Tiagabine

Tiagabine also called Gabitril is an anti-epileptic medication or anticonvulsant that is used in combination with other medications to treat partial seizures (a type of epilepsy) in adults and children who are at least 12 years old ¹, ², ³. Tiagabine is occasionally used off-label to treat anxiety disorders and neuropathic pain.

It is not known exactly how Tiagabine (Gabitril) works, but it increases the amount of natural chemical in your brain called gamma aminobutyric acid (GABA) that prevent seizure activity ⁴, ⁵.

Tiagabine is available in tablets of 2, 4, 12 and 16 mg to be taken by mouth. Tiagabine usually is taken with food two to four times a day. However, for the first week of treatment you will only take tiagabine once a day. The recommended initial dose in adults is 4 mg once daily, increasing by 4 to 8 mg at weekly intervals based upon clinical response, but not exceeding 56 mg daily. Your doctor will slowly increase your dose (not more often than once each week) until you reach the dose of tiagabine you are to take regularly. To help you remember to take tiagabine, take it around the same time(s) every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take tiagabine exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Continue to take tiagabine even if you feel well. Do not stop taking tiagabine without talking to your doctor, even if you experience side effects such as unusual changes in behavior or mood. Abruptly stopping this medication can cause seizures. Your doctor will probably decrease your dose gradually.

Your doctor or pharmacist will give you the manufacturer’s patient information sheet (Medication Guide) when you begin treatment with tiagabine and each time you refill your prescription. Read the information carefully and ask your doctor or pharmacist if you have any questions.

Tiagabine most common side effects are dose related and include dizziness, somnolence, impaired concentration, nervousness, nausea, weakness and tremor.

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

Drinking alcohol with Tiagabine can cause side effects.

Tiagabine special precautions

Before taking tiagabine:

• tell your doctor and pharmacist if you are allergic to tiagabine or any other medications.
• tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, and nutritional supplements you are taking or plan to take. Be sure to mention any of the following: amiodarone (Cordarone, Pacerone);anticonvulsants such as carbamazepine (Tegretol), ethosuximide (Zarontin), gabapentin (Neurontin), lamotrigine (Lamictal), phenobarbital (Luminal, Solfoton), phenytoin (Dilantin, Phenytek), primidone (Mysoline), and valproic acid (Depakene, Depakote); anticholinesterases such as neostigmine (Prostigmin), physostigmine (Antilirium), and pyridostigmine (Mestinon, Regonol); antidepressants; antifungals such as fluconazole (Diflucan), itraconazole (Sporanox), and ketoconazole (Nizoral); chloroquine sulfate (Aralen); clarithromycin (Biaxin, in Prevpac); contrast dyes used during radiology procedures (CAT scans, X-rays); cyclosporine (Neoral, Sandimmune); dexamethasone (Decadron, Dexpak); diazepam (Valium); dicloxacillin; diltiazem (Cardizem, Dilacor, Tiazac, others); erythromycin (E.E.S., E-Mycin, Erythrocin); furosemide (Lasix); griseofulvin (Fulvicin-U/F, Grifulvin V, Gris-PEG); isoniazid (INH, Laniazid, Nydrazid); imipenem-cilastatin (Primaxin); lovastatin (Altocor, Mevacor, in Advicor); medications to treat HIV infection including delavirdine (Rescriptor), efavirenz (Sustiva), nevirapine (Viramune), and ritonavir (Norvir, in Kaletra); medications that may make you drowsy such as cough, cold, and allergy products, medications for anxiety, muscle relaxants, pain medications, sedatives, sleeping pills, or tranquilizers; medications for mental illness; methocarbamol (Robaxin); mycophenolate mofetil (CellCept); penicillins; phenylbutazone (no longer available in the US);propranolol (Inderal, Inderide); quinidine (Quinidex); quinolones such as cinoxacin (Cinobac) (no longer available in the US), ciprofloxacin (Cipro), enoxacin (Penetrex) (no longer available in the US), gatifloxacin (Tequin), levofloxacin (Levaquin), lomefloxacin (Maxequin), nalidixic acid (NegGram) (no longer available in the US), norfloxacin (Noroxin), ofloxacin (Floxin), sparfloxacin (Zagam) and trovafloxacin/alatrofloxacin combination (Trovan) (no longer available in the US); rifabutin (Mycobutin ); rifampin (Rifadin, Rifamate, Rimactane, others); stimulants such as caffeine-containing products and decongestants; tacrolimus (Prograf); triazolam (Halcion); troleandomycin (TAO); verapamil (Calan, Covera, Isoptin, Verelan); warfarin (Coumadin); or zafirlukast (Accolate).
• tell your doctor what herbal products you are taking, especially St. John’s wort.
• tell your doctor if you have or have ever had a severe rash caused by taking a medication; status epilepticus (seizures following one another without a break); or eye or liver disease.
• tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking tiagabine, call your doctor immediately.
• if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking tiagabine.
• you should know that tiagabine may make you drowsy and may affect your ability to think clearly. Do not drive a car or operate machinery until you know how this drug will affect you.
• remember that alcohol may add to the drowsiness caused by this medication. Ask your doctor about the safe use of alcoholic beverages while you are taking tiagabine.
• you should know that seizures, including status epilepticus, have occurred in people without epilepsy who take tiagabine. These seizures usually occurred soon after beginning treatment with tiagabine or near the time of a dose increase, but also have also occurred at other times during treatment.
• you should know that your mental health may change in unexpected ways and you may become suicidal (thinking about harming or killing yourself or planning or trying to do so) while you are taking tiagabine for the treatment of epilepsy, mental illness, or other conditions. A small number of adults and children 5 years of age and older (about 1 in 500 people) who took anticonvulsants such as tiagabine to treat various conditions during clinical studies became suicidal during their treatment. Some of these people developed suicidal thoughts and behavior as early as one week after they started taking the medication. There is a risk that you may experience changes in your mental health if you take an anticonvulsant medication such as tiagabine, but there may also be a risk that you will experience changes in your mental health if your condition is not treated. You and your doctor will decide whether the risks of taking an anticonvulsant medication are greater than the risks of not taking the medication. You, your family, or your caregiver should call your doctor right away if you experience any of the following symptoms: panic attacks; agitation or restlessness; new or worsening irritability, anxiety, or depression; acting on dangerous impulses; difficulty falling or staying asleep; aggressive, angry, or violent behavior; mania (frenzied, abnormally excited mood); talking or thinking about wanting to hurt yourself or end your life; withdrawing from friends and family; preoccupation with death and dying; giving away prized possessions; or any other unusual changes in behavior or mood. Be sure that your family or caregiver knows which symptoms may be serious so they can call the doctor if you are unable to seek treatment on your own.

Breastfeeding women

Because there is very limited published experience with tiagabine during breastfeeding, other agents may be preferred, especially while nursing a newborn or preterm infant ⁶. Doctors and mothers are advised to monitor the infant for drowsiness, adequate weight gain, and developmental milestones, especially in younger, exclusively breastfed infants and when using combinations of anticonvulsant or psychotropic drugs.

No adverse effects were reported in 10 newborns who were 4 to 23 days old who were breastfed during maternal intake of levetiracetam 1000 to 3000 mg daily. One mother was also taking tiagabine 30 mg daily, clobazam 45 mg daily and oxcarbazepine 600 mg daily ⁷.

Drug interactions

Taking Tiagabine with other drugs that make you sleepy can worsen this effect. Ask your doctor before taking tiagabine with a sleeping pill, narcotic pain medicine, muscle relaxer, or medicine for anxiety, depression, or seizures.

Tell your doctor about all your current medicines and any you start or stop using, especially:

• medicine to treat a psychiatric disorder
• diet pills, stimulants, or ADHD medication
• narcotic medicine
• other seizure medicines–carbamazepine, phenytoin, phenobarbital, primidone, valproate.

This list is not complete. Other drugs may interact with tiagabine, including prescription and over-the-counter medicines, vitamins, and herbal products.

How does tiagabine work?

Tiagabine (Gabitril) is a selective gamma aminobutyric acid (GABA) reuptake inhibitor that selectively and specifically inhibits the uptake of gamma aminobutyric acid (GABA) into astrocytes and neurones, by the transporter GAT-1, and therefore increases the extracellular concentration of GABA in the brain, which decreases the spread of abnormal neuronal impulses that contribute to seizures ⁸, ⁹, ¹, ¹⁰, ¹¹, ¹², ¹³, ¹⁴.

Tiagabine has been shown to be effective both as single drug therapy and in combination with other anticonvulsants for partial seizures.

Tiagabine uses

Tiagabine was approved for use in epilepsy in the United States in 1997 and is currently used predominantly as add-on therapy with other major anticonvulsants for partial seizures. Tiagabine is also used off-label to treat anxiety disorders and neuropathic pain (nerve pain) ¹⁵, ¹⁶. Tiagabine has also been investigated for its effect on alcohol withdrawal symptoms ¹⁷, ¹⁸, anxiety disorders ¹⁹, ²⁰, ²¹ and depression ²².

Tiagabine dosage

The recommended initial tiagabine dose in adults is 4 mg once daily, increasing by 4 to 8 mg at weekly intervals based upon clinical response, but not exceeding 56 mg daily. Your doctor will slowly increase your dose (not more often than once each week) until you reach the dose of tiagabine you are to take regularly. To help you remember to take tiagabine, take it around the same time(s) every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take tiagabine exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Tiagabine is often given in combination with other medications. Your dose of tiagabine may need to be changed if you start or stop using other seizure medicines.

Follow your doctor’s dosing instructions very carefully.

Take tiagabine with food.

Your doctor will need to check your progress while you are using tiagabine. To make sure you are taking a safe dose of tiagabine, your blood may need to be tested on a regular basis.

Use tiagabine regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely.

Wear a medical alert tag or carry an ID card stating that you take tiagabine. Any medical care provider who treats you should know that you take seizure medication.

Do not stop using tiagabine suddenly, even if you feel fine. Stopping suddenly may cause increased seizures. Follow your doctor’s instructions about tapering your dose.

Store at room temperature away from moisture, heat, and light.

Adult dose for epilepsy

Use: As add-on therapy in the treatment of partial seizures

• Initial dose: Tiagabine 4 mg orally once a day; modification of concomitant antiepilepsy drugs is not necessary, unless clinically indicated
• Titration: The total daily Tiagabine 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)

Comments:

• Tiagabine 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.

Adult dose for partial seizures

Use: Use as add-on therapy in the treatment of partial seizures

• Initial dose: Tiagabine 4 mg orally once a day; modification of concomitant antiepilepsy drugs is not necessary, unless clinically indicated
• Titration: The total daily Tiagabine 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)

Comments:

• Tiagabine 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.

Children dose for partial seizures

Use: Use as add-on therapy in children 12 years and older in the treatment of partial seizures

• Initial dose: Tiagabine 4 mg orally once a day; modification of concomitant antiepilepsy drugs is not necessary, unless clinically indicated
• Titration: The total daily Tiagabine 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.

Comments:

• Tiagabine 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.

What should I do if I forget a dose?

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.

Tiagabine side effects

Tiagabine may cause side effects. See your doctor if any of these symptoms are severe or do not go away:

• dizziness or lightheadedness
• drowsiness
• lack of energy or weakness
• wobbliness, unsteadiness, or incoordination causing difficulty walking
• depression
• hostility or anger
• irritability
• confusion
• difficulty concentrating or paying attention
• abnormal thinking
• speech or language problems
• increased appetite
• nausea
• stomach pain
• nervousness
• difficulty falling asleep or staying asleep
• itching
• bruising
• painful or frequent urination

Some side effects can be serious. The following symptoms are uncommon, but if you experience any of them, see your doctor immediately:

• rash
• sores on the inside of your mouth, nose, eyes or throat
• flu-like symptoms
• changes in vision
• severe weakness
• shaking hands you cannot control
• numbness, pain, burning, or tingling in the hands or feet
• seizures, including status epilepticus

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.

Tiagabine overdose

Tiagabine overdose symptoms may include:

• tiredness
• weakness
• wobbliness, unsteadiness, or incoordination causing difficulty walking
• shaking hands you cannot control
• confusion
• speech or language problems
• agitation
• anger or hostility
• depression
• vomiting
• loss of consciousness
• abnormal, uncontrollable muscle contractions
• temporary inability to move (paralysis)
• seizures, including status epilepticus.

In the case of Tiagabine overdose seek emergency medical attention or call your local emergency services number.

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