GEFITINIB SANDOZ

Treatment with Gefitinib should be initiated and supervised by a physician experienced in the use of anticancer therapies. Posology The recommended posology of Gefitinib is one 250 mg tablet once a day. If a dose is missed, it should be taken as soon as the patient remembers.

If it is less than 12 hours to the next dose, the patient should not take the missed dose. Patients should not take a double dose (two doses at the same time) to make up for a forgotten dose. Paediatric population The safety and efficacy of gefitinib in children and adolescents aged less than 18 years have not been established.

There is no relevant use of gefitinib in the paediatric population in the indication of NSCLC. Hepatic impairment Patients with moderate to severe hepatic impairment (Child-Pugh B or C) due to cirrhosis have increased plasma concentrations of gefitinib.

These patients should be closely monitored for adverse events. 2). Renal impairment No dose adjustment is required in patients with impaired renal function at creatinine clearance > 20 ml/min. 2). 2). 2). 8). For patients unable to tolerate treatment after a therapy interruption, gefitinib should be discontinued and an alternative treatment should be considered.

Method of administration The tablet may be taken orally with or without food, at about the same time each day. The tablet can be swallowed whole with some water or if dosing of whole tablets is not possible, tablets may be administered as a dispersion in water (non-carbonated).

No other liquids should be used. Without crushing it, the tablet should be dropped in half a glass of drinking water. The glass should be swirled occasionally, until the tablet is dispersed (this may take up to 20 minutes). e. within 60 minutes).

The glass should be rinsed with half a glass of water, which should also be drunk. The dispersion can also be administered through a naso-gastric or gastrostomy tube.

Summary of the safety profile In the pooled dataset from the ISEL, INTEREST and IPASS phase III clinical trials (2462 Gefitinib-treated patients), the most frequently reported adverse drug reactions (ADRs), occurring in more than 20% of the patients, are diarrhoea and skin reactions (including rash, acne, dry skin and pruritus).

ADRs usually occur within the first month of therapy and are generally reversible. Approximately 8% of patients had a severe ADR (common toxicity criteria, (CTC) grade 3 or 4). Approximately 3% of patients stopped therapy due to an ADR.

3% of patients, often severe (CTC grade 3-4). Cases with fatal outcomes have been reported. Tabulated list of adverse reactions The safety profile presented in Table 1 is based on the gefitinib clinical development programme and postmarketed experience.

Adverse reactions have been assigned to the frequency categories in Table 1 where possible based on the incidence of comparable adverse event reports in a pooled dataset from the ISEL, INTEREST and IPASS phase III clinical trials (2462 Gefitinib -treated patients).

Frequencies of occurrence of undesirable effects are defined as: 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), not known (cannot be estimated from the available data).

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. Table 1 Adverse reactions Adverse reactions by system organ class and frequency Metabolism and nutrition disorders Very common Anorexia mild or moderate (CTC grade 1 or 2).

Common Conjunctivitis, blepharitis, and dry eye*, mainly mild (CTC grade 1). Corneal erosion, reversible and sometimes in association with aberrant eyelash growth. 12%) Vascular disorders Common Haemorrhage, such as epistaxis and haematuria.

When considering the use of gefitinib as a treatment for locally advanced or metastatic NSCLC, it is important that EGFR mutation assessment of the tumour tissue is attempted for all patients. If a tumour sample is not evaluable, then circulating tumour DNA (ctDNA) obtained from a blood (plasma) sample may be used.

1). 8). If patients experience worsening of respiratory symptoms such as dyspnoea, cough and fever, gefitinib should be interrupted and the patient should be promptly investigated. If ILD is confirmed, gefitinib should be discontinued and the patient treated appropriately.

In a Japanese pharmacoepidemiological case control study in 3,159 patients with NSCLC receiving gefitinib or chemotherapy who were followed up for 12 weeks, the following risk factors for developing ILD (irrespective of whether the patient received gefitinib or chemotherapy) were identified: smoking, poor performance status (PS≥ 2), CT scan evidence of reduced normal lung (≤ 50%), recent diagnosis of NSCLC (< 6 months), pre-existing ILD, older age (≥ 55 years old) and concurrent cardiac disease.

8). Risk of mortality among patients who developed ILD on gefitinib or chemotherapy was higher in patients with the following risk factors: smoking, CT scan evidence of reduced normal lung (≤ 50%), pre-existing ILD, older age (≥ 65 years old), and extensive areas adherent to pleura (≥ 50%).

8). There have been isolated reports of hepatic failure which in some cases led to fatal outcomes. Therefore, periodic liver function testing is recommended. Gefitinib should be used cautiously in the presence of mild to moderate changes in liver function.

Discontinuation should be considered if changes are severe. 2). Interactions with other medicinal products CYP3A4 inducers may increase metabolism of gefitinib and decrease gefitinib plasma concentrations. g. 5). In individual patients with CYP2D6 poor metaboliser genotype, treatment with a potent CYP3A4 inhibitor might lead to increased plasma levels of gefitinib.

1. 6).