Action and Spectrum

Actions and spectrum: 

deutetrabenazine is a medication that is primarily used to treat chorea associated with Huntington’s disease. It is a VMAT2 inhibitor, which means it works by reducing the levels of dopamine in certain areas of the brain. By decreasing dopamine levels, deutetrabenazine helps to control abnormal involuntary movements and improve motor function. 

The spectrum of deutetrabenazine’s action is primarily focused on reducing chorea symptoms associated with Huntington’s disease, a genetic neurological disorder characterized by uncontrolled movements, cognitive decline, and behavioural changes. It is specifically indicated for the treatment of chorea, and its effectiveness in other movement disorders or psychiatric conditions is not well-established. 

Drug Interaction

Adverse Reaction

Frequency defined 

1-10% 

Dry mouth (9%) 

UTI (7%) 

Anxiety (4%) 

Contusion (4%) 

Akathisia, restlessness, or agitation (4%) 

Suicidal ideation (2%) 

Diarrhea (9%) 

Fatigue (9%) 

Insomnia (7%) 

Constipation (4%) 

Dizziness (4%) 

Depression (4%) 

Parkinson disease  

>10% 

Somnolence (11%) 

Black Box Warning

Black Box Warning: 

deutetrabenazine carries a black box warning for the increased risk of depression and suicidality. It is important to closely monitor patients treated with deutetrabenazine for the emergence or worsening of depression, suicidal thoughts, or changes in behaviour. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Hypersensitivity: It should not be used in patients with a known hypersensitivity or allergic reaction to deutetrabenazine or any of its components. 
• Concomitant Use with Monoamine Oxidase Inhibitors (MAOIs): deutetrabenazine is contraindicated in patients who are taking or have recently taken (within 14 days) a monoamine oxidase inhibitor (MAOI) due to the risk of serotonin syndrome, a potentially life-threatening condition. MAOIs include medications such as phenelzine, tranylcypromine, isocarboxazid, selegiline, and rasagiline.

Caution: 

• Hepatic Impairment: deutetrabenazine is metabolized in the liver, so caution is advised in patients with moderate to severe hepatic impairment.  
• QT Prolongation: deutetrabenazine may prolong the QT interval on an electrocardiogram (ECG). Caution is advised in patients with a history of QT prolongation, congenital long QT syndrome, significant cardiac arrhythmias, or other factors that may increase the risk of QT prolongation.  
• Hypotension: deutetrabenazine has the potential to cause orthostatic hypotension, especially at higher doses. Caution is advised in patients with a history of hypotension or those taking medications that can lower blood pressure.  
• Central Nervous System (CNS) Depression: deutetrabenazine may cause sedation and somnolence. Caution is advised when operating machinery or driving, especially in the initial stages of treatment or when the dose is increased.  
• Drug Interactions: deutetrabenazine is metabolized by cytochrome P450 enzymes, particularly CYP2D6 and CYP3A4. Caution is advised when co-administering deutetrabenazine with drugs that inhibit or induce these enzymes, as they may affect the plasma concentrations and efficacy of deutetrabenazine.

Comorbidities: 

• Psychiatric Disorders: Huntington’s disease is often associated with psychiatric symptoms such as depression, anxiety, and psychosis. These conditions may coexist with the movement disorder and require additional treatment or management. 
• Cognitive Impairment: Cognitive impairment, including difficulties with memory, attention, and executive functions, is commonly seen in Huntington’s disease. It may impact the overall functioning and quality of life of patients. 
• Motor Impairment: Apart from chorea, Huntington’s disease can lead to other motor impairments, including rigidity, dystonia, bradykinesia, and impaired balance. These motor symptoms may require additional interventions or supportive therapies. 
• Dysphagia: Difficulties with swallowing, or dysphagia, can occur in Huntington’s disease, potentially leading to malnutrition, weight loss, and aspiration pneumonia. Close monitoring of swallowing function and appropriate management strategies are important. 
• Sleep Disorders: Patients with Huntington’s disease may have sleep disturbances, like insomnia, excessive daytime sleepiness, and abnormal sleep-wake patterns. 

Pregnancy / Lactation

Pregnancy consideration: US FDA pregnancy category: Not Assigned 

Lactation: Excreted into human milk: Unknown  

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.   
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

deutetrabenazine is a vesicular monoamine transporter-2 inhibitor. VMAT2 is responsible for the uptake of dopamine, norepinephrine, serotonin, and other neurotransmitters into presynaptic vesicles. By inhibiting VMAT2, deutetrabenazine reduces the uptake of these neurotransmitters into the presynaptic vesicles, leading to a decrease in their release into the synaptic cleft. 

The primary pharmacological effect of deutetrabenazine is the reduction of excessive dopaminergic neurotransmission, specifically targeting the dysregulated dopamine signalling implicated in the pathophysiology of movement disorders such as chorea. 

deutetrabenazine is rapidly metabolized by enzymes in the liver, primarily through the action of cytochrome P450 (CYP) enzymes, particularly CYP2D6 and CYP3A4. The metabolites of deutetrabenazine are inactive and are eliminated from the body through urine and feces.  

Pharmacodynamics: 

The pharmacodynamics of deutetrabenazine primarily involve its action as a selective vesicular monoamine transporter 2 (VMAT2) inhibitor. VMAT2 is responsible for the uptake of dopamine, norepinephrine, serotonin, and other neurotransmitters into presynaptic vesicles. By inhibiting VMAT2, deutetrabenazine reduces the uptake of these neurotransmitters into the vesicles, leading to a decrease in their release into the synaptic cleft. 

The main pharmacodynamic effect of deutetrabenazine is the reduction of excessive dopaminergic neurotransmission, particularly in the striatum. Excessive dopamine signalling in the striatum is associated with the motor symptoms seen in movement disorders such as chorea, including Huntington’s disease. 

By decreasing the release of dopamine, deutetrabenazine helps to regulate and normalize dopaminergic signalling in the brain, resulting in a reduction of chorea and improved motor control.  

Pharmacokinetics: 

Absorption 

deutetrabenazine is orally administered and is rapidly absorbed from the gastrointestinal tract. It reaches peak plasma concentrations within 1 to 2 hours after ingestion. The presence of food does not significantly affect the absorption of deutetrabenazine. 

Distribution 

deutetrabenazine has a high plasma protein binding, primarily to albumin. It has a large volume of distribution, indicating extensive distribution throughout the body. The drug crosses the blood-brain barrier and is distributed to the central nervous system, where it exerts its pharmacological effects. 

Metabolism 

deutetrabenazine undergoes extensive metabolism in the liver, primarily through the cytochrome P450 enzyme system. The major metabolic pathway is hydrolysis, mediated by carboxylesterase enzymes, which converts deutetrabenazine to its active metabolite, alpha-HTBZ (HTBZ-OH). Alpha-HTBZ is further metabolized to inactive metabolites through oxidation and glucuronidation. 

Elimination and excretion 

The elimination of deutetrabenazine and its metabolites occurs primarily through hepatic metabolism, followed by renal excretion. The half-life of deutetrabenazine is 9 to 10 hours. 

Adminstartion

Administration: 

• Dosage: Take deutetrabenazine as prescribed by your healthcare provider. The dosage may be adjusted based on your individual needs and response to treatment.  
• Timing: deutetrabenazine is usually taken once or twice daily, with or without food. Follow the prescribed dosing schedule and take the medication at the same time(s) each day for best results. It is important to maintain a consistent dosing regimen. 
• Swallowing: Swallow the tablets entirely with the water. Do not try to crush, break the tablets. 
• Adherence: It is essential to take deutetrabenazine regularly and as prescribed to ensure optimal therapeutic effects. If you miss a dose, take it as soon as you remember.  
• Duration of Treatment: It will be depended on the nature and severity of condition being treated. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: deutetrabenazine 

Pronounced: (Doo-ter-BEN-a-zeen)  

Why do we use deutetrabenazine? 

deutetrabenazine is primarily used for the treatment of chorea associated with Huntington’s disease. Chorea is a movement disorder characterized by involuntary, repetitive, and uncontrollable movements. deutetrabenazine helps to reduce the severity and frequency of these abnormal movements.

deutetrabenazine is FDA-approved for the treatment of chorea associated with Huntington’s disease. It helps to regulate the levels of a neurotransmitter called dopamine in the brain, which helps to improve motor control and reduce involuntary movements