hepatotoxicity
Grade 3 ALT (greater than 5 times the normal upper limit) or Grade 3 bilirubin (greater than 3 times the normal upper limit):
Stop neratinib until recovery to less than or equal to Grade 1
Evaluate alternative causes
Resume neratinib at next lowest dose if recovery to Grade 1 or less within 3 weeks. Discontinue if Grade 3 reoccurs despite dose reduction.
Contraindications
Children under 18 years
Breastfeeding
Pregnancy
Severe hepatic impairment
Severe renal impairment
Precautions and Warnings
Elderly
History of cardiac disorder
Reduced left ventricular function
Renal impairment
Advise ability to drive/operate machinery may be affected by side effects
Anti-diarrhoeals may be required during treatment
Avoid H2 antagonists 10 hours before or 2 hours after dose
Treatment to be initiated and supervised by a specialist
Consult local policy on the safe use of oral anti-cancer drugs
Staff: Not to be handled by pregnant staff
Perform liver tests at 1 week, monthly for 3 months, then every 6 weeks
Consider monitoring LVEF in patients who develop cardiac signs/symptoms
Monitor patients with renal impairment
Monitor renal function in elderly patients
Advise patient to monitor for and report any skin changes
Discontinue if grade 4 toxicity occurs
Discontinue permanently if AST or ALT level exceeds 20 x ULN
Discontinue permanently if grade 4 diarrhoea occurs
Discontinue treatment if total bilirubin > 10 x ULN
Interrupt therapy if elevations in bilirubin of > 3 x ULN occur
Interrupt treatment for any grade 3 toxicity
Interrupt treatment if ALT or AST > 5 x ULN
Recurrent grade 2 diarrhoea or higher at 120mg/day: Discontinue permanently
Advise patient not to take St John's wort concurrently
Avoid antacids within 3 hours of dose
Advise patient to avoid grapefruit products
Advise patient to avoid pomegranate products
Female: Barrier or non-hormonal contraception required during treatment
Female: Contraception required during and for 1 month after treatment
Male: Use barrier contraception during and for 3 months after treatment
Avoid concurrent use of proton pump inhibitors
Instruct patient to initiate prophylactic treatment with anti-diarrhoeal product with first dose of neratinib, and maintain regular dosing of anti-diarrhoeal for first 1 to 2 months of neratinib.
Monitor patients with chronic gastrointestinal disorder with diarrhoea as a major symptom.
Perform cardiac monitoring, including assessment of left ventricular ejection fraction in patients with known cardiac risk factors.
Pregnancy and Lactation
Pregnancy
Neratinib is contraindicated during pregnancy.
The manufacturer does not recommend using neratinib during pregnancy. Animal studies have shown teratogenic effects. Human data is limited and as such a potential risk cannot be ruled out.
Lactation
Neratinib is contraindicated during breastfeeding.
The manufacturer advises that the patient either discontinues neratinib or discontinues breastfeeding. The presence of neratinib in human breast milk and the effect on exposed infants are unknown.
Counselling
Take with or just after food, or a meal, preferably in the morning.
Swallow this medicine whole, do not chew or crush.
Do not take proton pump inhibitors while taking this drug.
Do not take H2 antagonists 10 hours before or 2 hours after dose.
Advise patient to avoid grapefruit products.
Advise patient to avoid pomegranate products.
Advise patient to report any skin changes.
Female patients should be advised that contraception is required during and for one month after treatment. Barrier or non hormonal contraception is required.
Male patients should be advised to use barrier contraception during and for three months after treatment.
May affect ability to drive or operate machinery.
Side Effects
Abdominal distension
Abdominal pain
Alanine aminotransferase increased
Aspartate aminotransferase increased
Decreased appetite
Dehydration
Diarrhoea
Dry mouth
Dry skin
Dyspepsia
Epistaxis
Fatigue
Mouth ulcers
Mucosal inflammation
Muscle spasm
Nail disorders
Nausea
Oral mucosal blistering
Rash
Renal failure
Serum bilirubin increased
Serum creatinine increased
Skin fissures
Stomatitis
Syncope
Upper abdominal pain
Urinary tract infections
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: November 2019
Reference Sources
Summary of Product Characteristics: Nerlynx 40mg Film-coated Tablets. Pierre Fabre Limited. Revised April 2022.
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.