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Tapentadol Side Effects: Common & Rare Risks to Look For

Peter Manza, PhD profile image
Reviewed By Peter Manza, PhD • Updated Nov 17, 2023 • 8 cited sources

Common side effects of tapentadol use include nausea, constipation, dizziness, drowsiness, headache and dry mouth. Less common side effects include confusion, hallucinations, allergic reactions and mood changes.[1]

What Are the Common Side Effects of Tapentadol?

Tapentadol can cause a few common side effects, especially when people first begin taking the drug. In most cases, the side effects will fade as the body adjusts to the medication, but in some cases, the effects will become more pronounced with higher doses.[1]

Common side effects of tapentadol include the following:[1]

  • Nausea
  • Constipation
  • Dizziness or feelings of vertigo
  • Drowsiness
  • Headache
  • Dry mouth

Although rare, there are a few less common side effects that may occur in addition to the more common ones listed above. These include the following:[1] 

  • Fatigue
  • Sweating
  • Itching
  • Vomiting

What Are Rare Side Effects of Tapentadol?

Tapentadol may trigger additional rare and risky side effects in very few users. Though they are very uncommon, it’s important to recognize the connection between the medication and these issues. If you experience them, reach out for medical assistance immediately.

Risky and rare side effects of tapentadol use include the following:[1,2]

Changes in Mental Health & Mood

Tapentadol can cause rare mood changes, such as feelings of anxiety, confusion and depression. It can also cause changes in behavior, such as engaging in risk-taking behavior and thinking about or engaging in acts of self-harm.

Low Blood Pressure

Tapentadol may cause low blood pressure in some cases. This can lead to dizziness, lightheadedness or fainting. It is more common to experience this when you stand up suddenly from a seated position or lying down.

Changes in Heartbeat

Tapentadol causes abnormal heart rhythm in rare cases, which may manifest as a fast or irregular heartbeat.

Urination Difficulties

Some people experience changes in their patterns of urination or difficulty urinating.  This can manifest as decreased urine production, urinary retention (inability to completely empty the bladder) or difficulty initiating urination.

Liver Problems

Tapentadol can cause liver problems, such as elevated liver enzymes and liver dysfunction. Yellowing of the skin and eyes (jaundice), pale stools or dark urine are all signs of liver disease.

What Dangerous Interactions Can Occur With Tapentadol Use?

Tapentadol may interact with other drugs and substances, which can trigger dangerous side effects in the user. Some of the most common risks to be aware of include the following:[3-5]

Central Nervous System Depressants

Tapentadol can have serious side effects when combined with central nervous system (CNS) depressants such as opioids, alcohol, benzodiazepines, or sedatives. These combinations increase the risk of respiratory depression, extreme drowsiness and impaired coordination. In severe cases, coma can occur.

Serotonergic Drugs

Tapentadol should not be taken with serotonergic medications like selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs) or monoamine oxidase inhibitors (MAOIs). These combinations can cause serotonin syndrome, which is characterized by mental changes, muscle rigidity, seizures and high body temperatures. Serotonin syndrome can be fatal if left untreated.


Antidepressants, including tricyclic antidepressants, can interact with tapentadol to increase the risk of serotonin syndrome and other adverse effects.

Liver Enzyme Medications

Tapentadol’s levels can be affected by medications that either inhibit or stimulate liver enzymes like rifampin and carbamazepine. Other drugs, such as phenytoin and St. John’s wort, may also require a dosage adjustment for tapentadol to be effective. In some cases, it may be necessary to choose an alternate form of pain management. 

Antiemetic Medication

Certain antiemetic medicines, like ondansetron, can increase your risk of serotonin syndrome when taken together with tapentadol.

Other Substances

There are many other substances that may negatively interact with tapentadol. It is important that you disclose all medication and supplement usage to your prescribing doctor and check in before starting any new medications or supplements.

Potential Risks & Warnings for Tapentadol Use

As an opioid medication, tapentadol has a high risk of misuse, dependence and opioid use disorder (OUD). Improper use can result in overdose, which could be fatal. 

Tapentadol can trigger respiratory depression, which means significantly slowed or shallow breathing. This effect can be life-threatening, especially for people who have pre-existing respiratory conditions. A clear sign of tapentadol overdose is respiratory depression.

Abrupt discontinuation or a rapid reduction in tapentadol dosage can lead to withdrawal symptoms. These are very uncomfortable and may include restlessness, anxiety, irritability, muscle aches, insomnia and nausea.[6]

If tapentadol is mixed with other medications, it can lead to serotonin syndrome or respiratory depression, both of which can be life-threatening conditions.[4,5]

Elderly people, individuals with compromised liver or kidney function, and people with pre-existing physical or mental health conditions should use caution when taking tapentadol. In some cases, the medication may simply not be a good choice for their needs or a lowered dose may be recommended. 

MAT for OUD Related to Tapentadol Use

If you have been misusing tapentadol and are unable to stop, it’s often a sign that you have an OUD. While it can be incredibly challenging to stop use on your own, Medication for Addiction Treatment (MAT) can make the process manageable.[7] It is a long-proven, evidence-based approach to recovery from OUD. 

Treatment begins with a thorough evaluation from a healthcare professional where your full medical and mental health history is taken into account. A unique treatment plan is then created. 

At Bicycle Health, we prescribe Suboxone, which is considered the gold standard in treatment for OUD. Suboxone includes buprenorphine, which works to reduce withdrawal symptoms and cravings, enabling the recovery process.[8] 

Counseling and therapy are included in the treatment plan, as they address the emotional and psychological aspects of OUD. In sessions, you’ll acquire coping skills that can help to prevent relapse.

MAT is a long-term treatment that includes ongoing monitoring and support. You can access this care no matter where you live, thanks to our telehealth offerings. Contact us to learn more about how this works. You can even get started today.

Reviewed By Peter Manza, PhD

Peter Manza, PhD received his BA in Psychology and Biology from the University of Rochester and his PhD in Integrative Neuroscience at Stony Brook University. He is currently working as a research scientist in Washington, DC. His research focuses on the role ... Read More

  1. Fidman B, Nogid A. Role of tapentadol immediate release (Nucynta) in the management of moderate-to-severe pain. P T. 2010;35(6):330-357
  2. Alshehri FS. Tapentadol: A review of experimental pharmacology studies, clinical trials, and recent findings. Drug Des Devel Ther. 2023;17:851-861. Published 2023 Mar 21. doi:10.2147/DDDT.S402362
  3. Interactions with tapentadol + antidepressants, antipsychotics. Reactions Weekly 1737, 4 (2019).
  4. Polati E, Canonico PL, Schweiger V, Collino M. Tapentadol: an overview of the safety profile. J Pain Res. 2019;12:1569-1576
  5. Chu A, Wadhwa R. Selective serotonin reuptake inhibitors. StatPearls. Published January 2023. Accessed September 28, 2023.
  6. Clinical guidelines for withdrawal management and treatment of drug dependence in closed settings. Geneva: World Health Organization; 2009. 4, Withdrawal Management. Accessed September 28, 2023. 
  7. Information about medication-assisted treatment (MAT). U.S. Food & Drug Administration. Published May 23, 2023. Accessed September 28, 2023.
  8. Buprenorphine. Substance Abuse and Mental Health Services Administration. Published September 18, 2023. Accessed September 28, 2023.

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