6 Cyclobenzaprine Interactions You Should Know About

Cyclobenzaprine (Amrix) is a prescription muscle relaxer. It's FDA approved to treat muscle spasms from muscle or bone problems. It acts in the brain and nervous system to lower pain and tenderness and improve mobility. Cyclobenzaprine is meant for short-term use only (2 to 3 weeks at a time), alongside physical therapy and getting adequate rest.

Like most medications, cyclobenzaprine has risks to be aware of, including drug interactions. Some interactions may require you to change your medication regimen. Others might just require close monitoring.

Below, we’ll discuss six important cyclobenzaprine interactions to know. But keep in mind, this is not a complete list. So, before starting cyclobenzaprine, give your prescriber and pharmacist a current medication list. This will help them screen for interactions.

1. Alcohol

Alcohol can cause drowsiness, mood changes, and decreased alertness. When combined with cyclobenzaprine, these effects may become more severe. This makes you more likely to experience extreme drowsiness and slowed breathing. This can lead to an overdose, which can be life-threatening. Cyclobenzaprine overdoses are rare but if they do happen, they usually involve other substances that can affect breathing, such as alcohol.

In fact, no muscle relaxer is considered safe to take if you drink alcohol. Even though some muscle relaxers are less likely than cyclobenzaprine to cause drowsiness, they all affect the brain.

Be honest with your prescriber about whether you drink alcohol before starting cyclobenzaprine. They may recommend a different medication.

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• Cyclobenzaprine side effects: Learning about the potential side effects of cyclobenzaprine, both common and rare, can help keep you safe.

• Comparing muscle relaxers: There are several muscle relaxers available, each with varying dosages and side effects.

• Alcohol and muscle relaxers: This combination is best avoided. Alcohol and muscle relaxers can cause drowsiness. In severe cases, this combination can slow your breathing.

2. Medications that affect the brain

Sedatives are medications that slow down brain activity. Sedative side effects include sleepiness, forgetfulness, and trouble concentrating. When combined with cyclobenzaprine, these side effects can worsen.

Drowsiness, fatigue, and trouble focusing are common cyclobenzaprine side effects as well. And in severe cases, oversedation can affect your breathing leading to an overdose.

Before taking cyclobenzaprine, ask your prescriber and pharmacist if any of your other medications have sedative effects. Examples of sedatives, and sedative-like medications, include:

• Sleep medications like zolpidem (Ambien, Edluar, and ZolpiMist)

• Barbiturates like phenobarbital

• Benzodiazepines like alprazolam (Xanax)

• Opioids like oxycodone (Roxicodone, OxyContin)

• Other muscle relaxers like tizanidine (Zanaflex)

• Gabapentinoids such as gabapentin (Neurontin) and pregabalin (Lyrica)

• Diphenhydramine (Benadryl)

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If you’re currently taking any of these medications, your prescriber may suggest avoiding cyclobenzaprine. Or they may recommend a lower dose. You should also look out for symptoms of oversedation, like sleepiness and poor coordination. 

It’s best to avoid tasks that require alertness, such as driving, when you first start taking cyclobenzaprine. This is especially important if you take other medications that cause drowsiness. Once you see how cyclobenzaprine affects you, talk to your prescriber about whether it’s safe to resume these activities.

3. Medications that affect serotonin

Serotonin is an important brain chemical that’s involved in regulating your sleep, mood, and more. In fact, many medications work by increasing serotonin levels. However, too much serotonin in your brain can lead to a medical condition called serotonin syndrome. 

Cyclobenzaprine doesn’t directly increase serotonin. But it’s thought to enhance serotonin actions in the brain. Although it’s rare, taking cyclobenzaprine with other substances that increase serotonin increases your risk of serotonin syndrome.

Several medications can increase serotonin. Be cautious when using these medications with cyclobenzaprine, including:

• Tricyclic antidepressants (TCAs) like amitriptyline

• Serotonin and norepinephrine reuptake inhibitors (SNRIs) like venlafaxine (Effexor XR)

• Selective serotonin reuptake inhibitors (SSRIs) like sertraline (Zoloft)

• Triptans like sumatriptan (Imitrex, Onzetra Xsail)

• Opioids like tramadol (ConZip, Qdolo)

• Monoamine oxidase inhibitors (MAOIs) like selegiline (Zelapar, Emsam)

• St. John’s wort

If any of your other medications can increase serotonin, watch for symptoms of serotonin syndrome such as trouble sleeping, tremors, and sweating. More severe symptoms include agitation, high fever, and high blood pressure. 

If you notice mild symptoms of serotonin syndrome, contact your healthcare team right away. If your symptoms feel severe, seek medical attention. Severe cases are medical emergencies and require immediate medical care.

4. MAOIs

As mentioned above, taking an MAOI with cyclobenzaprine can increase the risk of serotonin syndrome. But it can also cause MAOI toxicity. Examples of MAOIs include selegeline, rasagiline (Azilect), and phenelzine (Nardil).

MAOIs are known for having many drug and food interactions. This is because MAOIs raise levels of various chemicals in the body, including ​​norepinephrine. Cyclobenzaprine also increases these chemicals, which can result in MAOI toxicity. Severe effects of MAOI toxicity include high fever, high blood pressure, and seizures. In rare cases, death can occur. 

Although MAOI toxicity is rare, you shouldn’t take cyclobenzaprine within 14 days (2 weeks) of an MAOI. If your prescriber recommends cyclobenzaprine but you’re already taking an MAOI, let them know. Your prescriber will either stop your MAOI or consider an alternative to cyclobenzaprine. But don’t stop or start any medications without talking to them first.

5. Medications that increase seizure risk

Many medications, including cyclobenzaprine, can lower your “seizure threshold.” Your seizure threshold is a term that describes how likely you are to have a seizure. Medications that lower the seizure threshold can put you at higher risk of having a seizure. 

Some medications that lower the seizure threshold include: 

• Tramadol

• Bupropion (Wellbutrin SR, Wellbutrin XL)

• TCAs like amitriptyline

• Antipsychotic medications like clozapine (Clozaril)

Cyclobenzaprine is more likely to lower the seizure threshold at higher doses, especially doses above 1,000 mg. But keep in mind that a dose of 1,000 mg wouldn’t be prescribed; it’s much larger than the maximum daily dose of 30 mg. Still, your prescriber may recommend avoiding cyclobenzaprine with other medications that lower the seizure threshold.

6. Anticholinergic medications

One of the most common side effects of cyclobenzaprine is dry mouth. It can also cause dry eyes, constipation, and trouble urinating. Many other medications, such as anticholinergic medications, can also cause these side effects. Taking anticholinergics with cyclobenzaprine can make these side effects worse.

Anticholinergic medications treat many health conditions, including those affecting the bladder and lungs. Examples include:

• Hyoscyamine (Levsin)

• Glycopyrrolate (Robinul, Cuvposa)

• Benztropine (Cogentin)

• Diphenhydramine

• Scopolamine (Transderm Scop)

There are other medications that aren't considered true anticholinergics, but they have anticholinergic activity. Cyclobenzaprine is one of these medications. So are some antipsychotics and TCAs. 

Talk to your healthcare team before starting cyclobenzaprine. They can let you know whether any of your other medications have anticholinergic activity. In some cases, they may make adjustments to your medication regimen.

Of note, if you have angle-closure glaucoma, increased eye pressure, or conditions that involve trouble urinating, cyclobenzaprine may make these conditions worse due to its anticholinergic activity. So let your healthcare team know in advance of taking cyclobenzaprine if you have any of these medical conditions.

Frequently asked questions about cyclobenzaprine interactions

You may wonder whether it’s safe to take cyclobenzaprine with other medications not mentioned above. Here, we’ll discuss a few frequently asked questions about other cyclobenzaprine interactions.

Does cyclobenzaprine interact with NSAIDs like ibuprofen (Advil, Motrin), naproxen (Aleve, Naprosyn), and meloxicam (Mobic)?

No, cyclobenzaprine doesn’t have any known interactions with nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs include ibuprofen (Advil, Motrin), naproxen (Aleve, Naprosyn), and meloxicam (Mobic). 

NSAIDs help treat pain and inflammation. So they’re often taken alongside muscle relaxers to treat muscle pain or spasms. While they’re typically considered safe to take with cyclobenzaprine, check with your healthcare team before starting an NSAID. Even though most NSAIDs are available over the counter (OTC), they still have risks. This is especially true if you have certain health conditions such as kidney disease.

Does cyclobenzaprine interact with acetaminophen (Tylenol)?

Similar to NSAIDs, cyclobenzaprine doesn’t interact with acetaminophen (Tylenol), another common pain reliever. It also can be used alongside cyclobenzaprine to help with muscle pain.

Like NSAIDs, acetaminophen is available OTC. Although it doesn’t help as much with inflammation, it tends to have fewer side effects. In fact, it’s often the go-to pain reliever for people who can’t take NSAIDs. Still, it’s a good idea to let your healthcare team know before starting acetaminophen. It may be a risky medication for certain people, such as those with existing liver problems.

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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:

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.

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