Tiagabine

Definition

Tiagabine is an anticonvulsant medication indicated for the control of seizures in the treatment of epilepsy. Epilepsy is a neurological disorder in which excessive surges of electrical energy are emitted in the brain, causing seizures.

Purpose

Tiagabine decreases abnormal electrical activity within the brain that may trigger seizures. Although tiagabine controls some types of seizures associated with epilepsy, especially partial seizures, there is no known cure for the disorder.

Description

In the United States, tiagabine is sold under the brand name Gabitril. While the exact mechanism by which tiagabine reduces seizures is unknown, the drug boosts the levels of GABA, a neurotransmitter, in the brain. Neurotransmitters such as GABA are naturally occurring chemicals that transmit messages from one neuron (nerve cell) to another. When one neuron releases GABA, it normally binds to the next neuron, transmitting information and preventing the transmission of extra electrical activity. When levels of GABA are reduced, there may not be enough GABA to sufficiently bond to the neuron, leading to extra electrical activity in the brain and seizures. Tiagabine works to block GABA from being re-absorbed too quickly into the tissues, thereby increasing the amount available to bind to neurons.

Recommended dosage

Tiagabine is taken by mouth in tablet form and is prescribed by physicians in varying dosages.

Beginning a course of treatment with tiagabine requires a gradual dose-increasing regimen. Adults and teenagers 16 years or older typical take 4 mg a day at the beginning of treatment. The prescribing physician may raise a patient's daily dosage gradually over the course of several weeks. The usual dose is not greater than 56 mg per day. The full benefits of tiagabine may not be realized until after several weeks of therapy.

A person should not take a double dose of tiagabine. If a daily dose is missed, the next dose should be taken as soon as possible. However, if it is almost time for the next dose, the missed dose is skipped.

When discontinuing treatment including tiagabine, physicians typically direct patients to gradually reduce their daily dosages. Stopping the medicine suddenly may cause seizures to return or occur more frequently.

Precautions

A physician should be consulted before taking tiagabine with certain non-prescription medications. Patients should avoid alcohol and CNS depressants (medicines that can make one drowsy or less alert, such as antihistimines, sleep medications, and some pain medications) while taking tiagabine. Tiagabine can exacerbate (potentiate) the side effects of alcohol and other medications.

Tiagabine may not be suitable for persons with a history of liver or kidney disease, mental illness, high blood presure, angina (chest pain), irregular heartbeats, or other heart problems. Before beginning treatment with tiagabine, patients should notify their physician if they consume a large amount of alcohol, have a history of drug use, are pregnant, or plan to become pregnant. Physicians often advise the use of effective birth control while taking tiagabine. Studies in animals indicate that tiagabine may cause birth defects. Patients who become pregnant while taking tiagabine should contact their physician immediately.

Side effects

Patients and their physicians should weigh the risks and benefits of tiagabine before beginning treatment. Tiagabine is usually well-tolerated, but may case a variety of usually mild side effects. Dizziness, nausea and drowsiness are the most frequently reported side effects of tiagabine. Other possible side effects include:

• trouble sleeping
• fever
• headache
• unusual tiredness or weakness
• tremors
• abdominal pain
• increased appetite
• vomiting, diarrhea or constipation
• heartburn or indigestion
• aching joints and muscles or chills
• unpleasant taste in mouth or dry mouth tingling or prickly feeling on the skin

Many of these side effects disappear or occur less frequently during treatment as the body adjusts to the medication. However, if any symptoms persist or become too uncomfortable, the prescribing physician should be notified.

Other, uncommon side effects of tiagabine can be serious. A patient taking tiagabine who experiencs any of the following symptoms should contact their physician:

• rash or bluish patches on the skin
• mood or mental changes
• shakiness or unsteady walking
• excessive anxiety
• difficulty with memory
• double vision
• numbness in a limb.
• unsteadiness or clumsiness
• speech or language problems
• difficulty breathing
• chest pain
• irregular heartbeat
• faintness or loss of consciousness
• persistent severe headaches
• persistent fever or pain

Interactions

Tiagabine may have negative interactions with some antihistimines, antidepressants, antibiotics, and monoamine oxidase inhibitors (MAOIs). Other medications such as diazepam (Valium), phenobarbital (Luminal, Solfoton), nefazodone, metronidazole, acetazolamide (Diamox), phenytoin (Dilantin), primidone, and propranolol (Inderal) may also adversely react with triagabine. Tiagabine should be used with other other seizure prevention medications only if advised by a physician.

Many anticonvulsants may decrease the effectiveness of some forms of oral contraceptives (birth control pills).

Resources

BOOKS

Weaver, Donald F. Epilepsy and Seizures: Everything You Need to Know. Richmond Hill, Ontario: Firefly Books, 2001.

OTHER

"Tiagabine." Medline Plus. National Library of Medicine. (March 20, 2004). http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203392.html.

ORGANIZATIONS

American Epilepsy Society. 342 North Main Street, West Hartford, CT 06117-2507. http://www.aesnet.org.

Epilepsy Foundation. 4351 Garden City Drive, Landover, MD 20785-7223. (800) 332-1000. http://www.epilepsyfoundation.org.

Adrienne Wilmoth Lerner

Brand names: Gabitril®

Chemical formula:

Español:
• Clorhidrato de tiagabina, Tableta oral

Tiagabine Hydrochloride Oral tablet

What is this medicine?

TIAGABINE is used to control partial seizures in adults and children with epilepsy.

This medicine may be used for other purposes; ask your health care provider or pharmacist if you have questions.

What should I tell my health care provider before I take this medicine?

They need to know if you have any of these conditions:
•liver disease
•suicidal thoughts, plans, or attempt; a previous suicide attempt by you or a family member
•any unusual or allergic reaction to tiagabine, other medicines, foods, dyes, or preservatives
•pregnant or trying to get pregnant
•breast-feeding

How should I use this medicine?

Take this medicine by mouth with a glass of water. Follow the directions on the prescription label. Take with food. Take your doses at regular intervals. Do not take your medicine more often than directed. Do not stop taking this medicine unless instructed by your doctor or health care professional. Stopping your medicine suddenly can increase your seizures or their severity.

Talk to your pediatrician regarding the use of this medicine in children. Special care may be needed. While this drug may be prescribed for children as young as 12 years for selected conditions, precautions do apply.

Overdosage: If you think you have taken too much of this medicine contact a poison control center or emergency room at once.
NOTE: This medicine is only for you. Do not share this medicine with others.

What may interact with this medicine?

•carbamazepine
•phenobarbital
•phenytoin
•primidone
•triazolam
•valproic acid

This list may not describe all possible interactions. Give your health care provider a list of all the medicines, herbs, non-prescription drugs, or dietary supplements you use. Also tell them if you smoke, drink alcohol, or use illegal drugs. Some items may interact with your medicine.

What should I watch for while using this medicine?

Visit your doctor or health care professional for regular checks on your progress. Wear a medical identification bracelet or chain to say you have epilepsy, and carry a card that lists all your medications.

It is important to take this medicine exactly as directed. When first starting treatment, your dose will need to be adjusted slowly. It may take weeks or months before your dose is stable. You should contact your doctor or health care professional if your seizures get worse or if you have any new types of seizures.

You may get drowsy, dizzy, or have blurred vision. Do not drive, use machinery, or do anything that needs mental alertness until you know how this medicine affects you. To reduce dizzy or fainting spells, do not sit or stand up quickly, especially if you are an older patient. Alcohol can increase drowsiness and dizziness. Avoid alcoholic drinks.

The use of this medicine may increase the chance of suicidal thoughts or actions. Pay special attention to how you are responding while on this medicine. Any worsening of mood, or thoughts of suicide or dying should be reported to your health care professional right away.

What side effects may I notice from receiving this medicine?

Side effects that you should report to your doctor or health care professional as soon as possible:
•allergic reactions like skin rash, itching or hives, swelling of the face, lips, or tongue
•confusion
•depression
•difficulty remembering things
•difficulty speaking
•difficulty with movements or with walking
•redness, blistering, peeling or loosening of the skin, including inside the mouth
•sore throat or pain on swallowing
•tingling of the hands or feet
•vomiting
•weakness
•worsening of mood, thoughts or actions of suicide or dying

Side effects that usually do not require medical attention (report to your doctor or health care professional if they continue or are bothersome):
•diarrhea
•difficulty concentrating
•nausea
•nervousness
•stomach upset, indigestion
•tremors
•trouble sleeping

This list may not describe all possible side effects. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Where should I keep my medicine?

Keep out of reach of children.

Store at room temperature between 20 and 25 degrees C (68 and 77 degrees F). Protect from light or moisture. Throw away any unused medicine after the expiration date.

Last updated: 7/1/2002

Important Disclaimer: The drug information provided here is for educational purposes only. It is intended to supplement, not substitute for, the diagnosis, treatment and advice of a medical professional. This drug information does not cover all possible uses, precautions, side effects and interactions. It should not be construed to indicate that this or any drug is safe for you. Consult your medical professional for guidance before using any prescription or over the counter drugs.

Tiagabine
Systematic (IUPAC) name
(R)-1-[4,4-bis(3-methylthiophen-2-yl)but-3-enyl] piperidine-3-carboxylic acid
Identifiers
CAS number	115103-54-3
ATC code	N03AG06
PubChem	60648
DrugBank	APRD00344
Chemical data
Formula	C20H25NO2S2
Mol. mass	375.55 g/mol
Pharmacokinetic data
Bioavailability	90%
Protein binding	96%
Metabolism	Hepatic (CYP450 system)
Half life	7-9 hours
Excretion	Fecal and renal
Therapeutic considerations
Pregnancy cat.	B3 (Au), C (U.S.)
Legal status	POM (UK), ℞-only (U.S.)
Routes	Oral
Y(what is this?)  (verify)

Tiagabine (pronounced /taɪˈæɡəbiːn]/[1]) is an anti-convulsive medication produced by Cephalon and marketed under the brand name Gabitril. The drug was discovered at Novo Nordisk in Denmark in 1988 and was co-developed with Abbott. After a period of co-promotion, Cephalon licensed Tiagabine from Abbott/Novo and now is the exclusive producer. The medication is also used in the treatment of panic disorder, as are a few other anticonvulsants.

Contents 1 Pharmacology 2 Side effects 3 References 4 External links

Pharmacology

It is believed that the pharmacology is related to its ability, documented in in vitro experiments, to enhance the activity of gamma aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system. These experiments have shown that tiagabine binds to recognition sites associated with the GABA uptake carrier. It is thought that, by this action, tiagabine blocks GABA uptake into presynaptic neurons, permitting more GABA to be available for receptor binding on the surfaces of post-synaptic cells. Evidence is available that it operates as a selective GABA reuptake inhibitor.^[1]

Side effects

Tiagabine's most common side effects include confusion, difficulty speaking clearly/stuttering, mild sedation, and in doses over 8 mg, a tingling sensation (paresthesia) in the body's extremities, particularly the hands and fingers.

With overdoses in the range of 20/40 mg or more it will cause extreme sedation, temporary retardation, muscle tremors and spasms, uncontrollable bodily tremors, retrograde and anterograde amnesia, thrashing, screaming, flailing and extreme hostility, unconsciousness with seizures or seizure-like symptoms. Upon consciousness: extreme confusion with an inability to form coherent sentences, express ideas, or do the most basic activities for several hours.^{[original research?]} Unlike the benzodiazepines Tiagabine(Gabitril) has been shown to have no recreation value and any euphoria is most likely a placebo effect or because of consumption with alcohol.

References

1. ^ Pollack MH, Roy-Byrne PP, Van Ameringen M, et al. (November 2005). "The selective GABA reuptake inhibitor tiagabine for the treatment of generalized anxiety disorder: results of a placebo-controlled study". The Journal of clinical psychiatry 66 (11): 1401–8. PMID 16420077. http://article.psychiatrist.com/?ContentType=START&ID=10001907. 

External links

• Gabitril (manufacturer's website)
• Pharmacology

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