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).
PO: C, Z (Insufficient data to conclude its safety and risk during pregnancy. Use only when benefits outweigh risks.)
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.
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
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.
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