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As with any other medication, there is a risk of tramadol negatively interacting with other medications and substances, even when used correctly. Always consult with a physician or pharmacist before taking tramadol with any other prescription drug, over-the-counter medication, herbal medicine, or alcohol.

Drug Interactions

According to the U.S. National Library of Medicine, drugs that may interact with tramadol include the following.

Drugs that May Interact with TramadolExamples
Inhibitors of CYP2D6– Quinidine

Fluoxetine (Prozac)

– Paroxetine (Brisdelle, Paxil CR, Pexeva)

– Bupropion (Wellbutrin XL, Forfivo XL, Wellbutrin SR)
Inhibitors of CYP3A4– Macrolide antibiotics [e.g., erythromycin (E.E.S. 400, EryPed 200, E.E.S. Granules, Ery Pads, EryPed 400, Ery-tab, Eryc, Erygel, Pce)]

– Azole-antifungal agents (e.g., ketoconazole)

Protease inhibitors [e.g., ritonavir (Norvir)]
CYP3A4 Inducers– Rifampin (Rifadin)

– Carbamazepine (Tegretol XR, Equetro, Carbatrol, Epitol, and Tegretol)

– Phenytoin (Phenytek, Dilantin Kapseal, Dilantin Infatabs, Dilantin Extended,Dilantin-125)
Benzodiazepines and Other Central Nervous System (CNS) Depressants– Benzodiazepines [e.g., alprazolam (Alprazolam Intensol, Xanax, Xanax XR)]

– Other sedatives/hypnotics

– Anxiolytics (anti-anxiety medication)

– Tranquilizers

Muscle relaxants (listed below)

– General anesthetics

– Antipsychotics [e.g., risperidone (Risperdal), quetiapine (Seroquel), olanzapine (Zyprexa), ziprasidone (Zeldox), paliperidone (Invega), aripiprazole (Abilify), and clozapine (Clozaril)]

– Other opioids (e.g., codeine)

– Alcohol
Serotonergic Drugs– Selective serotonin reuptake inhibitors (SSRIs) [e.g., citalopram (Celexa), escitalopram (Lexapro), fluvoxamine (Luvox), paroxetine (Paxil), fluoxetine (Prozac), and sertraline (Zoloft)]

Serotonin and norepinephrine reuptake inhibitors (SNRIs) [e.g., desvenlafaxine (Pristiq), duloxetine (Cymbalta), venlafaxine (Effexor), milnacipran (Savella), and levomilnacipran (Fetzima)]

– Tricyclic antidepressants (TCAs) [e.g., amitriptyline (Elavil), amoxapine, clomipramine (Anafranil), desipramine (Norpramin), doxepin (Sinequan), imipramine (Tofranil), nortriptyline (Pamelor), protriptyline (Vivactil)]

Triptans [e.g., almotriptan (Axert), eletriptan (Relpax), frovatriptan (Frova), lasmiditan (Reyvow), naratriptan (Amerge), rizatriptan (Maxalt), sumatriptan (Imitrex, Onzetra Xsail, Sumavel DosePro, Zembrace), zolmitriptan (Zomig)]

– 5-HT3 receptor antagonists [e.g., ondansetron (Zuplenz, Zofran, Zofran ODT), granisetron (Sustol, Sancuso), dolasetron (Anzemet), palonosetron (Aloxi)]

– Drugs that affect the serotonin neurotransmitter system [e.g., mirtazapine (Remeron, Remeronsoltab), trazodone, tramadol (ConZip, Ultram]

– Certain muscle relaxants [i.e., cyclobenzaprine (Amrix, Fexmid), metaxalone (Metaxall, Skelaxin)]

– Monoamine oxidase (MAO) inhibitors [those intended to treat psychiatric disorders and also others, such as linezolid (Zyvox) and intravenous methylene blue]
Monoamine Oxidase Inhibitors (MAOIs)– Linezolid (Zyvox)

– Phenelzine (Nardil)

– Tranylcypromine (Parnate)
Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics– Buprenorphine (Belbuca, Probuphine, Buprenex, Butrans)

– Butorphanol


– Pentazocine (Talwin)
Muscle Relaxants– Metaxalone (Metaxall, Skelaxin)
Diuretics– Chlorothiazide (Diuril IV, Diuril)

– Spironolactone (CaroSpir, Aldactone)
Anticholinergic Drugs– Atropine (Atropen)

– Benztropine mesylate (Cogentin)

– Clidinium

– Dicyclomine (Bentyl)

– Fesoterodine (Toviaz)

Please note that this list may not be complete, and other interactions with drugs not listed here may occur. To learn more about some of these interactions, keep reading.

Tramadol Interaction with SSRI Medications

Selective serotonin reuptake inhibitors (SSRIs) (Ex. Sertraline) are currently the most commonly prescribed antidepressants in the United States. Unlike SNRIs, SSRIs work only to inhibit the reuptake of serotonin in the brain and the gut, which means the body has more serotonin available. This class of antidepressants is commonly used for both mental health conditions like depression, anxiety, and obsessive-compulsive disorder (OCD) and may help alleviate symptoms of gastrointestinal (GI) conditions like irritable bowel syndrome (IBS).

Since SSRIs naturally increase the availability of serotonin in the body, taking tramadol with any SSRI increases the risk of serotonin syndrome, which can be life-threatening (but rare).

The most popular SSRIs in the United States include:

  • Sertraline hydrochloride (Zoloft)
  • Citalopram hydrobromide (Celexa)
  • Fluoxetine hydrochloride (Prozac)
  • Escitalopram oxalate (Lexapro)

Tramadol Interaction with Lexapro (Escitalopram)

Escitalopram (Lexapro) is one of the most popular SSRI antidepressants in the United States. Taking tramadol with any SSRI, including Lexapro, increases the risk of the potentially life-threatening condition serotonin syndrome.

Tramadol Interactions with Zoloft (Sertraline)

Never combine these medications without first talking to a doctor to weigh the risks against the benefits. Why? Because both of these drugs can elevate the body’s levels of serotonin. Therefore, combining these drugs can increase the risk of serotonin syndrome (SS), a condition in which there is an excessive amount of serotonin on the central nervous system (CNS). 

Although rare, this condition is quite serious and can produce the following symptoms:

  • Confusion
  • Headache
  • Dilated (widened) pupils
  • Diarrhea
  • Goose bumps (piloerection, cutis anserina, horripilation)
  • Shivering
  • Rapid heart rate
  • High blood pressure (hypertension)
  • Agitation
  • Lack of muscle coordination
  • Twitching muscles
  • Rigid muscles
  • Intense sweating
  • Restlessness

In even rarer cases, serotonin syndrome can be lethal. Symptoms of potentially life-threatening serotonin syndrome are:

  • High fever (over 103° F or 39° C for adults)
  • Irregular heartbeat
  • Loss of consciousness
  • Seizures

If you experience these symptoms, it’s important to contact emergency medical help right away. To learn about other adverse reactions of tramadol, read our side effects page.

Sometimes combining Zoloft (sertraline) and tramadol can result in seizures for reasons unrelated to serotonin syndrome.

Tramadol Interactions with Other Antidepressants

While the risks of mixing tramadol with other classes of drugs is not as strong, there is evidence to suggest that mixing tramadol with other kinds of antidepressants (e.g., SSRIs or SNRIs) can increase the risk of serotonin syndrome. Therefore, patients should always consult with their prescribing physician before mixing tramadol with other antidepressants.

Tramadol Interaction with Cymbalta (Duloxetine)

Cymbalta is the brand name of duloxetine; it is a selective serotonin and norepinephrine reuptake inhibitor (SSNRI), also known as a serotonin-norepinephrine reuptake inhibitor (SNRI). This class of antidepressants works by inhibiting the reuptake (reabsorption) of the neurotransmitters serotonin and norepinephrine, both of which are strongly associated with regulating mood.

Taking tramadol with duloxetine or any other SNRI antidepressant increases the risk of potentially life-threatening serotonin syndrome.

Tramadol Interactions with MAOIs

Doctors currently advise against both using tramadol with MAOIs (monoamine oxidase inhibitors) (ex. Rasagiline) or taking tramadol within 14 days after stopping MAOIs.

MAOIs are a class of antidepressants that inhibit the enzyme monoamine oxidase. By inhibiting this enzyme, MAOIs increase the body’s levels of the chemicals norepinephrine, serotonin, and dopamine. MAOIs are well-known for interacting with food and other drugs, including tramadol.

Since both tramadol and MAOIs elevate the body’s levels of serotonin, taking both together increases the risk of serotonin syndrome (SS). SS is a potentially life-threatening condition in which excess serotonin floods the central nervous system

  • Rasagiline (Azilect)
  • Selegiline (Zelapar, Eldepryl)

Tramadol Interactions with Methadone

Methadone (Diskets, Methadone Intensol, Methadose) is a narcotic that can both treat moderate to severe pain as well as manage narcotic addiction. You should not combine multiple kinds of narcotics, as it can lead to serious side effects. Mixing tramadol with methadone specifically can result in serious side effects like precipitating opioid withdrawal symptoms.

Opioid withdrawal symptoms include:

  • Anxiousness
  • Muscle pain
  • Nausea and vomiting
  • Abdominal pain
  • Diarrhea
  • Sweating
  • Restlessness
  • Dilated (widened) pupils
  • Watery eyes
  • Increased heart rate
  • Insomnia
  • Tremors
  • Goose bumps
  • Severe yawning

Why does this interaction occur? Experts believe it is because methadone can decrease tramadol’s metabolism.

Tramadol Interactions with Ibuprofen

Currently, there is not much information available regarding interactions between tramadol and the nonsteroidal anti-inflammatory drug (NSAID) ibuprofen. However, it’s important to note that drug interactions may occur even when not reported. It’s always best to ask a doctor first before combining a prescription medication like tramadol with an over-the-counter drug like ibuprofen.

Tramadol Interaction with Meloxicam

Both meloxicam and tramadol are used to treat pain, although they work in different ways.

Meloxicam (Vivlodex, Mobic, Comfort Pac-Meloxicam) is a prescription-only nonsteroidal anti-inflammatory drug (NSAID), the same class of drugs to which the common over-the-counter medication ibuprofen (Advil, Motrin) belongs. Meloxicam reduces pain and inflammation in the body by blocking the enzyme cyclooxygenase (COX), a process that prevents the synthesis (creation) of prostaglandins, which play a key function in the immune system’s inflammatory response. Meloxicam is therefore commonly used for managing symptoms of conditions like arthritis.

Meloxicam and tramadol may be taken together under the approval and supervision of a licensed healthcare professional.

What Does the Research Say?

Research suggests that taking these medications together can have a positive pain-relieving effect in certain cases.

For example, one pilot study found that the combination of 25 mg of tramadol and 7.5 mg of meloxicam was more effective in relieving pain post-molar surgery than 50mg of tramadol alone. Furthermore, this combination had a similar pain-relieving effect as 15 mg of meloxicam alone. Given the small size of this study, further research is necessary to confirm these findings. This research proves promising, though, as the combination treatment included lower levels of meloxicam. Considering that most doctors recommend taking meloxicam in as low a dose for as short a period of time as possible, this combination may be preferable for some people who experience unpleasant side effects from meloxicam.

Another study examined the combined pain-relieving and anti-inflammatory effects of tramadol and meloxicam in rats undergoing surgery. The study found that combining meloxicam and tramadol pre-surgery produced significant pain-relieving effects. While this research is promising, further studies will be needed to confirm these dosages and subsequent effects in humans.

Tramadol Interaction with Warfarin

Warfarin (Coumadin, Jantoven) belongs to a class of drugs known as anticoagulants, or blood thinners. It is prescribed to treat or prevent blood clots and is commonly used to manage conditions like

  • Deep vein thrombosis (DVT)
  • Pulmonary embolism (blocked arteries in the lungs)
  • Atrial fibrillation (abnormal, often rapid, heart beat)
  • Embolic stroke (clot or debris blocking blood supply to the brain)
  • Transient ischemic attack (TIA, “mini stroke”)
  • Stroke

Warfarin and tramadol are known to interact. Although why these drugs interact isn’t exactly known, it is known that combining these medications can increase international normalized ratio (INR), meaning this combination increases the time it takes for blood to clot. Tramadol and warfarin interactions therefore make it easier for you to bleed, increasing the risk of bruising and even hemorrhaging.

In cases where it’s necessary to take these medications simultaneously, patients must be closely supervised by their physician and dosages likely need to be adjusted.

Tramadol Interaction with Ambien (Zolpidem)

What is Ambien (Zolpidem)?

Zolpidem, better known by the brand name Ambien, is a prescription-only sedative (aka, tranquilizer, hypnotic, depressant). This medication is effectively a central nervous system (CNS) depressant, meaning that it can calm down the CNS and slow down brain activity; the result is an overall calming effect. Doctors commonly prescribe Ambien primarily for the treatment of insomnia, although some prescribe it to combat the negative effects of jet lag.

Can You Take Ambien with Tramadol?

You should not mix tramadol with zolpidem unless no other treatment options are effective; in these cases, combining Ambien and tramadol must be closely monitored by the prescribing physician.

Why Should You Not Mix Tramadol and Ambien?

Combining an opioid (like tramadol) with a CNS depressant (like zolpidem) can result in serious side effects, including:

  • Low blood pressure (hypotension)
  • Lightheadedness
  • Dizziness
  • Intense sleepiness
  • Slow and ineffective breathing (hypoventilation, respiratory depression)
  • Unresponsiveness
  • Coma
  • Death

Tramadol Interactions with Antibiotics

Antibiotics are drugs that fight bacterial infections.


Amoxicillin (Moxatag) is one of the most commonly prescribed drugs in the United States and is among the most commonly prescribed antibiotics in the country. Not much is known about the interactions between amoxicillin and tramadol. However, it is believed that tramadol may decrease the rate at which the kidneys excrete amoxicillin, which may mean higher levels of amoxicillin in the blood.

Erythromycin (E.E.S. 400, EryPed 200, Ery Pads)

Erythromycin is a macrolide antibiotic, which means it works by halting bacterial growth. Interactions when taking erythromycin with tramadol may occur. Experts believe that erythromycin can increase the amount of tramadol in the blood as well as heighten its effects, which may result in side effects like:

  • Concentration problems
  • Constipation
  • Dizziness
  • Drowsiness
  • Impaired decision-making skills
  • Lightheadedness
  • Low blood pressure (hypotension)
  • Nausea
  • Respiratory depression

Therefore, it is only in rare cases that erythromycin and tramadol may be taken together, and then only under the direct supervision of a licensed professional.

Linezolid (Zyvox)

Linezolid is a synthetic (man-made) antibiotic; it is officially classified as an oxazolidinone antibiotic. It works by preventing bacterial protein synthesis. It may also function as an monoamine oxidase (MAO) inhibitor. Specifically, it may inhibit the enzyme monoamine oxidase. When this enzyme is inhibited, it may lead to higher levels of norepinephrine, dopamine, and serotonin in the body.

Since tramadol can also increase serotonin levels, taking linezolid with tramadol increases the risk of serotonin syndrome, and as a result the use of both together should be avoided and/ or closely supervised by a physician.

Food Interactions

Sometimes the foods we eat and the beverages we drink can also interact with our medications.

Food and drink that may interact with tramadol include:

  • Alcohol (ethanol)
  • Grapefruit and grapefruit juice

Please note that this list may not be complete, and there may be other foods and beverages that interact with this drug.

Tramadol Interactions with Alcohol

Please see our page for a full discussion of tramadol interactions with alcohol.

Tramadol and Grapefruit

Tramadol should not be taken with large amounts of grapefruit juice (anything more than 8 oz.) Always speak with a physician or pharmacist about taking large amounts of grapefruit juice with any medication.

Grapefruit juice can affect how well some medicines work, and it may cause dangerous side effects.
FDA graphic by Michael J. Ermarth

Disease Interactions

Sometimes certain medications can increase the risk of negative side effects for patients with certain diseases or other medical conditions.

According to the U.S. National Library of Medicine, diseases and medical conditions that are known to negatively interact with tramadol include:

  • Breathing problems like asthma
  • Other lung problems
  • Acute abdominal conditions
  • Hepatitis or other liver problems
  • Thyroid problems
  • Renal (kidney) problems
  • Pancreas problems
  • Gallbladder problems
  • Issues urinating
  • Bowel blockages and constrictions
  • Allergies or sensitivities to tramadol or other opioids
  • Epilepsy or other history of seizures
  • Any condition or injury that could increase the risk of seizures
  • Increased intracranial pressure
  • Head injury
  • Abuse or addiction problems
  • Mental health conditions

Please note that this list may not be complete, and there may be other diseases and medical conditions where patients should not take tramadol.

Disclaimer: this article does not constitute or replace medical advice. If you have an emergency or a serious medical question, please contact a medical professional or call 911 immediately. To see our full medical disclaimer, visit our Terms of Use page.

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