Alcohol, Xanax, and More: 8 Zolpidem (Ambien) Interactions You Should Know About

For a lot of people, insomnia (trouble sleeping) is a consistent struggle. In fact, about 15% of U.S. adults have trouble sleeping on a regular basis. .

Often, implementing sleep hygiene habits can improve your sleep. But if they don’t work, some people may turn to medications. Zolpidem (Ambien, Intermezzo, Edluar) is one medication that’s FDA approved for insomnia. It can help you fall asleep more quickly by activating areas in the brain called gamma aminobutyric acid (GABA) receptors. Activating GABA receptors makes you feel sleepy.

Although zolpidem can be an effective option for insomnia, it isn’t without risks and side effects. As a controlled substance, it has a risk of dependence and misuse. Additionally, zolpidem has several drug interactions to keep in mind. Here, we’ll cover eight notable zolpidem interactions you should know about.

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1. Opioids, such as Oxycontin and hydrocodone

Opioids treat pain that can’t be relieved by non-opioid medications. Examples include morphine (MS Contin, Mitigo, Duramorph PF), oxycodone (Roxicodone, Oxycontin), and hydrocodone (Hysingla ER). Like zolpidem, opioids are also controlled substances. 

Combining opioids with zolpidem can be risky because both medications affect the brain. When taken together, there’s a risk for extreme dizziness and sleepiness. This can lead to falls, injuries, and disability, especially for older adults.

The combination of opioids and zolpidem also makes it more likely to experience slowed breathing and overdose. This is why it’s recommended to avoid opioids with zolpidem in most cases.

2. Benzodiazepines, such as Xanax

Benzodiazepines treat multiple medical conditions, including panic disorder, anxiety, and insomnia. Like zolpidem, benzodiazepines activate GABA receptors in the body. Similarly, they can cause drowsiness and dizziness. They’re also controlled substances. Examples of benzodiazepines include alprazolam (Xanax), lorazepam (Ativan), and diazepam (Valium).

Combining benzodiazepines and zolpidem can cause excessive drowsiness. And it can impact your ability to focus and control your movements. In fact, taking zolpidem or benzodiazepines alone makes it more likely you’ll get in a car accident or have a fall. And combining these medications can make accidents and falls even more likely. This combination can also cause an overdose, which can be life-threatening.

For these reasons, it’s best to avoid combining benzodiazepines with zolpidem.

EXPERT PICKS: WHAT TO READ NEXT

• Common sleep medications: Zolpidem is one of many medications used to treat insomnia. Learn about the different options here. 

• Sleep medications and alcohol: Find out why mixing alcohol and sleep medications can be risky, and why this combination is best avoided.

• Zolpidem side effects: Review these common side effects of zolpidem so you can be prepared to manage them or seek out medical care.

3. Some antidepressants, including Zoloft

Tricyclic antidepressants (TCAs) treat multiple medical conditions, including depression and migraines. Examples of TCAs are amitriptyline and nortriptyline (Pamelor).

TCAs can cause dizziness and drowsiness as a side effect. Therefore, combining TCAs and zolpidem can lower alertness and cause excessive sleepiness. It can also affect your ability to control your movements. In more dangerous situations, it can slow your breathing. 

Other types of antidepressants may also interact with zolpidem. Along with possibly causing drowsiness, selective serotonin reuptake inhibitors (SSRIs) like sertraline (Zoloft) and fluoxetine (Prozac) may increase levels of zolpidem in the body. This can lead to an increased risk of zolpidem side effects.

If you need to take both an antidepressant and zolpidem, talk to your prescriber. They can let you know if your antidepressant might interact with zolpidem. And they can help you decide if another antidepressant would be better for you. Or they may recommend stopping zolpidem altogether.

4. Alcohol

Alcohol can cause many of the same side effects as zolpidem. This includes dizziness, sleepiness, and headache. Like zolpidem, it has an effect on GABA, which can cause drowsiness.

As you might expect, combining Ambien and alcohol can cause you to become too drowsy. It can affect your normal body movements and slow down your breathing. These effects are even more dangerous if you’re operating machinery or driving the day after taking zolpidem. So, if you’re taking zolpidem regularly, it’s best to avoid drinking alcohol completely.

However, if you take zolpidem on an as-needed basis, talk to your prescriber about whether it's safe to drink alcohol on days you don’t take zolpidem. While it can take over 12 hours for zolpidem to clear your system, it may be safe to have an alcoholic drink on days you don’t take it.

5. Antimicrobials, such as fluconazole

Some medications, such as zolpidem, are broken down (metabolized) in the liver. Other medications can either block or enhance this process. This affects levels of zolpidem in the body.

If zolpidem levels become too high, dangerous side effects are more likely. This can include excessive drowsiness, dizziness, and trouble breathing. Medications that block zolpidem metabolism and may raise zolpidem levels include some antibiotics, antifungals, and antivirals, such as:

• Clarithromycin

• Ketoconazole 

• Fluconazole (Diflucan)

• Ritonavir-containing medications, such as Kaletra (lopinavir / ritonavir) and Paxlovid (nirmatrelvir / ritonavir)

On the other hand, rifampin (Rifadin) is an antibiotic that can decrease zolpidem levels, making it less effective.

The antimicrobials listed here aren't the only medications that can increase zolpidem levels. So talk to your healthcare team about drug interactions before starting zolpidem. They can help you check whether you’re at risk of any interactions.

6. Seizure medications, such as carbamazepine

Some seizure medications may lower zolpidem levels by speeding up its metabolism. This can make zolpidem less effective. Examples of these medications include carbamazepine (Tegretol, Equetro), phenytoin (Dilantin, Phenytek), and phenobarbital.

Additionally, these medications can worsen drowsiness and dizziness when combined with zolpidem. Other seizure medications, such as gabapentin (Neurontin) and topiramate (Topamax), can also worsen these side effects.

If you take a seizure medication, it’s likely an important medication. So don’t stop taking it without talking to your prescriber.

7. Muscle relaxers, such as cyclobenzaprine

Muscle relaxers are medications that treat muscle pain and spasms. Examples include cyclobenzaprine (Amrix), tizanidine (Zanaflex), and carisoprodol (Soma).

Muscle relaxers can cause drowsiness as a side effect. So when combined with zolpidem, they can lead to feeling extremely sleepy or having disorganized or slowed movements. Experiencing an overdose is also more likely.

Your prescriber may suggest an alternative to muscle relaxers while you’re taking zolpidem. Nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen (Aleve, Naprosyn) can relieve muscle pain without drowsiness. They work in a different way than muscle relaxers. But these medications may not be the best option for everyone.

8. Some OTC antihistamines, such as Benadryl

Over-the-counter (OTC) antihistamines, such as diphenhydramine (Benadryl, ZzzQuil) and doxylamine (Unisom SleepTabs), treat a wide range of conditions. This includes allergies and trouble sleeping. Combining these medications with zolpidem can increase your risk for excessive drowsiness. This may lead to falls and injuries.

Typically, you shouldn’t combine multiple sleep medications. That goes for OTC medications like Benadryl and doxylamine too. These OTC products are also part of many nighttime cough and cold medications, which should also be avoided with zolpidem.

If you feel that you aren’t sleeping well, even with your current treatment, talk to your healthcare team. Don’t start any new sleep medications without your prescriber’s OK.

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Written by:

Austin Ulrich, PharmD, BCACP

Austin Ulrich, PharmD, BCACP, is a board-certified ambulatory care clinical pharmacist. In his early career, he provided direct patient care in a variety of settings, including hospital and community pharmacies, and in a primary care clinic as a clinical pharmacist.

Edited by:

Amy B. Gragnolati, PharmD, BCPS

Amy Gragnolati, PharmD, BCPS, is a pharmacy editor for GoodRx. Amy currently holds her pharmacist license in Georgia and California.

Reviewed 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.

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