Safety & Tolerability

Polypharmacy

Consider the potential for drug-drug interactions when
choosing a VMAT2 inhibitor

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.

Drug classes associated with CYP3A4/5, CYP2D6, and P-gp3-12

Examples of Drug Classes Associated With CYP3A4/5

Inhibitors

  • Antiarrhythmics
  • Antibiotics
  • Antidepressants
  • Antifungals
  • Antihypertensives
  • Antiretrovirals/
    antivirals

Inducers

  • Antibiotics
  • Anticonvulsants/
    sedatives
  • Antifungals
  • Antihypertensives
  • Corticosteroids
  • Wakefulness-promoting agents

Substrates

  • Antianginals
  • Antidiabetics
  • Antihistamines
  • Antihypertensives
  • Corticosteroids
  • Diuretics
  • Statins
  • Vasodilators

Examples of Drug Classes Associated With CYP2D6

Inhibitors

  • Antiarrhythmics
  • Antidepressants
  • Antifungals
  • Antihistamines
  • Antiparasitics
  • Antipsychotics
  • Calcium reducers

Inducers

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

Substrates

  • Antiarrhythmics
  • Antiemetics
  • Antihistamines
  • Antihypertensives
  • Antidepressants
  • Antipsychotics

Examples of Drug Classes Associated With P-gp

Inhibitors

  • Antiarrhythmics
  • Antidepressants
  • Antihypertensives
  • Antimicrobials
  • Statins
  • Vasodilators

Inducers

  • Antiarrhythmics
  • Anticonvulsants
  • Antidiabetics
  • Antihypertensives
  • Antimicrobials
  • Corticosteroids
  • Opioids

Substrates

  • Antimicrobials
  • Anticoagulants
  • Antiemetics
  • Anticonvulsants
  • Antihistamines
  • Antihypertensives
  • Beta blockers
  • Corticosteroids
  • Opioids
  • Statins
  • Vasodilators
  • For a list of medications that can help determine potential drug-drug interactions with your patients’ concomitant treatments, see the Flockhart Table TM

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

Watch: Visualizing the role of metabolic pathways in DDIs

For more videos, visit the YouTube page.YouTube play icon

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.

SEE DOSING & GETTING STARTED Add person icon Request a rep

Patients in the pivotal study received the AUSTEDO BID formulation.1

AUSTEDO XR is metabolized primarily through CYP2D6, with minor contributions from CYP3A4/5.1

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.