ERLOTINIB SANDOZ

Erlotinib treatment should be supervised by a physician experienced in the use of anti-cancer therapies. 1) The recommended daily dose of Erlotinib is 150 mg taken at least one hour before or two hours after the ingestion of food.

Patients with pancreatic cancer:

The recommended daily dose of Erlotinib is 100 mg taken at least one hour before or two hours after the ingestion of food, in combination with gemcitabine (see the summary of product characteristics of gemcitabine for the pancreatic cancer indication).

1). 4). Erlotinib is not available in 50 mg strength. For these dosages, you should take other medicinal products available on the market. Erlotinib is available in strengths of 25 mg, 100 mg and 150 mg. 5).

Hepatic impairment:

Erlotinib is eliminated by hepatic metabolism and biliary excretion. Although erlotinib exposure was similar in patients with moderately impaired hepatic function (Child- Pugh score 7-9) compared with patients with adequate hepatic function, caution should be used when administering Erlotinib to patients with hepatic impairment.

Dose reduction or interruption of Erlotinib should be considered if severe adverse reactions occur. The safety and efficacy of erlotinib has not been studied in patients with severe hepatic dysfunction (AST/SGOT and ALT/SGPT> 5 x ULN).

2). 5 times the upper normal limit). 2). Use of Erlotinib in patients with severe renal impairment is not recommended. Paediatric population The safety and efficacy of erlotinib in the approved indications has not been established in patients under the age of 18 years.

Use of Erlotinib in paediatric patients is not recommended.

Smokers:

Cigarette smoking has been shown to reduce erlotinib exposure by 50-60%. The maximum tolerated dose of Erlotinib in NSCLC patients who currently smoke cigarettes was 300 mg. The 300 mg dose did not show improved efficacy in second line treatment after failure of chemotherapy compared to the recommended 150 mg dose in patients who continue to smoke cigarettes.

Safety data were comparable between the 300 mg and 150 mg doses; however, there was a numerical increase in the incidence of rash, interstitial lung disease and diarrhoea, in patients receiving the higher dose of erlotinib. 2).

Safety evaluation of erlotinib is based on the data from more than 1500 patients treated with at least one 150 mg dose of erlotinib monotherapy and more than 300 patients who received erlotinib 100 or 150 mg in combination with gemcitabine.

The incidence of adverse drug reactions (ADRs) from clinical trials reported with erlotinib alone or in combination with chemotherapy are summarised by National Cancer Institute – Common Toxicity Criteria (NCI – CTC) Grade in Table 1.

The listed ADRs were those reported in at least 10% (in the erlotinib group) of patients and occurred more frequently (>3%) in patients treated with erlotinib than in the comparator arm. Other ADRs including those from other studies are summarized in Table 2.

Adverse drug reactions from clinical trials (Table 1) and other ADRs (Table 2) are listed by MedDRA system organ class. The corresponding frequency category for each adverse drug reaction is based on the following convention: 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, adverse reactions are presented in order of decreasing seriousness.

Non-small cell lung cancer (Erlotinib administered as monotherapy):

First- Line Treatment of Patients with EGFR Mutations In an open-label, randomised phase III study, ML20650 conducted in 154 patients, the safety of erlotinib for first-line treatment of NSCLC patients with EGFR activating mutations was assessed in 75 patients; no new safety signals were observed in these patients.

The most frequent ADRs seen in patients treated with erlotinib in study ML20650 were rash and diarrhoea (any Grade 80% and 57%, respectively), most were Grade 1/2 in severity and manageable without intervention. Grade 3 rash and diarrhoea occurred in 9% and 4% of patients, respectively.

Assessment of EGFR mutation status When considering the use of erlotinib as a first line or maintenance treatment for locally advanced or metastatic NSCLC, it is important that the EGFR mutation status of a patient is determined. A validated, robust, reliable and sensitive test with a pre-specified positivity threshold and demonstrated utility for the determination of EGFR mutation status, using either tumor DNA derived from a tissue sample or circulating free DNA (cfDNA) obtained from a blood (plasma) sample, should be performed according to local medical practice.

If a plasma-based cfDNA test is used and the result is negative for activating mutations, perform a tissue test wherever possible due to the potential for false negative results from a plasma-based test. Smokers Current smokers should be advised to stop smoking, as plasma concentrations of erlotinib in smokers as compared to non-smokers are reduced.

2). Interstitial Lung Disease Cases of interstitial lung disease (ILD)-like events, including fatalities, have been reported uncommonly in patients receiving erlotinib for treatment of non- small cell lung cancer (NSCLC), pancreatic cancer or other advanced solid tumours.

8%) was the same in both the placebo and erlotinib groups. 4% in patients in the control arms. 4% in the placebo plus gemcitabine treated group. Reported diagnoses in patients suspected of having ILD-like events included pneumonitis, radiation pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis, pulmonary fibrosis, Acute Respiratory Distress Syndrome (ARDS), alveolitis, and lung infiltration.

Symptoms started from a few days to several months after initiating erlotinib therapy. Confounding or contributing factors such as concomitant or prior chemotherapy, prior radiotherapy, pre-existing parenchymal lung disease, metastatic lung disease, or pulmonary infections were frequent.

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