AUSTEDO XR is a recommended first-line treatment option for adults with tardive dyskinesia1,2

Treat with AUSTEDO XR while maintaining your patient’s current regimen3,4

AUSTEDO XR is the only once-daily VMAT2 inhibitor with no restrictions or recommendations against use with strong CYP3A4/5 inducers or inhibitors3,5

  • ~75% of drugs are metabolized through the CYP3A4/5 or CYP2D6 pathways, which may increase the likelihood of drug-drug interactions (DDIs) with subsequent medications in the treatment plan6-8
Now Available One Pill, Once-Daily AUSTEDO XR
Coadministration per Pathway Recommended Maximum Therapeutic Dose
  AUSTEDO XR3 Ingrezza® (valbenazine) and Ingrezza® sprinkle (valbenazine)5
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.

Drug classes with significant interactions related to CYP3A4/5 and CYP2D6, as seen in clinical practice of psychiatric and diverse medical conditions

Examples of Drug Classes Associated With CYP3A4/5

Inhibitors

  • Antiarrhythmics9,10
  • Antibiotics9,11
  • Antidepressants9,10
  • Antifungals9,10
  • Antihypertensives9,11
  • Antiretrovirals/ antivirals11,12

Inducers

  • Antibiotics9,10
  • Anticonvulsants/ sedatives9,11
  • Antifungals9,10
  • Antihypertensives9,11
  • Corticosteroids9,10
  • Wakefulness-promoting agents11,13

Substrates

  • Antianginals9,11
  • Antidiabetics9,10
  • Antihistamines9,10
  • Antihypertensives9,10
  • Corticosteroids9,10
  • Diuretics11,13
  • Statins11,13
  • Vasodilators10,13

Examples of Drug Classes Associated With CYP2D6

Inhibitors

  • Antiarrhythmics13,14
  • Antidepressants9,11
  • Antifungals9,11
  • Antihistamines9,14
  • Antiparasitics11,13
  • Antipsychotics9,14
  • Calcium reducers9,14

Inducers

Evidence suggests that, unlike most other
CYP450 enzymes, CYP2D6 is not very susceptible
to enzyme induction.14

Substrates

  • Antiarrhythmics9,14
  • Antiemetics9,14
  • Antihistamines9,14
  • Antihypertensives9,14
  • Antidepressants9,11
  • Antipsychotics9,14
  • For a list of medications that can help determine potential DDIs with your patients’ concomitant treatments, see the FlockhartTM Table

Watch: Visualizing the role of metabolic pathways in DDIs

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.

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

 

VMAT2, vesicular monoamine transporter 2.

The brands listed are registered trademarks of their respective owners.

REFERENCES: 1. Bhidayasiri R, Jitkritsadakul O, Friedman JH, Fahn S. Updating the recommendations for treatment of tardive syndromes: a systematic review of new evidence and practical treatment algorithm. J Neurol Sci. 2018;389:67-75. 2. American Psychiatric Association. Practice Guideline for the Treatment of Patients with Schizophrenia. 3rd ed. American Psychiatric Association; 2021. 3. AUSTEDO® XR (deutetrabenazine) extended-release tablets and AUSTEDO® current Prescribing Information. Parsippany, NJ: Teva Neuroscience, Inc. 4. Data on file. Parsippany, NJ: Teva Neuroscience, Inc. 5. Ingrezza® (valbenazine) capsules. Prescribing Information. San Diego, CA: Neurocrine Biosciences, Inc. 6. Lee S-J, Goldstein JA. Comparison of CYP3A4 and CYP3A5: the effects of cytochrome b5 and NADPH-cytochrome P450 reductase on testosterone hydroxylation activities. Drug Metab Pharmacokinet. 2012;27(6):663-667. 7. Basheer L, Kerem Z. Interactions between CYP3A4 and dietary polyphenols. Oxid Med Cell Longev. 2015;2015:854015. 8. Zhou SF. Polymorphism of human cytochrome P450 2D6 and its clinical significance: part I. Clin Pharmacokinet. 2009;48(11):689-723. 9. NIH National Library of Medicine. Drugs, herbs and supplements. MedlinePlus. Updated April 28, 2015. Accessed June 9, 2022. https://medlineplus.gov/druginformation.html  10. 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 11. 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 12. PubChem Compound Database. National Center for Biotechnology Information. Accessed November 12, 2022. https://pubchem.ncbi.nlm.nih.gov 13. PubMed Central. National Center for Biotechnology Information. Accessed November 12, 2022. https://www.ncbi.nlm.nih.gov/pmc 14. 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