Benign arrhythmias such as ventricular premature beats and more rarely serious arrhythmias have been reported in some patients. If excessive tachycardia occurs during Dopacard administration, then a reduction or temporary discontinuation of the infusion should be considered.

As with other parenteral catecholamines, there have been occasional reports of partial tolerance, with some attenuation of the haemodynamic response developing during long-term infusions of Dopacard.

The risk of thrombophlebitis and local necrosis may be increased if the concentration of Dopacard administered via a peripheral vein exceeds 1 mg/ml. Thrombophlebitis is rare when the concentration of drug used for peripheral administration is less than 1 mg/ml.

4.5 Interaction with other medicinal products and other forms of interaction

 As Dopacard inhibits Uptake-1, it may potentiate the effects of exogenous catecholamines such as noradrenaline. Caution is recommended when these agents are administered concomitantly with Dopacard or soon after discontinuation of its use.

In the case of dopamine, there is no evidence of an interaction, other than possible attenuation of the indirect sympathomimetic inotropic effects of higher doses of dopamine due to Uptake-1 blockade by Dopacard.

Concomitant use with β2-adrenergic antagonists and dopamine receptor antagonists requires caution since attenuation of the pharmacological effects of Dopacard may occur.

4.6 Pregnancy and lactation

 There is no experience of the use of Dopacard in pregnant or lactating women and therefore its safety in these situations has not been established. There is insufficient evidence from animal studies to indicate it is free from hazard. Dopacard is not therefore currently recommended for use in pregnant or lactating women.

4.7 Effects on ability to drive and use machines

 Not applicable.

4.8 Undesirable effects

 The most common undesirable effect reported with Dopacard administration is tachycardia (11.8% in studies of acute exacerbations of chronic heart failure; 19.4% in studies of use in cardiac surgery). The increases in heart rate are dose related and in most cases not clinically significant.

Other undesirable effects reported in clinical trials in both acute exacerbations of chronic heart failure and cardiac surgery at an incidence of 1% or more include:

Cardiovascular: A number of tachyarrhythmias such as premature ventricular contractions (PVCs) and atrial fibrillation; bradycardia, both sinus and nodal; worsening heart failure leading to asystole and cardiac arrest; angina; myocardial infarction; cardiac enzyme changes and non- specific ECG changes. Hypotension and hypertension have also been reported, the latter with a higher incidence in patients following cardiac surgery.

Non-cardiovascular: Nausea and vomiting; tremor; headache; diaphoresis and dyspnoea.

Careful titration of the dose may minimise the incidence of adverse events.

More rarely a number of serious adverse events have been reported in patients undergoing cardiac surgery: renal failure, acute respiratory distress syndrome (ARDS), pulmonary oedema, pulmonary hypertension, bleeding and septicaemia. However, such events may also be due to the condition of the patients in such a population.

4.9 Overdose

 The half-life of Dopacard in blood is short (