Tiagabine


Generic Medicine Info
Indications and Dosage
Oral
Adjunct in refractory partial seizures
Adult: Dose is individualised based on patient response and concomitant medications. As tiagabine (base) or tiagabine hydrochloride monohydrate: Initially, 5-10 mg daily as single or in 2 divided doses, may increase gradually in increments of 5-10 mg per day every week. Maintenance: Dose is given in 2 or 3 divided doses. In patients taking enzyme-inducing antiepileptic drugs (e.g. carbamazepine, phenytoin, phenobarbital, primidone): 30-45 mg daily. In patients not taking enzyme-inducing antiepileptic drugs: 15-30 mg daily. As tiagabine hydrochloride: In patients taking enzyme-inducing antiepileptic drugs: Initially, 4 mg once daily for 1 week, may gradually increase by 4-8 mg daily at weekly intervals until clinical response is achieved or up to 56 mg daily. Usual maintenance: 32-56 mg daily. Total daily dose is given in 2-4 divided doses. In patients not taking enzyme-inducing antiepileptic drugs: Lower doses are required; slower dose titration may also be needed. May consider dosage adjustments when changes in enzyme-inducing status occur (e.g. addition, discontinuation or dose adjustment of enzyme-inducing drugs). Dosage recommendations may vary among countries and individual products (refer to detailed product guideline).
Child: ≥12 years As tiagabine (base) or tiagabine hydrochloride monohydrate: Same as adult dose. As tiagabine hydrochloride: In patients taking enzyme-inducing antiepileptic drugs (e.g. carbamazepine, phenytoin, phenobarbital, primidone): Initially, 4 mg once daily for 1 week, then 8 mg daily in 2 divided doses for another week, then may further increase by 4-8 mg daily at weekly intervals. Doses are given in 2-4 divided doses daily. Titrate dose according to response. Max: 32 mg daily. In patients not taking enzyme-inducing antiepileptic drugs: Lower doses are required; slower dose titration may also be needed. May consider dosage adjustments when changes in enzyme-inducing status occur (e.g. addition, discontinuation or dose adjustment of enzyme-inducing drugs). Dosage recommendations may vary among countries and individual products (refer to detailed product guideline).
Hepatic Impairment
Mild to moderate: Dosage reduction and/or prolonged dose intervals may be required. Severe: Contraindicated.
Administration
Should be taken with food.
Contraindications
Severe hepatic impairment. Concurrent administration with St. John's Wort.
Special Precautions
Patients with history of serious behavioural problems. Patients who are not receiving enzyme-inducing drugs. Avoid abrupt withdrawal (may taper off treatment over a period of 2-3 weeks), rapid titration or large dose increments. Mild to moderate hepatic impairment. Children and elderly. Pregnancy and lactation.
Adverse Reactions
Significant: Suicidal ideation and behaviour, spontaneous bruising, moderately severe to incapacitating generalised weakness, CNS depression (impaired physical or mental abilities). Rarely, visual field defects.
Eye disorders: Blurred vision.
Gastrointestinal disorders: Nausea, diarrhoea, vomiting, abdominal pain.
General disorders and administration site conditions: Tiredness.
Injury, poisoning and procedural complications: Accidental injury.
Musculoskeletal and connective tissue disorders: Muscle twitching.
Nervous system disorders: Dizziness, tremor, ataxia, abnormal gait, speech disorder.
Psychiatric disorders: Nervousness, concentration difficulties, depressed mood, emotional lability, confusion, insomnia, hostility or aggression.
Respiratory, thoracic and mediastinal disorders: Pharyngitis.
Potentially Fatal: Rarely, severe skin reactions (e.g. Stevens-Johnson syndrome).
Patient Counseling Information
This drug may cause dizziness or drowsiness, if affected, do not drive or operate machinery.
Monitoring Parameters
Monitor for signs and symptoms of emergence or worsening of depression, suicidal ideation and behaviour, or unusual changes in mood or behaviour; therapeutic efficacy (seizure activity, type, duration); LFTs (periodically). May consider obtaining tiagabine plasma levels before and after changes in the therapeutic regimen.
Overdosage
Symptoms: Seizures (e.g. status epilepticus in patients with and without underlying seizure disorder), respiratory depression or arrest, coma, loss of consciousness, spike-wave stupor, encephalopathy, amnesia, confusion, disorientation, somnolence, dyskinesia, myoclonus, tremors, ataxia or incoordination, dizziness, nystagmus, impaired speech, headache, psychotic disorder, hallucinations, hostility, aggression, agitation, depression, lethargy, vomiting, hypersalivation, bradycardia, tachycardia, ST wave changes, hypertension, hypotension, urinary incontinence. Severe cases: Mute and withdrawn appearance, risk of convulsion. Management: Supportive treatment. Maintain airway, monitor vital signs and observe clinical status of the patient. Administration of activated charcoal in patients presenting within 1 hour of ingestion of >2 mg/kg may be considered. Perform gastric lavage or induce emesis.
Drug Interactions
Decreased plasma concentration with hepatic enzyme-inducing anti-epileptics (e.g. phenytoin, carbamazepine, phenobarbital, primidone).
Food Interaction
Reduced rate but not the extent of absorption with food. May lead to decreased exposure and loss of efficacy with St. John's Wort (potent CYP3A4 inducer); avoid concomitant use.
Action
Description: Tiagabine is a potent and selective inhibitor of neuronal and glial gamma-aminobutyric acid (GABA) uptake. Although its exact mechanism for antiseizure activity is unknown, it is believed that it enhances the activity of GABA (major inhibitory neurotransmitter in CNS) by binding to the GABA uptake carrier resulting in inhibition of the GABA uptake into presynaptic neurons. This action leads to an increased amount of GABA available for receptor binding on the surfaces of postsynaptic neurons.
Pharmacokinetics:
Absorption: Rapidly and well absorbed. Decreased rate but not the extent of absorption with food. Bioavailability: Approx 90% (absolute). Time to peak plasma concentration: 45 minutes (fasting state).
Distribution: Widely distributed throughout the body. Volume of distribution: 1.3-1.6 L/kg. Plasma protein binding: Approx 96%, mainly to albumin and α1-acid glycoprotein.
Metabolism: Extensively metabolised in the liver mainly by CYP3A4 isoenzyme; undergoes enterohepatic recirculation.
Excretion: Via faeces (63%) and urine (25%) mainly as metabolites; approx 2% as unchanged drug. Elimination half-life: 7-9 hours; 2-5 hours (in patients taking enzyme-inducing antiepileptic drugs).
Chemical Structure

Chemical Structure Image
Tiagabine

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 60648, Tiagabine. https://pubchem.ncbi.nlm.nih.gov/compound/Tiagabine. Accessed Apr. 26, 2021.

Storage
Store between 20-25°C. Protect from moisture and light.
MIMS Class
Anticonvulsants
ATC Classification
N03AG06 - tiagabine ; Belongs to the class of fatty acid derivatives antiepileptic.
References
Anon. Tiagabine. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 29/03/2021.

Buckingham R (ed). Tiagabine Hydrochloride. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 29/03/2021.

Gabitril 10 mg Film-Coated Tablets (Cephalon UK Limited). MHRA. https://products.mhra.gov.uk. Accessed 29/03/2021.

Joint Formulary Committee. Tiagabine. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 29/03/2021.

Tiagabine Tablet (Amneal Pharmaceuticals NY LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 29/03/2021.

Disclaimer: This information is independently developed by MIMS based on Tiagabine from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2021 MIMS. All rights reserved. Powered by MIMS.com
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