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Three Rx pill bottles: Tramadol interactions
Drug Info

Tramadol interactions to avoid

Tramadol may also have interactions with dietary supplements and herbal remedies, which can affect the medication's effectiveness or lead to additional side effects
Gerardo Sison medical writer headshot
By | Jan. 12, 2024

Key takeaways

  • Tramadol is a pain medication that belongs to the class of drugs called opioids. It may be recommended when other non-opioid treatments, like over-the-counter ibuprofen or acetaminophen, fail to work. 

  • As a powerful opioid medication, tramadol may cause CNS-depressant side effects like drowsiness, dizziness, and lightheadedness. These effects may be worsened when tramadol is taken with drugs with similar effects, such as anxiety and sleep medications. 

  • Tramadol is heavily metabolized or processed in the body by certain liver enzymes. As a result, other drugs that affect these liver enzymes can affect the levels of tramadol in the body, which could increase the side effects of tramadol or make the drug less effective.

  • Consult a healthcare provider about any medications you take before starting tramadol. Avoiding or minimizing possible interactions is key to managing pain safely and effectively. 

Drug interactions | Food interactions | Other interactions | Avoiding interactions | When to see a doctor

Tramadol, commonly known by the brand names Ultram and ConZip, is approved by the Food and Drug Administration (FDA) to treat moderate to severe pain. As a synthetic opioid, it works in the central nervous system (CNS) to reduce the body’s response to pain signals. Healthcare providers may recommend an opioid analgesic or pain reliever if non-opioid drugs don’t provide adequate pain relief.

Like many other prescription drugs, tramadol has the potential to interact with other medications, which can lead to increased side effects or decreased effectiveness. For example, some interactions can increase drowsiness, seizures, or serotonin syndrome. Read on to learn more about potential tramadol interactions, including those that might involve prescription drugs and herbal supplements.

Tramadol-drug interactions

If you’re taking tramadol for acute or chronic pain, you might also be taking other medications for different conditions and ailments. You may want to be aware of tramadol drug interactions that could lead to potentially severe adverse effects. Let’s go over the most common ones. 

Medications that increase serotonin

Tramadol may interact with medications that increase serotonin levels, such as antidepressants. This interaction can increase the risk of serotonin syndrome, a potentially life-threatening condition caused by high levels of serotonin in the body. Serotonin syndrome may cause agitation, confusion, rapid heartbeat, and muscle stiffness. Examples of medications involved in this potential interaction include:

In most cases, tramadol may be taken with antidepressants with close monitoring. However, tramadol should not be taken in people who are taking MAOIs or within two weeks of stopping treatment with an MAOI due to a high risk of serotonin syndrome. 

CNS depressants

Tramadol can interact with other CNS depressants, including sleep medications like sedative-hypnotics and anxiety medications like benzodiazepines. These drug interactions may increase the risk of breathing problems like respiratory depression and extreme sedation. Examples of CNS depressants include:

  • Opioids, such as OxyContin (oxycodone), Vicodin (hydrocodone), and codeine
  • Benzodiazepines, such as Valium (diazepam), Xanax (alprazolam), and Ativan (lorazepam)
  • Antipsychotics, such as Haldol (haloperidol), Seroquel (quetiapine), and Risperdal (risperidone)
  • Sedative-hypnotics, such as Ambien (zolpidem), Lunesta (eszopiclone), and Sonata (zaleplon)
  • Barbiturates, such as Luminal (Phenobarbital), Seconal (Secobarbital), and Amytal (Amobarbital)

Medications that affect how tramadol is processed in the body

Several drugs can alter how tramadol is processed, which may lead to increased side effects or reduced effectiveness. Examples of such medications include:

  • Certain antibiotics, such as Erythrocin (erythromycin) and Rifadin (rifampin). Erythrocin may increase tramadol levels, leading to increased side effects. Rifadin can decrease tramadol’s effectiveness by reducing its levels in the body.
  • Certain azole-antifungal agents, such as Nizoral (ketoconazole), may increase tramadol levels in the body, increasing the risk of side effects.
  • Protease inhibitors, such as Norvir (ritonavir), often used in HIV/AIDS treatment, may increase tramadol blood levels and increase its potential side effects.
  • Quinidine, a medication used for heart rhythm disorders, can affect the metabolism of tramadol, potentially increasing its levels.
  • Certain antidepressants, including Prozac (fluoxetine), Paxil (paroxetine), and Wellbutrin (bupropion), may increase tramadol levels, leading to a higher risk of side effects.
  • Certain anticonvulsants, such as Tegretol (carbamazepine) and Dilantin (phenytoin), may decrease tramadol’s effectiveness by reducing its levels in the body.

Muscle relaxants

Tramadol may increase the action of muscle relaxants and increase the risk of respiratory depression. Adjusting the dosage of tramadol or the muscle relaxant may be necessary. Examples of muscle relaxants include:

  • Soma (carisoprodol)
  • Flexeril (cyclobenzaprine)
  • Robaxin (methocarbamol)

Anticholinergic drugs

The use of tramadol with anticholinergic drugs may increase the risk of urinary retention and severe constipation. This can be serious and cause your intestines to stop working correctly, leading to what’s known as paralytic ileus. Common anticholinergic drugs include:

  • Atropine
  • Bentyl (dicyclomine)
  • Detrol (tolterodine)

Diuretics

Tramadol can reduce the effectiveness of water pills or diuretics. Blood pressure may need to be monitored, and the diuretic dosage may need to be increased while taking tramadol. Diuretics that may interact with tramadol include:

  • Lasix (furosemide)
  • Microzide (hydrochlorothiazide)
  • Aldactone (spironolactone)

Opioid antagonists

Tramadol’s effectiveness as a pain reliever may be reduced when combined with opioid antagonists, which are medications designed to block opioid effects. These drugs can cause withdrawal symptoms in people who have been using opioids for an extended period. Commonly used opioid antagonists include:

  • Narcan (naloxone)
  • Revia (naltrexone)

Warfarin 

Tramadol may interfere with warfarin, a blood thinner. This interference can lead to increased blood clotting times. If you are taking warfarin, your doctor may need to check your blood clotting ability and adjust your dose regularly.

Digoxin

Some cases of digoxin toxicity have been reported in people taking tramadol and digoxin. People taking both medications should be monitored for any adverse reactions from digoxin. Changing the digoxin dosage may also be necessary to avoid harmful effects.

Tramadol-food interactions

Taking tramadol with meals does not significantly affect its absorption into the body. Therefore, tramadol can be administered with or without food. However, caution may be recommended when taking tramadol with specific food or beverages. 

Tramadol and grapefruit juice

Grapefruit juice is known for its potential to interact with certain medications, including tramadol. It blocks how the liver breaks down tramadol, which could cause more tramadol to stay in your body and increase the chance of mild to serious side effects. Avoid grapefruit juice while taking tramadol. 

Tramadol and alcohol

Alcohol has CNS-depressant effects that can amplify those of tramadol. Combining alcohol with tramadol may lead to increased drowsiness, sedation, and dizziness. It’s generally recommended to avoid or limit alcohol consumption while taking this medication. 

Other tramadol interactions

Tramadol may also have interactions with dietary supplements and herbal remedies, which can affect the medication’s effectiveness or lead to additional side effects. These interactions include:

  • St. John’s wort: Often used for its potential benefits in alleviating symptoms of depression, St. John’s Wort can interact with tramadol. This combination may lead to an increased risk of serotonin syndrome. Therefore, it’s recommended to use caution when combining the two. 
  • Tryptophan: This essential amino acid, sometimes taken as a supplement to support sleep or improve mood, is a precursor to serotonin. Combining tryptophan with tramadol may lead to high serotonin levels, increasing the risk of serotonin syndrome.
  • 5-HTP (5-Hydroxytryptophan): Like tryptophan, 5-HTP is another supplement contributing to serotonin production. Its use alongside tramadol might increase the medication’s effect on serotonin levels, increasing the risk for serotonin syndrome. 

Discuss any dietary supplements or herbal remedies you’re taking with your healthcare provider before using tramadol. 

Other considerations

While taking tramadol, it can also be helpful to be aware of the following precautions:

  • Dependence and addiction: Tramadol is a controlled substance with a potential risk for dependence or abuse, and its misuse may lead to addiction.
  • Gastrointestinal obstruction, including paralytic ileus: Tramadol should be used with caution in people with a history of gastrointestinal issues, as it may worsen symptoms or cause complications.
  • Hypersensitivity: Individuals with a known hypersensitivity or previous allergic reaction to tramadol or any of its ingredients should avoid this medication.
  • Seizure disorder: As tramadol may increase the likelihood of seizures, individuals with a history of seizures should discuss this risk with a healthcare professional.
  • Serotonin syndrome: Taking high doses of tramadol or combining it with other medications that affect serotonin levels may lead to a potentially life-threatening condition known as serotonin syndrome.
  • Brain tumors or head injuries: People with these or similar conditions should exercise caution when taking tramadol, as it may worsen symptoms. Tramadol should be avoided in people with impaired consciousness or coma. 

Consult a healthcare provider about any medical conditions you have before taking tramadol. 

How to minimize tramadol interactions

Tell your healthcare provider about any medical conditions and additional medications you take to minimize interactions. A complete, updated list of all your medications might include the following:

  • Prescription medications
  • Over-the-counter drugs
  • Herbal supplements
  • Vitamins and minerals

Recognizing the potential warning signs of drug interactions can also help you detect potential issues early on. Some common warning signs may include:

  • Unexpected side effects
  • New symptoms 
  • Worsening of existing symptoms 

Always follow the prescribing instructions provided by your healthcare provider. They may suggest using the extended-release form of tramadol, adjusting the dosage, or changing the schedule of your medications to minimize potential tramadol interactions and side effects.

When to talk to a healthcare provider about tramadol interactions

You should speak with a healthcare provider about tramadol interactions during the initial visit when they prescribe the medication. You can also consult your local pharmacist if you have concerns about drug interactions. In general, you should seek medical advice about tramadol interaction if you:

  • Take any prescription or over-the-counter medications
  • Use any dietary supplements or herbal products
  • Have any medical conditions or a history of certain illnesses
  • Experience any unexpected side effects or changes in health

This is not a complete list of tramadol interactions. Discuss your overall medical history, including medical conditions and other medications you take, with your healthcare provider before starting treatment. A healthcare provider can assess the risks and benefits of tramadol, especially if you’re taking other medications. 

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