Glivec Special Precautions

Glivec should be taken with food and a large glass of water to minimise the risk of gastrointestinal disturbances.
When Glivec is co-administered with other medications, there is a potential for drug interactions (see Interactions).
One patient, who was taking paracetamol/acetaminophen regularly for fever, died of acute liver failure. Although the aetiology is currently unknown, special caution should be exercised when using paracetamol/acetaminophen (see Interactions).
Clinical cases of hypothyroidism have been reported in thyroidectomy patients undergoing levothyroxine replacement during treatment with Glivec. Thyroid-stimulating hormone (TSH) levels should be closely monitored in such patients.
In patients with hepatic dysfunction (mild, moderate or severe), peripheral blood counts and liver enzymes should be carefully monitored (see Pharmacology and Pharmacokinetics under Actions, Dosage & Administration and Adverse Reactions).
When imatinib is combined with high-dose chemotherapy regimens, transient liver toxicity in the form of transaminase elevation and hyperbilirubinaemia has been observed. Additionally, there have been uncommon reports of acute liver failure. Monitoring of hepatic function is recommended in circumstances where imatinib is combined with chemotherapy regimens also known to be associated with hepatic dysfunction (see Adverse Reactions).
Occurrences of severe fluid retention (pleural effusion, oedema, pulmonary oedema, ascites, superficial oedema) have been reported in approximately 2.5% of newly diagnosed CML patients taking Glivec. Therefore, it is recommended that patients be weighed regularly. An unexpected rapid weight gain should be carefully investigated and if necessary, appropriate supportive care and therapeutic measures should be undertaken. In clinical trials, there was an increased incidence of these events in elderly patients and those with a prior history of cardiac disease.
Patients with cardiac disease or risk factors for cardiac failure should be monitored carefully and any patient with signs or symptoms consistent with cardiac failure should be evaluated and treated.
In patients with hypereosinophilic syndrome (HES) and cardiac involvement, isolated cases of cardiogenic shock/left ventricular dysfunction have been associated with the initiation of imatinib therapy. The condition was reported to be reversible with the administration of systemic steroids, circulatory support measures and temporarily withholding imatinib. Myelodysplastic/myeloproliferative diseases and systemic mastocytosis might be associated with high eosinophil levels. Performance of an echocardiogram and determination of serum troponin should therefore be considered in patients with HES/CEL, and in patients with MDS/MPD or SM associated with high eosinophil levels. If either is abnormal, the prophylactic use of systemic steroids (1-2 mg/kg) for 1-2 weeks concomitantly with imatinib should be considered at the initiation of therapy.
In the phase III GIST studies in patients with unresectable or metastatic malignant GIST 211 patients (12.9%) reported grade 3/4 haemorrhage at any site. In the phase II GIST study in patients with unresectable or metastatic malignant GIST (study B2222), 8 patients (5.4%) were reported to have had gastrointestinal (GI) haemorrhage and 4 patients (2.7%) were reported to have had haemorrhages at the site of tumour deposits. The tumour haemorrhages have been either intra-abdominal or intrahepatic, depending on the anatomical location of tumour lesions. Gastrointestinal sites of tumour may have contributed to reports of GI bleeding in this patient population (see Adverse Reactions).
Laboratory Tests: Complete blood counts must be performed regularly during therapy with Glivec. Treatment of CML patients with Glivec has been associated with neutropenia or thrombocytopenia. However, the occurrence of these cytopenias is dependent on the stage of the disease being treated and they were more frequent in patients with accelerated phase CML or blast crisis as compared to patients with chronic phase CML. Treatment with Glivec may be interrupted or the dose be reduced, as recommended under Dosage & Administration.
Liver function (transaminases, bilirubin, alkaline phosphatase) should be monitored regularly in patients receiving Glivec. As recommended in Dosage & Administration nonhaematological adverse reactions, these laboratory abnormalities should be managed with interruption and/or dose reduction of the treatment with Glivec.
Glivec and its metabolites are not excreted via the kidney to a significant extent. Creatinine clearance (CrCl) is known to decrease with age, and age did not significantly affect Glivec kinetics. In patients with impaired renal function, imatinib plasma exposure seems to be higher than that in patients with normal renal function, probably due to an elevated plasma level of α-acid glycoprotein (AGP), an imatinib-binding protein, in these patients. There is no correlation between imatinib exposure and the degree of renal impairment, as classified by the measurement of CrCl, between patients with mild (CrCl 40-59 ml/min) and severe (CrCl <20 ml/min) renal impairment. However, as recommended in Dosage & Administration, the starting dose of imatinib can be reduced if not tolerated.
Women of Childbearing Potential: Women of childbearing potential must be advised to use effective contraception during treatment.
Effects on the Ability to Drive or Operate Machinery: While no specific reports have been received, patients should be advised that they may experience undesirable effects eg, dizziness or blurred vision during treatment with imatinib. Therefore, caution should be recommended when driving a car or operating machinery.
Use in Pregnancy: There are no adequate data on the use of imatinib in pregnant women. Studies in animals have, however, shown reproductive toxicity (see Toxicology under Actions) and the potential risk for the foetus is unknown. Glivec should not be used during pregnancy unless clearly necessary. If it is used during pregnancy, the patient must be informed of the potential risk to the foetus.
Use in Lactation: It is not known whether imatinib is excreted in human milk. In animals, imatinib and/or its metabolites were extensively excreted in milk. Women who are taking Glivec should therefore not breastfeed.