ethod of administration
MEPACT must be reconstituted, filtered using the filter provided and further diluted prior to administration. The reconstituted, filtered and diluted suspension for infusion is a homogenous, white to off-white, opaque liposomal suspension, free of visible particles and free of foam and lipid lumps.
After reconstitution, filtering using the filter provided and further dilution, MEPACT is administered by intravenous infusion over a period of 1 hour.
MEPACT must not be administered as a bolus injection.
For further instructions on reconstitution, filtering using the filter provided and dilution prior to administration, see section 6.6.
4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients.
Concurrent use with ciclosporin or other calcineurin inhibitors (see section 4.5).
Concurrent use with high-dose non-steroidal anti-inflammatory drugs (NSAIDs, cyclooxygenase inhibitors) (see section 4.5).
4.4 Special warnings and precautions for use
Respiratory distress
In patients with a history of asthma or other chronic obstructive pulmonary disease, consideration should be given to administration of bronchodilators on a prophylactic basis. Two patients with pre-existing asthma developed mild to moderate respiratory distress associated with the treatment. If a severe respiratory reaction occurs, administration of MEPACT should be discontinued and appropriate treatment initiated.
Neutropenia
Administration of MEPACT was commonly associated with transient neutropenia, usually when used in conjunction with chemotherapy. Episodes of neutropenic fever should be monitored and managed appropriately. MEPACT may be given during periods of neutropenia, but subsequent fever attributed to the treatment should be monitored closely. Fever or chills persisting for more than 8 hours after administration of MEPACT should be eva luated for possible sepsis.
Inflammatory response
Association of MEPACT with signs of pronounced inflammatory response, including pericarditis and pleuritis, was uncommon. It should be used with caution in patients with a history of autoimmune, inflammatory or other collagen diseases. During MEPACT administration, patients should be monitored for unusual signs or symptoms, such as arthritis or synovitis, suggestive of uncontrolled inflammatory reactions.
Cardiovascular disorders
Patients with a history of venous thrombosis, vasculitis or unstable cardiovascular disorders should be closely monitored during MEPACT administration. If symptoms are persistent and worsening, administration should be delayed or discontinued. Haemorrhage was observed in animals at very high doses. These are not expected at the recommended dose, however monitoring of clotting parameters after the first dose and once again after several doses is recommended.
Allergic reactions
Occasional allergic reactions have been associated with MEPACT treatment, including rash, shortness of breath and Grade 4 hypertension. It may be difficult to distinguish allergic reactions from exaggerated inflammatory responses, but patients should be monitored for signs of allergic reactions.
Gastrointestinal toxicity
Nausea, vomiting and loss of appetite are very common adverse reactions to MEPACT. Gastrointestinal toxicity may be exacerbated when MEPACT is used in combination with high dose, multi-agent chemotherapy and was associated with an in |
