Gecita 200/Gecita Special Precautions

Prolongation of the infusion time and increased dosing frequency have been shown to increase toxicity.
Haematological toxicity: Gemcitabine can suppress bone marrow function as manifested by leucopenia, thrombocytopenia and anaemia. Patients receiving gemcitabine should be monitored prior to each dose for platelet, leucocyte and granulocyte counts. Suspension or modification of therapy should be considered when drug-induced bone marrow depression is detected. However, myelosuppression is short lived and usually does not result in dose reduction and rarely in discontinuation.
Peripheral blood counts may continue to deteriorate after gemcitabine administration has been stopped. In patients with impaired bone marrow function, the treatment should be started with caution. As with other cytotoxic treatments, the risk of cumulative bone-marrow suppression must be considered when gemcitabine treatment is given together with other chemotherapy.
Concomitant radiotherapy: Concomitant radiotherapy (given together or ≤7 days apart): Toxicity has been reported.
Live vaccinations: Yellow fever vaccine and other live attenuated vaccines are not recommended in patients treated with gemcitabine.
Cardiovascular: Due to the risk of cardiac and/or vascular disorders with gemcitabine, particular caution must be exercised with patients presenting a history of cardiovascular events.
Capillary leak syndrome (CLS): Capillary leak syndrome has been reported in patients receiving gemcitabine as single agent or in combination with chemotherapeutic agents. The condition is usually treatable if recognised early and managed appropriately, but fatal cases have been reported. The condition involves systemic capillary hyperpermeability during which fluid and proteins from the intravascular space leak into the interstitium. The clinical features include generalised oedema, weight gain, hypoalbuminaemia, severe hypotension, acute renal impairment and pulmonary oedema. Gemcitabine should be discontinued and supportive measures implemented if capillary leak syndrome develops during therapy. Capillary leak syndrome can occur in later cycles and has been associated in the literature with adult respiratory distress syndrome.
Posterior reversible encephalopathy syndrome: Reports of posterior reversible encephalopathy syndrome (PRES) with potentially severe consequences have been reported in patients receiving gemcitabine as single agent or in combination with other chemotherapeutic agents. Acute hypertension and seizure activity were reported in most gemcitabine patients experiencing PRES, but other symptoms such as headache, lethargy, confusion and blindness could also be present. Diagnosis is optimally confirmed by magnetic resonance imaging (MRI). PRES was typically reversible with appropriate supportive measures. Gemcitabine should be permanently discontinued and supportive measures implemented, including blood pressure control and anti-seizure therapy, if PRES develops during therapy.
Pulmonary: Pulmonary effects, sometimes severe (such as pulmonary oedema, interstitial pneumonitis or adult respiratory distress syndrome (ARDS)) have been reported in association with gemcitabine therapy. The aetiology of these effects is unknown. If such effects develop, consideration should be made to discontinuing gemcitabine therapy. Early use of supportive care measure may help ameliorate the condition.
Renal: Haemolytic uraemic syndrome: Clinical findings consistent with the haemolytic uraemic syndrome (HUS) were rarely reported in patients of microangiopathic haemolytic anaemia, such as rapidly falling haemoglobin with concomitant thrombocytopenia, elevation of serum bilirubin, serum creatinine, blood urea nitrogen, or LDH. Renal failure may not be reversible with discontinuation of therapy and dialysis may be required.
Sodium: Gemcitabine 100 mg/mL Concentrate for solution for Infusion contains 199.6 mg (8.68 mmol) of sodium per maximum daily dose (2250 mg). This should be taken into consideration by patients on a controlled sodium diet.
Ethanol: Gemcitabine 100 mg/L concentrate for solution for infusion contains 440 mg ethanol anhydrous per mL concentrate. This may be harmful in patients suffering from alcoholism and should also be taken into consideration in high-risk groups such as patients with liver disease or epilepsy. Consideration should be given to possible effects on the central nervous system and other effects.
Hepatic insufficiency: Administration of gemcitabine in patients with concurrent liver metastases or a preexisting medical history of hepatitis, alcoholism or liver cirrhosis may lead to exacerbation of the underlying hepatic insufficiency.
Laboratory evaluation of renal and hepatic function (including virological tests) should be performed periodically. Gemcitabine should be used with caution in patients with hepatic insufficiency or with impaired renal function as there is insufficient information from clinical studies to allow clear dose recommendation for this patient population.