AUSTEDO XR is a recommended first-line treatment option for adults with tardive dyskinesia1,2
No dose restrictions up to 36 mg/day for patients starting AUSTEDO XR1
| Drug coadministered with VMAT2 inhibitor |
Recommended Maximum Therapeutic Dose | |
|---|---|---|
| AUSTEDO XR1 | Ingrezza® (valbenazine)2 | |
| Strong CYP3A4/5 inducer | No dose restriction | Concomitant use is not recommended |
| Strong CYP3A4/5 inhibitor | 40 mg/day | |
| Strong CYP2D6 inhibitor | 36 mg/day | 40 mg/day |
| Poor CYP2D6 metabolizer |
||
These differences should not be construed to imply difference in safety, efficacy, or clinical outcome.
Evidence suggests that, unlike most other CYP450 enzymes, CYP2D6 is not very susceptible to enzyme induction
Additionally, no dose adjustments are required when taking AUSTEDO XR with P-gp substrates (eg, calcium channel blockers, statins, and antimicrobials)1,9,11,13
In pharmacokinetic studies, increased plasma levels correlated with higher potential for treatment success, but not higher potential for adverse events14,15*
For more videos, visit the YouTube page.
Onscreen text:
CYP enzymes mediate the breakdown of active drug to inactive metabolites for clearance.
Together, CYP3A4/5 and CYP2D6 enzymes are involved in metabolizing ~75% drugs.
CYP enzymes play a key role in converting VMAT2 inhibitors into their active and inactive metabolites.
Certain drugs can act as strong CYP inhibitors or inducers, affecting the metabolism of coadministered medications…
…resulting in drug-drug interactions.
Inhibited metabolism
Inhibited metabolism results in elevated levels of active metabolites.
Elevated levels of active metabolites lead to increased drug potency and potential for adverse events.
Induced metabolism
Induced metabolism results in decreased levels of active metabolites.
Decreased levels of active metabolites diminish therapeutic effect.
For VMAT2 inhibitors, drug-drug interactions are determined by:
The CYP enzymes critical in metabolizing the VMAT2 inhibitor
AND
The metabolic profiles of the medications the patient is taking concomitantly (whether they are strong inhibitors or inducers)
To avoid drug-drug interactions associated with inhibited or induced metabolism, limiting VMAT2 inhibitor dose or avoiding use with strong inhibitors and inducers may be recommended.
>When choosing a VMAT2 inhibitor, considering these drug-drug interactions is key.
>VMAT2, vesicular monoamine transporter 2.
For more videos, visit the YouTube page.
[title]
TREATING TD WHILE MANAGING UNDERLYING CONDITIONS
SUSAN’S STORY
[description]
See how Susan reduced her TD movements with AUSTEDO while maintaining her existing medication regimen.
Onscreen text:
TREATING TD WHILE MANAGING UNDERLYING CONDITIONS
SUSAN’S STORY
Age: 62
Primary conditions: Bipolar type II, seizure disorder
Disclaimer at bottom of screen:
This was an individual patient’s experience. Results may vary.
TD, tardive dyskinesia.
Susan:
My name is Susan Wheeler.
As a person who has tardive dyskinesia, I'm passionate to tell the story because there are treatments…
Onscreen text:
When Susan sought help for involuntary movements caused by antipsychotics, her psychiatrist prescribed a VMAT2 inhibitor.
Disclaimer on bottom of screen:
VMAT2, vesicular monoamine transporter 2.
But when Susan developed a seizure disorder, her TD treatment got more complicated.
Susan:
When I first received the diagnosis of TD and went to my doctor, I was prescribed another medication, and it worked for a while. But I then got another diagnosis of seizure disorder, and when I got that diagnosis, the new medications came on board and caused a conflict with that medication.
Onscreen text:
Susan is now on AUSTEDO XR because it can be taken with her seizure medication.
Onscreen Indication and Black Box Warning:
AUSTEDO XR® and AUSTEDO® are indicated in adults for the treatment of tardive dyskinesia and for the treatment of chorea associated with Huntington's disease.
IMPORTANT SAFETY INFORMATION
Depression and Suicidality in Patients with Huntington’s Disease: AUSTEDO XR and AUSTEDO can increase the risk of depression and suicidal thoughts and behavior (suicidality) in patients with Huntington’s disease. Balance the risks of depression and suicidality with the clinical need for treatment of chorea. Closely monitor patients for the emergence or worsening of depression, suicidality, or unusual changes in behavior. Inform patients, their caregivers, and families of the risk of depression and suicidality and instruct them to report behaviors of concern promptly to the treating physician. Exercise caution when treating patients with a history of depression or prior suicide attempts or ideation. AUSTEDO XR and AUSTEDO are contraindicated in patients who are suicidal, and in patients with untreated or inadequately treated depression.
Please see additional Important Safety Information at the end of this video.
Susan:
My doctor said that AUSTEDO was a good option for me, that it was a medication that would help my tardive dyskinesia but wouldn't interact with the medications I took for both my mental health and seizure disorders…
Onscreen text:
After Susan started on AUSTEDO, she noticed an improvement in her movements.
Susan:
AUSTEDO has helped me. I don't see the mouth tics anymore, which is a great relief to me, because I do a lot of public speaking, and sing with groups.
Even in retirement, you still want to feel good about yourself, and not have to deal with explaining your TD symptoms.
Onscreen text:
Learn more about how AUSTEDO XR can work with your patient’s concomitant medications at AUSTEDOhcp.com.
Disclaimer at bottom of screen:
Patient was compensated for her participation.
Onscreen ISI scroll:
INDICATIONS AND USAGE
AUSTEDO XR and AUSTEDO are indicated in adults for the treatment of tardive dyskinesia and for the treatment of chorea associated with Huntington's disease.
IMPORTANT SAFETY INFORMATION
Depression and Suicidality in Patients with Huntington’s Disease: AUSTEDO XR and AUSTEDO can increase the risk of depression and suicidal thoughts and behavior (suicidality) in patients with Huntington’s disease. Balance the risks of depression and suicidality with the clinical need for treatment of chorea. Closely monitor patients for the emergence or worsening of depression, suicidality, or unusual changes in behavior. Inform patients, their caregivers, and families of the risk of depression and suicidality and instruct them to report behaviors of concern promptly to the treating physician. Exercise caution when treating patients with a history of depression or prior suicide attempts or ideation. AUSTEDO XR and AUSTEDO are contraindicated in patients who are suicidal, and in patients with untreated or inadequately treated depression.
Contraindications: AUSTEDO XR and AUSTEDO are contraindicated in patients with Huntington’s disease who are suicidal, or have untreated or inadequately treated depression. AUSTEDO XR and AUSTEDO are also contraindicated in: patients with hepatic impairment; patients taking reserpine or within 20 days of discontinuing reserpine; patients taking monoamine oxidase inhibitors (MAOIs), or within 14 days of discontinuing MAOI therapy; and patients taking tetrabenazine or valbenazine.
Clinical Worsening and Adverse Events in Patients with Huntington’s Disease: AUSTEDO XR and AUSTEDO may cause a worsening in mood, cognition, rigidity, and functional capacity. Prescribers should periodically re-evaluate the need for AUSTEDO XR or AUSTEDO in their patients by assessing the effect on chorea and possible adverse effects.
QTc Prolongation: AUSTEDO XR and AUSTEDO may prolong the QT interval, but the degree of QT prolongation is not clinically significant when AUSTEDO XR or AUSTEDO is administered within the recommended dosage range. AUSTEDO XR and AUSTEDO should be avoided in patients with congenital long QT syndrome and in patients with a history of cardiac arrhythmias.
Neuroleptic Malignant Syndrome (NMS), a potentially fatal symptom complex reported in association with drugs that reduce dopaminergic transmission, has been observed in patients receiving tetrabenazine. The risk may be increased by concomitant use of dopamine antagonists or antipsychotics. The management of NMS should include immediate discontinuation of AUSTEDO XR and AUSTEDO; intensive symptomatic treatment and medical monitoring; and treatment of any concomitant serious medical problems.
Akathisia, Agitation, and Restlessness: AUSTEDO XR and AUSTEDO may increase the risk of akathisia, agitation, and restlessness. The risk of akathisia may be increased by concomitant use of dopamine antagonists or antipsychotics. If a patient develops akathisia, the AUSTEDO XR or AUSTEDO dose should be reduced; some patients may require discontinuation of therapy.
Parkinsonism: AUSTEDO XR and AUSTEDO may cause parkinsonism in patients with Huntington’s disease or tardive dyskinesia. Parkinsonism has also been observed with other VMAT2 inhibitors. The risk of parkinsonism may be increased by concomitant use of dopamine antagonists or antipsychotics. If a patient develops parkinsonism, the AUSTEDO XR or AUSTEDO dose should be reduced; some patients may require discontinuation of therapy.
Sedation and Somnolence: Sedation is a common dose-limiting adverse reaction of AUSTEDO XR and AUSTEDO. Patients should not perform activities requiring mental alertness, such as operating a motor vehicle or hazardous machinery, until they are on a maintenance dose of AUSTEDO XR or AUSTEDO and know how the drug affects them. Concomitant use of alcohol or other sedating drugs may have additive effects and worsen sedation and somnolence.
Hyperprolactinemia: Tetrabenazine elevates serum prolactin concentrations in humans. If there is a clinical suspicion of symptomatic hyperprolactinemia, appropriate laboratory testing should be done and consideration should be given to discontinuation of AUSTEDO XR and AUSTEDO.
Binding to Melanin-Containing Tissues: Deutetrabenazine or its metabolites bind to melanin-containing tissues and could accumulate in these tissues over time. Prescribers should be aware of the possibility of long-term ophthalmologic effects.
Common Adverse Reactions: The most common adverse reactions for AUSTEDO (>8% and greater than placebo) in a controlled clinical study in patients with Huntington’s disease were somnolence, diarrhea, dry mouth, and fatigue. The most common adverse reactions for AUSTEDO (4% and greater than placebo) in controlled clinical studies in patients with tardive dyskinesia were nasopharyngitis and insomnia. Adverse reactions with AUSTEDO XR extended-release tablets are expected to be similar to AUSTEDO tablets.
Please see full Prescribing Information, including Boxed Warning, at AUSTEDOhcp.com.
References: 1. AUSTEDO® XR (deutetrabenazine) extended- release tablets and AUSTEDO® current Prescribing Information. Parsippany, NJ: Teva Neuroscience, Inc. 2. Data on file. Parsippany, NJ: Teva Neuroscience, Inc.
© 2024 Teva Neuroscience, Inc
AUS-47391 November 2024
Patients in the pivotal studies received the AUSTEDO BID formulation.3
AUSTEDO XR is metabolized primarily through CYP2D6, with minor contributions from CYP3A4/5.3
*Treatment success defined as “much improved” or “very much improved” based on Patient Global Impression of Change (PGIC) and Clinical Global impression of Change (CGIC).13
DDI, drug-drug interactions; VMAT2, vesicular monoamine transporter 2.
The brands listed are registered trademarks of their respective owners.
REFERENCES: 1. AUSTEDO XR® (deutetrabenazine) extended-release tablets and AUSTEDO® current Prescribing Information. Parsippany, NJ: Teva Neuroscience, Inc. 2. Ingrezza® (valbenazine) capsules. Prescribing Information. San Diego, CA: Neurocrine Biosciences, Inc. 3. NIH National Library of Medicine. Drugs, herbs and supplements. MedlinePlus. Updated April 28, 2015. Accessed June 9, 2022. https://medlineplus.gov/druginformation.html 4. Horn JR, Hansten PD. Get to know an enzyme: CYP3A4. Pharm Times. September 1, 2008. Accessed November 12, 2022.
https://www.pharmacytimes.com/view/2008-09-8687 5. US Food and Drug Administration. Drug development and drug interactions: Table of substrates, inhibitors and inducers. US Food and Drug Administration. Updated March 10, 2020. Accessed November 12, 2022. https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers 6. PubChem Compound Database. National Center for Biotechnology Information. Accessed November 12, 2022. https://pubchem.ncbi.nlm.nih.gov 7. PubMed Central. National Center for Biotechnology Information. Accessed November 12, 2022. https://www.ncbi.nlm.nih.gov/pmc 8. Horn JR, Hansten PD. Get to know an enzyme: CYP2D6. Pharm Times. July 1, 2008. Accessed November 12, 2022. https://www.pharmacytimes.com/view/2008-07-8624 9. Zhou SF. Structure, function and regulation of P-glycoprotein and its clinical relevance in drug disposition. Xenobiotica. 2008;38(7-8):802-832. 10. Grymonprez M, Vanspranghe K, Capiau A, Boussery K, Steurbaut S, Lahousse L. Impact of P-glycoprotein and/or CYP3A4-interacting drugs on effectiveness and safety of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation: A meta-analysis. Br J Clin Pharmacol. 2022;88(7):3039-3051. 11. Ahmed Juvale II, Abdul Hamid AA, Abd Halim KB, Che Has AT. P-glycoprotein: new insights into structure, physiological function, regulation and alterations in disease. Heliyon. 2022;8(6):e09777. 12. Agrawal A, Kerndt CC, Manna B. Apixaban. [Updated 2024 Feb 22]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; January 2024. Available from: https://www.ncbi.nlm.nih.gov/books/NBK507910 13. Data on file. Parsippany, NJ: Teva Neuroscience, Inc. 14. Singh R, Sunzel EM, Kang DK, et al. Assessment of the deutetrabenazine exposure-response relationships for patients with moderate-to-severe tardive dyskinesia. Poster presented at: Psych Congress, September 17-20, 2022; New Orleans, LA. 15. Levi, M, Schneider, F, Gosselin NH, et al. Population pharmacokinetic and exposure safety analyses of deutetrabenazine in patients with moderate to severe tardive dyskinesia. Presented at: American Conference on Pharmacometrics: October 20-23, 2019; Orlando, FL.
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AUS-47454 December 2024
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