Metabolic profile allows for few restrictions related to drug-drug interactions1
With AUSTEDO XR1:
Multiple once-daily dosing options for patients who are
No clinically significant QT prolongation up to the maximum dose (48 mg/day)†
AUSTEDO XR has few restrictions related to DDIs
| Drug coadministered with VMAT2 inhibitor |
Recommended Dosing | |
|---|---|---|
| AUSTEDO XR | Valbenazine | |
| Strong CYP3A4/5 inducer | No dose restriction | Concomitant use is not recommended |
| Strong CYP3A4/5 inhibitor | No dose restriction | 40 mg/day lowest dose available |
| Strong CYP2D6 inhibitor (or if patient is a poor CYP2D6 metabolizer) |
Up to 36 mg/day |
40 mg/day lowest dose available |
| P-gp substrate (eg, calcium channel blockers, statins, antimicrobials, and digoxin) |
No dose adjustment to P-gp substrate required |
Dose adjustment to P-gp substrate may be required |
These differences should not be construed to imply difference in safety, efficacy, or clinical outcome.
AUSTEDO XR is primarily metabolized by CYP2D6‡
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.
VMAT2, vesicular monoamine transporter 2.
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.
VMAT 2, vesicular monoamine transporter 2.
Evidence suggests that, unlike most other CYP450 enzymes, CYP2D6 is not very susceptible to enzyme induction
Patients in the pivotal studies received the AUSTEDO BID formulation.1
DDI, drug-drug interaction; VMAT2, vesicular monoamine transporter 2.
*36 mg/day maximum dose for patients taking strong CYP2D6 inhibitors (or poor CYP2D6 metabolizers); 48 mg/day maximum dose for all others.1
†Based on studies in healthy patients. For patients with congenital long QT syndrome or arrhythmias associated with prolonged QT interval, all VMAT2 inhibitors should be avoided. Caution should be used for patients taking drugs that prolong the QT interval.1,2,16
‡Minor contributions from the CYP3A4/5 pathways.1
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. Zhou SF. Structure, function and regulation of P-glycoprotein and its clinical relevance in drug disposition. Xenobiotica. 2008;38(7-8):802-832. 4. 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. 5. Basheer L, Kerem Z. Interactions between CYP3A4 and dietary polyphenols. Oxid Med Cell Longev. 2015;2015:854015. 6. Lynch T, Price A. The effect of cytochrome P450 metabolism on drug response, interactions, and adverse effects. Am Fam Physician. 2007;76(3):391-396. 7. Zhou SF. Polymorphism of human cytochrome P450 2D6 and its clinical significance: part I. Clin Pharmacokinet. 2009;48(11):689-723. 8. Flockhart DA. Drug Interactions Flockhart TableTM. Indiana University. School of Medicine. Accessed November 18, 2025. https://drug-interactions.medicine.iu.edu/main-table 9. Olson JM, Troxell T. Griseofulvin. [Updated 2023 Jul 31]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; January 2025. Available from: https://www.ncbi.nlm.nih.gov/books/NBK537323/ 10. Paul GA, Gibbs JSR, Boobis AR, Abbas A, Wilkins MR. Bosentan decreases the plasma concentration of sildenafil when coprescribed in pulmonary hypertension. Br J Clin Pharmacol. 2005;60(1):107-112. 11. Horn JR, Hansten PD. Get to know an enzyme: CYP2D6. Pharm Times. July 1, 2008. Accessed November 20, 2025. https://www.pharmacytimes.com/view/2008-07-8624 12. 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. 13. 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 14. Stahl SM. Comparing pharmacologic mechanism of action for the vesicular monoamine transporter 2 (VMAT2) inhibitors valbenazine and deutetrabenazine in treating tardive dyskinesia: does one have advantages over the other? CNS Spectr. 2018;23(4):239-247. 15. Broner NB, Magid L, Griffin T, Schmukler E, Fishbein I. Potency and specificity of deutetrabenazine deuterated metabolites for VMAT2 as confirmed by binding affinity and functional activity studies. Poster presented at: NEI Spring Congress; May 8-10, 2025; Philadelphia, PA. 16. Xenazine® (tetrabenazine) tablets. Prescribing Information. Deerfield, IL: Lundbeck Inc.
Request a rep