Drugs List

Therapeutic Indications

Uses

Chorea
Chorea - senile
Hemiballismus
Treatment of moderate to severe tardive dyskinesia

Hyperkinetic movement disorders due to Huntington�s chorea, hemiballismus, senile chorea, and related neurological conditions.

Moderate to severe tardive dyskinesia which is disabling and/or socially embarrassing. Only to be used where the condition persists despite reducing or withdrawing any antipsychotic medication, changing treatment to an atypical antipsychotic or where changes to antipsychotic medication are not clinically appropriate.

Not all brands are licensed for all indications.

Contraindications

Children under 18 years
Suicidal ideation
Within 2 weeks of discontinuing MAOIs
Breastfeeding
Galactosaemia
Hepatic impairment
Long QT syndrome
Parkinsonism
Phaeochromocytoma
Pregnancy
Prolactin-dependent neoplasm
Severe depression
Torsade de pointes

Precautions and Warnings

Family history of long QT syndrome
Depression
Electrolyte imbalance
Glucose-galactose malabsorption syndrome
History of depression
History of torsade de pointes
Lactose intolerance
Renal impairment

Correct electrolyte disorders before treatment
Advise patient not to drive until they know how the medicine affects them
Not all available brands are licensed for all indications
Treatment to be prescribed under the supervision of a specialist
Contains lactose
Consider monitoring ECG in patients at risk of QT prolongation
Monitor patients for adverse reactions including restlessness & agitation
Monitor prolactin levels where prolactin related side effects occur
Monitor serum electrolytes
Reassess need for continued treatment at regular intervals
Advise patient to report any new or worsening depression/suicidal ideation
Consider discontinuing if depression develops
May cause postural hypotension especially in elderly
Discontinue if patient develops neuroleptic malignant syndrome
Advise that effects are potentiated by CNS depressants (including alcohol)

Some brands allow the use of tetrabenazine with caution in hepatic impairment.

Parkinsonism
Tetrabenazine can induce parkinsonism and exacerbate pre-existing symptoms of Parkinson's disease. Monitor patients for symptoms (see Dosage; Additional).

Depression and/or suicidal ideation.
Tetrabenazine may cause depression or worsen any pre-existing depression. Cases of suicidal ideation have been reported.
Use caution when treating patients with a history of severe depression or suicidal ideation. Monitor patients closely for changes in mental state (see Dosage; Additional).
A risk of anger or aggressive behaviour occurring/worsening in patients with a history of depression or other psychiatric illness has been reported.

Akathisia, restlessness, agitation and extrapyramidal symptoms.
Monitor for symptoms of akathisia and extrapyramidal symptoms (see Dosage; Additional). Early indicators of akathisia include restlessness and agitation. As tetrabenazine is a central monoamine depleting agent it can theoretically cause tardive dyskinesia in addition to treating it.

Orthostatic hypotension
Orthostatic hypotension is commonly reported in patients taking tetrabenazine. In patients who are more vulnerable to the effects of hypotension, regularly monitor lying (or sitting) and standing blood pressure.

Hyperprolactinemia
If symptoms of hyperprolactinemia develop (including amenorrhoea, galactorrhea, gynecomastia and impotence), measure prolactin levels (see Dosage; Additional). Chronic raised prolactin may lower oestrogen levels and increase the risk of osteoporosis. This risk should be carefully considered in patients with additional osteoporosis risk factors.

Neuroleptic Malignant Syndrome
Neuroleptic Malignant Syndrome has been reported rarely in patients using tetrabenazine. Presentation usually occurs in early treatment, following dose changes or in prolonged treatment. The main symptoms include mental changes, rigidity, hyperthermia, autonomic dysfunction (sweating and fluctuations in blood pressure) and elevated creatinine phosphokinase levels (see Dosage; Additional).

Pregnancy and Lactation

Pregnancy

Contraindicated in pregnancy.

Human pregnancy experience is very limited and available animal studies have shown reproductive toxicity. The potential risk for humans is unknown however tetrabenazine rapidly distributes into the brain where it reversibly depletes monoamines. As such it should not be used during pregnancy unless no alternative options are available.

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 14-17 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

Contraindicated in lactation.

At the time of writing, there are no reports of the use of tetrabenazine during breast feeding. It is unknown if tetrabenazine is excreted into breast milk however Briggs (2015) suggests that at least the metabolites will be excreted based on the molecular weight of the parent compound (about 317) and the plasma protein binding and half-lives of the two metabolites. Common side effects observed in adults (sedation, depression, akathisia) would also present potential complications should exposure occur.

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

Agitation
Akathisia
Anxiety
Ataxia
Bradycardia
Confusion
Constipation
Depression
Diarrhoea
Difficulty in swallowing
Disorientation
Dizziness
Drowsiness
Dry mouth
Dystonia
Epigastric pain
Extrapyramidal effects
Fatigue
Gastro-intestinal symptoms
Hypersalivation
Hypertensive crisis
Hyperthermia
Hypotension
Hypothermia
Insomnia
Irregular menstruation
Leucopenia
Memory loss
Nausea
Nervousness
Neuroleptic malignant syndrome
Oculogyric crisis
Parkinson-like symptoms
Photophobia
Postural hypotension
Restlessness
Sleep disturbances
Tremor
Vomiting
Weakness

Presentation

Oral formulations of tetrabenazine.

Drugs List

Therapeutic Indications

Uses

Chorea
Chorea - senile
Hemiballismus
Treatment of moderate to severe tardive dyskinesia

Hyperkinetic movement disorders due to Huntington�s chorea, hemiballismus, senile chorea, and related neurological conditions.

Moderate to severe tardive dyskinesia which is disabling and/or socially embarrassing. Only to be used where the condition persists despite reducing or withdrawing any antipsychotic medication, changing treatment to an atypical antipsychotic or where changes to antipsychotic medication are not clinically appropriate.

Not all brands are licensed for all indications.

Dosage

Doses should be gradually titrated up over several weeks, aiming for a dose that provides clinical benefit with no intolerable adverse effects.

Once a stable dose is achieved, periodically reassess the need for it to continue.

Adults

Elderly

Additional Dosage Information

Contraindications

Children under 18 years
Suicidal ideation
Within 2 weeks of discontinuing MAOIs
Breastfeeding
Galactosaemia
Hepatic impairment
Long QT syndrome
Parkinsonism
Phaeochromocytoma
Pregnancy
Prolactin-dependent neoplasm
Severe depression
Torsade de pointes

Precautions and Warnings

Family history of long QT syndrome
Depression
Electrolyte imbalance
Glucose-galactose malabsorption syndrome
History of depression
History of torsade de pointes
Lactose intolerance
Renal impairment

Correct electrolyte disorders before treatment
Advise patient not to drive until they know how the medicine affects them
Not all available brands are licensed for all indications
Treatment to be prescribed under the supervision of a specialist
Contains lactose
Consider monitoring ECG in patients at risk of QT prolongation
Monitor patients for adverse reactions including restlessness & agitation
Monitor prolactin levels where prolactin related side effects occur
Monitor serum electrolytes
Reassess need for continued treatment at regular intervals
Advise patient to report any new or worsening depression/suicidal ideation
Consider discontinuing if depression develops
May cause postural hypotension especially in elderly
Discontinue if patient develops neuroleptic malignant syndrome
Advise that effects are potentiated by CNS depressants (including alcohol)

Some brands allow the use of tetrabenazine with caution in hepatic impairment.

Parkinsonism
Tetrabenazine can induce parkinsonism and exacerbate pre-existing symptoms of Parkinson's disease. Monitor patients for symptoms (see Dosage; Additional).

Depression and/or suicidal ideation.
Tetrabenazine may cause depression or worsen any pre-existing depression. Cases of suicidal ideation have been reported.
Use caution when treating patients with a history of severe depression or suicidal ideation. Monitor patients closely for changes in mental state (see Dosage; Additional).
A risk of anger or aggressive behaviour occurring/worsening in patients with a history of depression or other psychiatric illness has been reported.

Akathisia, restlessness, agitation and extrapyramidal symptoms.
Monitor for symptoms of akathisia and extrapyramidal symptoms (see Dosage; Additional). Early indicators of akathisia include restlessness and agitation. As tetrabenazine is a central monoamine depleting agent it can theoretically cause tardive dyskinesia in addition to treating it.

Orthostatic hypotension
Orthostatic hypotension is commonly reported in patients taking tetrabenazine. In patients who are more vulnerable to the effects of hypotension, regularly monitor lying (or sitting) and standing blood pressure.

Hyperprolactinemia
If symptoms of hyperprolactinemia develop (including amenorrhoea, galactorrhea, gynecomastia and impotence), measure prolactin levels (see Dosage; Additional). Chronic raised prolactin may lower oestrogen levels and increase the risk of osteoporosis. This risk should be carefully considered in patients with additional osteoporosis risk factors.

Neuroleptic Malignant Syndrome
Neuroleptic Malignant Syndrome has been reported rarely in patients using tetrabenazine. Presentation usually occurs in early treatment, following dose changes or in prolonged treatment. The main symptoms include mental changes, rigidity, hyperthermia, autonomic dysfunction (sweating and fluctuations in blood pressure) and elevated creatinine phosphokinase levels (see Dosage; Additional).

Pregnancy and Lactation

Pregnancy

Contraindicated in pregnancy.

Human pregnancy experience is very limited and available animal studies have shown reproductive toxicity. The potential risk for humans is unknown however tetrabenazine rapidly distributes into the brain where it reversibly depletes monoamines. As such it should not be used during pregnancy unless no alternative options are available.

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 14-17 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

Contraindicated in lactation.

At the time of writing, there are no reports of the use of tetrabenazine during breast feeding. It is unknown if tetrabenazine is excreted into breast milk however Briggs (2015) suggests that at least the metabolites will be excreted based on the molecular weight of the parent compound (about 317) and the plasma protein binding and half-lives of the two metabolites. Common side effects observed in adults (sedation, depression, akathisia) would also present potential complications should exposure occur.

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

Counselling

Inform patient and carers of the risk of developing symptoms of depression and/or suicidal ideation. Advise them to report any changes to the patient's mental state.

Advise patient and carers of the potential for orthostatic hypotension including advice to take care when standing from a sitting or lying position.

Sedation is the most common dose-limiting side effect. Advise patient not to drive until they know how the medicine affects them.

Side Effects

Agitation
Akathisia
Anxiety
Ataxia
Bradycardia
Confusion
Constipation
Depression
Diarrhoea
Difficulty in swallowing
Disorientation
Dizziness
Drowsiness
Dry mouth
Dystonia
Epigastric pain
Extrapyramidal effects
Fatigue
Gastro-intestinal symptoms
Hypersalivation
Hypertensive crisis
Hyperthermia
Hypotension
Hypothermia
Insomnia
Irregular menstruation
Leucopenia
Memory loss
Nausea
Nervousness
Neuroleptic malignant syndrome
Oculogyric crisis
Parkinson-like symptoms
Photophobia
Postural hypotension
Restlessness
Sleep disturbances
Tremor
Vomiting
Weakness

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: October 2017

Reference Sources

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

Summary of Product Characteristics: Tardiben 25mg tablets. AOP Orphan Pharmaceuticals. Revised May 2018.

Summary of Product Characteristics: Tetrabenazine 25mg tablets. Sun Pharmaceuticals Ltd. Revised August 2016.

Summary of Product Characteristics: Xenazine 25. Alliance Pharmaceuticals. Revised June 2020.