The main differences between deutetrabenazine (Austedo, Austedo XR) and tetrabenazine (Xenazine) are in their chemical structure and pharmacokinetics. The addition of deuterium to the Austedo compound lengthens the duration of action and may reduce certain side effects compared to Xenazine. Overall, the drugs are fairly similar with regards to drug class, warnings, side effects and potential drug interactions, but differ in their FDA-approved uses.

Overview

• Deutetrabenazine (Austedo, Austedo XR) and tetrabenazine (Xenazine) are all approved by the FDA to treat chorea (involuntary body movements) associated with Huntington's disease (HD chorea).
• Deutetrabenazine is also approved to treat tardive dyskinesia.
• Tetrabenazine is not FDA-approved for tardive dyskinesia. It has been used off-label to treat this condition, although studies are limited.

Deutetrabenazine (Austedo, Austedo XR) contains the addition of the compound deuterium (2H) in its chemical structure. This addition helps to lengthen the duration of action of the drug and may help to improve some side effects.

High-quality, head-to-head, randomized clinical studies are lacking for these medicines. However, in a formulary review of deutetrabenazine and tetrabenazine, the authors concluded that the evidence suggests these agents have similar effectiveness in the treatment of HD chorea. The primary differences are found in the dosing frequency and cost, with some data suggesting better tolerability with deutetrabenazine.

How does deuterium affect deutetrabenazine (Austedo)?

Deuterium (2H) a naturally occurring, nontoxic form of hydrogen that bonds strongly to carbon. It has an increased mass compared to regular hydrogen. Deutetrabenazine (Austedo) contains deuterium (2H) in its chemical structure, which helps to prolong the drug’s action in the body and may help to improve its tolerability compared to tetrabenazine (Xenazine).

Structurally, the medicines are fairly similar with the exception of the deuterium compound in Austedo. The molecular structure of deutetrabenazine, a racemic mixture, is C19H21D6NO3. The structure for tetrabenazine is C19H27NO3.

Deutetrabenazine (Austedo) is extensively biotransformed, mainly by carbonyl reductase, to its major active metabolites, α-HTBZ and β- HTBZ, which are subsequently metabolized primarily by the CYP2D6 enzyme. Metabolism by CYP2D6 also results in numerous clinically significant drug interactions for both drugs.

The active metabolites of Austedo have a half-life in the range of 9 to 11 hours, while the Xenazine metabolites have a half-life of about 5 to 7 hours.

The metabolism of Austedo in the liver by the CYP2D6 enzyme is reduced and duration of action prolonged due to the deuterium in its chemical structure. This may also improve tolerability compared to tetrabenazine (Xenazine), although data is limited.

Do Austedo and Xenazine work the same way? What is their mechanism of action?

Austedo (deutetrabenazine) and Xenazine (tetrabenazine) are both prescription medicines in a class known as vesicular monoamine transporter 2 (VMAT2) inhibitors. VMAT2 is a protein which lowers the amount of messenger chemicals (also called neurotransmitters), such as dopamine, serotonin, norepinephrine, and histamine, in nerve cells to help relieve involuntary body movements.

The inhibition of VMAT2 leads to a depletion of presynaptic dopamine and lowers the amount of dopamine released from nerves. This is thought to help control involuntary body movements in conditions like chorea associated with Huntington's disease and tardive dyskinesia.

Nerve cells talk to each other through chemical messengers (neurotransmitters) that go from one cell to another. In certain movement disorders, lowering the amount of brain chemical messengers like dopamine may help to relieve uncontrolled movements due to the disease.

Ingrezza (valbenazine) is another VMAT2 inhibitor medicine approved to treat tardive dyskinesia.

Why are Austedo and Xenazine prescribed?

Austedo and Austedo XR are approved to treat chorea (involuntary body movements) associated with Huntington's disease (HD chorea) and Tardive Dyskinesia (TD).
Xenazine is approved to treat chorea associated with Huntington's disease, but is not approved to treat tardive dyskinesia (but may be used off-label by some doctors).

These medicines are not considered cures but may help to control the involuntary body movements associated with these conditions.

Chorea associated with Huntington's disease is a rare, inherited (genetic), and fatal disorder that causes nerve cell death in the brain.

• This leads to involuntary and random body movements (called chorea). Chorea is usually mild at first and affects hands and facial muscles. This later progresses to more intense jerky, twisting or writhing movements of the arms, legs and body.
• Psychiatric symptoms such as psychosis, agitation, anxiety, depression, and cognitive impairment may also occur.
• Treatment may improve quality of life and symptoms of chorea, depression, anxiety, and memory problems.

Tardive dyskinesia results in involuntary movements, often in the lower face and mouth.

• These movements can occur in patients who have taken dopamine-blocking drugs such as antipsychotics or metoclopramide. In some people it can remain permanent, even after drug discontinuation.
• These abnormal movements include tongue thrusting, repetitive chewing, jaw swinging and facial grimacing. It can occur in other parts of the body, too, such as the hands, feet, legs or torso.

Is the dose different for Austedo and Xenazine?

Doses of oral Austedo or Xenzine are determined individually for each patient based on the clinical response. Doses for both drugs are initiated slowly and increased weekly based on effectiveness and how well the patient tolerates any side effects. Patients can switch from Xenazine to Austedo or Austedo XR under their physican’s direction.

Austedo dosing

• Austedo is normally taken twice per day with food. The recommended starting dose is 6 mg twice per day. Austedo comes in strengths of 6 mg, 9 mg or 12 mg tablets.
• Austedo XR is an oral, extended-release tablet form that is given once daily, and can be taken with or without food. Austedo XR (extended-release) comes as a 6 mg, 12 mg or 24 mg tablet.
• Swallow Austedo or Austedo XR tablets whole, do not crush, chew, or break the tablet before you swallow it.

The maximum recommended dose is 48 mg per day for both Austedo and Austedo XR.

Dose adjustments may be needed in patients who are poor CYP2D6 metabolizers or are taking medicines that are strong CYP2D6 inhibitors. In patients receiving strong CYP2D6 inhibitors or who are poor CYP2D6 metabolizers, the total daily dosage of Austedo or Austedo XR should not exceed 36 mg.

Xenazine dosing

Xenazine is usually given as an oral treatment 2 to 3 times daily, depending upon dose. For the first week, your dose will be given once per day. It may be taken with or without food.

It comes as a 12.5 and 25 mg tablet. Doses of 37.5 mg to 50 mg daily should be given as 3 divided doses per day. The maximum recommended single dose is 25 mg.

Patients requiring doses over 50 mg per day of Xenazine should be genotyped for CYP2D6, a liver enzyme that is responsible for the breakdown (metabolism) of Xenazine in the body. Your doctor may need to adjust your dose if you are a poor metabolizer or an extensive metabolizer of 2D6. A genotype test is usually done with a simple blood test.

The daily dose of tetrabenazine should not exceed 50 mg per day and the maximum single dose of tetrabenazine should not exceed 25 mg in patients taking strong CYP2D6 inhibitors (for example: paroxetine, fluoxetine, quinidine) or in poor metabolizers.

How do side effects and warnings compare for Austedo and Xenazine?

Austedo and Xenazine share many of the same side effects and warnings. If you have questions about side effects, ask your doctor for further information.

Side effects

Both Austedo and Xenazine share common side effects like drowsiness, fatigue, and trouble sleeping (insomnia).

In Austedo studies, common side effects differed between patients being treated for Huntington's disease (HD chorea) and tardive dyskinesia (TD).

The most common side effects for Austedo (8% or more of patients with HD chorea) included:

• extreme drowsiness (somnolence)
• diarrhea
• dry mouth
• fatigue

In patients taking Austedo for tardive dyskinesia, the most common side effects (4% or more of patients) were:

• nasopharyngitis (common cold symptoms)
• trouble sleeping (insomnia)

The most common Xenazine side effects (10% or more of patients) include:

• sedation (somnolence or extreme drowsiness)
• fatigue
• trouble sleeping (insomnia)
• depression
• akathisia (restlessness, inability to sit still)
• anxiety or worsened anxiety
• nausea

Warnings

Both Austedo and Xenazine carry a Boxed Warning for an increase in the risk of depression and suicidal thoughts and behavior (suicidality) in patients with Huntington’s disease. This is a very serious side effect. You should NOT start these treatments if you are depressed or have suicidal thoughts. Call your doctor right away if you have symptoms of depression or thoughts of suicide.

Neither Austedo nor Xenazine should be used in patients:

• Who are suicidal or have thoughts of suicide
• With untreated or inadequately treated depression
• With hepatic (liver) problems
• Taking reserpine or a monoamine oxidase inhibitor (MAOI). Ask your doctor or pharmacist if you are not sure.
• Taking any other drug from the VMAT-2 inhibitor class (including valbenazine)

Warnings and precautions shared between with Austedo and Xenazine include:

• QT Prolongation
• Neuroleptic Malignant Syndrome
• Risk of akathisia, agitation, restlessness, and parkinsonism that may require dose adjustment or discontinuation of treatment
• Sedation/somnolence: May impair the patient’s ability to drive or operate complex machinery
• Hyperprolactinemia (elevated prolactin levels)
• Binding to Melanin-Containing Tissues

Other warnings and precautions with Xenazine include:

• Hypotension and orthostatic hypotension

It s not known if Austedo, Austedo XR or Xenazine are safe and effective in children.

Drug interactions

Both Austedo and Xenazine have many drug interactions which may affect how well the drug works or increase its side effects. Always tell your doctor and pharmacist about any medicines you take now, and before you start or stop any medicine. Tell them about all prescription, over-the-counter (OTC), vitamin, herbal or dietary supplements you take.

Do not start any medicines while taking either of these drugs without talking to your doctor first.

Significant drug interactions that are common for both Austedo and Xenazine include:

• Strong CYP2D6 enzyme inhibitors (e.g., paroxetine, fluoxetine, quinidine)
• Alcohol or other sedating drugs: may increase sedation

This is not a complete listing of warnings, side effects or drug interactions. To learn more information, review:

• Austedo (in more detail)
• Xenazine (in more detail)

Which is more expensive: Austedo or Xenazine?

Tetrabenazine is available as a generic option, which makes this product more affordable than Austedo or Austedo XR if you are paying cash.

• The cost for 100 tablets of tetrabenazine 12.5 mg (generic Xenazine) is about $620.
• The cost for 100 tablets of brand name Xenazine 12.5 mg runs about $19,000.

Austedo was first approved in 2017 and a generic option is not yet available. It is only available as a brand name product.

• The cost for 60 tablets of 12 mg brand name Austedo is around $7,465.
• The cost for 60 tablets of the 12 mg Austedo XR is $7,465.

Related: Costs for Austedo, Austedo XR or Xenazine (in more detail)

If you have prescription insurance, contact your insurance company to determine which drugs may be covered under your plan and the associated copays.

The manufacturers of brand name products may offer financial support in the form of copay coupons or patient assistance programs. Contact the manufacturer to determine what levels of financial support is offered and your eligibility.

• Austedo is manufactured by Teva Pharmaceuticals (1-800-887-8100)
• Xenazine is made by Lundbeck (1-888-882-6013)

This is not all the information you need to know about Austedo or Austedo XR (deutetrabenazine) or Xenazine (tetrabenazine) for safe and effective use and does not take the place of your doctor’s directions. Review the full product information and discuss this information and any questions you have with your doctor or other health care provider.