GIOTRIF Film-coated tablets Ref.[6091] Active ingredients: Afatinib

Treatment with GIOTRIF should be initiated and supervised by a physician experienced in the use of anticancer therapies.

EGFR mutation status should be established prior to initiation of GIOTRIF therapy (see section 4.4).

Posology

The recommended dose is 40 mg once daily.

This medicinal product should be taken without food. Food should not be consumed for at least 3 hours before and at least 1 hour after taking this medicinal product (see sections 4.5 and 5.2).

GIOTRIF treatment should be continued until disease progression or until no longer tolerated by the patient (see Table 1 below).

Dose escalation

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 patients with a prior dose reduction. The maximum daily dose is 50 mg.

Dose adjustment for adverse reactions

Symptomatic adverse reactions (e.g. severe/persistent diarrhoea or skin related adverse reactions) may be successfully managed by treatment interruption and dose reductions or treatment discontinuation of GIOTRIF as outlined in Table 1 (see sections 4.4 and 4.8).

Table 1. Dose adjustment information for adverse reactions:

^a NCI Common Terminology Criteria for Adverse Events
^b In case of diarrhoea, anti-diarrhoeal medicinal products (e.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 treatmentshould be interrupted pending evaluation. If ILD is diagnosed, GIOTRIF should be discontinued and appropriate treatment initiated as necessary (see section 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.

Use of P-glycoprotein (P-gp) inhibitors

If P-gp inhibitors need to be taken, they should be administered using staggered dosing, i.e. the P-gp inhibitor dose should be taken as far apart in time as possible from the GIOTRIF dose. This means preferably 6 hours (for P-gp inhibitors dosed twice daily) or 12 hours (for P-gp inhibitors dosed once daily) apart from GIOTRIF (see section 4.5).

Special populations

Patients with renal impairment

Exposure to afatinib was found to be increased in patients with moderate or severe renal impairment (see section 5.2). Adjustments to the starting dose are not necessary in patients with mild (eGFR 60-89 mL/min/1.73m²), moderate (eGFR 30-59 mL/min/1.73m²) or severe (eGFR 15-29 mL/min/1.73m²) renal impairment. Monitor patients with severe renal impairment (eGFR 15-29 mL/min/1.73m²) and adjust GIOTRIF dose if not tolerated. GIOTRIF treatment in patients with eGFR <15 mL/min/1.73m² or on dialysis is not recommended.

Patients with hepatic impairment

Exposure to afatinib is not significantly changed in patients with mild (Child Pugh A) or moderate (Child Pugh B) hepatic impairment (see section 5.2). 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. Treatment in this population is not recommended (see section 4.4).

Paediatric population

There is no relevant use of GIOTRIF in the paediatric population in the indication of NSCLC. 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. The glass should be rinsed with approximately 100 ml of water which should also be consumed. The dispersion can also be administered through a gastric tube.

Symptoms

The highest dose of afatinib studied in a limited number of patients in Phase I clinical trials was 160 mg once daily for 3 days and 100 mg once daily for 2 weeks. The adverse reactions observed at these doses were primarily dermatological (rash/acne) and gastrointestinal events (especially diarrhoea). Overdose in 2 healthy adolescents involving the ingestion of 360 mg each of afatinib (as part of a mixed drug ingestion) was associated with adverse events of nausea, vomiting, asthenia, dizziness, headache, abdominal pain and elevated amylase (<1.5 times ULN). Both individuals recovered from these adverse events.

Treatment

There is no specific antidote for overdose with this medicinal product. In cases of suspected overdose, GIOTRIF should be withheld and supportive care initiated.

If indicated, elimination of unabsorbed afatinib may be achieved by emesis or gastric lavage.

Shelf life: 3 years.

Store in the original package in order to protect from moisture and light.

PVC/PVDC perforated unit dose blister. Each blister is packed together with a desiccant sachet in a laminated aluminium pouch and contains 7 × 1 film-coated tablets. Pack sizes of 7 × 1, 14 × 1 or 28 × 1 film-coated tablets.

Not all pack sizes may be marketed.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.