Tiagabine

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one. If you have missed more than one dose, call your doctor for instructions about re-starting your medication.

Dosing Forms & Strength

tablet

• 2mg
• 4mg
• 12mg
• 16mg

Partial Seizures (With Hepatic Enzyme-Inducing Anticonvulsants)

Initial: 4 mg/day PO for 1Week

Titrate weekly by 4-8 mg, not to exceed 56 mg/day divided q8-12hr

Partial Seizures (Without Hepatic Enzyme-Inducing Anticonvulsants)

12-22 mg/day PO divided q8-12hr

Other Information

Take with food

Monitor seizure frequency, CBC, renal funtion tests, liver function tests

Dosing Forms & Strength

tablet

• 2mg
• 4mg
• 12mg
• 16mg

Partial Seizures (With Hepatic Enzyme-Inducing Anticonvulsants)

<12 years

• Not established

>12 years

• Initial: 4 mg/day PO for one Week, THEN
• 4 mg PO q12hr for one Week
• Titrate weekly by 4-8 mg, not to exceed 32 mg/day divided q6-12hr

Partial Seizures (Without Hepatic Enzyme-Inducing Anticonvulsants)

<12 years: Not established

>12 years old: same as adult

Other Information

<12 years old: not recommended

Take with food

Partial seizures (with hepatic enzyme-inducing anticonvulsants)

Initial: 4 mg/day PO for 1Week

Titrate weekly by 4-8 mg, not to exceed 56 mg/day divided q8-12hr

Partial seizures (without hepatic enzyme-inducing anticonvulsants)

12-22 mg/day PO divided q8-12hr

Pregnancy Category: C

Lactation: Unknown; use caution

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

Medicines can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of tiagabine there are no specific foods that you must exclude from your diet when receiving tiagabine.

Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The dose your doctor recommends may be based on the following:

• the condition being treated
• other medical conditions you have
• other medications you are taking
• how you respond to this medication
• your age 
• your liver function

In adolescents 12 to 18 years old who are on enzyme-inducing antiepilepsy drugs (AEDs) such as carbamazepine, phenytoin, primidone, and phenobarbital:

The recommended starting dose is 4mg/day and can be titrated up to a maximum dose of 32 mg/day, and will be given in divided doses.

Adults who are on enzyme-inducing antiepilepsy drugs (AEDs) such as carbamazepine, phenytoin, primidone, and phenobarbital:

The recommended dose range of tiagabine is 32 mg-56 mg/day in divided doses.

Dose will be lower for those patients who are not taking enzyme-inducing antiepilepsy drugs (AEDs).

Call your doctor at once if you have new or worsening seizures.

Do not stop using tiagabine suddenly. Stopping suddenly may cause increased seizures.

Usual Adult Dose for Epilepsy:

Patients receiving enzyme-inducing AED regimens:
-Initial dose: 4 mg orally once a day; modification of concomitant antiepilepsy drugs is not necessary, unless clinically indicated
-Titration: The total daily dose may be increased by 4 to 8 mg at weekly intervals until clinical response is achieved or, up to 56 mg/day; the total daily dose should be given in divided doses 2 to 4 times a day
-Maximum dose: 56 mg/day (in 2 to 4 divided doses)

Patients not receiving enzyme-inducing AED regimens:
-The estimated plasma concentrations of this drug in non-induced patients is twice that of patients receiving enzyme-inducing AEDs. Lower doses are required and slower titration may be necessary.

Comments:
-This drug should be taken with food.
-Do not use a loading dose.
-Rapid escalation and/or large dose increments should not be used.
-If a scheduled dose is missed, the patient should not make up for the missed dose by increasing the next dose; if several doses are missed, retitration may be required.
-Dosage adjustment may be needed whenever a change in the patient enzyme-inducing status occurs as a result of the addition, discontinuation, or dose change of the enzyme-inducing agent.

Use: For use as adjunctive therapy in the treatment of partial seizures

Usual Adult Dose for Seizures:

Patients receiving enzyme-inducing AED regimens:
-Initial dose: 4 mg orally once a day; modification of concomitant antiepilepsy drugs is not necessary, unless clinically indicated
-Titration: The total daily dose may be increased by 4 to 8 mg at weekly intervals until clinical response is achieved or, up to 56 mg/day; the total daily dose should be given in divided doses 2 to 4 times a day
-Maximum dose: 56 mg/day (in 2 to 4 divided doses)

Patients not receiving enzyme-inducing AED regimens:
-The estimated plasma concentrations of this drug in non-induced patients is twice that of patients receiving enzyme-inducing AEDs. Lower doses are required and slower titration may be necessary.

Comments:
-This drug should be taken with food.
-Do not use a loading dose.
-Rapid escalation and/or large dose increments should not be used.
-If a scheduled dose is missed, the patient should not make up for the missed dose by increasing the next dose; if several doses are missed, retitration may be required.
-Dosage adjustment may be needed whenever a change in the patient enzyme-inducing status occurs as a result of the addition, discontinuation, or dose change of the enzyme-inducing agent.

Use: For use as adjunctive therapy in the treatment of partial seizures

Usual Pediatric Dose for Epilepsy:

Less than 12 years: No dosing guidelines established.

Patients 12 years or older receiving enzyme-inducing AED regimens:
-Initial dose: 4 mg orally once a day; modification of concomitant antiepilepsy drugs is not necessary, unless clinically indicated
-Titration: The total daily dose may be increased by 4 mg at the beginning of Week 2; thereafter, the total daily dose may be increased by 4 to 8 mg at weekly intervals until clinical response is achieved or up to 32 mg/day (in divided doses 2 to 4 times a day); doses above 32 mg/day have been tolerated in a small number of adolescent patients for a relatively short duration

Patients 12 years or older not receiving enzyme-inducing AED regimens:
-The estimated plasma concentrations of this drug in non-induced patients is twice that of patients receiving enzyme-inducing AEDs. Lower doses are required and slower titration may be necessary.

Comments:
-This drug should be taken with food.
-Do not use a loading dose.
-Rapid escalation and/or large dose increments of should not be used.
-If a scheduled dose is missed, the patient should not make up for the missed dose by increasing the next dose; if several doses are missed, retitration may be required.
-Dosage adjustment may be needed whenever a change in the patient enzyme-inducing status occurs as a result of the addition, discontinuation, or dose change of the enzyme-inducing agent.

Use: For use as adjunctive therapy in children 12 years and older in the treatment of partial seizures

Usual Pediatric Dose for Seizures:

Less than 12 years: No dosing guidelines established.

Patients 12 years or older receiving enzyme-inducing AED regimens:
-Initial dose: 4 mg orally once a day; modification of concomitant antiepilepsy drugs is not necessary, unless clinically indicated
-Titration: The total daily dose may be increased by 4 mg at the beginning of Week 2; thereafter, the total daily dose may be increased by 4 to 8 mg at weekly intervals until clinical response is achieved or up to 32 mg/day (in divided doses 2 to 4 times a day); doses above 32 mg/day have been tolerated in a small number of adolescent patients for a relatively short duration

Patients 12 years or older not receiving enzyme-inducing AED regimens:
-The estimated plasma concentrations of this drug in non-induced patients is twice that of patients receiving enzyme-inducing AEDs. Lower doses are required and slower titration may be necessary.

Comments:
-This drug should be taken with food.
-Do not use a loading dose.
-Rapid escalation and/or large dose increments of should not be used.
-If a scheduled dose is missed, the patient should not make up for the missed dose by increasing the next dose; if several doses are missed, retitration may be required.
-Dosage adjustment may be needed whenever a change in the patient enzyme-inducing status occurs as a result of the addition, discontinuation, or dose change of the enzyme-inducing agent.

Use: For use as adjunctive therapy in children 12 years and older in the treatment of partial seizures

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:

• 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 or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• If seizures are worse or not the same after starting this medicine.
• Change in balance.
• Feeling confused.
• Change in eyesight or in the way you see color.
• Feeling very tired or weak.
• Feeling very sleepy.
• Not able to focus.
• Trouble speaking.
• Trouble walking.
• Patients who take tiagabine may be at a greater risk of having thoughts or actions of suicide. The risk may be greater in people who have had these thoughts or actions in the past. Call the doctor right away if signs like low mood (depression), nervousness, restlessness, grouchiness, panic attacks, or changes in mood or actions are new or worse. Call the doctor right away if any thoughts or actions of suicide occur.
• A very bad skin reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis) may happen. It can cause very bad health problems that may not go away, and sometimes death. Get medical help right away if you have signs like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in your mouth, throat, nose, or eyes.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• This medicine comes with an extra patient fact sheet called a Medication Guide. Read it with care. Read it again each time this medicine is refilled. If you have any questions about tiagabine, please talk with the doctor, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

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 brief summary of general information about tiagabine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using tiagabine.

Review Date: October 4, 2017

Tiagabine hydrochloride is an antiepilepsy drug available as 2 mg and 4 mg tablets for oral administration. Its chemical name is (-)-(R)-1-[4,4-Bis(3-methyl-2-thienyl)-3-butenyl]nipecotic acid hydrochloride, its molecular formula is C20H25NO2S2 HCl, and its molecular weight is 412.0. Tiagabine HCl is a white to off-white, odorless, crystalline powder. It is insoluble in heptane, sparingly soluble in water, and soluble in aqueous base. The structural formula is:

Inactive Ingredients

Tiagabine HCl tablets contain the following inactive ingredients: Ascorbic acid, colloidal silicon dioxide, crospovidone, hydrogenated vegetable oil wax, hydroxypropyl cellulose, hypromellose, lactose, magnesium stearate, microcrystalline cellulose, pregelatinized starch, stearic acid, and titanium dioxide.

In addition, individual tablets contain:

Tiagabine HCl is contraindicated in patients who have demonstrated hypersensitivity to the drug or its ingredients.

• Tiagabine HCl
• Tiagabine Hydrochloride

• Anticonvulsant, Miscellaneous

>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% (Limited to important or life-threatening): Abnormal electroencephalogram, abnormal erythrocytes, abnormal hepatic function tests, abnormal pap smear, abnormal stools, abscess, 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, ECG abnormality, exfoliative dermatitis, eye pain, facial edema, fecal incontinence, fibrocystic breast disease, furunculosis, gastritis, gastrointestinal hemorrhage, gingival hyperplasia, glossitis, goiter, hematuria, hemiplegia, hemoptysis, hemorrhage, hepatomegaly, hernia, herpes simplex infection, herpes zoster, hirsutism, hyperacusis, hypercholesteremia, hyperglycemia, hypermenorrhea, hyperreflexia, hyperventilation, hypoglycemia, hypokalemia, hyponatremia, hypotension, hypothyroidism, impotence, increased libido, keratoconjunctivitis, laryngitis, leg cramps, leukopenia, maculopapular rash, mastalgia, melena, movement disorder, muscle spasm, myocardial infarction, neuritis, oral paresthesia, orthostatic hypotension, osteoarthrosis, otitis externa, pallor, paralysis, pelvic pain, periodontal abscess, peripheral neuritis, peripheral vascular disease, petechia, phlebitis, photophobia, 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, vaginal hemorrhage, vesiculobullous dermatitis, visual field defect, voice disorder, withdrawal syndrome (seizures with abrupt withdrawal)

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.

Data not available