Gefitero Special Precautions

When considering the use of GEFITERO for the naïve treatment of patients with locally advanced or metastatic NSCLC, it is recommended that EGFR mutation assessment of the tumour tissue is attempted for all patients. When assessing the mutation status of a patient it is important that a well-validated and robust methodology is chosen to minimize the possibility of false negative or false positive determinations. Tumour sample which are used for the diagnosis of advanced NSCLC are preferred sample type for EGFR mutation testing. A tumour sample should be collected and tested where possible. If a tumour sample is not available or evaluable, then circulating tumour DNA (ctDNA) obtained from a blood (plasma) sample may be used. Only robust, reliable, sensitive test(s) with demonstrated utility on ctDNA should be used for the determination of EGFR mutation status of ctDNA. EGFR mutations identified in ctDNA are highly predictive of EGFR mutation positive tumours). However it is not always possible to detect EGFR mutations using this sample type.
Interstitial Lung Disease (ILD), which may be acute in onset, has been observed in 1,3% of patients receiving Gefitinib, and some cases have been fatal (see ADVERSE REACTIONS).
Patients with concurrent idiopathic pulmonary fibrosis/interstitial pneumonia/pneumoconiosis/ radiation pneumonia/drug-induced pneumonia have been observed to have an increased rate of mortality from this condition. If patients present with worsening of respiratory symptoms such as dyspnea, cough and fever, GEFITERO should be interrupted and prompt investigation initiated. If ILD is confirmed, GEFITERO should be discontinued and the patient treated appropriately.
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. An increase risk of ILD on Gefitinib relative to chemotherapy was seen predominantly during the first 4 weeks of treatment; thereafter the relative risk was lower. 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%).
Liver function abnormalities (including increases in alanine aminotransferase, aspartate aminotransferase, bilirubin) have been observed (see ADVERSE REACTIONS), uncommonly presenting as hepatitis. There have been isolated reports of hepatic failure which in some cases led to fatal outcomes. Therefore, periodic liver function testing is recommended. GEFITERO should be used cautiously in the presence of mild to moderate changes in liver function. Discontinuation should be considered if changes are severe. Impaired liver function due to cirrhosis has been shown to lead to increased plasma concentrations of Gefitinib.
Cerebrovascular events have been reported. A relationship with GEFITERO has not been established.
Substances that are inducers of CYP3A4 activity may increase metabolism and decrease Gefitinib plasma concentrations. Therefore, co-medication with CYP3A4 inducers (e.g. Phenytoin, Carbamazepine, Rifampicin, Barbiturates or St. John's Wort) may reduce efficacy.
International Normalized Ratio (INR) elevations and/or bleeding events have been reported in some patients taking Warfarin (see INTERACTIONS). Patients taking Warfarin should be monitored regularly for changes in Prothrombin Time (PT) or INR.
Drugs that cause significant sustained elevation in gastric pH may reduce plasma concentrations of Gefitinib and therefore may reduce efficacy (see INTERACTIONS).
Patients should be advised to seek medical advice promptly in the event of developing: Severe or persistent diarrhea, nausea, vomiting or anorexia. These symptoms should be managed as clinically indicated (see ADVERSE REACTIONS).
Patients presenting with signs and symptoms suggestive of keratitis 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 GEFITERO should be interrupted, and if symptoms do not resolve, or recur on reintroduction of GEFITERO, permanent discontinuation should be considered.
Radiation in pediatric patients, newly diagnosed with brain stem glioma or incompletely resected supratentorial malignant glioma of Central Nervous System hemorrhages were reported. A further case of Central Nervous System hemorrhage has been reported in a child with an ependymoma with GEFITERO alone. An increased risk of cerebral hemorrhage in adult patients with NSCLC receiving GEFITERO has not been established.
Where GEFITERO and Vinorelbine have been used concomitantly, indicate that GEFITERO may exacerbate the neutropenic effect of Vinorelbine.
Gastrointestinal perforation has been reported in patients taking GEFITERO. In most cases this is associated with other known risk factors, including increasing age, concomitant medications such as steroids or NSAIDs, underlying history of GI ulceration, age, smoking or bowel metastases at sites of perforation.
Effects on ability to drive and use machines: During treatment with GEFITERO, asthenia has been reported and those patients who experience this symptom should observe caution when driving or using machines.
Use in Pregnancy and Lactation: There is no data from the use of Gefitinib in pregnant or breast-feeding women. Studies in animals have shown reproductive toxicity. Animal studies also indicate that Gefitinib and certain metabolites pass into rats breast-milk. Women of childbearing potential must be advised to avoid becoming pregnant, and breast-feeding mothers must be recommended to discontinue nursing while receiving GEFITERO therapy.