Tramadol extended-release oral tablet interactions: A detailed guide

This article describes possible interactions with tramadol extended-release* (ER) oral tablet. Interactions can cause a drug to have a different effect on the body than expected. Interactions can occur due to medications, alcohol, or certain health conditions.

Tramadol comes as ER tablets that you swallow. It’s also available as immediate-release† oral tablets. Interactions of tramadol may vary depending on the form of tramadol your doctor prescribes.

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* Extended-release tablets release the medication into your body slowly over a period of time.† Immediate-release tablets release all the medication into your body right away.

Boxed warnings

This drug has boxed warnings about the following risks. A boxed warning is the most serious warning from the Food and Drug Administration (FDA).

• risk of misuse and addiction
• risk of serious breathing problems
• risk of accidental ingestion
• risk of life threatening effects in children
• risk of neonatal opioid withdrawal syndrome (NOWS)
• risk of interactions with certain medications
• risk of interactions with benzodiazepines and other central nervous system (CNS) depressants

See the end of this article for more information about these warnings.

Other drugs and tramadol

The drugs in the list below may interact with tramadol extended-release (ER) oral tablet. This article doesn’t include all drugs that may interact with tramadol.

Drug classes or drugs that may interact with tramadol ER oral tablet include:

• antidepressants:*
  • drug examples: citalopram (Celexa), amitriptyline, nefazodone
  • what might happen: can increase the risk of tramadol side effects
• benzodiazepines (drugs for anxiety and sleep problems):*
  • drug examples: alprazolam (Xanax), lorazepam (Ativan), diazepam (Valium)
  • what might happen: can increase the risk of tramadol side effects
• hypnotics (sleeping pills):*
  • drug examples: eszopiclone (Lunesta), zolpidem (Ambien)
  • what might happen: can increase the risk of tramadol side effects
• other opioid pain relievers:*
  • drug examples: morphine (MS Contin), hydrocodone (Hysingla ER), oxycodone (OxyContin)
  • what might happen: can increase the risk of tramadol side effects
• seizure medications:*
  • drug examples: carbamazepine (Tegretol, Carbatrol), phenytoin (Dilantin), gabapentin (Neurontin)
  • what might happen: some can make tramadol less effective or cause withdrawal symptoms;‡ some can increase the risk of tramadol side effects
• muscle relaxants:*
  • drug examples: cyclobenzaprine (Amrix), baclofen (Lyvispah)
  • what might happen: can increase the risk of tramadol side effects
• triptans (drugs for migraine):
  • drug examples: sumatriptan (Imitrex), eletriptan (Relpax), rizatriptan (Maxalt)
  • what might happen: can increase the risk of tramadol side effects
• certain antibiotics* and antifungals:*
  • drug examples: clarithromycin, erythromycin (Eryc, Ery-Tab), itraconazole (Sporanox), ketoconazole
  • what might happen: can increase the risk of tramadol side effects
• certain HIV drugs:*
  • drug examples: ritonavir (Norvir), cobicistat (Tybost), nelfinavir (Viracept)
  • what might happen: can increase the risk of tramadol side effects
• certain antiarrhythmics* (drugs for irregular heartbeat):
  • drug examples: amiodarone (Pacerone), quinidine
  • what might happen: can increase the risk of tramadol side effects
• monoamine oxidase inhibitors (MAOIs):†
  • drug examples: phenelzine (Nardil), isocarboxazid (Marplan), linezolid (Zyvox)
  • what might happen: can increase the risk of tramadol side effects

* Tramadol ER oral tablet has boxed warnings for interactions with these medications. A boxed warning is the most serious warning from the Food and Drug Administration (FDA). For more information about these warnings, see the end of this article.† Your doctor likely won’t prescribe tramadol ER oral tablet if you’ve taken an MAOI in the past 14 days. This is a tramadol contraindication. See the “When to avoid tramadol” section below for more information.‡ Withdrawal symptoms are side effects that can occur when you stop taking a drug on which your body has become dependent. With dependence, your body needs the drug to function as usual.

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When to avoid tramadol

Certain health conditions or other factors could increase some risks with tramadol extended-release (ER) oral tablet. Because of this, doctors may not prescribe tramadol in these cases. These health conditions or other factors are called contraindications.

Here’s a list of tramadol’s contraindications for the ER oral tablet:

• Children under age 12 years. In this age group, tramadol ER oral tablet can cause life threatening breathing problems and even lead to death.
• Children under age 18 years who’ve had surgery to remove their tonsils or adenoids. In this age group, tramadol ER oral tablet is not safe for relieving pain from these surgeries. It can cause life threatening breathing problems and even lead to death.
• Severe breathing problems. If you have very slow and shallow breathing, taking tramadol ER oral tablet could stop your breathing completely. If you have severe asthma, taking tramadol ER oral tablet may not be safe for you.
• Blockage in your digestive system. If you have a blockage in your stomach or intestines, taking tramadol ER oral tablet could worsen this condition.
• Monoamine oxidase inhibitors (MAOIs). If you take a type of drug called an MAOI, taking tramadol ER oral tablet could cause serious or life threatening side effects. Your doctor likely won’t prescribe tramadol if you’ve taken an MAOI in the last 14 days. Examples of MAOIs include the antibiotic linezolid (Zyvox) and the antidepressants phenelzine (Nardil) and isocarboxazid (Marplan).
• Past allergic reaction to tramadol. If you’ve ever had an allergic reaction to tramadol ER oral tablet or any of its ingredients, taking it again may cause another allergic reaction.

Before you start taking tramadol, tell your doctor if anything listed above relates to you. They can recommend whether you should take tramadol.

Other interactions and tramadol

Interactions can occur with supplements, foods, vaccines, and some lab tests. Below you can learn whether tramadol extended-release (ER) oral tablet has these interactions.

The information below doesn’t include all other interactions possible with tramadol.

Tramadol and supplements

Before taking tramadol ER oral tablet, tell your doctor and pharmacist about any herbs you take, as well as vitamins and supplements. Doing so may help you avoid interactions.

Tramadol ER oral tablet may interact with supplements used to aid sleep, such as melatonin and valerian. Taking tramadol with these supplements may cause severe sleepiness.

If you have questions about interactions that may affect you, talk with your doctor or pharmacist.

Tramadol interactions with herbs

Tramadol ER oral tablet may interact with St. John’s wort. This herb is often used for depression and other conditions.

Taking tramadol with St. John’s wort may cause serotonin syndrome. This is a serious condition caused by a buildup of serotonin in your body. It may also make tramadol less effective at treating pain.

If you’re dependent on tramadol, St. John’s wort could also cause tramadol withdrawal symptoms. (With dependence, your body needs the drug to function as usual. Withdrawal symptoms are side effects that can occur when you stop taking a drug on which your body has become dependent.)

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Because of this, you should avoid taking St. John’s wort with tramadol ER oral tablet. Also ask your doctor or pharmacist before taking any other herbs while taking tramadol ER oral tablet.

Tramadol interactions with vitamins

Tramadol ER oral tablet isn’t known to interact with any vitamins. But this doesn’t mean interactions with vitamins can’t happen or won’t be identified later.

Because of this, ask your doctor or pharmacist before taking any of these products while taking tramadol ER oral tablet.

Tramadol and food

Tramadol ER oral tablet can interact with grapefruit and grapefruit juice. You should avoid consuming grapefruit and grapefruit juice while taking this medication. Both could make tramadol build up in your body. This could raise your risk of serious side effects, such as slowed breathing.

To learn about other foods to avoid when taking tramadol ER oral tablet, talk with your doctor or pharmacist.

Tramadol and vaccines

Tramadol ER oral tablet isn’t known to interact with any vaccines. But this doesn’t mean interactions with vaccines can’t happen or won’t be identified later.

Because of this, talk with your doctor or pharmacist before receiving any vaccines while taking tramadol ER oral tablet.

Tramadol and lab tests

Tramadol ER oral tablet isn’t known to interact with lab tests. But this doesn’t mean interactions with lab tests can’t happen or won’t be identified later.

Because of this, talk with your doctor or pharmacist before having any tests while taking tramadol ER oral tablet.

Tramadol and cannabis or CBD

Reports have shown cannabis (commonly called marijuana) and cannabis products may interact with tramadol. Cannabidiol (CBD) is an example of a cannabis product.

Taking tramadol and cannabis may lead to severe sleepiness, confusion, and slowed breathing.

Before you take tramadol, tell your doctor and pharmacist if you use cannabis. Doing so may help prevent possible interactions.

Note: Cannabis is illegal at a federal level but is legal in many states to varying degrees.

Health factors and tramadol

Certain medical conditions or other health factors may increase the risk of interactions with tramadol extended-release (ER) oral tablet. Keep in mind that interactions could lead to side effects or affect how well the drug works. Before taking tramadol, tell your doctor about your health history. They’ll determine whether tramadol is right for you.

These health conditions or other factors might interact with tramadol ER oral tablet:

• past drug or alcohol misuse or dependence*
• mental health conditions or thoughts of suicide
• lung or breathing problems, such as obstructive sleep apnea or chronic obstructive pulmonary disease (COPD)
• low blood pressure
• head injury, brain tumor, or raised pressure in your skull
• seizures
• difficulty urinating
• constipation
• liver or kidney problems
• thyroid or adrenal gland problems
• pancreas or gallbladder problems
• pregnancy† or breastfeeding
• past allergic reaction to tramadol

Some of these health factors are tramadol contraindications. See the “When to avoid tramadol” section above to learn more about these.

* Misuse refers to taking a drug in a way other than how a doctor prescribes it. With dependence, your body needs the drug to function as usual.† Tramadol ER oral tablet has a boxed warning for the risk of neonatal opioid withdrawal syndrome (NOWS) if the medication is taken during pregnancy. A boxed warning is the most serious warning from the Food and Drug Administration (FDA). For more information, see the end of this article.

Suicide prevention

If you or someone you know is in crisis and considering suicide or self-harm, please seek support:

• Call the 988 Suicide and Crisis Lifeline at 988.
• Text HOME to the Crisis Text Line at 741741.
• Not in the United States? Find a helpline in your country with Befrienders Worldwide.
• Call 911 or your local emergency services number if you feel safe to do so.

If you’re calling on behalf of someone else, stay with them until help arrives. You may remove weapons or substances that can cause harm if you can do so safely.

If you are not in the same household, stay on the phone with them until help arrives.

Preventing tramadol interactions

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You may be able to help avoid certain interactions with tramadol extended-release (ER) oral tablet. Before taking this drug, you may want to discuss possible interactions with your doctor and pharmacist.

Things to consider include:

• Whether you drink alcohol or use cannabis.
• Other medications and herbs you take, as well as vitamins and supplements. Your doctor or pharmacist can help you fill out a medication list.
• What to do if you’re prescribed a new drug while taking tramadol ER oral tablet.

Taking tramadol exactly as prescribed also can help prevent interactions.

What to ask your doctor

If you have questions about tramadol and possible interactions, talk with your doctor.

Questions you may want to ask your doctor include:

• Does my risk of interactions depend on my dosage of tramadol extended-release oral tablet?
• Do I have other factors that raise my risk of interactions with tramadol extended-release oral tablet?
• Can I take allergy medications with tramadol extended-release oral tablet?

Boxed warnings for tramadol

This drug has boxed warnings about the following risks. A boxed warning is the most serious warning from the Food and Drug Administration (FDA).

Risk of misuse and addiction. Tramadol extended-release (ER) oral tablet has a risk of misuse and addiction. Misuse refers to taking a drug in a way other than how a doctor prescribes it. With addiction, you may feel unable to stop using the drug, even if it’s causing harm.

Take tramadol ER oral tablet only as your doctor prescribes. Misusing this medication can cause overdose and even lead to death. This includes dissolving the tablet and injecting it, as well as breaking, chewing, crushing, or snorting it.

Risk of serious breathing problems. Tramadol ER oral tablet can cause serious or life threatening breathing problems. The risk is highest in the 3 days after starting treatment and if your doctor increases your dosage.

Your doctor may recommend keeping naloxone nasal spray (Narcan) on hand while you’re taking tramadol. Narcan is a medication that can be used in an emergency to reverse the effects of tramadol. Discuss this with your doctor.

Risk of accidental ingestion. Accidentally taking even one dose of tramadol ER oral tablet can cause overdose and even lead to death. This is especially true in children. Be sure to keep this medication in a secure place, out of the sight and reach of children and others.

Risk of life threatening effects in children. Certain children have a higher risk of life threatening breathing problems with tramadol. Due to this risk, doctors likely will not prescribe tramadol ER oral tablet to:

• children under age 12 years
• children under age 18 years who’ve had surgery to remove their tonsils or adenoids
• children under age 18 years who have certain other risk factors, such as lung problems

Risk of neonatal opioid withdrawal syndrome (NOWS). If you take tramadol for a long time during pregnancy, your newborn may have opioid withdrawal symptoms. (Withdrawal symptoms are side effects that can occur when you stop taking a drug on which your body is dependent. Dependence means your body needs the drug to function as usual.) NOWS can be life threatening, and a doctor will need to monitor the baby.

If you’re pregnant or plan to become pregnant, talk with your doctor before taking tramadol ER oral tablet.

Risk of interactions with certain medications. Certain medications can affect the way your liver breaks down tramadol. Taking tramadol ER oral tablet with these medications can have different effects. It may increase the risk of tramadol side effects. Or it could make tramadol less effective at treating pain. If you’re dependent on tramadol, it could cause withdrawal symptoms. (Withdrawal symptoms are side effects that can occur when you stop taking a drug on which your body is dependent. Dependence means your body needs the drug to function as usual.)

Examples of these medications include certain antiarrhythmics, antibiotics, antifungals, and HIV medications. Be sure to tell your doctor about any medications that you take before starting tramadol.

Risk of interactions with benzodiazepines and other central nervous system (CNS) depressants. Taking tramadol with benzodiazepines, alcohol, or CNS depressants can cause life threatening side effects. Side effects include severe sleepiness and breathing problems. They can also include coma in extreme cases or if untreated.

CNS depressants are medications that slow activity in your CNS, which is your brain and spinal cord. Examples of CNS depressants include sleeping pills, other opioid pain relievers, certain antidepressants, muscle relaxants, antipsychotics, and seizure medications.

If your doctor prescribes tramadol ER oral tablet with one of these medications, they’ll likely recommend keeping naloxone nasal spray (Narcan) on hand. Narcan is a medication that can be used in an emergency to reverse the effects of tramadol. Learn more about this from your doctor.

To learn more about any of these boxed warnings, talk with your doctor.

Disclaimer: Optum Perks has made every effort to make certain that all information is factually correct, comprehensive, and up to date. However, this article should not be used as a substitute for the knowledge and expertise of a licensed healthcare professional. You should always consult your doctor or another healthcare professional before taking any medication. The drug information contained herein is subject to change and is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. The absence of warnings or other information for a given drug does not indicate that the drug or drug combination is safe, effective, or appropriate for all patients or all specific uses.

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