7 Eszopiclone (Lunesta) Interactions to Be Aware of

If you struggle with falling asleep, your healthcare team may prescribe a sleeping pill such as eszopiclone (Lunesta). It’s FDA approved to treat insomnia in adults. Eszopiclone can help people fall asleep faster and stay sleeping longer, but it also has several risks — including interactions.

Some eszopiclone interactions can raise the risk of side effects. Other drug interactions may reduce how well eszopiclone works. Eszopiclone is a central nervous system (CNS) depressant, which means it slows brain activity. So it can also interact with other CNS depressants, such as alcohol.

Here are seven key eszopiclone interactions to know about. Keep in mind that this isn’t a complete list, so be sure to review your medication list with your healthcare team before starting treatment.

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1. Alcohol

It’s not recommended to combine eszopiclone with alcohol. Both of these substances are CNS depressants. So the combination can raise your risk of side effects, such as impaired motor skills and hand-eye coordination. It can also increase the chance of these symptoms continuing into the next day. What’s more, alcohol may also raise the chance of complex sleep behaviors, such as walking, eating, or even driving while you’re asleep, after taking eszopiclone.

If you plan to take eszopiclone to help you sleep, it’s best to avoid alcohol. Even daytime drinking could raise the risk of unwanted side effects. Talk to your prescriber if you have questions or concerns about avoiding alcohol while taking eszopiclone.

If you or someone you know struggles with substance use, help is available. Call SAMHSA’s National Helpline at 1-800-662-4357 to learn about resources in your area.

2. Benzodiazepines, such as diazepam

Taking benzodiazepines, such as diazepam (Valium), with eszopiclone can also increase the risk of brain-related side effects. The combo could make you overly sedated, feel groggy the next day, or cause slowed breathing (respiratory depression).

To be safe, it’s best to avoid taking these medications together. If your prescriber recommends a benzodiazepine for you, be sure they’re aware you’re taking eszopiclone (and vice versa). They may want to lower your dosage or suggest a different medication that’s safer for you.

3. Opioid pain medications

Opioid medications are used to treat severe pain. Examples include hydrocodone / acetaminophen (Norco) and oxycodone (Roxicodone, OxyContin).

Like alcohol and benzodiazepines, opioids are CNS depressants. Taking eszopiclone with opioids raises the risk of serious side effects, such as slowed breathing, extreme sedation, and next-day impairment or sluggishness. The combination can also raise the risk of an overdose, which can be fatal.

If your healthcare team prescribes an opioid for pain, be sure they’re aware you’re taking eszopiclone. They may lower your dosage or have you stop taking eszopiclone until you no longer need opioid treatment.

4. Some antifungals, such as ketoconazole

Certain antifungal medications, such as oral ketoconazole and itraconazole (Sporanox), can interact with eszopiclone. Ketoconazole blocks an enzyme (protein) that breaks down eszopiclone in the body. So taking the medications together can raise the levels of eszopiclone in your body. This raises the risk of side effects, such as headache, dizziness, and dry mouth.

You may need a lower dose of eszopiclone if you’re taking an antifungal medication. So be sure to let your prescriber know you’re taking it if you’re seeking treatment for a fungal infection.

Good to know: Topical antifungals aren’t absorbed into the bloodstream the same way as oral antifungals. So they’re usually fine to use while you’re taking Lunesta.

5. Some antibiotics, such as clarithromycin

Some antibiotics can also cause eszopiclone interactions. Two examples are clarithromycin (Biaxin XL) and rifampin (Rifadin).

The combination of clarithromycin and eszopiclone can increase the levels of eszopiclone in your body. This interaction can make the side effects of eszopiclone worse.

Rifampin, on the other hand, can decrease the levels of eszopiclone in your body. This can lower the effectiveness of eszopiclone. This drug interaction can happen because rifampin causes eszopiclone to get broken down and removed from your body faster than usual.

If your healthcare team recommends an antibiotic for an infection, be sure to tell them you’re taking eszopiclone. Knowing this information can help prescribers choose the right antibiotic treatment for you or make changes to your eszopiclone dosage if needed.

6. Some antiviral medications, including Paxlovid

Certain medications for viral infections can interact with eszopiclone. For example, ritonavir (Norvir) and nelfinavir (Viracept) are HIV medications that can increase the levels of eszopiclone, raising the risk of side effects. Ritonavir is also an active ingredient in Paxlovid (nirmatrelvir / ritonavir), an antiviral treatment for COVID-19.

A lower dose of eszopiclone is recommended if you’re taking an interacting antiviral medication. As mentioned, let your prescriber know about the medications you’re taking so they can make the necessary adjustments if needed.

When should you contact your healthcare team about eszopiclone interactions?

Any time you have questions or concerns about eszopiclone interactions, it’s best to play it safe by reaching out to your healthcare team. Check with your prescriber or pharmacist before starting any new medications or dietary supplements. Sharing your current medication list with them can also help you avoid or lessen your risk for potentially harmful eszopiclone interactions.

If you notice increased eszopiclone side effects or that it isn’t working as well as it used to, these could be signs of an interaction. So let your prescriber know if these occur. If at any point you have trouble breathing, hallucinations, or confusion, seek medical care right away.

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Written by:

Patricia Weiser, PharmD

Patricia has 16 years of pharmacist experience. She previously held positions as a community pharmacist, pharmacy manager, and hospital pharmacist.

Edited by:

Stacia Woodcock, PharmD

Stacia Woodcock, PharmD, is a pharmacy editor for GoodRx. She earned her Doctor of Pharmacy degree from the University of Kentucky and is licensed in New York and Massachusetts.

Reviewed by:

Christina Aungst, PharmD

Christina Aungst, PharmD, is a pharmacy editor for GoodRx. She began writing for GoodRx Health in 2019, transitioning from freelance writer to editor in 2021.

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