Giotrif

Treatment with GIOTRIF should be initiated and supervised by a physician experienced in the use of anticancer therapies. 4). Posology The recommended dose is 40 mg once daily. This medicinal product should be taken without food. 2). GIOTRIF treatment should be continued until disease progression or until no longer tolerated by the patient (see Table 1 below).

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 patients with a prior dose reduction.

The maximum daily dose is 50 mg. g. 8). g. loperamide) should be taken immediately and continued for persistent diarrhoea until loose bowel movements cease. c > 48 hours of diarrhoea and/or > 7 days of rash d If patient cannot tolerate 20 mg/day, permanent discontinuation of GIOTRIF should be considered Interstitial Lung Disease (ILD) should be considered if a patient develops acute or worsening of respiratory symptoms in which case treatment should be interrupted pending evaluation.

4). 4 Missed dose If a dose is missed, it should be taken within the same day as soon as the patient remembers. However, if the next scheduled dose is due within 8 hours then the missed dose must be skipped. e. the P-gp inhibitor dose should be taken as far apart in time as possible from the GIOTRIF dose.

5). 2). 73 m²) renal impairment. 73 m²) and adjust GIOTRIF dose if not tolerated. 73 m² or on dialysis is not recommended. 2). Adjustments to the starting dose are not necessary in patients with mild or moderate hepatic impairment. This medicinal product has not been studied in patients with severe (Child Pugh C) hepatic impairment.

4). Paediatric population There is no relevant use of GIOTRIF in the paediatric population in the indication of NSCLC. 2). Safety and efficacy have not been established. Therefore, treatment of children or adolescents with this medicinal product is not recommended.

Method of administration This medicinal product is for oral use. The tablets should be swallowed whole with water. If swallowing of whole tablets is not possible, these can be dispersed in approximately 100 mL of non-carbonated drinking water.

No other liquids should be used. The tablet should be dropped into the water without crushing it, and stirred occasionally for up to 15 min until it is broken up into very small particles. The dispersion should be consumed immediately.

Summary of the safety profile The types of adverse reactions (ADRs) were generally associated with the EGFR inhibitory mode of action of afatinib. The summary of all ADRs is shown in Table 2. 4) as well as stomatitis and paronychia (see also Table 3, 4 and 5).

2) led to a lower frequency of common adverse reactions. In patients treated with once daily GIOTRIF 40 mg, dose reductions due to ADRs occurred in 57% of the patients in the LUX-Lung 3 trial and in 25% of the patients in the LUX-Lung 8 trial.

0% in LUX-Lung 8, respectively. 7% of afatinib treated patients. 4). Tabulated list of adverse reactions Table 2 summarises the frequencies of ADRs from all NSCLC trials and from post-marketing experience with daily GIOTRIF doses of 40 mg or 50 mg as monotherapy.

The following terms are used to rank the ADRs by frequency: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1 000 to < 1/100); rare (≥ 1/10 000 to < 1/1 000); very rare (< 1/10 000). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

9 Table 2: Summary of ADRs per frequency category Body System Very common Common Uncommon Rare Infections and infestations Paronychia1 Cystitis Metabolism and nutrition disorders Decreased appetite Dehydration Hypokalaemia Nervous system disorders Dysgeusia Eye disorders Conjunctivitis Dry eye Keratitis Aberrant eyelash growth Respiratory, thoracic and mediastinal disorders Epistaxis Rhinorrhoea Interstitial lung disease Gastrointestinal disorders Diarrhoea Stomatitis2 Nausea Vomiting Dyspepsia Cheilitis Pancreatitis Gastrointestinal perforation Hepatobiliary disorders Alanine aminotransferase increased Aspartate aminotransferase increased Skin and subcutaneous tissue disorders Rash3 Dermatitis acneiform4 Pruritus5 Dry skin6 Palmar-plantar erythrodysaesthesia syndrome Nail disorders8 Stevens-Johnson syndrome7 Toxic epidermal necrolysis7 Musculoskeletal and connective tissue disorders Muscle spasms Renal and urinary disorders Renal impairment/ Renal failure General disorders and administration site conditions Pyrexia Investigations Weight decreased 1 Includes Paronychia, Nail infection, Nail bed infection 2 Includes Stomatitis, Aphthous stomatitis, Mucosal inflammation, Mouth ulceration, Oral mucosa erosion, Mucosal erosion, Mucosal ulceration 3 Includes group of rash preferred terms 4 Includes Acne, Acne pustular, Dermatitis acneiform 5 Includes Pruritus, Pruritus generalised 6 Includes Dry skin, Skin chapped 7 Based on post-marketing experience 8 Includes Nail disorder, Onycholysis, Nail toxicity, Onychoclasis, Ingrowing nail, Nail pitting, Onychomadesis, Nail discoloration, Nail dystrophy, Nail ridging, and Onychogryphosis Description of selected adverse reactions Very common ADRs in GIOTRIF-treated patients occurring in at least 10% of patients in trial LUX-Lung 3 and LUX-Lung 7 are summarised by National Cancer Institute-Common Toxicity Criteria (NCI-CTC) Grade in Tables 3 and 4.

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. 8). Diarrhoea may result in dehydration with or without renal impairment, which in rare 5 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 medicinal products especially within the first 6 weeks of the treatment is important and should start at first signs of diarrhoea.

g. loperamide) should be used and if necessary their dose should be escalated to the highest recommended approved dose. Anti-diarrhoeal medicinal products 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.

2). Patients who become dehydrated may require administration of intravenous electrolytes and fluids. 8). 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 use of sun screen is advisable. Early intervention (such as emollients, antibiotics) of dermatologic reactions can facilitate continuous GIOTRIF treatment. 2), 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 and toxic epidermal necrolysis. 8). 2). This could result in a higher risk of developing adverse reactions in particular diarrhoea, rash/acne and stomatitis.

1.