In these patients it is recommended that an electrocardiogram (ECG) is recorded before initiation of treatment with Trobalt and in those with a corrected QT interval >440ms at baseline, an ECG should be recorded on reaching the maintenance dose.
Psychiatric disorders

Confusional state, psychotic disorders and hallucinations were reported in controlled clinical studies with retigabine (see section 4.8). These effects generally occurred within the first 8 weeks of treatment, and frequently led to treatment withdrawal in affected patients. It is recommended that patients are advised about the risk of these possible effects.

Suicide risk

Suicidal ideation and behaviour have been reported in patients treated with antiepileptic agents in several indications. A meta-analysis of randomised placebo-controlled trials of antiepileptic drugs has also shown a small increased risk of suicidal ideation and behaviour. The mechanism of this risk is not known and the available data do not exclude the possibility of an increased risk for Trobalt.

Therefore patients should be monitored for signs of suicidal ideation and behaviours and appropriate treatment should be considered. Patients (and caregivers of patients) should be advised to seek medical advice if signs of suicidal ideation or behaviour emerge.

Elderly (65 years of age and above)

Elderly patients may be at increased risk of central nervous system events, urinary retention and atrial fibrillation. Trobalt must be used with caution in this population and a reduced initial and maintenance dose is recommended (see sections 4.2 and 5.2).

Withdrawal seizures

As with other antiepileptic drugs, Trobalt must be withdrawn gradually to minimise the potential for rebound seizures. It is recommended that the Trobalt dose is reduced over a period of at least 3 weeks, unless safety concerns require an abrupt withdrawal.

4.5 Interaction with other medicinal products and other forms of interaction

 Interaction studies have only been performed in adults.

Other antiepileptic drugs

In vitro data indicated a low potential for interaction with other antiepileptic drugs (see section 5.2). The drug interaction potential was therefore eva luated based on a pooled analysis across clinical studies and whilst not considered as robust as stand-alone clinical interaction studies, the results support the in vitro data.

Based on these pooled data, retigabine did not cause clinically significant effects on the plasma trough concentrations of the following antiepileptic drugs:

- carbamazepine, clobazam, clonazepam, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, phenobarbitone, phenytoin, pregabalin, topiramate, valproate, zonisamide.

Further, based on pooled data, there were no clinically significant effects of the following antiepileptic drugs on retigabine pharmacokinetics:

- lamotrigine, levetiracetam, oxcarbazepine, topiramate, valproate.

This analysis also showed no clinically significant effect of the inducers (phenytoin, carbamazepine and phenobarbital) on retigabine clearance.

However, steady-state data from a limited number of patients in smaller phase II studies indicated that:

- phenytoin can reduce retigabine systemic exposure by 35%

- carbamazepine can reduce retigabine systemic exposure by 33%

Interaction with digoxin

Data f