Tiagabine Hydrochloride

The most commonly observed adverse events in placebo-controlled, parallel-group, add-on epilepsy trials associated with the use of GABITRIL in combination with other antiepilepsy drugs not seen at an equivalent frequency among placebo-treated patients were dizziness/lightheadedness, asthenia/lack of energy, somnolence, nausea, nervousness/irritability, tremor, abdominal pain, and thinking abnormal/difficulty with concentration or attention.

Approximately 21% of the 2531 patients who received GABITRIL in clinical trials of epilepsy discontinued treatment because of an adverse event. The adverse events most commonly associated with discontinuation were dizziness (1.7%), somnolence (1.6%), depression (1.3%), confusion (1.1%), and asthenia (1.1%).

In Studies 1 and 2 (U.S. studies), the double-blind, placebo-controlled, parallel-group, add-on studies, the proportion of patients who discontinued treatment because of adverse events was 11% for the group treated with GABITRIL and 6% for the placebo group. The most common adverse events considered the primary reason for discontinuation were confusion (1.2%), somnolence (1.0%), and ataxia (1.0%).

Adverse Event Incidence In Controlled Clinical Trials

Table 5 lists treatment-emergent signs and symptoms that occurred in at least 1% of patients treated with GABITRIL for epilepsy participating in parallel-group, placebo-controlled trials and were numerically more common in the GABITRIL group. In these studies, either GABITRIL or placebo was added to the patient’s current antiepilepsy drug therapy. Adverse events were usually mild or moderate in intensity.

The prescriber should be aware that these figures, obtained when GABITRIL was added to concurrent antiepilepsy drug therapy, cannot be used to predict the frequency of adverse events in the course of usual medical practice when patient characteristics and other factors may differ from those prevailing during clinical studies. Similarly, the cited frequencies cannot be directly compared with figures obtained from other clinical investigations involving different treatments, uses, or investigators. An inspection of these frequencies, however, does provide the prescribing physician with one basis to estimate the relative contribution of drug and non-drug factors to the adverse event incidences in the population studied.

Table 5: Treatment-Emergent Adverse Event1 Incidence in Parallel-Group, Placebo-Controlled, Add-On Trials (events in at least 1% of patients treated with GABITRIL and numerically more frequent than in the placebo group)

Other events reported by 1% or more of patients treated with GABITRIL but equally or more frequent in the placebo group were: accidental injury, chest pain, constipation, flu syndrome, rhinitis, anorexia, back pain, dry mouth, flatulence, ecchymosis, twitching, fever, amblyopia, conjunctivitis, urinary tract infection, urinary frequency, infection, dyspepsia, gastroenteritis, nausea and vomiting, myalgia, diplopia, headache, anxiety, acne, sinusitis, and incoordination.

Study 1 was a dose-response study including doses of 32 mg and 56 mg. Table 6 shows adverse events reported at a rate of ≥ 5% in at least one GABITRIL group and more frequent than in the placebo group. Among these events, depression, tremor, nervousness, difficulty with concentration/attention, and perhaps asthenia exhibited a positive relationship to dose.

Table 6: Treatment-Emergent Adverse Event Incidence in Study 1† (events in at least 5% of patients treated with GABITRIL 32 or 56 mg and numerically more frequent than in the placebo group)

The effects of GABITRIL in relation to those of placebo on the incidence of adverse events and the types of adverse events reported were independent of age, weight, and gender. Because only 10% of patients were non-Caucasian in parallel-group, placebo-controlled trials, there is insufficient data to support a statement regarding the distribution of adverse experience reports by race.

Other Adverse Events Observed During All Clinical Trials

GABITRIL has been administered to 2531 patients during all phase 2/3 clinical trials, only some of which were placebo-controlled. During these trials, all adverse events were recorded by the clinical investigators using terminology of their own choosing. To provide a meaningful estimate of the proportion of individuals having adverse events, similar types of events were grouped into a smaller number of standardized categories using modified COSTART dictionary terminology. These categories are used in the listing below. The frequencies presented represent the proportion of the 2531 patients exposed to GABITRIL who experienced events of the type cited on at least one occasion while receiving GABITRIL. All reported events are included except those already listed above, events seen only three times or fewer (unless potentially important), events very unlikely to be drug-related, and those too general to be informative. Events are included without regard to determination of a causal relationship to tiagabine.

Events are further classified within body system categories and enumerated in order of decreasing frequency using the following definitions: frequent adverse events are defined as those occurring in at least 1/100 patients; infrequent adverse events are those occurring in 1/100 to 1/1000 patients; rare events are those occurring in fewer than 1/1000 patients.

Frequent: Allergic reaction, chest pain, chills, cyst, neck pain, and malaise.

Infrequent

Abscess, cellulitis, facial edema, halitosis, hernia, neck rigidity, neoplasm, pelvic pain, photosensitivity reaction, sepsis, sudden death, and suicide attempt.

Frequent: Hypertension, palpitation, syncope, and tachycardia.

Infrequent: Angina pectoris, cerebral ischemia, electrocardiogram abnormal, hemorrhage, hypotension, myocardial infarct, pallor, peripheral vascular disorder, phlebitis, postural hypotension, and thrombophlebitis.

Frequent: Gingivitis and stomatitis.

Infrequent: Abnormal stools, cholecystitis, cholelithiasis, dysphagia, eructation, esophagitis, fecal incontinence, gastritis, gastrointestinal hemorrhage, glossitis, gum hyperplasia, hepatomegaly, increased salivation, liver function tests abnormal, melena, periodontal abscess, rectal hemorrhage, thirst, tooth caries, and ulcerative stomatitis.

Infrequent: Goiter and hypothyroidism.

Frequent: Lymphadenopathy.

Infrequent: Anemia, erythrocytes abnormal, leukopenia, petechia, and thrombocytopenia.

Frequent: Edema, peripheral edema, weight gain, and weight loss.

Infrequent: Dehydration, hypercholesteremia, hyperglycemia, hyperlipemia, hypoglycemia, hypokalemia, and hyponatremia.

Frequent: Arthralgia.

Infrequent: Arthritis, arthrosis, bursitis, generalized spasm, and tendinous contracture.

Frequent: Depersonalization, dysarthria, euphoria, hallucination, hyperkinesia, hypertonia, hypesthesia, hypokinesia, hypotonia, migraine, myoclonus, paranoid reaction, personality disorder, reflexes decreased, stupor, twitching, and vertigo.

Infrequent: Abnormal dreams, apathy, choreoathetosis, circumoral paresthesia, CNS neoplasm, coma, delusions, dry mouth, dystonia, encephalopathy, hemiplegia, leg cramps, libido increased, libido decreased, movement disorder, neuritis, neurosis, paralysis, peripheral neuritis, psychosis, reflexes increased, and urinary retention.

Frequent: Bronchitis, dyspnea, epistaxis, and pneumonia.

Infrequent: Apnea, asthma, hemoptysis, hiccups, hyperventilation, laryngitis, respiratory disorder, and voice alteration.

Frequent: Alopecia, dry skin, and sweating.

Infrequent: Contact dermatitis, eczema, exfoliative dermatitis, furunculosis, herpes simplex, herpes zoster, hirsutism, maculopapular rash, psoriasis, skin benign neoplasm, skin carcinoma, skin discolorations, skin nodules, skin ulcer, subcutaneous nodule, urticaria, and vesiculobullous rash.

Frequent: Abnormal vision, ear pain, otitis media, and tinnitus.

Infrequent: Blepharitis, blindness, deafness, eye pain, hyperacusis, keratoconjunctivitis, otitis externa, parosmia, photophobia, taste loss, taste perversion, and visual field defect.

Frequent: Dysmenorrhea, dysuria, metrorrhagia, urinary incontinence, and vaginitis.

Infrequent: Abortion, amenorrhea, breast enlargement, breast pain, cystitis, fibrocystic breast, hematuria, impotence, kidney failure, menorrhagia, nocturia, papanicolaou smear suspicious, polyuria, pyelonephritis, salpingitis, urethritis, urinary urgency, and vaginal hemorrhage.

Postmarketing Reports

The following adverse reactions have been identified during postapproval use of GABITRIL. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Skin and subcutaneous tissue disorders: bullous dermatitis

Eye disorders: vision blurred

Seizures in Patients Without Epilepsy: Post-marketing reports have shown that GABITRIL use has been associated with new onset seizures and status epilepticus in patients without epilepsy. Dose may be an important predisposing factor in the development of seizures, although seizures have been reported in patients taking daily doses of GABITRIL as low as 4 mg/day. In most cases, patients were using concomitant medications (antidepressants, antipsychotics, stimulants, narcotics) that are thought to lower the seizure threshold. Some seizures occurred near the time of a dose increase, even after periods of prior stable dosing.

The GABITRIL dosing recommendations in current labeling for treatment of epilepsy were based on use in patients with partial seizures 12 years of age and older, most of whom were taking enzyme-inducing antiepileptic drugs (AEDs; e.g., carbamazepine, phenytoin, primidone and phenobarbital) which lower plasma levels of GABITRIL by inducing its metabolism. Use of GABITRIL without enzyme-inducing antiepileptic drugs results in blood levels about twice those attained in the studies on which current dosing recommendations are based (see DOSAGE AND ADMINISTRATION).

Safety and effectiveness of GABITRIL have not been established for any indication other than as adjunctive therapy for partial seizures in adults and children 12 years and older.

In nonepileptic patients who develop seizures while on GABITRIL treatment, GABITRIL should be discontinued and patients should be evaluated for an underlying seizure disorder.

Seizures and status epilepticus are known to occur with GABITRIL overdosage (see OVERDOSE).

Suicidal Behavior And Ideation

Antiepileptic drugs (AEDs), including GABITRIL, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.

Pooled analyses of 199 placebo-controlled clinical trials (mono-and adjunctive therapy) of 11 different AEDs showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated. There were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide.

The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed.

The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5-100 years) in the clinical trials analyzed.

Table 4 shows absolute and relative risk by indication for all evaluated AEDs.

Table 4: Risk by Indication for Antiepileptic Drugs in the Pooled Analysis

The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications.

Anyone considering prescribing GABITRIL or any other AED must balance the risk of suicidal thoughts or behavior with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated.

Patients, their caregivers, and families should be informed that AEDs increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of the signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Behaviors of concern should be reported immediately to healthcare providers.

Withdrawal Seizures

As a rule, antiepilepsy drugs should not be abruptly discontinued because of the possibility of increasing seizure frequency. In a placebo-controlled, double-blind, dose-response study (Study 1 described in CLINICAL STUDIES) designed, in part, to investigate the capacity of GABITRIL to induce withdrawal seizures, study drug was tapered over a 4-week period after 16 weeks of treatment. Patients’ seizure frequency during this 4-week withdrawal period was compared to their baseline seizure frequency (before study drug). For each partial seizure type, for all partial seizure types combined, and for secondarily generalized tonic-clonic seizures, more patients experienced increases in their seizure frequencies during the withdrawal period in the three GABITRIL groups than in the placebo group. The increase in seizure frequency was not affected by dose. GABITRIL should be withdrawn gradually to minimize the potential of increased seizure frequency, unless safety concerns require a more rapid withdrawal.

Cognitive/Neuropsychiatric Adverse Events

Adverse events most often associated with the use of GABITRIL were related to the central nervous system. The most significant of these can be classified into 2 general categories: 1) impaired concentration, speech or language problems, and confusion (effects on thought processes); and 2) somnolence and fatigue (effects on level of consciousness). The majority of these events were mild to moderate. In controlled clinical trials, these events led to discontinuation of treatment with GABITRIL in 6% (31 of 494) of patients compared to 2% (5 of 275) of the placebo-treated patients. A total of 1.6% (8 of 494) of the GABITRIL treated patients in the controlled trials were hospitalized secondary to the occurrence of these events compared to 0% of the placebo treated patients. Some of these events were dose related and usually began during initial titration.

Patients with a history of spike and wave discharges on EEG have been reported to have exacerbations of their EEG abnormalities associated with these cognitive/neuropsychiatric events. This raises the possibility that these clinical events may, in some cases, be a manifestation of underlying seizure activity (see PRECAUTIONS, Laboratory Tests, EEG). In the documented cases of spike and wave discharges on EEG with cognitive/neuropsychiatric events, patients usually continued tiagabine, but required dosage adjustment.

Additionally, there have been postmarketing reports of patients who have experienced cognitive/neuropsychiatric symptoms, some accompanied by EEG abnormalities such as generalized spike and wave activity, that have been reported as nonconvulsant status epilepticus. Some reports describe recovery following reduction of dose or discontinuation of GABITRIL.

Status Epilepticus

In the three double-blind, placebo-controlled, parallel-group studies (Studies 1, 2, and 3), the incidence of any type of status epilepticus (simple, complex, or generalized tonic-clonic) in patients receiving GABITRIL was 0.8% (4 of 494 patients) versus 0.7% (2 of 275 patients) receiving placebo. Among the patients treated with GABITRIL across all epilepsy studies (controlled and uncontrolled), 5% had some form of status epilepticus. Of the 5%, 57% of patients experienced complex partial status epilepticus. A critical risk factor for status epilepticus was the presence of a previous history; 33% of patients with a history of status epilepticus had recurrence during GABITRIL treatment. Because adequate information about the incidence of status epilepticus in a similar population of patients with epilepsy who have not received treatment with GABITRIL is not available, it is impossible to state whether or not treatment with GABITRIL is associated with a higher or lower rate of status epilepticus than would be expected to occur in a similar population not treated with GABITRIL.

Sudden Unexpected Death In Epilepsy (SUDEP)

There have been as many as 10 cases of sudden unexpected deaths during the clinical development of tiagabine among 2531 patients with epilepsy (3831 patient-years of exposure).

This represents an estimated incidence of 0.0026 deaths per patient-year. This rate is within the range of estimates for the incidence of sudden and unexpected deaths in patients with epilepsy not receiving GABITRIL (ranging from 0.0005 for the general population with epilepsy, 0.003 to 0.004 for clinical trial populations similar to that in the clinical development program for GABITRIL, to 0.005 for patients with refractory epilepsy). The estimated SUDEP rates in patients receiving GABITRIL are also similar to those observed in patients receiving other antiepilepsy drugs, chemically unrelated to GABITRIL, that underwent clinical testing in similar populations at about the same time. This evidence suggests that the SUDEP rates reflect population rates, not a drug effect.

Tiagabine is an anti-epileptic medication, also called an anticonvulsant.

Tiagabine is used to alone or in combination with other medications to treat partial seizures in adults and children who are at least 12 years old.

Tiagabine may also be used for purposes other than those listed in this medication guide.

You should not use this medication if you are allergic to tiagabine.

If you have liver disease, you may need a dose adjustment or special tests to safely take this medication.

You may have thoughts about suicide while taking this medication. Tell your doctor if you have new or worsening depression or suicidal thoughts during the first several months of treatment, or whenever your dose is changed.

Your family or other caregivers should also be alert to changes in your mood or symptoms. Your doctor will need to check you at regular visits. Do not miss any scheduled appointments.

FDA pregnancy category C. It is not known whether tiagabine is harmful to an unborn baby. Before taking this medication, tell your doctor if you are pregnant or plan to become pregnant during treatment.

It is not known whether tiagabine passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

Tiagabine can cause side effects that may impair your vision or reactions. Be careful if you drive or do anything that requires you to be alert and able to see clearly.

Avoid drinking alcohol. It can increase some of the side effects of tiagabine.

General

• Withdraw gradually to minimize potential for increased seizure frequency.1 13 (See Discontinuance of Therapy under Cautions.)

• Closely monitor for notable changes in behavior that could indicate emergence or worsening of suicidal thoughts or behavior or depression.20 21 24 (See Suicidality Risk under Cautions.)

• Therapeutic plasma concentration range has not been established; determination of plasma concentrations may be useful before and after changes to drug regimen.1

Administration

Oral Administration

Administer orally with food.1

Administer initial dosage (4 mg) once daily; following dosage increases, administer in 2–4 divided doses daily.1 Limited experience exists for dosages >32 mg daily given in a twice-daily regimen.1

Dosage

Available as tiagabine hydrochloride; dosage expressed in terms of the salt.1

Dosage is based on whether a hepatic enzyme-inducing anticonvulsant drug (e.g., carbamazepine, phenobarbital, phenytoin, primidone) is administered concomitantly.1 5 6 13 11 (See Specific Drugs under Interactions.)

Patients receiving a combination of enzyme-inducing and non-enzyme-inducing anticonvulsants (e.g., carbamazepine and valproate) should be considered to have induced hepatic microsomal enzymes.1

Modification of tiagabine dosage may be required with the addition of a hepatic enzyme-inducing anticonvulsant, dosage change of these drugs, or their discontinuance from the regimen.1

Unless clinically indicated, modification of concomitant anticonvulsant therapy is not necessary when tiagabine is added to an anticonvulsant regimen.1 (See Specific Drugs under Interactions.)

Administration of a loading dose is not recommended.1 Increase dosage slowly; avoid rapid increases in dosage and/or large dosage increments.1

Consider dosage retitration if a patient misses multiple doses.1

Pediatric Patients

Adolescents 12–18 years of age: Initially, 4 mg once daily for the first week.1 Daily dosage may be increased to 4 mg twice daily beginning with the second week; thereafter, the total daily dosage (administered in 2–4 divided doses) may be increased by 4–8 mg at weekly intervals until a clinical response is achieved or a total daily dosage of 32 mg is reached.1

See manufacturer’s prescribing information for typical dosing titration regimen.1

Adolescents 12–18 years of age: Use lower dosage and a slower dosage titration schedule than that used in those receiving an enzyme-inducing anticonvulsant.1

Systemic exposure following administration of a 12-mg dose in a patient not receiving a hepatic enzyme-inducing drug is expected to be comparable to that of a 32-mg dose in a patient receiving a hepatic enzyme-inducing drug.1

Adults

Initially, 4 mg once daily for the first week.1 Beginning with the second week, the total daily dosage (administered as 2–4 divided doses) may be increased by 4–8 mg at weekly intervals until a clinical response is achieved or a total daily dosage of 56 mg is reached.1

Usual maintenance dosage: 32–56 mg daily administered as 2–4 divided doses.1

See manufacturer’s prescribing information for typical dosing titration regimen.1

Use lower dosage and a slower dosage titration schedule than that used in those receiving an enzyme-inducing anticonvulsant.1

Systemic exposure following administration of a 12- or 22-mg dose in a patient not receiving a hepatic enzyme-inducing drug is expected to be comparable to that of a 32- or 56-mg dose in a patient receiving a hepatic enzyme-inducing drug.1

Prescribing Limits

Pediatric Patients

Daily dosages >32 mg have been tolerated in a limited number of adolescents for a relatively short duration.1

Adults

Dosages >56 mg daily have not been systemically evaluated.1

Special Populations

Hepatic Impairment

Decreased initial and maintenance dosages and/or longer dosing intervals may be required.1 (See Special Populations under Pharmacokinetics.)

Renal Impairment

No special population dosage recommendations at this time.1

Geriatric Patients

No special population dosage recommendations at this time.1

Contraindications

Known hypersensitivity to tiagabine or any ingredient in the formulation.1

Warnings/Precautions

Warnings

New-onset seizures and status epilepticus reported in patients without epilepsy; may be dose-related and may occur in patients using concomitant drugs that lower seizure threshold (e.g., antidepressants, antipsychotics, stimulants, narcotics).1 14

Safety and efficacy not established for any indication other than the management of partial seizures.1 Use of tiagabine for unlabeled indications is strongly discouraged.14

Discontinue therapy if seizures develop in nonepileptic patients and evaluate patient for underlying seizure disorder.1

Abrupt withdrawal may result in increased seizure frequency; withdraw gradually and reduce dosage slowly unless safety concerns require a more rapid withdrawal.1 13

Possible somnolence and fatigue, impaired concentration, speech or language problems, and confusion; usually mild to moderate in severity, may be dose-related, and usually begins during initial dosage titration.1

Cognitive/neuropsychiatric events may be accompanied by EEG abnormalities (e.g., generalized spike and wave activity). 1 May be a manifestation of underlying seizure activity; dosage adjustment may be required.1

Increased risk of suicidality (suicidal behavior or ideation) observed in an analysis of studies using various anticonvulsants in patients with epilepsy, psychiatric disorders (e.g., bipolar disorder, depression, anxiety), and other conditions (e.g., migraine, neuropathic pain); risk in patients receiving anticonvulsants (0.43%) was approximately twice that in patients receiving placebo (0.24%).20 21 24 Increased suicidality risk was observed ≥1 week after initiation of anticonvulsant therapy and continued through 24 weeks.20 21 24 Relative risk was higher for patients with epilepsy compared with those receiving anticonvulsants for other conditions.20

Closely monitor all patients currently receiving or beginning anticonvulsant therapy for changes in behavior that may indicate emergence or worsening of suicidal thoughts or behavior or depression.20 21 24 Anxiety, agitation, hostility, insomnia, and mania may be precursors to emerging suicidality.20

Balance risk of suicidality with risk of untreated illness.20 24 Epilepsy and other illnesses treated with anticonvulsants are themselves associated with morbidity and mortality and an increased risk of suicidality.23 24 If suicidal thoughts or behavior emerges during anticonvulsant therapy, consider whether these symptoms may be related to the illness itself.23 24 (See Advice to Patients.)

Not established whether incidence of status epilepticus (5% in controlled and uncontrolled trials of tiagabine) is higher or lower than would be expected to occur in patients with epilepsy not treated with the drug.1

Seizures and status epilepticus may occur with tiagabine overdosage.1

Higher incidence of sudden and unexplained deaths than would be expected in a healthy (nonepileptic) population; however, incidence is within range of estimates for patients with epilepsy or refractory epilepsy.1

Sensitivity Reactions

Serious rash (i.e., Stevens-Johnson syndrome, maculopapular rash, vesiculobullous rash), potentially fatal, reported rarely.1

General Precautions

Generalized weakness (moderately severe to incapacitating) reported; resolves after a reduction in dose or discontinuance of tiagabine.1

Possible long-term ophthalmologic effects.1 Accumulation of tiagabine in melanin-containing cells in the eye observed in dogs; however ophthalmologic changes were not noted in long-term studies in these animals.1

Manufacturer makes no specific recommendations for periodic ophthalmologic monitoring.1

Specific Populations

Category C.1

Distributed into milk in rats; not known whether distributed into human milk.1 Use only if potential benefits outweigh the risks.1

Safety and efficacy not established in children <12 years of age.1 Pharmacokinetics evaluated in a limited number of children 3–10 years of age.1 (See Special Populations under Pharmacokinetics.)

Insufficient experience in patients ≥65 years of age to determine whether safety and efficacy of tiagabine in geriatric patients differ from safety and efficacy in younger adults.1 The pharmacokinetic profile in healthy geriatric adults does not appear to differ from that in younger adults.1 11

Decreased clearance in patients with moderate hepatic impairment (Child-Pugh class B); dosage adjustments recommended.1 (See Hepatic Impairment under Dosage and Administration.)

Pharmacokinetics not altered in patients with mild, moderate, or severe renal impairment or in those undergoing hemodialysis.1

Common Adverse Effects

Dizziness/light-headedness, asthenia, somnolence, nausea, nervousness/irritability, tremor, abdominal pain, abnormal thinking/difficulty with concentration or attention.1

Metabolized by CYP isoenzymes, principally CYP3A.1 May also be metabolized by CYP1A2, CYP2D6, or CYP2C19.1

Does not appear to induce or inhibit hepatic microsomal enzymes.1 6

Does not appear to have clinically important effects on the pharmacokinetics of other anticonvulsants.1 6

Drugs Affecting Hepatic Microsomal Enzymes

Inducers of CYP3A4: Potential pharmacokinetic interaction (decreased plasma tiagabine concentrations).1

Tiagabine does not induce or inhibit hepatic microsomal enzymes responsible for metabolizing antipyrine.1

Protein-bound Drugs

Potential for tiagabine to displace or to be displaced by other protein-bound drugs.1 6

Specific Drugs