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• Description

  Tiagabine is a second- generation antiepileptic drug (AED) known under the proprietary brand name of Gabitril® (Teva, Petah Tikva, Israel) in the UK and USA. ;

• Generic formulation

  MHRA/ CHM advice to minimize risk when switching patients with epilepsy between different manufacturers’ products (including generic products):
  • It is usually unnecessary to ensure that patients are maintained on a specific manufacturer’s product unless there are specific concerns, such as patient anxiety and risk of confusion/ dosing error.
  ;

• Indications

  Epilepsy: adjunctive therapy for focal seizures with or without secondary generalization that are not satisfactorily controlled by other AEDs.
  
  Recommendations summarized from NICE (2012)
  • Seizure types: on referral to tertiary care (focal seizures), contraindicated (generalized tonic- clonic seizures, tonic/ atonic seizures, absence seizures, myoclonic seizures).
  • Epilepsy types: on referral to tertiary care (benign epilepsy with centrotemporal spikes, panayiotopoulos syndrome, late- onset childhood occipital epilepsy), contraindicated (absence syndromes, idiopathic generalized epilepsy, juvenile myoclonic epilepsy, Dravet syndrome, Lennox– Gastaut syndrome).
  ;

• Dose titration

  • Epilepsy— adjunctive therapy (with enzyme- inducing AEDs): 5–10 mg daily divided into 1 or 2 doses for 7 days, then increased by 5–10 mg daily every 7 days; usual maintenance 30– 45 mg daily divided into 2 or 3 doses.
  • Epilepsy— adjunctive therapy (without enzyme- inducing AEDs): 5–10 mg daily divided into 1 or 2 doses for 7 days, then increased by 5–10 mg daily every 7 days; usual maintenance 30– 45 mg daily divided into 2–3 doses.
  ;

• Plasma levels monitoring

  The inter- individual variation in liver metabolism makes Tiagabine a strong candidate for therapeutic drug monitoring. A broad reference range of 20– 200 ng/ mL has been proposed, however, the relatively short half- life of Tiagabine under most conditions means that care must be taken in drawing blood for therapeutic drug monitoring. The high binding to serum proteins further suggests that measurement of free drug concentrations may be useful. However, there has been little investigation of the relationship between serum/ plasma concentrations and therapeutic efficacy. ;

• Cautions

  • Patients with acute porphyrias.
  • Patients with absence, myoclonic, tonic and atonic seizures (risk of exacerbation).
  ;

• Adverse effects

  Tiagabine can be associated with adverse effects at the level the nervous system and other systems. ;

• Interactions

  With AEDs
  • AEDs that induce hepatic enzymes (such as carbamazepine, phenytoin, phenobarbital, and primidone) enhance the metabolism of tiagabine: the plasma concentration of tiagabine may be reduced by a factor .5– 3 by concomitant use of these AEDs.
  • Tiagabine reduces the plasma concentration of valproate by about 0% (this is not considered clinically important and does not warrant a dose modification).
  With other drugs
  • Cimetidine increases the bioavailability of tiagabine by about 5% (this is not considered clinically important and does not warrant a dose modification).
  • The combination of tiagabine with St John Wort (Hypericum perforatum) may lead to lower exposure and loss of efficacy of tiagabine, due to the potent induction of CYP3A4 by St John Wort, resulting in increased tiagabine metabolism. Therefore, the combination of tiagabine with St John’s Wort is contraindicated.
  With alcohol/food
  There are no known specific interactions between alcohol and tiagabine and there are no specific foods that must be excluded from diet when taking tiagabine. Administration with food results in a decreased rate and not extent of absorption ;

• Special populations

  Hepatic impairment
  • Reduce dose, prolong the dose interval, or both, in mild to moderate impairment.
  • Avoid in severe impairment.
  
  Renal impairment
  Renal insufficiency does not affect the pharmacokinetics of Tiagabine, therefore its dosage does not need to be modified.
  
  Pregnancy
  • Clinical experience of the use of tiagabine in pregnant women is limited and no information on tiagabine during breastfeeding is available. Therefore, as a precautionary measure, it is preferable not to use tiagabine during pregnancy or breast- feeding unless the potential benefits of treatment outweigh the potential risks.
  • In case of tiagabine treatment during pregnancy, the dose should be monitored carefully and adjustments made on a clinical basis.
  ;

• Behavioural and cognitive effects in patients with epilepsy

  Treatment with tiagabine has often been associated with depression and irritability. Results from randomized double- blind, controlled trials with tiagabine as adjunctive treatment have confirmed the incidence of psychiatric problems, which can be mild- to- moderate in severity and can be reported more frequently by patients with a personal history of affective disorders, or in case of rapid initial titration. Tiagabine is characterized by a good profile in terms of cognitive adverse effects, with mild effects on concentration and memory, which can be minimized by slow initial titration.;

• Psychiatric use

  Tiagabine has no approved indications in psychiatry and there is no conclusive evidence for its efficacy in the treatment of any behavioural problems. ;

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