Drugs List

Therapeutic Indications

Uses

Epilepsy (inadequately controlled) - partial seizures: adjunctive therapy

Contraindications

Children under 12 years
Galactosaemia
Porphyria
Severe hepatic impairment

Precautions and Warnings

Breastfeeding
Glucose-galactose malabsorption syndrome
Lactose intolerance
Mild hepatic impairment
Pregnancy

Advise patient ability to drive or operate machinery may be impaired
Folic acid 5mg daily required pre-conception to end of 1st trimester
Contains lactose
If visual disturbances occur, perform ophthalmic evaluation
Monitor patients with hepatic impairment for adverse effects
Perform full blood count if spontaneous bruising occurs
Advise patients/carers to seek medical advice if suicidal intent develops
Avoid abrupt withdrawal
To discontinue, reduce dose gradually for last 2-4 weeks of therapy
Advise patient to seek advice at first indications of pregnancy
Advise patient not to take St John's wort concurrently
Female: Ensure adequate contraception during treatment

Use of tiagabine has been associated with new onset seizures and status epilepticus in patients without epilepsy. Underlying medical conditions or concomitant medications that can reduce seizure threshold, reported overdose and manner of dose administration (e.g. high dosage, fast titration rate), may have contributed to the development of seizures.

Pregnancy and Lactation

Pregnancy

Use tiagabine with caution in pregnancy.

Schaefer suggests there is no reason to terminate a pregnancy which has occurred during treatment, however a detailed ultrasound during the second trimester should be carried out to eliminate major structural abnormalities. Briggs suggests if the use of tiagabine is unavoidable, there is no evidence to suggest foetal harm but use the lowest effective dose, if possible, as well as 4 to 5 mg per day of folic acid. Other sources suggest that the essential treatment of taking antiepileptic drugs outweighs the unknown concern of the potential harm to the foetus as the likelihood of a women taking antiepileptic drugs to have a baby with no malformation is 90%.

Studies in animals have not shown teratogenic effects of tiagabine, however at very high doses revealed peri and post-natal toxicity. There is limited experience in the use of tiagabine in human pregnancy.

Antiepileptic drugs may reduce the efficiency of hormonal contraceptives and some hormonal contraceptives may reduce the efficiency of antiepileptic drugs, therefore women who have child-bearing potential should be given advice for an affective contraception to avoid unplanned pregnancy.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Use tiagabine with caution in breastfeeding.

The Drugs and Lactation Database (LactMed) suggests if using tiagabine, the infant should be closely monitored for drowsiness, adequate weight gain, and developmental milestones, especially younger and/or exclusively breastfed infants, and those on combinations of anticonvulsant drugs. Some sources suggest mothers on anti-epileptic drugs should be encouraged to breastfeed as it is generally considered safe, however if a women is on a combination therapy advice should be sought. The risk of injury to the infant caused by a maternal seizure is low but if toxicity develops consider advising supplementing the feed with formula milk or ceasing breastfeeding periodically to limit exposure.

There is very little information available on the use of tiagabine in breastfeeding.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Accidental injury
Activation of new seizure types
Aggression
Ataxia
Behavioural disturbances
Blurred vision
Bruising
Bullous dermatoses
Chills
Concentration disturbances
Confusion
Delusions
Depressed mood
Depression
Diarrhoea
Dizziness
Drowsiness
Emotional lability
Encephalopathy
Exfoliative dermatitis
Fever
Gait abnormality
Hallucinations
Headache
Hostility
Insomnia
Irritability
Leucopenia
Muscle twitch
Myalgia
Nausea
Nervousness
Nystagmus
Precipitation of status epilepticus
Psychosis
Rash
Somnolence
Speech disturbances
Suicidal tendencies
Tiredness
Tremor
Vesiculo-bullous reactions
Visual field defects
Vomiting
White blood cell count decreased

Presentation

Oral formulations of tiagabine

Drugs List

Therapeutic Indications

Uses

Epilepsy (inadequately controlled) - partial seizures: adjunctive therapy

Dosage

Rapid titration and/or large dose increments may not be well-tolerated and should be avoided.

Adults

Children

Patients with Hepatic Impairment

Contraindications

Children under 12 years
Galactosaemia
Porphyria
Severe hepatic impairment

Precautions and Warnings

Breastfeeding
Glucose-galactose malabsorption syndrome
Lactose intolerance
Mild hepatic impairment
Pregnancy

Advise patient ability to drive or operate machinery may be impaired
Folic acid 5mg daily required pre-conception to end of 1st trimester
Contains lactose
If visual disturbances occur, perform ophthalmic evaluation
Monitor patients with hepatic impairment for adverse effects
Perform full blood count if spontaneous bruising occurs
Advise patients/carers to seek medical advice if suicidal intent develops
Avoid abrupt withdrawal
To discontinue, reduce dose gradually for last 2-4 weeks of therapy
Advise patient to seek advice at first indications of pregnancy
Advise patient not to take St John's wort concurrently
Female: Ensure adequate contraception during treatment

Use of tiagabine has been associated with new onset seizures and status epilepticus in patients without epilepsy. Underlying medical conditions or concomitant medications that can reduce seizure threshold, reported overdose and manner of dose administration (e.g. high dosage, fast titration rate), may have contributed to the development of seizures.

Pregnancy and Lactation

Pregnancy

Use tiagabine with caution in pregnancy.

Schaefer suggests there is no reason to terminate a pregnancy which has occurred during treatment, however a detailed ultrasound during the second trimester should be carried out to eliminate major structural abnormalities. Briggs suggests if the use of tiagabine is unavoidable, there is no evidence to suggest foetal harm but use the lowest effective dose, if possible, as well as 4 to 5 mg per day of folic acid. Other sources suggest that the essential treatment of taking antiepileptic drugs outweighs the unknown concern of the potential harm to the foetus as the likelihood of a women taking antiepileptic drugs to have a baby with no malformation is 90%.

Studies in animals have not shown teratogenic effects of tiagabine, however at very high doses revealed peri and post-natal toxicity. There is limited experience in the use of tiagabine in human pregnancy.

Antiepileptic drugs may reduce the efficiency of hormonal contraceptives and some hormonal contraceptives may reduce the efficiency of antiepileptic drugs, therefore women who have child-bearing potential should be given advice for an affective contraception to avoid unplanned pregnancy.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Use tiagabine with caution in breastfeeding.

The Drugs and Lactation Database (LactMed) suggests if using tiagabine, the infant should be closely monitored for drowsiness, adequate weight gain, and developmental milestones, especially younger and/or exclusively breastfed infants, and those on combinations of anticonvulsant drugs. Some sources suggest mothers on anti-epileptic drugs should be encouraged to breastfeed as it is generally considered safe, however if a women is on a combination therapy advice should be sought. The risk of injury to the infant caused by a maternal seizure is low but if toxicity develops consider advising supplementing the feed with formula milk or ceasing breastfeeding periodically to limit exposure.

There is very little information available on the use of tiagabine in breastfeeding.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Accidental injury
Activation of new seizure types
Aggression
Ataxia
Behavioural disturbances
Blurred vision
Bruising
Bullous dermatoses
Chills
Concentration disturbances
Confusion
Delusions
Depressed mood
Depression
Diarrhoea
Dizziness
Drowsiness
Emotional lability
Encephalopathy
Exfoliative dermatitis
Fever
Gait abnormality
Hallucinations
Headache
Hostility
Insomnia
Irritability
Leucopenia
Muscle twitch
Myalgia
Nausea
Nervousness
Nystagmus
Precipitation of status epilepticus
Psychosis
Rash
Somnolence
Speech disturbances
Suicidal tendencies
Tiredness
Tremor
Vesiculo-bullous reactions
Visual field defects
Vomiting
White blood cell count decreased

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last full review date: September 2016

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 8th edition (2008) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Summary of Product Characteristics: Gabitril 5mg Tablets. Cephalon (UK) Ltd. Revised July 2016.

Summary of Product Characteristics: Gabitril 10mg Tablets. Cephalon (UK) Ltd. Revised July 2016.

Summary of Product Characteristics: Gabitril 15mg Tablets. Cephalon (UK) Ltd. Revised July 2016.

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Last revised: 30 January 2015
Last accessed: 08 September 2016

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 17 August 2017