Gafvex Warnings

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.
Interstitial lung disease (ILD): ILD, which may be acute in onset, has been observed in 1.3% of patients receiving Gefitinib Tablets 250 mg, and some cases have been fatal. If patients experience worsening of respiratory symptoms such as dyspnoea, cough and fever, Gefitinib Tablets 250 mg should be interrupted and the patient should be promptly investigated. If ILD is confirmed, Gefitinib Tablets 250 mg should be discontinued and the patient treated appropriately.
In a Japanese pharmacoepidemiological case control study in 3159 patients with NSCLC receiving Gefitinib Tablets 250 mg or chemotherapy who were followed up for 12 weeks, the following risk factors for developing ILD (irrespective of whether the patient received Gefitinib Tablets 250 mg 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 increased risk of ILD on gefitinib relative to chemotherapy was seen predominantly during the first 4 weeks of treatment (adjusted OR 3.8; 95% CI 1.9 to 7.7); thereafter the relative risk was lower (adjusted OR 2.5; 95% CI 1.1 to 5.8). Risk of mortality among patients who developed ILD on Gefitinib Tablets 250 mg 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%).
Hepatotoxicity and liver impairment: Liver function test abnormalities (including increases in alanine aminotransferase, aspartate aminotransferase, bilirubin) have been observed, 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. Gefitinib Tablets 250 mg 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.
Interactions with other medicinal products: CYP3A4 inducers may increase metabolism of gefitinib and decrease gefitinib plasma concentrations. Therefore, concomitant administration of CYP3A4 inducers (e.g. phenytoin, carbamazepine, rifampicin, barbiturates or herbal preparations containing St John's wort/Hypericum perforatum) may reduce efficacy of the treatment and should be avoided.
In individual patients with CYP2D6 poor metaboliser genotype, treatment with a potent CYP3A4 inhibitor might lead to increased plasma levels of gefitinib. At initiation of treatment with a CYP3A4 inhibitor, patients should be closely monitored for gefitinib adverse reactions.
International normalised ratio (INR) elevations and/or bleeding events have been reported in some patients taking warfarin together with gefitinib. Patients taking warfarin and gefitinib concomitantly should be monitored regularly for changes in prothrombin time (PT) or INR.
Medicinal products that cause significant sustained elevation in gastric pH, such as proton-pump inhibitors and h₂-antagonists may reduce bioavailability and plasma concentrations of gefitinib and, therefore, may reduce efficacy. Antacids if taken regularly close in time to administration of Gefitinib Tablets 250 mg may have a similar effect.
Data from phase II clinical trials, where gefitinib and vinorelbine have been used concomitantly, indicate that gefitinib may exacerbate the neutropenic effect of vinorelbine.
Lactose: Gefitinib Tablets 250 mg contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactose deficiency or glucose-galactose malabsorption should not take this medicinal product.
Further precautions for use: Patients should be advised to seek medical advice immediately if they experience: Severe or persistent diarrhoea, nausea, vomiting or anorexia as these may indirectly lead to dehydration.
These symptoms should be managed as clinically indicated.
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 Gefitinib tablets 250 mg should be interrupted, and if symptoms do not resolve, or if symptoms recur on reintroduction of Gefitinib tablets 250 mg, permanent discontinuation should be considered.
In a phase I/II trial studying the use of gefitinib and radiation in paediatric patients, with newly diagnosed brain stem glioma or incompletely resected supratentorial malignant glioma, 4 cases (1 fatal) of Central Nervous System (CNS) haemorrhages were reported from 45 patients enrolled. A further case of CNS haemorrhage has been reported in a child with an ependymoma from a trial with gefitinib alone. An increased risk of cerebral haemorrhage in adult patients with NSCLC receiving gefitinib has not been established.
Gastrointestinal perforation has been reported in patients taking Gefitinib tablets 250 mg. In most cases this is associated with other known risk factors, including concomitant medications such as steroids or NSAIDs, underlying history of GI ulceration, age, smoking or bowel metastases at sites of perforation.