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TiaGABine

Medically reviewed by Drugs.com. Last updated on Jul 1, 2020.

Pronunciation

(tye AG a been)

Index Terms

  • Tiagabine HCl
  • Tiagabine Hydrochloride

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral, as hydrochloride:

Gabitril: 2 mg [contains fd&c yellow #6 (sunset yellow)]

Gabitril: 4 mg [contains fd&c yellow #10 (quinoline yellow)]

Gabitril: 12 mg [contains brilliant blue fcf (fd&c blue #1), fd&c yellow #10 (quinoline yellow)]

Gabitril: 16 mg [contains fd&c blue #2 (indigotine)]

Generic: 2 mg, 4 mg, 12 mg, 16 mg

Brand Names: U.S.

  • Gabitril

Pharmacologic Category

  • Anticonvulsant, Miscellaneous

Pharmacology

The exact mechanism by which tiagabine exerts antiseizure activity is not definitively known; however, in vitro experiments demonstrate that it enhances the activity of gamma aminobutyric acid (GABA). It is thought that the binding of tiagabine to the GABA uptake carrier inhibits the uptake of GABA into presynaptic neurons, allowing an increased amount of GABA to be available to postsynaptic neurons; based on in vitro studies, tiagabine does not inhibit the uptake of dopamine, norepinephrine, serotonin, glutamate, or choline

Absorption

Rapid (45 minutes), well absorbed (>95%); prolonged with food

Distribution

Note: Vd values are more similar between children and adults when expressed as L/m2 (Gustavson 1997); Mean Vd:

Children 3 to 10 years: 2.4 L/kg

Adults: 1.3 to 1.6 L/kg

Metabolism

Hepatic via CYP (primarily 3A4); undergoes enterohepatic recirculation

Excretion

Feces (63%); urine (25%); 2% as unchanged drug; primarily as metabolites

Clearance: Note: Clearance values are more similar between children and adults when expressed as mL/minute/m2 (Gustavson 1997)

Children 3 to 10 years: 4.2 ± 1.6 mL/minute/kg

Children 3 to 10 years receiving enzyme-inducing AEDs: 8.6 ± 3.3 mL/minute/kg

Adults (normal volunteers): 109 mL/minute

Adult patients: 1.9 ± 0.5 mL/minute/kg

Adult patients receiving enzyme-inducing AEDs: 6.3 ± 3.5 mL/minute/kg

Hepatic impairment: Clearance of unbound drug is decreased by 60%

Time to Peak

Plasma: Fasting state: 45 minutes

Half-Life Elimination

Children 3 to 10 years: Mean: 5.7 hours (range: 2 to 10 hours); receiving enzyme-inducing AEDs: Mean: 3.2 hours (range: 2 to 7.8 hours)

Adults: 7 to 9 hours; receiving enzyme-inducing AEDs: 2 to 5 hours

Protein Binding

96%, primarily to albumin and alpha-1 acid glycoprotein

Special Populations: Hepatic Function Impairment

Moderate hepatic impairment (Child-Pugh class B) caused a 60% decrease in the Cl of unbound tiagabine.

Use: Labeled Indications

Partial seizures: Adjunctive therapy in adults and children ≥12 years in the treatment of partial seizures

Contraindications

Hypersensitivity to tiagabine or any component of the formulation

Dosing: Adult

Partial seizures (adjunct): Oral: Note: Do not use a loading dose, rapid titration, and/or increases with large dose increments.

Patients receiving enzyme-inducing AED regimens: Initial: 4 mg once daily for 1 week; may increase by 4 to 8 mg at weekly intervals, based on clinical response, up to 56 mg daily in 2 to 4 divided doses; usual maintenance: 32 to 56 mg/day

Patients not receiving enzyme-inducing AED regimens: The estimated plasma concentrations of tiagabine in patients not taking enzyme-inducing medications is twice that of patients receiving enzyme-inducing AEDs. Lower doses are required; slower titration may be necessary.

Dosage adjustment: Consider dosage adjustment when a change in enzyme-inducing status occurs due to the addition, discontinuation, or dose change of the enzyme-inducing agent. If multiple doses are missed, evaluate if retitration is clinically indicated.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Partial seizures; adjunctive therapy: Note: Do not use loading doses of tiagabine in any patient; do not use a rapid dosage escalation or increase the dose in large increments.

Children and Adolescents 12 to 18 years:

Patients receiving enzyme-inducing AED regimens: Oral: Initial: 4 mg once daily for 1 week, then 8 mg/day given in 2 divided doses for 1 week, then increase weekly by 4 to 8 mg/day; administer in 2 to 4 divided doses per day; titrate dose to response; maximum dose: 32 mg/day (doses >32 mg/day have been used in select adolescent patients for short periods of time)

Patients not receiving enzyme-inducing AED regimens: Oral: The estimated plasma concentrations of tiagabine in patients not taking enzyme-inducing medications is twice that of patients receiving enzyme-inducing AEDs. Lower doses are required; slower titration may be necessary.

Dosage adjustment: Consider dosage adjustment when a change in enzyme-inducing status occurs due to the addition, discontinuation, or dose change of the enzyme-inducing agent. If multiple doses are missed, evaluate if retitration is clinically indicated.

Extemporaneously Prepared

A 1 mg/mL tiagabine hydrochloride oral suspension may be made with tablets and a 1:1 mixture of Ora-Sweet® and Ora-Plus®. Crush ten 12 mg tablets in a mortar and reduce to a fine powder. Add small portions of the vehicle and mix to a uniform paste; mix while adding the vehicle in incremental proportions to almost 120 mL; transfer to a graduated cylinder; rinse mortar with vehicle, and add quantity of vehicle sufficient to make 120 mL. Label "shake well" and "refrigerate". Store in amber plastic prescription bottles; stable for 70 days at room temperature or 91 days refrigerated (preferred) (Nahata 2004).

A 1 mg/mL oral suspension may be made with tablets and a 6:1 mixture of simple syrup, NF and methylcellulose 1%. Crush ten 12 mg tablets in a mortar and reduce to a fine powder. Add 17 mL of methylcellulose 1% gel and mix to a uniform paste; mix while adding simple syrup, NF in incremental proportions to almost 120 mL; transfer to a graduated cylinder, rinse mortar with syrup, and add quantity of syrup sufficient to make 120 mL. Label "shake well" and "refrigerate". Store in amber plastic prescription bottles; stable for 42 days at room temperature or 91 days refrigerated (preferred) (Nahata 2004).

Administration

Oral: Administer with food.

Storage

Store at controlled room temperature of 20°C to 25°C (68°F to 77°F). Protect from moisture and light.

Drug Interactions

Abametapir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Monitor therapy

Alizapride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Aprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Consider therapy modification

Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Monitor therapy

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Bromopride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Avoid combination

Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Consider therapy modification

Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of TiaGABine. Management: Approximately 2-fold higher tiagabine doses and a more rapid dose titration will likely be required in patients concomitantly taking a strong CYP3A4 inducer. Consider therapy modification

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination. Some combinations are specifically contraindicated by manufacturers; others may have recommended dose adjustments. If combined, monitor for increased substrate effects. Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Consider therapy modification

Duvelisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification

Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Esketamine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Consider therapy modification

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fosnetupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Larotrectinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Consider therapy modification

Lisuride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Mefloquine: May diminish the therapeutic effect of Anticonvulsants. Mefloquine may decrease the serum concentration of Anticonvulsants. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of convulsions. If anticonvulsants are being used for another indication, monitor anticonvulsant concentrations and treatment response closely with concurrent use. Consider therapy modification

Methotrimeprazine: May enhance the CNS depressant effect of CNS Depressants. CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Consider therapy modification

Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy

Mianserin: May diminish the therapeutic effect of Anticonvulsants. Monitor therapy

MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification

Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Netupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Orlistat: May decrease the serum concentration of Anticonvulsants. Monitor therapy

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Avoid combination

Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interupt oxybate salt treatment during short-term opioid use. Consider therapy modification

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Palbociclib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Monitor therapy

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Consider therapy modification

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Tetrahydrocannabinol and Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Consider therapy modification

Adverse Reactions

>10%:

Central nervous system: Dizziness (27% to 31%), drowsiness (18% to 21%), nervousness (10% to 14%), lack of concentration (7% to 14%)

Gastrointestinal: Nausea (11%)

Infection: Infection (19%)

Neuromuscular & skeletal: Weakness (18% to 23%), tremor (9% to 21%)

Miscellaneous: Accidental injury (21%)

1% to 10%:

Cardiovascular: Vasodilation (2%), chest pain (≥1%), edema (≥1%), hypertension (≥1%), palpitations (≥1%), peripheral edema (≥1%), syncope (≥1%), tachycardia (≥1%)

Central nervous system: Ataxia (5% to 9%), pain (5% to 7%), depression (1% to 7%), insomnia (5% to 6%), confusion (5%), status epilepticus (5%), abnormal gait (3% to 5%), hostility (2% to 5%), memory impairment (4%), paresthesia (4%), speech disturbance (4%), emotional lability (3%), chills (≥1%), depersonalization (≥1%), dysarthria (≥1%), euphoria (≥1%), hallucination (≥1%), hypertonia (≥1%), hypoesthesia (≥1%), hyporeflexia (≥1%), hypotonia (≥1%), malaise (≥1%), migraine (≥1%), myoclonus (≥1%), paranoia (≥1%), personality disorder (≥1%), stupor (≥1%), twitching (≥1%), vertigo (≥1%), agitation (1%), myasthenia (1%)

Dermatologic: Bruise (6%), skin rash (5%), pruritus (2%), alopecia (≥1%), xeroderma (≥1%)

Gastrointestinal: Diarrhea (7% to 10%), vomiting (7%), abdominal pain (5% to 7%), increased appetite (2%), gingivitis (≥1%), stomatitis (≥1%), oral mucosa ulcer (1%)

Endocrine & metabolic: Weight gain (≥1%), weight loss (≥1%)

Genitourinary: Urinary tract infection (5%), abnormal uterine bleeding (≥1%), dysmenorrhea (≥1%), dysuria (≥1%), urinary incontinence (≥1%), vaginitis (≥1%)

Hematologic & oncologic: Lymphadenopathy (≥1%)

Hypersensitivity: Hypersensitivity reaction (≥1%)

Neuromuscular & skeletal: Myalgia (5%), arthralgia (≥1%), hyperkinesia (≥1%), hypokinesia (≥1%), neck pain (≥1%)

Ophthalmic: Amblyopia (9%), nystagmus (2%), visual disturbance (≥1%)

Otic: Otalgia (≥1%), otitis media (≥1%), tinnitus (≥1%)

Respiratory: Flu-like symptoms (6% to 9%), pharyngitis (7% to 8%), increased cough (4%), bronchitis (≥1%), dyspnea (≥1%), epistaxis (≥1%), pneumonia (≥1%)

Miscellaneous: Language problems (2%), cyst (≥1%), diaphoresis (≥1%)

<1%, postmarketing, and/or case reports: Abnormal dreams, abnormal electroencephalogram, abnormal erythrocytes, abnormal hepatic function tests, abnormal pap smear, abnormal stools, abscess, ageusia, altered sense of smell, amenorrhea, anemia, angina pectoris, apathy, aphthous stomatitis, apnea, arthritis, asthma, benign skin neoplasm, blepharitis, blindness, blurred vision, brain disease, breast hypertrophy, bullous dermatitis, bursitis, cellulitis, cerebral ischemia, cholecystitis, cholelithiasis, CNS neoplasm, coma, contact dermatitis, cutaneous nodule, cystitis, deafness, dehydration, delusions, dental caries, dermal ulcer, dysgeusia, dysphagia, dystonia, ECG abnormality, eczema, eructation, esophagitis, exfoliative dermatitis, eye pain, facial edema, fecal incontinence, fibrocystic breast disease, furunculosis, gastritis, gastrointestinal hemorrhage, gingival hyperplasia, glossitis, goiter, halitosis, hematuria, hemiplegia, hemoptysis, hemorrhage, hepatomegaly, hernia, herpes simplex infection, herpes zoster, hiccups, hirsutism, hyperacusis, hypercholesteremia, hyperglycemia, hyperlipemia, hypermenorrhea, hyperreflexia, hyperventilation, hypoglycemia, hypokalemia, hyponatremia, hypotension, hypothyroidism, impotence, increased libido, increased thirst, keratoconjunctivitis, laryngitis, leg cramps, leukopenia, maculopapular rash, mastalgia, melena, movement disorder, muscle spasm, myocardial infarction, neck stiffness, neoplasm, neuritis, nocturia, oral paresthesia, orthostatic hypotension, osteoarthrosis, otitis externa, pallor, paralysis, pelvic pain, periodontal abscess, peripheral neuritis, peripheral vascular disease, petechia, phlebitis, photophobia, polyuria, psoriasis, psychoneurosis, psychosis, pyelonephritis, rectal hemorrhage, renal failure, salpingitis, seizure (in patients with or without underlying seizure disorder), sepsis, sialorrhea, skin carcinoma, skin discoloration, skin photosensitivity, status epilepticus, Stevens-Johnson syndrome, subcutaneous nodule, suicidal ideation, suicidal tendencies, tendinous contracture, thrombocytopenia, thrombophlebitis, urethritis, urinary retention, urinary urgency, urticaria, vaginal hemorrhage, vesiculobullous dermatitis, visual field defect, voice disorder, withdrawal syndrome (seizures with abrupt withdrawal), xerostomia

Warnings/Precautions

Concerns related to adverse effects:

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).

• Dermatologic reactions: Severe reactions, including Stevens-Johnson syndrome, although rarely reported, have resulted in fatalities.

• Generalized weakness: Moderately severe to incapacitating generalized weakness has been reported after administration of tiagabine. The weakness resolved in all cases after a reduction in dose or discontinuation of tiagabine.

• Ophthalmic effects: Evidence of residual binding of tiagabine in the retina and uvea after 3 weeks has been observed in animal studies; although not directly measured, melanin binding is suggested. Long-term (up to 1 year) toxicological studies of tiagabine in animals showed no treatment-related ophthalmoscopic changes and macro- and microscopic examinations of the eye were unremarkable. The ability of available tests to detect potentially adverse consequences, if any, of the binding of tiagabine to melanin-containing tissue is unknown, and there was no systematic monitoring for relevant ophthalmological changes during the clinical development of tiagabine. Prescribers should be aware of the possibility of long-term ophthalmologic effects.

• Suicidal ideation: Pooled analysis of trials involving various antiepileptics (regardless of indication) showed an increased risk of suicidal thoughts/behavior (incidence rate: 0.43% treated patients compared to 0.24% of patients receiving placebo); risk observed as early as 1 week after initiation and continued through duration of trials (most trials ≤24 weeks). Monitor all patients for notable changes in behavior that might indicate suicidal thoughts or depression; notify health care provider immediately if symptoms occur.

Disease-related concerns:

• Hepatic impairment: Use with caution in patients with hepatic impairment.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

• Enzyme-inducing drugs: Experience in patients not receiving enzyme-inducing drugs has been limited; caution should be used in treating any patient who is not receiving one of these medications (decreased dose and slower titration may be required).

Other warnings/precautions:

• Off-label use: New-onset seizures and status epilepticus have been associated with tiagabine use when taken for off-label indications. Seizures have occurred with doses as low as 4 mg/day and shortly after a dosage increase, even after stable therapy. In most cases, patients were using concomitant medications (eg, antidepressants, antipsychotics, stimulants, opioids). In these instances, the discontinuation of tiagabine, followed by an evaluation for an underlying seizure disorder, is suggested. Use for unapproved indications, however, has not been proven to be safe or effective and is not recommended.

• Withdrawal: Anticonvulsants should not be discontinued abruptly because of the possibility of increasing seizure frequency; therapy should be withdrawn gradually to minimize the potential of increased seizure frequency, unless safety concerns require a more rapid withdrawal.

Monitoring Parameters

Seizure frequency, liver function tests (periodically), suicidality (eg, suicidal thoughts, depression, behavioral changes)

Pregnancy Considerations

Adverse events were observed in animal reproduction studies. Information specific to the use of tiagabine in pregnancy is limited (Leppik 1999; Neppe 2000).

Patients exposed to tiagabine during pregnancy are encouraged to enroll themselves into the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling 1-888-233-2334. Additional information is available at www.aedpregnancyregistry.org.

Patient Education

What is this drug used for?

• It is used to treat seizures.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Dizziness

• Nausea

• Vomiting

• Abdominal pain

• Anxiety

• Diarrhea

• Trouble sleeping

• Sore throat

• Flu-like signs

• Muscle pain

• Tremors

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Depression like thoughts of suicide, anxiety, emotional instability, or confusion

• Seizures

• Change in balance

• Confusion

• Vision changes

• Change in color vision

• Severe loss of strength and energy

• Severe fatigue

• Trouble focusing

• Trouble speaking

• Abnormal gait

• Agitation

• Irritability

• Panic attacks

• Mood changes

• Restlessness

• Stevens-Johnson syndrome/toxic epidermal necrolysis like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in mouth, throat, nose, or eyes

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.