Giotrif Special Precautions

Assessment of EGFR Mutation Status: When assessing the EGFR mutation status of a patient, it is important that a well-validated and robust methodology is chosen to avoid false negative or false positive determinations.
Diarrhoea: Diarrhoea, including severe diarrhoea, has been reported during treatment with GIOTRIF (see Side Effects). Diarrhoea may result in dehydration with or without renal impairment, which in rare cases has resulted in fatal outcomes. Diarrhoea usually occurred within the first 2 weeks of treatment. Grade 3 diarrhoea most frequently occurred within the first 6 weeks of treatment. Proactive management of diarrhoea including adequate hydration combined with anti-diarrhoeal especially within the first 6 weeks of the treatment is important and should start at first signs of diarrhoea. Antidiarrhoeal agents (e.g. loperamide) should be used and if necessary their dose should be escalated to the highest recommended approved dose. Antidiarrhoeal agents should be readily available to the patients so that treatment can be initiated at first signs of diarrhoea and continued until loose bowel movements cease for 12 hours. Patients with severe diarrhoea may require interruption and dose reduction or discontinuation of therapy with GIOTRIF (see Dosage & Administration). Patients who become dehydrated may require administration of intravenous electrolytes and fluids.
Skin Related Adverse Events: Rash/acne has been reported in patients treated with GIOTRIF (see Side Effects). In general, rash manifests as a mild or moderate erythematous and acneiform rash, which may occur or worsen in areas exposed to sun. For patients who are exposed to sun, protective clothing, and/or use of sun screen is advisable. Early intervention (e.g. emollients, antibiotics) of dermatologic reactions can facilitate continuous GIOTRIF treatment. Patients with prolonged or severe skin reactions may also require temporary interruption of therapy, dose reduction (see Dosage & Administration), additional therapeutic intervention, and referral to a specialist with expertise in managing these dermatologic effects. Bullous, blistering and exfoliative skin conditions have been reported including rare cases suggestive of Stevens-Johnson syndrome. GIOTRIF treatment should be interrupted or discontinued if the patient develops severe bullous, blistering or exfoliating conditions.
Female Gender, Lower Body Weight, and Underlying Renal Impairment: Higher exposure to afatinib has been observed in female patients, patients with lower body weight and those with underlying renal impairment (see Pharmacology: Pharmacokinetics under Actions). This could result in a higher risk of developing EGFR mediated adverse events such as diarrhoea, rash/acne and stomatitis. Closer monitoring is recommended in patients with these risk factors.
Interstitial Lung Disease (ILD): There have been reports of ILD or ILD-like events (such as Lung infiltration, Pneumonitis, Acute respiratory distress syndrome, Alveolitis allergic), including fatalities, in patients receiving GIOTRIF for treatment of NSCLC. Drug related ILD-like events were reported in 0.7% of more than 3,800 patients treated. CTCAE Grade ≥3 ILD-like events, regardless of causality, were reported in 1% of patients (see Side Effects). Patients with a history of ILD have not been studied. Careful assessment of all patients with an acute onset and/ or unexplained worsening of pulmonary symptoms (dyspnoea, cough, fever) should be performed to exclude ILD. GIOTRIF should be interrupted pending investigation of these symptoms. If ILD is diagnosed, GIOTRIF should be permanently discontinued and appropriate treatment instituted as necessary (see Dosage & Administration).
Severe Hepatic Impairment: Hepatic failure, including fatalities, has been reported during treatment with GIOTRIF in less than 1% of patients. In these patients, confounding factors have included pre-existing liver disease and/or comorbidities associated with progression of underlying malignancy. Periodic liver function testing is recommended in patients with pre-existing liver disease. GIOTRIF dose interruption may become necessary in patients who experience worsening of liver function (see Dosage & Administration). In patients who develop severe hepatic impairment while taking GIOTRIF, treatment should be discontinued.
Keratitis: 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. If a diagnosis of ulcerative keratitis is confirmed, treatment with GIOTRIF should be interrupted or discontinued. If keratitis is diagnosed, the benefits and risks of continuing treatment should be carefully considered. GIOTRIF should be used with caution in patients with a history of keratitis, ulcerative keratitis or severe dry eye. Contact lens use is also a risk factor for keratitis and ulceration (see Side Effects).
Left Ventricular Function: Left ventricular dysfunction has been associated with HER2 inhibition. Based on the available clinical trial data, there is no suggestion that GIOTRIF causes an adverse effect on cardiac contractility. However, GIOTRIF has not been studied in patients with abnormal left ventricular ejection fraction (LVEF) or those with significant cardiac history. In patients with cardiac risk factors and those with conditions that can affect LVEF, cardiac monitoring, including an assessment of LVEF at baseline and during GIOTRIF treatment, should be considered. In patients that develop relevant cardiac signs/symptoms during treatment, cardiac monitoring including LVEF assessment should be considered.
In patients with an ejection fraction below the institution's lower limit of normal, cardiac consultation as well as GIOTRIF treatment interruption or discontinuation should be considered.
P-glycoprotein (P-gp) Interactions: Strong inhibitors of P-gp if administered prior to GIOTRIF may lead to increased exposure to afatinib and therefore should be used with caution. If P-gp inhibitors need to be taken, they should be administered simultaneously with or after GIOTRIF. Concomitant treatment with strong inducers of P-gp may decrease exposure to afatinib (see Pharmacology: Pharmacokinetics under Actions, Dosage & Administration, and Interactions).
Lactose: GIOTRIF contains lactose. Patients with rare hereditary conditions of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Effects on Ability to Drive and Use Machines: No studies on the effects on the ability to drive or operate machinery have been performed.
Impairment of Fertility: Fertility studies in humans have not been performed with GIOTRIF. Available nonclinical toxicology data have shown effects on reproductive organs at higher doses (see Pharmacology: Toxicology under Actions). Therefore, an adverse effect of GIOTRIF therapy on human fertility cannot be excluded.