What It Is and What It Treats
Hernix contains neratinib, an irreversible pan-HER
(HER1/HER2/HER4) tyrosine kinase inhibitor. Unlike reversible HER2 inhibitors
(e.g. lapatinib), neratinib forms a covalent bond with the kinase domain,
resulting in sustained HER signalling blockade. This helps prevent residual
microscopic cancer from recurring and evolving resistance.
Indications:
• Extended adjuvant treatment:
early-stage HER2-positive breast cancer in adults who have completed adjuvant
trastuzumab-based therapy — 1 year of neratinib reduces the risk of distant
relapse.
• Metastatic disease: in combination
with capecitabine for HER2-positive metastatic or locally advanced breast
cancer after two or more prior anti-HER2-based regimens.
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HER2 TESTING REQUIRED - HER2 overexpression
or amplification must be confirmed by validated testing (IHC 3+ or ISH
amplified) before initiating neratinib. |
Dosing and Administration
Standard dose: 240mg (six 40mg tablets) once daily WITH
food — never on an empty stomach. For the extended adjuvant indication,
treatment duration is 1 year.
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CAUTION:
MANDATORY
LOPERAMIDE PROPHYLAXIS: Diarrhoea affects up to 95% of patients on neratinib
and can be severe. Loperamide must be co-prescribed from day one. Weeks 1–2:
4mg three times daily. Weeks 3–8: 4mg twice daily. Week 9 onwards: 4mg once
daily or as needed. Inadequate prophylaxis significantly increases
hospitalisation risk. |
Dose Modifications
• Grade 1–2 diarrhoea (uncontrolled
despite loperamide): interrupt until resolved, restart at the same dose with
optimised anti-diarrhoeal support
• Grade 3 diarrhoea or Grade 3+
non-haematological toxicity: interrupt; on recovery to ≤Grade 1, restart at
200mg/day
• Grade 4 or intolerable toxicity:
permanently discontinue
• Hepatic impairment (Child-Pugh C /
severe): not recommended
Side Effects
|
Frequency |
Side Effects |
|
Very Common (>1 in 4) |
Diarrhoea (95%), nausea (43%), abdominal pain
(36%), fatigue, vomiting — diarrhoea is the dominant toxicity |
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Common |
Acneiform rash, dry skin, paronychia (nail
fold infections), reduced appetite, muscle cramps, elevated liver enzymes
(ALT/AST) |
|
Serious — Seek Urgent Help |
Severe diarrhoea leading to dehydration
(dizziness, reduced urination, dry mouth) — seek urgent medical review.
Hepatotoxicity: jaundice, dark urine, upper right abdominal pain. Severe skin
reactions (rare). |
Contraindications and Cautions
• Known hypersensitivity to neratinib
• Severe hepatic impairment (Child-Pugh
C)
• Prior history of inflammatory bowel
disease — increased diarrhoea risk; use with heightened monitoring
• Pregnancy: neratinib causes
embryo-fetal harm. Effective contraception is required during treatment and for at
least 1 month after the last dose.
Key Drug Interactions
• Strong CYP3A4 inhibitors
(ketoconazole, clarithromycin, itraconazole): significantly increase neratinib
plasma levels — avoid combination; if unavoidable, reduce neratinib dose
• Strong CYP3A4 inducers (rifampicin,
carbamazepine, phenytoin): markedly reduce neratinib efficacy — avoid
• PPIs (omeprazole, pantoprazole) and
H2 receptor antagonists: reduce neratinib absorption — avoid concurrent use. If an antacid is needed, separate by at least 3 hours from neratinib.
• Capecitabine (when used in
combination): standard interaction monitoring applies; no pharmacokinetic
interaction, but combined GI toxicity may be additive
Clinical Monitoring Schedule
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PRESCRIBER NOTE: LFTs: monthly for
first 3 months, then every 3 months. Document diarrhoea grade at each visit.
Confirm HER2-positive status before dispensing. Ensure loperamide
prescription is co-issued — this is mandatory, not optional. Counsel on
dehydration warning signs and when to seek urgent review. |
Frequently Asked Questions
Q: Why do I take six tablets at once?
Each tablet is 40mg.
The total daily dose is 240mg, which requires six tablets taken together once a
day with food. Taking them with a meal improves absorption and reduces stomach
upset.
Q: Why is anti-diarrhoea medicine prescribed from day one?
Diarrhoea is the most
common and most serious side effect of neratinib, affecting up to 95% of
patients. Taking loperamide (Imodium) on a fixed schedule from the very first
dose — not waiting until diarrhoea starts — dramatically reduces the severity
and the risk of hospitalisation.
Q: Can I take my stomach acid medicine?
No — proton pump
inhibitors (omeprazole, lansoprazole) and H2 blockers significantly reduce
neratinib absorption. Discuss alternatives with your oncologist. If an antacid
is essential, separate its use from neratinib by at least 3 hours.