Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
Gabitril (Novo Nordisk Pharmaceuticals)
5 mg, 10 mg and 15 mg tablets
Indication: epilepsy
Not all patients with partial seizures can be controlled by conventional antiepileptic drugs. Tiagabine adds to the list of second-line drugs which includes gabapentin, vigabatrin and lamotrigine.
Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter. By inhibiting reuptake of GABA, tiagabine can reduce the frequency of seizures.
In clinical trials, patients have had tiagabine or a placebo added to their usual treatment. These trials had a baseline period of 8-12 weeks followed by a double-blind titration period of 4-6 weeks, then a 8-12 week assessment period. The results showed tiagabine was significantly more effective than placebo in reducing the frequency of partial seizures. Tiagabine may also reduce the frequency of secondary generalised tonic-clonic seizures.
Although the trials have used a variety of dose frequencies, patients are recommended to take tiagabine 3 times a day. Treatment begins with a total dose of 7.5-15 mg and is increased at weekly intervals by 5-15 mg. The dose is increased until the patient responds or adverse effects develop. Most patients are maintained on 30-50 mg daily, but doses of 70 mg daily have been tolerated.
Tiagabine is well absorbed. Although food delays absorption, the tablets should be taken with food. Tiagabine is almost totally metabolised by the liver. Its clearance is increased by drugs which induce liver metabolism including phenytoin and carbamazepine. Enzyme induction can reduce the half-life from 7-9 hours to 2-3 hours.
Adverse events more frequently associated with tiagabine than placebo include dizziness, tiredness, nervousness and diarrhoea. Paradoxical status epilepticus has occurred when the dose of tiagabine has been increased. Although withdrawal seizures have not been reported, it is also recommended that the dose be gradually reduced.
With several second-line drugs now available, there is a need to establish the best approach to treatment. This may include studies of any synergistic effects between the drugs.
