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Drug Details

Gabitril film-coated tablets (5 , 10, 15 mg)

• Drug Class Description
  GABA uptake inhibitors (anticonvulsants / anti- epileptics).
• Generic Name
  tiagabine hydrochloride monohydrate
• Presentation
  5 mg: Tablet. White, round biconvex film-coated tablet embossed on one side with '251'. 10 mg: Tablet. White, oval biconvex film-coated tablet embossed on one side with '252'. 15 mg: Tablet. White, oval biconvex film-coated tablet embossed on one side with '253'.
• Description
  Each Gabitril 5 mg tablet contains: Tiagabine anhydrous, INN 5 mg (as hydrochloride monohydrate) Each Gabitril 10 mg tablet contains: Tiagabine anhydrous, INN 10 mg (as hydrochloride monohydrate) Each Gabitril 15 mg tablet contains: Tiagabine anhydrous, INN 15 mg (as hydrochloride monohydrate)
• Indications
  Gabitril is an anti-epileptic drug indicated as add-on therapy for partial seizures with or without secondary generalisation where control is not achieved by optimal doses of at least one other anti-epileptic drug.
• Adult Dosage
  

  Gabitril should be taken orally with meals.

  Dosing schemes may need to be individualised based upon a patient's particular characteristics such as age and concomitant medications.

  Concomitant use with drugs involving CYP 3A4/5 metabolism: As CYP3A4/5 is involved in the metabolism of tiagabine, it is recommended that the dose of tiagabine is adjusted when it is taken in combination with CYP3A4/5 inducers.

  Following a given dose of tiagabine, the estimated plasma concentration in non-induced patients is more than twice that in patients receiving enzyme-inducing agents. To achieve similar systemic exposures of tiagabine, non-induced patients require lower and less frequent doses of tiagabine than induced patients. These patients may also require a slower titration of tiagabine compared to that of induced patients.

  Adults and children over 12 years: The initial daily dose is 5-10 mg tiagabine, followed by weekly increments of 5-10 mg/day. The usual maintenance dose in patients taking enzyme-inducing drugs is 30-45 mg/day. In patients not taking enzyme-inducing drugs, the maintenance dose should initially be reduced to 15-30 mg/day. The initial daily dose should be taken as a single dose or divided into two doses. The daily maintenance dose should be divided into two or three single doses.

  Patients with renal insufficiency: Renal insufficiency does not affect the pharmacokinetics of tiagabine, therefore the dosage does not need to be modified in this type of patient.

  Patients with impaired liver function: Tiagabine is metabolised in the liver and since the pharmacokinetics of tiagabine in patients with mild to moderate impaired liver function is modified, the Gabitril dosage should be adjusted by reducing the individual doses and/or prolonging the dose intervals.

  Gabitril should not be used in patients with severely impaired hepatic function.

• Child Dosage
  

  Children under 12 years: There is no experience with Gabitril in children under 12 years of age and as such Gabitril should not be used in this age group.

• Elderly Dosage
  

  There is limited information available on the use of Gabitril in elderly patients, but pharmacokinetics of tiagabine are unchanged, hence there should be no need for dose modification.

• Contra Indications
  

  Gabitril should not be given to patients with a history of hypersensitivity to tiagabine or one of the excipients.

  Severely impaired liver function

• Special Precautions
  

  Suicidal ideation and behaviour have been reported in patients treated with anti-epileptic agents in several indications. A meta-analysis of randomised placebo controlled trials of anti-epileptic 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 Gabitril.

  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 should signs of suicidal ideation or behaviour emerge.

  Post-marketing reports have shown that Gabitril use has been associated with new onset seizures and status epilepticus in patients without epilepsy. Confounding factors that may have contributed to development of seizures include underlying medical conditions or concomitant medications that can reduce seizure threshold, reported overdose and manner of dose administration (e.g. high dosage, fast titration rate).

  Safety and effectiveness of Gabitril have not been established for any indication other than as adjunctive therapy for partial seizures in adults and adolescents over 12 years.

  Gabitril is eliminated by hepatic metabolism and therefore caution should be exercised when administering the product to patients with impaired hepatic function. Reduced doses and/or dose intervals should be used and patients should be monitored closely for adverse events such as dizziness and tiredness.

  Although Gabitril may slightly prolong the CNS depressant effect of triazolam, this interaction is unlikely to be relevant to clinical practice.

  Anti-epileptic agents that induce hepatic enzymes (such as phenytoin, carbamazepine, phenobarbital and primidone) enhance the metabolism of tiagabine. Consequently, patients taking enzyme-inducing drugs may require doses of tiagabine above the usual dose range.

  Although there is no evidence of withdrawal seizures following Gabitril, it is recommended to taper off treatment over a period of 2-3 weeks.

  Serious rash, including vesiculobullous rash, has occured in patients receiving Gabitril.

  Spontaneous bruising has been reported. Therefore, if bruising is observed full blood count, including platelet count is to be performed.

  Rare cases of visual field defects have been reported with tiagabine. If visual symptoms develop, the patient should be referred to an ophthalmologist for further evaluation including perimetry.

  Gabitril tablets contain lactose and therefore should not be used in patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption.

• Interactions
  

  Anti-epileptic agents that induce hepatic enzymes (such as phenytoin, carbamazepine, phenobarbital and primidone) enhance the metabolism of tiagabine. The plasma concentration of tiagabine may be reduced by a factor 1.5-3 by concomitant use of these drugs.

  Gabitril does not have any clinically significant effect on the plasma concentrations of phenytoin, carbamazepine, phenobarbital, warfarin, digoxin, theophylline and hormones from oral contraceptive pills. Gabitril reduces the plasma concentration of valproate by about 10%, and cimetidine increases the bioavailability of tiagabine by about 5%. Neither of these findings are considered clinically important and do not warrant a dose modification.

• Adverse Drug Reactions
  

  Adverse events are mainly CNS related.

  A full list of adverse reactions reported with Gabitril during clinical studies and post marketing experience is shown in the table below. Adverse reactions are listed below as MedDRA preferred term by system organ class and frequency (frequencies are defined as: very common 1/10, common 1/100 to <1/10, uncommon 1/1,000 to <1/100, rare (1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data):

  The following undesirable effects have been reported with Gabitril:

  System Organ Class	Frequency	Undesirable effects
  Nervous system disorders	Very common	Dizziness, tremor
  	Common	Ataxia, abnormal gait, speech disorder
  	Uncommon	Somnolence
  	Rare	Non-convulsive status epilepticus
  	Not known	Encephalopathy
  Psychiatric disorders	Very common	Nervousness (non-specific)
  	Common	Concentration difficulties, depressed mood, emotional lability, confusion, insomnia, hostility/aggression
  	Uncommon	Depression, psychosis
  	Rare	Hallucinations, delusion
  Injury, poisoning and procedural complications	Common	Accidental injury
  General disorders and administration site conditions	Very common	Tiredness
  Eye disorders	Common	Vision blurred
  	Rare	Visual field defects
  Skin and subcutaneous tissue disorders	Uncommon	Dermatitis bullous, bruising
  	Not known	Vesiculobullous rash, exfoliative dermatitis
  Gastrointestinal disorders	Very common	Nausea
  	Common	Diarrhoea, vomiting, abdominal pain
  Musculoskeletal and connective tissue disorders	Common	Muscle twitching

  In patients with a history of serious behavioural problems there is a risk of recurrence of these symptoms during treatment with Gabitril, as occurs with certain other anti-epileptic drugs.

  Although not statistically significant, routine laboratory screening during placebo controlled studies showed a low white blood cell count (<2.5 x 10⁹ per litre) more frequently during Gabitril treatment (4.1%) than placebo (1.5%).

  Postmarketing reports have shown that Gabitril use has been associated with new onset seizures and status epilepticus in patients without epilepsy