Is there an interaction between lemborexant and aripiprazole (Abilify)?

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Last updated: April 26, 2025View editorial policy

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From the Guidelines

There is a potential interaction between lemborexant and Abilify that patients and healthcare providers should be aware of, primarily due to their combined effects on the central nervous system (CNS) which may increase the risk of sedation, drowsiness, and impaired coordination. Both medications can cause CNS depression, and when taken together, they may have additive effects. The mechanism behind this interaction involves lemborexant's action on orexin receptors to promote sleep and Abilify's effects on multiple neurotransmitter systems, including dopamine and serotonin.

According to the study on antipsychotic polypharmacy 1, drug-drug interactions, especially those arising from using drugs affecting the same metabolic pathways, may have additive or reductive effects on plasma concentrations as well as the severity of side effects and adverse reactions. Although this study does not specifically address the interaction between lemborexant and Abilify, it highlights the importance of considering potential interactions when combining medications that affect the CNS.

Key considerations for patients taking both lemborexant and Abilify include:

  • Exercising caution with activities requiring mental alertness, such as driving or operating machinery, especially when starting either medication or adjusting doses.
  • Monitoring for increased side effects, such as sedation, and reporting excessive sedation to their healthcare provider.
  • Maintaining consistent timing with both medications and not adjusting dosing without medical supervision.

The combination of lemborexant and Abilify can be used safely under proper medical guidance with appropriate monitoring, emphasizing the need for healthcare providers to be aware of this potential interaction and to counsel patients accordingly.

From the Research

Interaction Between Lemborexant and Abilify

  • There are no direct studies on the interaction between lemborexant and Abilify (aripiprazole) in the provided evidence.
  • However, studies have investigated the drug-drug interaction potential of lemborexant with other medications, including CYP3A inhibitors and inducers 2, 3.
  • Lemborexant is primarily metabolized by CYP3A, and its pharmacokinetics can be affected by strong and moderate CYP3A inhibitors and inducers 2, 3.
  • Abilify is partially metabolized by CYP3A, but it is also a substrate of CYP2D6 [4 is not relevant to this information, but other sources may be].
  • Although there is no direct evidence on the interaction between lemborexant and Abilify, it is possible that co-administration of these medications could affect the pharmacokinetics of one or both drugs.
  • Further studies are needed to fully understand the potential interaction between lemborexant and Abilify 2, 3.

Pharmacokinetics of Lemborexant

  • Lemborexant exposure increases with increasing dose, and its time to maximum concentration ranges from approximately 1 to 3 hours for the 5- and 10-mg doses 4.
  • The mean effective half-life of lemborexant is 17 hours for the 5-mg dose and 19 hours for the 10-mg dose 4.
  • Lemborexant is well tolerated across the doses tested, with no clinically relevant effects on next-morning residual sleepiness 4.

Drug-Drug Interactions with Lemborexant

  • Coadministration of lemborexant with strong and moderate CYP3A inhibitors (e.g., itraconazole and fluconazole) results in increased lemborexant exposure 2, 3.
  • Coadministration of lemborexant with a strong CYP3A inducer (e.g., rifampin) results in decreased lemborexant exposure 2.
  • Lemborexant does not affect the pharmacokinetics of CYP3A substrates, but it has the potential to induce CYP2B6 2.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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