8 Zaleplon Interactions to Watch For

Zaleplon (Sonata) is medication that’s prescribed for short-term treatment of insomnia (trouble sleeping). It’s part of a group of medications called “z-drugs,” which belong to a larger class of medications called sedatives. Sedatives slow down the brain and have several effects, including making you drowsy. 

Although making you sleepy is the point of taking zaleplon, this also comes with risks — especially if you take it with other medications and substances that cause drowsiness.

It’s important to be aware of zaleplon interactions and the side effects they can cause, which range from mild to severe. We’ll cover eight medications and substances that may interact with zaleplon below, with a few tips on how to manage them.

Promotion disclosure

Zaleplon

Avg retail price

$127.45(Save 87.56%)

GoodRx discount

$15.86

See all discounts

How it works

Use GoodRx to find medications, pharmacies, and discounts.

GoodRx discounts can help you pay less for your prescription.

Bring your free coupon or savings card to the pharmacy.

1. Alcohol

Alcohol can affect the way your brain works. It can also have lasting effects on the brain if it’s misused long term. Zaleplon also affects your brain. When taken together, alcohol and zaleplon increase your risk for worsening coordination, falls, and memory issues. 

More seriously, combining alcohol and zaleplon can increase your risk of overdose. So it’s best to avoid drinking alcohol completely while taking zaleplon. 

Before starting zaleplon, have an honest conversation with your healthcare professional (HCP) about whether you drink alcohol and how much. Your HCP can let you know if zaleplon is a safe option for you. And if you’re having trouble cutting back on alcohol use, your HCP can help you stop or reduce your drinking. You can also call SAMHSA’s National Helpline at 1-800-662-4357 to learn about resources in your area.

2. Opioids

Opioids are prescription pain medications. They’re usually only prescribed when nonopioid pain medications don’t work. Examples of opioids include tramadol (Ultram, ConZip, Qdolo) and oxycodone (Roxicodone, Oxycontin).

Opioids act on areas of the brain that recognize pain, but they can also cause drowsiness, dizziness, and “brain fog.” Taking opioids with zaleplon can increase your risk of these side effects. It can also increase your risk of falls, injuries, and complex sleep behaviors (like driving, making phone calls, or preparing food while asleep). 

Taken together, zaleplon and opioids can also increase your risk of slowed breathing and overdose, which can be life-threatening.

What’s more, chronic opioid use may worsen sleep. Due to these risks, your HCP will probably recommend avoiding taking zaleplon and opioids together. So talk to them if you have pain or sleep problems that don’t feel well-managed. They can recommend alternative treatment options to help you avoid the need to take opioids with zaleplon.

3. Benzodiazepines

Benzodiazepines are prescription medications used to treat a variety of health conditions, including anxiety and sleep problems. Examples of benzodiazepines include alprazolam (Xanax), clonazepam (Klonopin), and lorazepam (Ativan).

Benzodiazepines slow down brain activity. This can lead to a variety of side effects that are similar to zaleplon. Examples include drowsiness, dizziness, and slowed breathing. And combining zaleplon with a benzodiazepine increases your risk of overdose. So it’s best to avoid benzodiazepines if you take zaleplon.

Zaleplon is a controlled substance. This means it has an increased risk for dependence and misuse. So if you have a history of substance use disorder, zaleplon may not be the best medication option for you. In addition, opioids and benzodiazepines are also controlled substances that can cause dependence and misuse. Taking multiple types of controlled substances together increases your risk of overdose.

4. Benadryl (diphenhydramine)

Benadryl (diphenhydramine) is a commonly used antihistamine. It’s available over the counter (OTC) and can treat a variety of ailments, including allergies and itching. It’s also used as a sleep aid in some cases, since one of its major side effects is drowsiness.

Taking Benadryl and zaleplon together may cause excessive drowsiness. This may carry over into the next day, impacting your ability to drive, make decisions, and think clearly. Taking Benadryl with zaleplon can also increase your risk of falls and injuries.

Even though Benadryl is available OTC, combining it with zaleplon isn’t usually recommended. So talk to your HCP if you’re taking zaleplon and any OTC medications. If you’re taking Benadryl, they may recommend an alternative. For example, other antihistamines like Claritin (loratadine) may be a better option for allergies.

5. Some antidepressants

Zaleplon may interact with tricyclic antidepressants (TCAs), such as imipramine (Tofranil), amitriptyline, and doxepin (Silenor). This combination has been shown to affect the brain, causing problems with movement, talking, and alertness. Like zaleplon, TCAs can cause symptoms like drowsiness and dizziness.

Doxepin is FDA approved to treat insomnia. And other TCAs may be used off-label to help with sleep. In fact, it’s possible that your HCP may suggest trying a TCA instead of zaleplon. But it’s unlikely that they’ll recommend taking both medications due to the risk of side effects.

Other antidepressants may affect how zaleplon is metabolized (broken down). This may increase or decrease levels of zaleplon. Increasing zaleplon levels makes it more likely you’ll experience side effects. Decreasing zaleplon levels can make zaleplon less effective. So if you take an antidepressant with zaleplon, check with your prescriber or pharmacist about whether it may interact with zaleplon.

6. Some seizure medications

Some seizure medications speed up how quickly zaleplon is metabolized. This shortens the amount of time zaleplon is in your body, making it less effective. Examples include phenobarbital, phenytoin (Dilantin, Phenytek), and carbamazepine (Tegretol). 

If you take one of these seizure medications, you may need to take something besides zaleplon for sleep. Your prescriber can go over other medication options with you.

7. Some antibiotics and antifungals

Some antibiotics can speed up your metabolism of zaleplon and make it less effective. This includes rifampin (Rifadin), which is used to treat bacterial infections like tuberculosis. So your HCP may recommend an alternative sleep medication if you’re taking rifampin.

Other antibiotics and antifungals can decrease zaleplon metabolism. This increases levels of zaleplon in your body and makes side effects, like excessive drowsiness and falls, more likely. Antibiotics that can increase zaleplon levels include ciprofloxacin (Cipro), erythromycin (Ery-tab) and clarithromycin. Examples of antifungals that can increase zaleplon levels include ketoconazole, itraconazole (Sporanox), and fluconazole (Diflucan). 

If you’re taking one of these antibiotics or antifungals with zaleplon, your HCP may monitor you more closely for side effects. They may also change the dose of zaleplon or the interacting medication.

8. Cimetidine

Like other medications described above, cimetidine (Tagamet HB) can increase zaleplon levels. Cimetidine treats conditions that cause too much stomach acid, including heartburn and gastroesophageal reflux disease (GERD).

By increasing zaleplon levels, cimetidine raises your risk for zaleplon side effects. If you need cimetidine, your HCP may recommend a lower zaleplon dosage than usual. Or they may recommend trying another heartburn or GERD medication.

Good to know: Several other medications can increase or decrease zaleplon levels in the body. That’s why it's a good idea to ask your HCP and pharmacist to review your medication list before starting zaleplon and anytime you’re considering a new medication. They can let you know if there are any possible interactions and how to manage them.

Why trust our experts?

Written by:

Alex Brewer, PharmD, MBA

Alex Brewer, PharmD, MBA, is a licensed pharmacist specializing in chronic disease and health and wellness. Upon completing his residency, he worked in the managed care field, conducting medication therapy management and adherence counseling sessions with Medicaid, Medicare, and private insurance patients, before transitioning to a career in medical writing.

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:

Soojin Jun, PharmD

Soojin has 10 years of experience in various pharmacy settings, from inpatient to outpatient settings, and population health in value-based healthcare models. She completed training in various areas of healthcare to ensure patient safety, from activism, geriatric pharmacy, medication safety, healthcare quality, patient safety, death and dying, and trauma-informed care.

Our editorial standards

Meet our experts