gic reactions
Early onset diarrhoea may be accompanied by cholinergic symptoms such as rhinitis, increased salivation, flushing, diaphoresis, bradycardia, miosis and hyperperistalsis. In case of cholinergic symptoms atropine should be administered.
Acute infusion and related reactions
Infusion reactions primarily consisting of rash, urticaria, periorbital oedema or pruritus were reported in patients receiving ONIVYDE treatment. New events (all grade 1 or grade 2) occurred generally early during ONIVYDE treatment, with only 2 out of 10 patients noted with events after the fifth dose. Hypersensitivity reactions, including acute infusion reaction may occur. ONIVYDE should be discontinued in case of severe hypersensitivitiy reactions.
Prior Whipple procedure
Patients with a history of a Whipple procedure have a higher risk of serious infections following ONIVYDE in combination with 5-FU and leucovorin (see section 4.8). Patients should be monitored for signs of infections.
Vascular disorders
Onivyde has been associated with thromboembolic events such as pulmonary embolism, venous thrombosis and arterial thromboembolism. A thorough medical history should be obtained in order to identify patients with multiple risk factors in addition to the underlying neoplasm. Patients should be informed about the signs and symptoms of thromboembolism and advised to contact their physician or nurse immediately if any such signs or symptoms should occur.
Pulmonary toxicity
Interstitial Lung Disease (ILD)-like events leading to fatalities have occurred in patients receiving non-liposomal irinotecan. No cases of ILD-like events have been reported with ONIVYDE therapy in clinical studies. Risk factors include pre-existing lung disease, use of pneumotoxic medicinal products, colony stimulating factors or having previously received radiation therapy. Patients with risk factors should be closely monitored for respiratory symptoms before and during ONIVYDE therapy. A reticulo-nodular pattern on chest X-ray was observed in a small percentage of patients enrolled in a clinical study with irinotecan. New or progressive dyspnoea, cough, and fever should prompt interruption of ONIVYDE treatment, pending diagnostic eva luation. ONIVYDE should be discontinued in patients with a confirmed diagnosis of ILD.
Hepatic impairment
Patients with hyperbilirubinaemia had higher concentrations for total SN-38 (see section 5.2) and therefore the risk of neutropenia is increased. Regular monitoring of complete blood counts should be conducted in patients with total bilirubin of 1.0-2.0 mg/dl. Caution should be exercised in patients with hepatic impairment (bilirubin > 2 times upper limit of normal [ULN]; transaminases > 5 times ULN). Caution is required when ONIVYDE is given in combination with other hepatotoxic medicinal products, especially in patients with pre-existing hepatic impairment.
Renal impairment
The use of ONIVYDE in patients with significant renal impairment has not been established (see section 5.2).
Underweight patients (body mass index < 18.5 kg/m2)
In the clinical study eva luating ONIVYDE+5-FU/LV, 5 of 8 underweight patients experienced a Grade 3 or 4 adverse reactions, mostly myelosuppression, while 7 of the 8 patients required dose modification such as dose delay, dose reduction or dose discontinuation. Caution should be exercised when using ONIVYDE in patients with body mass index <18.5 kg/m2.
Excipients
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