12 Tramadol Interactions You Should Know About

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 have several risks, and tramadol is no different. Along with side effects, tramadol has possible drug interactions. Some interactions are mild and may only need monitoring. Others are more serious and may require a change to your medications. So be sure to share your current medication list with your healthcare team for review. 

Here are 12 tramadol interactions to know about so you can take this medication safely.

1. Alcohol

Alcohol can have harmful effects on the body, especially when consumed 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. 

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 new or worsening side effects. Your prescriber can help you decide what’s best.

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

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 an 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:

• Gabapentin (Neurontin)

• Benzodiazepines like alprazolam (Xanax)

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

• Barbiturates like phenobarbital

• Muscle relaxers like tizanidine and methocarbamol

• Diphenhydramine (Benadryl)

• Other opioids like oxycodone (Roxicodone, Oxycontin) and hydrocodone

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 prescriber may 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

Tramadol and several other medications increase levels of serotonin, a chemical involved in mood, sleep, and other body functions. Taking tramadol with other medications that raise serotonin can increase the risk of serotonin syndrome — a rare but potentially serious condition caused by too much serotonin.

Some medications and supplements that raise serotonin levels include:

• Tricyclic antidepressants (TCAs), such as amitriptyline

• Selective serotonin reuptake inhibitors (SSRIs), such as escitalopram (Lexapro) and sertraline (Zoloft)

• Serotonin-norepinephrine reuptake inhibitors (SNRIs), such as duloxetine (Cymbalta)

• Triptans, such as sumatriptan (Imitrex, Onzetra)

• St. John’s wort

• Trazodone

Serotonin syndrome symptoms can include sweating, tremors, and trouble sleeping. More severe symptoms can include high fever, agitation, and high blood pressure.

Tell your healthcare team about medications and supplements you take before starting tramadol. They may recommend avoiding certain combinations or monitoring you more closely. 

Contact a healthcare professional right away if you develop symptoms of serotonin syndrome. Seek immediate attention for severe symptoms. Don’t stop taking tramadol suddenly unless instructed to do so, since this can cause withdrawal symptoms.

6. Monoamine oxidase inhibitors, such as selegiline

Monoamine oxidase inhibitors (MAOIs) are medications used for conditions such as depression and Parkinson’s disease. Examples of MAOIs include selegiline (Zelapar, Emsam) and rasagiline (Azilect). Combining an MAOI with tramadol can increase the risk of serious side effects, including serotonin syndrome, slowed breathing, and overdose.

Because of these risks, don’t take tramadol within 14 days of taking an MAOI. Make sure your prescriber knows if you’re currently taking an MAOI or have recently stopped one.

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, a lower tramadol dose, or a different medication altogether.

9. Diuretics, such as furosemide and hydrochlorothiazide

Diuretics (water pills) help remove extra fluid from the body. Examples include furosemide (Lasix), torsemide (Soaanz), and hydrochlorothiazide (Microzide).

Tramadol and other opioids may make diuretics not work as well. That’s because opioids can increase the release of antidiuretic hormone, which causes your body to hold onto more fluid.

If you take tramadol with a diuretic, your healthcare team may have you check your blood pressure more often. They may also ask you to watch for signs of fluid buildup, such as peeing less than usual or swelling in your feet and ankles.

10. Anticholinergic medications, such as oxybutynin and scopolamine

Anticholinergic medications can cause side effects such as constipation, trouble urinating, and dry mouth. Tramadol can cause some of these same side effects, which may be worse if they’re taken together.

Examples of anticholinergic medications include:

• Oxybutynin (Ditropan XL)

• Dicyclomine (Bentyl)

• Scopolamine (Transderm Scop)

• Antipsychotic medications such as clozapine (Clozaril) and quetiapine (Seroquel)

• First-generation antihistamines such as diphenhydramine and doxylamine (Unisom)

Your healthcare team may recommend avoiding certain combinations or monitoring you for these side effects. Contact them if you develop worsening constipation or trouble urinating.

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 suggest lowering your digoxin dose. If you have symptoms of digoxin toxicity, seek medical attention immediately.

12. Warfarin

Warfarin (Jantoven) is a blood thinner that helps prevent and treat blood clots. It has a narrow therapeutic index, meaning that small changes in its effects can increase the risk of bleeding or blood clots.

Tramadol can increase warfarin’s blood-thinning effects, raising the risk of bruising and bleeding. If you take both medications, your prescriber may recommend more frequent blood tests, adjusting your warfarin dose if needed. They may also recommend a different pain medication.

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) such as 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 in the same tablet.

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Written by:

Austin Ulrich, PharmD, BCACP

​​Austin Ulrich, PharmD, BCACP, is a board-certified ambulatory care clinical pharmacist. Ulrich’s experience includes direct patient care in hospital and community pharmacies.

Edited by:

Alyssa Billingsley, PharmD

Alyssa Billingsley, PharmD, is the director of pharmacy content for GoodRx. She has over a decade of experience as a pharmacist and has worked in clinical, academic, and administrative roles.

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