Gefitinib Sandoz

Gefitinib Sandoz Special Precautions





Zuellig Pharma


Full Prescribing Info
Special Precautions
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.
Only robust, reliable and sensitive test(s) with demonstrated utility for the determination of EGFR mutation status of tumours or ctDNA should be used to avoid false negative or false positive determinations (see Pharmacology: Pharmacodynamics under Actions).
Interstitial lung disease (ILD): 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). 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. 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% Cl 1.9 to 7.7); thereafter the relative risk was lower (adjusted OR 2.5; 95% Cl 1.1 to 5.8). 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%).
Hepatotoxicity and liver impairment: Liver function test abnormalities (including increases in alanine aminotransferase, aspartate aminotransferase, bilirubin) have been observed, uncommonly presenting as hepatitis (see Adverse Reactions). 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.
Impaired liver function due to cirrhosis has been shown to lead to increased plasma concentrations of gefitinib (see Pharmacology: Pharmacokinetics under Actions).
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 (see Interactions).
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 (see Interactions).
International normalised ratio (INR) elevations and/or bleeding events have been reported in some patients taking warfarin together with gefitinib (see Interactions). 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 protonĀ­-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 may have a similar effect (see Interactions and Pharmacology: Pharmacokinetics under Actions).
Data from phase II clinical trials, where gefitinib and vinorelbine have been used concomitantly, indicate that gefitinib may exacerbate the neutropenic effect of vinorelbine.
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 (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 gefitinib should be interrupted, and if symptoms do not resolve, or if symptoms recur on reintroduction of gefitinib, 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. 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.
Effects on ability to drive and use machines: During treatment with gefitinib, asthenia has been reported. Therefore, patients who experience this symptom should be cautious when driving or using machines.
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