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12 Tramadol Interactions You Should Know About

Austin Ulrich, PharmD, BCACPSoojin Jun, PharmD, BCGP
Updated on June 10, 2024

Key takeaways:

  • Tramadol (ConZip, Qdolo) is an opioid medication used to treat pain. It has many possible drug interactions. Examples include gabapentin (Neurontin), cyclobenzaprine (Flexeril), and alcohol. Sertraline (Zoloft), trazodone, and tizanidine are other common culprits.

  • Some tramadol interactions raise the risk of side effects from tramadol. Examples include sleepiness, an increased risk of seizures, or serotonin syndrome.

  • Always check with your prescriber and pharmacist before starting tramadol. They can help you check for possible tramadol interactions.

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Tramadol (Conzip, Qdolo) is an opioid medication that’s FDA approved to treat pain. It should only be used for pain that can’t be managed by non-opioid medications. 

Opioids like tramadol are controlled substances. They have a higher risk of dependence and misuse compared to non-controlled medications. And there’s restrictions around prescribing and refilling controlled substances.

Opioids have several risks, and tramadol is no different. Along with side effects, tramadol has possible drug interactions. Some tramadol interactions are mild and may only need monitoring. Others are more serious and may require a change to your medications.

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1. Alcohol

Alcohol can have harmful effects on the body, especially when used in an excess amount. And when combined with opioids like tramadol, there are serious risks, such as overdose, coma, and even death. Combining tramadol and alcohol can also raise the risk of more common tramadol side effects, such as drowsiness, dizziness, and nausea.

For these reasons, it’s best to avoid alcohol entirely while taking tramadol or any other opioid. Before starting tramadol, be honest with your prescriber about whether you drink alcohol, and whether you’re willing to avoid alcohol while taking tramadol. If you aren’t able to cut out alcohol, they’ll likely recommend another pain medication that isn’t as risky.

Additionally, if you think you’re drinking too much alcohol, help is available. Call SAMHSA’s National Helpline at 1-800-662-4357 to learn about resources in your area. 

GoodRx icon
  • Alternatives to tramadol: Non-opioid medications, and non-medication therapies, are often first-choice options for pain. Learn about several pain-relieving alternatives to tramadol.

  • Tramadol side effects: Like all opioids, tramadol has risks to know about. Learn about common and rare side effects, and how to manage them. 

  • Avoiding alcohol with tramadol: Severe tramadol risks, such as misuse and overdose, are more likely if you combine tramadol with alcohol. That’s why it’s best to avoid this combination.

2. Medications that increase tramadol levels, such as bupropion or fluoxetine 

Tramadol is metabolized (broken down) in the liver. Some medications prevent tramadol from being metabolized normally. This could lead to higher tramadol levels in the body and more side effects. Examples of medications that can increase tramadol levels include:

  • Bupropion (Wellbutrin XL, Wellbutrin SR)

  • Fluoxetine (Prozac)

  • Paroxetine (Paxil)

  • Ketoconazole 

  • Clarithromycin

  • Medications containing ritonavir (Norvir)

In some cases, it may be best to avoid these combinations altogether by using an alternative to tramadol or the interacting medication. In other cases, your prescriber may recommend just monitoring for Tramadol side effects. Your prescriber can help you decide what’s best.

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3. Medications that decrease tramadol levels, such as phenytoin and St. John’s wort

Other medications can cause tramadol to be metabolized more quickly. This lowers tramadol level in the body, making it less effective. Examples of these medications and substances include:

  • Phenytoin (Dilantin, Phenytek)

  • Carbamazepine (Tegretol, Tegretol XR)

  • Rifampin (Rifadin)

  • St. John’s wort

Before starting tramadol, give your healthcare team a list of your current medications, including over-the-counter (OTC) products. They can check for tramadol interactions and help you decide if tramadol is a safe medication for you.

If you take medications that can make Tramadol less effective, your prescriber may adjust your dose of tramadol. But don’t make any changes without talking to them first.

4. Benzodiazepines, gabapentin, and other sedative medications

Many medications and substances slow down brain activity. These are known as sedatives. Sedatives and medications with sedative-like qualities (such as tramadol) can cause several side effects, such as poor coordination, confusion, and sleepiness. More seriously, sedatives can cause overdose, especially if you take more than one.

This is why it’s best to avoid combining tramadol with sedatives or other sedative-like medications. Examples include: 

Keep in mind that some sedative-like medications, such as diphenhydramine, are available over-the-counter (OTC). So make sure to let your healthcare team know about all the medications and products you take, even those available OTC. Depending on what you take, your prescribermay recommend avoiding tramadol. Or they may prescribe a lower tramadol dose and ask you to watch for signs of oversedation.

5. Medications that increase serotonin, such as Zoloft, Lexapro, and trazodone

Some medications increase the levels of a chemical in the body called serotonin. Serotonin is involved in many body functions. It helps regulate your mood, sleep, bowel movements, and more.

When serotonin levels get too high, serotonin syndrome may occur. Mild symptoms include sweating, tremors, and trouble sleeping. Severe symptoms include high fever, agitation, and high blood pressure.

This condition is rare. But it’s more likely to happen if you take multiple medications that raise serotonin, especially at high doses. Some medications and supplements that raise serotonin levels include:

If you take any of these medications, talk to your healthcare team. They may recommend avoiding tramadol. If you're taking tramadol and show signs of serotonin syndrome, contact your prescriber immediately. They’ll likely ask you to stop tramadol. But this can cause withdrawal symptoms, so don’t do it without talking to your prescriber first. If your symptoms are severe, seek immediate medical attention.

6. Monoamine oxidase inhibitors, such as selegiline

Monoamine oxidase inhibitors (MAOIs) are a group of medications that treat conditions such as depression and Parkinson’s disease. Examples include selegiline (Zelapar, Emsam) and rasagiline (Azilect). However, MAOIs are notorious for having many risks, and may require you to adjust your diet and pay attention to drug interactions.

MAOIs can increase serotonin, and may lead to serotonin syndrome when combined with tramadol. This combination can also increase your risk of slowed breathing and overdose. 

For these reasons, tramadol and MAOIs shouldn’t be taken within 14 days of each other.

7. Naltrexone

Opioid antagonists are medications that treat opioid use disorder and alcohol use disorder. One of the most common opioid antagonists is naltrexone (Vivitrol). 

If you start naltrexone while taking tramadol (or any opioid), opioid withdrawal could occur. Symptoms include muscle aches, agitation, and vomiting. This is why it’s typically recommended to avoid opioids for 7 to 10 days before starting naltrexone. 

If you’re taking naltrexone for opioid use disorder and you relapse to opioids (including tramadol), contact your healthcare team. You may be more sensitive to opioids after stopping naltrexone. This means that opioid doses you tolerated in the past may now be too much for you. This can lead to an overdose, which can be life-threatening.

It’s important not to confuse naltrexone with naloxone (Narcan, Zimhi). Although naloxone is an opioid antagonist like naltrexone, they aren’t used in the same way. Naloxone is used to quickly reverse the effects of an opioid overdose, but naltrexone does not have this effect. In fact, it’s a good idea to keep naloxone on you at all times if you or a loved one takes an opioid such as tramadol. There are several ways to access naloxone, including OTC.

8. Medications that lower the seizure threshold, such as cyclobenzaprine

Some medications can increase the likelihood of having a seizure. Another way to say this is that they “lower the seizure threshold”.

Tramadol can lower the seizure threshold, making it more likely to experience a seizure. This is more likely in people with a history of seizures or people who are at greater risk of seizures. It’s also more likely if you combine tramadol with other medications that lower the seizure threshold, such as:

  • Bupropion 

  • TCAs, such as amitriptyline

  • Antipsychotics, such as clozapine (Clozaril)

  • Cyclobenzaprine (Amrix, commonly known as Flexeril)

  • Diphenhydramine

Before starting tramadol, tell your prescriber if you take one of these medications. They may recommend closer monitoring for seizures or a lower dose of tramadol. They might also suggest a different medication altogether.

9. Diuretics, such as furosemide and hydrochlorothiazide

Diuretics (water pills) help remove fluid from the body. They treat conditions like heart failure, high blood pressure, and fluid overload (edema). Opioids like tramadol can decrease the effectiveness of diuretics. This is because opioids can release antidiuretic hormone in the body. Antidiuretic hormone has the opposite goal of diuretics: it prevents your body from getting rid of fluids. Examples of diuretics include furosemide (Lasix), torsemide (Soaanz), and hydrochlorothiazide (Microzide).

If you’re taking a diuretic and tramadol, your healthcare team may ask you to check your blood pressure more often. They may also ask you to watch for signs of fluid buildup, such as peeing less or swollen ankles and feet. These signs may mean your diuretic isn’t working as well as it should.

10. Anticholinergic medications, such as oxybutynin and scopolamine

Anticholinergic medications block the effects of acetylcholine in the body. Acetylcholine is a chemical that helps your brain and muscles work properly. Anticholinergica can cause side effects like trouble urinating, constipation, and dry mouth — just to name a few.

Examples of anticholinergic medications include oxybutynin (Ditropan XL), dicyclomine (Bentyl), and scopolamine (Transderm Scop). Many medications also have anticholinergic-like properties, including antipsychotics, TCAs, and diphenhydramine.

Tramadol also has anticholinergic effects. When taken with other anticholinergic medications (including several, like scopolamine, that are available OTC), side effects become more likely. To avoid this interaction, your healthcare team may suggest avoiding tramadol. Or they may just monitor for signs of an interaction. This includes the inability to pee or worsening constipation.

11. Digoxin

Digoxin (Lanoxin) is used to treat symptoms of heart failure and help control your heart rate. It’s a “narrow therapeutic index” medication. This means that the difference between harmful and safe doses of digoxin is very small.

Tramadol can raise digoxin levels in the body and cause digoxin toxicity. Reports of this are rare, but symptoms include vision problems and gastrointestinal side effects. Serious toxicity can cause life-threatening heart problems.

If you take digoxin, your prescriber may recommend avoiding tramadol. Or, they may suggest lowering your digoxin dose. If you have symptoms of digoxin toxicity, seek medical attention immediately.

12. Warfarin

Warfarin (Jantoven) is a blood thinner. It helps prevent and treat blood clots. Like digoxin, it has a narrow therapeutic index.

Tramadol can increase levels of warfarin in the body and increase the risk of warfarin side effects, including bruising or bleeding. If you take warfarin, your prescriber may suggest a different pain medication. Or they may do more frequent blood tests to make sure you’re taking an appropriate warfarin dose.

Frequently asked questions about tramadol interactions

Can you take tramadol with NSAIDs like ibuprofen (Advil, Motrin) and naproxen (Aleve, Naprosyn)?

Yes, tramadol can typically be taken with nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen (Advil, Motrin) and naproxen (Aleve, Naprosyn). In fact, taking NSAIDs with opioids like tramadol can be an effective way to relieve pain in some situations. Just be sure to check with a prescriber before adding an NSAID to your routine.

Can you take tramadol with Tylenol (acetaminophen)?

Yes, you can take tramadol with Tylenol (acetaminophen). Tylenol is a common OTC pain reliever that helps treat mild to moderate pain and fever. There aren’t any known risks from combining Tylenol with tramadol. In fact, there is a combination pill that contains tramadol and acetaminophen (Ultracet) in the same tablet.

The bottom line

Tramadol (ConZip, Qdolo) is an opioid medication that treats pain. It can interact with many medications. Some possible tramadol interactions may only require extra monitoring. But others can be serious and require changing your medications. 

Tramadol and alcohol are best avoided. This interaction can lead to increased drowsiness, dizziness, and more seriously, overdose. Other tramadol interactions include benzodiazepines like alprazolam (Xanax), gabapentin (Neurontin), and selective serotonin reuptake inhibitors like sertraline (Zoloft) and escitalopram (Lexapro). It can also interact with bupropion (Wellbutrin SR, Wellbutrin XL), seizure medications like phenytoin (Dilantin, Phenytek), and monoamine oxidase inhibitors like selegiline (Zelapar).

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Why trust our experts?

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.
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.
Soojin Jun, PharmD, BCGP
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.
View All References (2)

Sam, C., et al. (2023). Physiology, acetylcholine. StatPearls.

You and Your Hormones. (2021). Anti-diuretic hormone.

GoodRx Health has strict sourcing policies and relies on primary sources such as medical organizations, governmental agencies, academic institutions, and peer-reviewed scientific journals. Learn more about how we ensure our content is accurate, thorough, and unbiased by reading our editorial guidelines.

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