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Irreversible ErbB family TKI Pregnancy: UK SPC §4.6: as a precautionary measure, women of childbearing potential should be advised to avoid becoming pregnant while receiving GIOTRIF, and adequate contraceptive methods should be used during therapy and for at least 1 month after the last dose. PREGNANCY: mechanistically, all EGFR targeting medicinal products have the potential to cause foetal harm. Animal studies with afatinib did not indicate direct or indirect harmful effects with respect to reproductive toxicity and showed no signs of teratogenicity up to and including maternally lethal dose levels, with adverse changes restricted to toxic dose levels; however, systemic exposures achieved in animals were either in a similar range or below the levels observed in patients. There are no or limited data from use in pregnant women and the risk for humans is unknown — if used during pregnancy, or if the patient becomes pregnant while or after receiving GIOTRIF, she should be informed of the potential hazard to the foetus. BREAST-FEEDING: pharmacokinetic data in animals have shown excretion of afatinib in milk, so it is likely to be excreted in human milk and a risk to the breast-feeding child cannot be excluded — mothers should be advised against breast-feeding while receiving this medicine. FERTILITY: no human fertility studies have been performed; non-clinical toxicology data have shown effects on reproductive organs at higher doses, so an adverse effect on human fertility cannot be excluded.

Afatinib [Specialist drug]

Brand names: Giotrif

Afatinib is an oral tyrosine kinase inhibitor used as a specialist anticancer treatment for non-small-cell lung cancer with activating epidermal growth factor receptor (EGFR) mutations.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: Non-small cell lung cancer (NSCLC — the indication named throughout the fetched §4.2/§4.8, covering EGFR mutation positive NSCLC and squamous NSCLC) — 40 mg once daily, taken without food. EGFR mutation status should be established prior to initiation of therapy.
Route: Oral. Tablets should be swallowed whole with water. If swallowing whole tablets is not possible they can be dispersed in approximately 100 mL of non-carbonated drinking water (no other liquids should be used): drop the tablet into the water without crushing it, stir occasionally for up to 15 min until it is broken up into very small particles, consume the dispersion immediately, then rinse the glass with approximately 100 mL of water which should also be consumed. The dispersion can also be administered through a gastric tube. FOOD: no food for at least 3 hours before and at least 1 hour after taking the dose.
Frequency: Once daily, continued until disease progression or until no longer tolerated by the patient
Max: 50 mg daily — VERBATIM §4.2: 'The maximum daily dose is 50 mg.' A dose escalation to a maximum of 50 mg/day may be considered in patients who tolerate a 40 mg/day starting dose (i.e. absence of diarrhoea, skin rash, stomatitis, and other adverse reactions with CTCAE Grade > 1) in the first cycle of treatment — 21 days for EGFR mutation positive NSCLC and 28 days for squamous NSCLC. The dose should NOT be escalated in any patient with a prior dose reduction.
Source: UK SPC (eMC) for Giotrif 20 mg film-coated tablets, §4.2 (https://www.medicines.org.uk/emc/product/5147/smpc). Giotrif is this page's own named brand and the UK product for afatinib; the SPC is an oral irreversible ErbB-family/EGFR tyrosine kinase inhibitor, matching the page's category and route exactly, and §4.2 and §4.8 both name NSCLC as the indication ('no relevant use of GIOTRIF in the paediatric population in the indication of NSCLC'; 'ADRs from all NSCLC trials'). ⚠ STRENGTH NOTE: the SPC fetched is the 20 mg strength, but its §4.2 states the recommended dose as 40 mg once daily and the maximum as 50 mg/day — Giotrif's §4.2 is written for the range of strengths. Confirm locally which tablet strengths are stocked before dispensing; this bundle records only the 20 mg presentation. ⚠ PAGE FILING ANOMALY: page identity records this page in rheumatology.json, but neither afatinib nor the Giotrif SPC has any rheumatological indication — this looks like a specialty-file mis-filing of a bulk-imported 'specialist drug' stub, worth correcting separately. It does not affect the dose above, which is molecule-specific. SUPERVISION: treatment should be initiated and supervised by a physician experienced in the use of anticancer therapies. 🔴 DOSE ADJUSTMENT FOR ADVERSE REACTIONS (Table 1): CTCAE Grade 1 or Grade 2 — no interruption, no dose adjustment. Grade 2 that is prolonged (> 48 hours of diarrhoea and/or > 7 days of rash) or intolerable, or Grade ≥ 3 — interrupt until Grade 0/1, then resume with dose reduction by 10 mg decrements. If a patient cannot tolerate 20 mg/day, permanent discontinuation should be considered. For diarrhoea, anti-diarrhoeal medicinal products (e.g. loperamide) should be taken immediately and continued for persistent diarrhoea until loose bowel movements cease. INTERSTITIAL LUNG DISEASE: consider ILD if a patient develops acute or worsening respiratory symptoms, in which case treatment should be interrupted pending evaluation; if ILD is diagnosed, discontinue GIOTRIF and initiate appropriate treatment. MISSED DOSE: take within the same day as soon as the patient remembers; however, if the next scheduled dose is due within 8 hours, the missed dose must be skipped. P-GLYCOPROTEIN INHIBITORS: if P-gp inhibitors need to be taken, use staggered dosing — the P-gp inhibitor dose taken as far apart in time as possible from the GIOTRIF dose, preferably 6 hours apart for P-gp inhibitors dosed twice daily or 12 hours apart for those dosed once daily. RENAL IMPAIRMENT: no starting-dose adjustment is necessary in mild (eGFR 60-89 mL/min/1.73 m²), moderate (eGFR 30-59) or severe (eGFR 15-29) renal impairment; monitor patients with severe renal impairment and adjust the dose if not tolerated; treatment in patients with eGFR < 15 mL/min/1.73 m² or on dialysis is not recommended. Higher exposure to afatinib has been observed in female patients, patients with lower body weight and those with underlying renal impairment, which could mean a higher risk of diarrhoea, rash/acne and stomatitis — closer monitoring is recommended in patients with these risk factors. HEPATIC IMPAIRMENT: no starting-dose adjustment is necessary in mild (Child Pugh A) or moderate (Child Pugh B) impairment; the medicine has not been studied in severe (Child Pugh C) impairment and treatment in this population is not recommended. PAEDIATRIC: paedDose is null — VERBATIM §4.2: 'There is no relevant use of GIOTRIF in the paediatric population in the indication of NSCLC. Treatment of children or adolescents with GIOTRIF was not supported by a clinical trial conducted in paediatric patients with other conditions. Safety and efficacy have not been established. Therefore, treatment of children or adolescents with this medicinal product is not recommended.' Do not scale the adult dose. SOURCE NOTE: §4.4 and §4.8 in this bundle are truncated at the source-fetch limit and §4.5 was not retrieved — the P-gp staggering rule above comes from §4.2 itself, but verify the full interaction, warning and adverse-reaction sections before use. §4.2 was retrieved complete and is the basis of every figure above.

Dose auto-extracted from UK Summary of Product Characteristics (SPC) via the eMC — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

  • Hypersensitivity to afatinib or to any of the excipients listed in section 6.1 — the only contraindication in the fetched §4.3

Side effects

  • Very common — gastrointestinal: diarrhoea (including severe diarrhoea), stomatitis, nausea, vomiting. Diarrhoea may result in dehydration with or without renal impairment, which in rare cases has resulted in fatal outcomes; it usually occurred within the first 2 weeks of treatment and Grade 3 diarrhoea most frequently within the first 6 weeks
  • Very common — skin: rash, dermatitis acneiform, pruritus, dry skin. Rash/acne generally manifests as a mild or moderate erythematous and acneiform rash which may occur or worsen in areas exposed to sun
  • Very common — infections: paronychia (including nail infection and nail bed infection); metabolism: decreased appetite; respiratory: epistaxis
  • Common: cystitis, dehydration, hypokalaemia, dysgeusia, conjunctivitis, dry eye, rhinorrhoea, dyspepsia, cheilitis, alanine aminotransferase increased, aspartate aminotransferase increased, palmar-plantar erythrodysaesthesia syndrome, nail disorders, muscle spasms, renal impairment/renal failure, pyrexia, weight decreased
  • Uncommon: keratitis, interstitial lung disease — ILD-like adverse reactions were reported in 0.7% of afatinib-treated patients
  • Rare: aberrant eyelash growth, pancreatitis, gastrointestinal perforation, Stevens-Johnson syndrome and toxic epidermal necrolysis. Bullous, blistering and exfoliative skin conditions have been reported, including rare cases suggestive of Stevens-Johnson syndrome and toxic epidermal necrolysis, although in these cases there were potential alternative aetiologies
  • Dose reduction led to a lower frequency of common adverse reactions: in patients treated with 40 mg once daily, dose reductions due to adverse reactions occurred in 57% of patients in the LUX-Lung 3 trial and 25% in the LUX-Lung 8 trial

Monitoring

  • EGFR mutation status must be established prior to initiation of therapy, using a well-validated and robust methodology to avoid false negative or false positive determinations (§4.4)
  • Diarrhoea — proactive management including adequate hydration combined with anti-diarrhoeal medicines is important especially within the first 6 weeks, and should start at the first signs. Anti-diarrhoeal medicines (e.g. loperamide) should be readily available to the patient, escalated if necessary to the highest recommended approved dose, and continued until loose bowel movements cease for 12 hours. Severe diarrhoea may require interruption and dose reduction or discontinuation; patients who become dehydrated may require intravenous electrolytes and fluids
  • Skin reactions — advise protective clothing and sun screen for patients exposed to sun; early intervention (such as emollients, antibiotics) can facilitate continuous treatment. Severe skin reactions may require temporary interruption, dose reduction, additional therapeutic intervention and referral to a specialist. Interrupt or discontinue if severe bullous, blistering or exfoliating conditions develop
  • Respiratory symptoms — consider interstitial lung disease if acute or worsening respiratory symptoms develop; interrupt treatment pending evaluation and discontinue if ILD is diagnosed
  • Closer monitoring is recommended in female patients, patients with lower body weight and patients with underlying renal impairment, who have higher afatinib exposure and therefore a higher risk of diarrhoea, rash/acne and stomatitis
  • Patients with severe renal impairment (eGFR 15-29 mL/min/1.73 m²) should be monitored and the dose adjusted if not tolerated

Clinical monograph

How it works

It irreversibly inhibits the ErbB family of receptor tyrosine kinases, including EGFR, blocking downstream signalling that drives tumour growth.

Prescribing in practice

  • Diarrhoea is very common and can be severe; manage early with antidiarrhoeals and fluids and modify the dose to prevent dehydration and renal impairment.
  • Severe skin reactions, including rash and stomatitis, and rarely interstitial lung disease can occur and may require treatment interruption.
  • It is affected by P-glycoprotein interactions, so review concomitant inhibitors and inducers as described in the SPC.

Monitoring

Monitor for diarrhoea, skin and mucosal toxicity, hydration and renal function, and for respiratory symptoms suggestive of interstitial lung disease.

Counselling the patient

  • Begin antidiarrhoeal treatment promptly at the first loose stool and keep well hydrated.
  • Report severe rash, mouth ulcers, or new breathlessness.
  • Take the tablets on an empty stomach and avoid food close to the dose as advised.

Evidence & guidelines

NICE technology appraisals support afatinib for EGFR mutation-positive non-small-cell lung cancer.

Reference: NICE TA310/TA422; ESMO; SmPC Giotrif; Confirm identity and dosing against the manufacturer SPC (eMC) and NICE. Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Related

Curated clinical cross-links plus same-class fallbacks.

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