tetrabenazine

Action and Spectrum

Actions and spectrum: 

tetrabenazine is a medication used for the symptomatic management of hyperkinetic movement disorders, including Huntington’s disease, tardive dyskinesia, and other related conditions.

It is a reversible and selective inhibitor of the vesicular monoamine transporter 2 (VMAT2) that depletes presynaptic monoamine stores, thereby reducing dopamine release in the brain.

tetrabenazine is believed to work by reducing the dopaminergic activity in the basal ganglia, which helps to reduce the involuntary movements that are characteristic of hyperkinetic disorders. 

Drug Interaction

Adverse Reaction

Frequency defined:  

>10% 

Sedation/somnolence (31%) 

Insomnia (22%) 

Akathisia (19%) 

Anxiety (15%) 

Fatigue (22%) 

Depression (19%) 

Extrapyramidal event (15%) 

Nausea (13%)  

1-10% 

Irritability (9%) 

Vomiting (6%) 

Dysuria (4%) 

Imbalance (9%) 

Dizziness (4%) 

Unsteady gait (4%) 

Bruising (6%) 

Decreased appetite (4%) 

Obsessive reaction (4%) 

Parkinsonism/bradykinesia (9%) 

Dysarthria (4%) 

Headache (4%)  

Frequency undefined: 

QTc prolongation 

Orthostatic Hypotension 

Dysphagia 

Neuroleptic malignant syndrome 

Restlessness and agitation 

Depression and suicidality  

Post marketing Reports 

Nervous system disorders 

Respiratory disorders 

Skin disorders 

Hyperprolactinemia 

Black Box Warning

Black Box Warning  

tetrabenazine can increase the risk of depression and suicidal thoughts, particularly in patients with a history of depression or a prior suicide attempt. 

Contraindication / Caution

Contraindication/Caution 

Contraindication 

• Hypersensitivity to tetrabenazine 
• Reserpine use or within 20 days of discontinuing reserpine due to the risk of depression, parkinsonism, and sedation. 
• Monoamine oxidase inhibitor (MAOI) use or within 14 days of discontinuing an MAOI due to the risk of serotonin syndrome. 
• Active suicidal ideation or untreated depression 
• Congenital long QT syndrome 
• History of cardiac arrhythmias 
• Concomitant use of drugs may prolong the QT interval, such as antiarrhythmics of class IA and III, certain antipsychotic medications, and some antibiotics.

Caution 

• Depression and suicidal ideation: tetrabenazine may increase the risk of depression and suicidal ideation, particularly in patients with a history of depression or who are taking other medications that affect the central nervous system.  
• Parkinson’s disease: tetrabenazine may worsen symptoms of Parkinson’s disease, such as tremors, rigidity, and bradykinesia. It is generally not recommended for patients with Parkinson’s disease, unless the benefits outweigh the risks. 
• Akathisia: tetrabenazine may cause or worsen akathisia, which is a feeling of restlessness and an inability to sit still.  
• Sedation and drowsiness: tetrabenazine may cause sedation and drowsiness, which can impair the patient’s ability to drive or operate machinery.  
• Hepatic impairment: tetrabenazine is primarily metabolized in the liver and should be used with caution in patients with hepatic impairment. Dose adjustments may be necessary in these patients. 
• QT prolongation: tetrabenazine may prolong the QT interval, which can lead to life-threatening arrhythmias.

Comorbidities 

tetrabenazine is a medication used to treat chorea associated with Huntington’s disease, a hereditary neurological disorder that affects the ability to think, walk, talk, and reason. tetrabenazine may be contraindicated or require caution in patients with a history of depression, suicidal ideation, or suicidal attempts, as the medication can increase the risk of depression and suicidal behaviour.

tetrabenazine may also require caution in patients with a history of or current liver disease, as the medication is metabolized in the liver. Additionally, patients taking tetrabenazine should be closely monitored for symptoms of parkinsonism or other movement disorders, as the medication can cause these adverse effects. 

Pregnancy / Lactation

Pregnancy consideration: Category C 

Lactation:  safety and efficacy not established  

Pregnancy category: 

• Category A: Satisfactory and well-controlled studies show no risk to the fetus in the first or later trimester. 
• Category B: There is no evidence of risk to the fetus found in animal reproduction studies and there are not enough studies on pregnant women. 
• Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for an effect in humans, care must be taken for potential risks in pregnant women 
• Category D: There is adequate data available with sufficient evidence of human fetal risk from various platforms, but despite potential risks may be used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh risks over benefits These category drugs should be prohibited for pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

 Pharmacology 

tetrabenazine is a reversible and selective vesicular monoamine transporter 2 (VMAT2) inhibitor. It inhibits the uptake of monoamines such as dopamine, norepinephrine, and serotonin into presynaptic vesicles, resulting in their depletion and reducing monoaminergic neurotransmission.

This leads to a decrease in the movement and other hyperkinetic symptoms associated with Huntington’s disease and other hyperkinetic movement disorders. tetrabenazine has the highest affinity for VMAT2 among all the VMAT isoforms, and its binding is long-lasting due to its covalent binding with the transporter protein.

The pharmacological effect of tetrabenazine develops slowly, with maximal effect taking several weeks to manifest. tetrabenazine is rapidly and completely metabolized to active metabolites, with a half-life of approximately 4-8 hours. It is primarily metabolized by the liver and excreted in the urine.  

Pharmacodynamics 

tetrabenazine is a reversible inhibitor of the vesicular monoamine transporter 2 (VMAT2), a protein that is responsible for the uptake of monoamines (dopamine, norepinephrine, serotonin, and histamine) into synaptic vesicles. By inhibiting VMAT2, tetrabenazine decreases the uptake and storage of monoamines, which leads to a decrease in dopamine release. This results in a decrease in abnormal and excessive movements associated with Huntington’s disease and other hyperkinetic movement disorders. The exact mechanism of tetrabenazine in the treatment of tardive dyskinesia is unknown, but it is thought to involve similar actions on dopamine transmission.  

pharmacokinetics 

tetrabenazine is readily absorbed from the gastrointestinal tract following oral administration. It undergoes extensive first-pass metabolism in the liver by the cytochrome P450 system, primarily via the CYP2D6 isoenzyme, and is converted to its active metabolites, α-HTBZ (alpha-dihydrotetrabenazine) and β-HTBZ (beta-dihydrotetrabenazine), which are then metabolized to inactive metabolites.

The elimination half-life of tetrabenazine is about 4 to 8 hours, while the half-lives of the active metabolites range from 8 to 12 hours. tetrabenazine and its metabolites are mainly excreted in the urine. The pharmacokinetics of tetrabenazine can be influenced by factors such as age, gender, race, and liver function. Patients with impaired hepatic function may have slower metabolism of tetrabenazine and its metabolites, leading to higher plasma concentrations and increased risk of adverse effects. 

Adminstartion

Administration 

tetrabenazine is available as an oral tablet and is usually taken two to three times daily with or without food. The exact dosing instructions will depend on the condition being treated and should be determined by a healthcare provider. The medication should be swallowed whole and not crushed, chewed, or broken.

It may take several weeks for the full effects of the medication to be seen, and treatment should not be stopped suddenly, as this may cause withdrawal symptoms. If a dose is skipped, it should be taken as soon as possible, but two doses should not be taken at once to make up for the missed dose. It is important to follow the prescribed dosing schedule and contact a healthcare provider with any questions or concerns. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: tetrabenazine 

Pronounced: [ tet-ra-ben-a-zeen ]  

Why do we use tetrabenazine? 

tetrabenazine is a medication used to treat involuntary movements (chorea) in Huntington’s disease and other hyperkinetic movement disorders, such as tardive dyskinesia. It works by decreasing the amount of dopamine available in certain areas of the brain, thereby reducing the abnormal movements.

It is not a cure for these conditions but can help to manage the symptoms. tetrabenazine is usually taken orally in tablet form and the dosage is individualized for each patient based on their response to the medication and other factors.