APA and AAN guidelines: VMAT2 inhibitor as first-line treatment for TD1,2

Only VMAT2 inhibitor indicated for TD with no dose restrictions for—or recommendations against—use in patients taking strong CYP3A4/5 inducers or inhibitors3

Patients with TD take a variety of concomitant medications—it is important to consider metabolic pathways in the treatment of tardive dyskinesia (TD).3,4

  • ~50% of drugs are metabolized through the CYP3A4/5 pathway, which may increase the likelihood of drug-drug interactions with subsequent medications in the treatment plan4,5
  • AUSTEDO is metabolized primarily through CYP2D6—with minor contributions of CYP3A4/5 and other enzymes to form several minor metabolites3

Coadministration per pathway dosing for AUSTEDO and INGREZZA® (valbenazine).

Coadministration per pathway dosing for AUSTEDO and INGREZZA® (valbenazine).

In patients who are poor CYP2D6 metabolizers or are taking strong CYP2D6 inhibitors, the total daily dosage of AUSTEDO should not exceed 36 mg (maximum single dose of 18 mg).3

Drug classes with significant interactions related to CYP3A4/5 and CYP2D6, as seen in clinical practice of psychiatric and diverse medical conditions.
Drug classes with significant interactions related to CYP3A4/5 and CYP2D6, as seen in clinical practice of psychiatric and diverse medical conditions.Drug classes with significant interactions related to CYP3A4/5 and CYP2D6, as seen in clinical practice of psychiatric and diverse medical conditions.
  • For a list of medications that can help determine potential drug-drug interactions with your patients’ concomitant treatments, see the FlockhartTM Table

In the pivotal studies, most patients taking AUSTEDO were able to stay on their concomitant psychiatric medications.13

Watch Dr.
Rakesh Jain discuss drug metabolism as a crucial consideration for TD treatment

AAN, American Academy of Neurology; APA, American Psychiatric Association; VMAT2, vesicular monoamine transporter 2.

REFERENCES: 1. American Psychiatric Association. Practice Guideline for the Treatment of Patients with Schizophrenia. 3rd ed. American Psychiatric Association; 2021. 2. 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. 3. AUSTEDO® (deutetrabenazine) tablets current Prescribing Information. Parsippany, NJ, Teva Neuroscience, Inc. 4. 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. 5. 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. 6. INGREZZA® (valbenazine) capsules Prescribing Information. San Diego, CA: Neurocrine Biosciences, Inc.; April 2021. 7. US National Library of Medicine. Drugs, herbs and supplements. MedlinePlus. Updated April 28, 2015. Accessed October 29, 2021. https://medlineplus.gov/druginfo/meds 8. Horn JR, Hansten PD. Get to know an enzyme: CYP3A4. Pharmacy Times. September 1, 2008. Accessed October 26, 2021. https://www.pharmacytimes.com/view/2008-09-8687 9. 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 October 29, 2021. https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers 10. PubChem. PubChem Compound Database. National Center for Biotechnology Information. Accessed October 29, 2021. https://pubchem.ncbi.nlm.nih.gov/compound/ 11. National Center for Biotechnology Information. Home- PMC- NCBI. National Center for Biotechnology Information. Accessed October 29, 2021. https://www.ncbi.nlm.nih.gov/pmc/articles 12. Horn JR, Hansten PD. Get to know an enzyme: CYP2D6. Pharmacy Times. July 1, 2008. Accessed October 29, 2021. https://www.pharmacytimes.com/view/2008-07-8624 13. Data on file. Parsippany, NJ: Teva Neuroscience, Inc.