What's in Tramadol

TramadolDrug groupsOpioideTramadol is a pain reliever from the group of opioids for the treatment of moderate to severe pain of various causes. It is not a pure and typical opioid and also has noradrenergic and serotonergic effects like some antidepressants. Tramadol has a high potential for drug-drug interactions due to its mechanism of action and biotransformation via CYP3A4 and CYP2D6. The numerous precautionary measures must be observed. The most common adverse effects include nausea, headache, drowsiness, vomiting, constipation, dry mouth, sweating, and exhaustion. The risk of respiratory depression and the development of addiction is considered to be low.

synonymous: Tramadolum, Tramadoli hydrochloridumPhEur, Tramadolhydrochlorid


Tramadol is available in the form of tablets, capsules, orodispersible tablets, drops, effervescent tablets, suppositories and as a solution for injection. (Tramal®, generics). Fixed combinations with paracetamol are also available (Zaldiar®, generics).

Tramadol was developed by Grünenthal in Germany in 1962 and has been approved in Switzerland since 1977 and in the USA since 1995.

Structure and properties

Tramadol (C.16H25NO2, Mr = 263.38 g / mol) is a cyclohexanolamine and is present in medicinal products as tramadol hydrochloride, a white, crystalline powder that is easily soluble in water. It is a racemate and both enantiomers and a metabolite are involved in the effect. Tramadol is structurally closely related to SSNRIVenlafaxine.


Tramadol (ATC N02AX02) has central analgesic properties. It is an opioid with a dual mechanism of action. On the one hand, tramadol binds to opioid receptors. On the other hand, it is noradrenergic and serotonergic in that it inhibits the reuptake of neurotransmitters and thus influences the perception of pain. So it can be seen as a combination of an opioid and a reuptake inhibitor such as venlafaxine. For the opioid effect, the O-Desmethyl metabolite M1 and not the parent compound blamed.


Tramadol is used to treat moderate to severe, persistent pain when non-opioid pain relievers such as the non-steroidal anti-inflammatory drugs NSAID and paracetamol are not effective enough.

According to a Cochrane review, like some antidepressants, it is also suitable for treating neuropathic pain. It is also used for pain relief in fibromyalgia.


Like other opioids, tramadol can also be abused as an intoxicant, be addictive and trigger withdrawal symptoms.


The full precautionary measures can be found in the product information.


Tramadol is made up of CYP3A4 and CYP2D6 too N- and O-Desmethyl metabolites biotransformed and glucuronidated. O-Desmethyltramadol (M1), which is formed via CYP2D6, is active as an opioid. Interactions with CYP inducers such as carbamazepine and CYP inhibitors such as azole antimycotics or macrolides are therefore possible.

The combination with MAOIs is contraindicated and potentially life threatening.

Since Tramadol is serotonergic, the combination with other serotonergic drugs can lead to serotonin syndrome (see under Serotonin syndrome).

Centrally depressant drugs such as sleeping pills, sedatives and alcohol can increase the depressant effect of tramadol.

When using vitamin K antagonists such as phenprocoumon, the bleeding time should be monitored. Since tramadol can cause seizures, it should not be given at the same time as medicines that lower the seizure threshold. Opioid antagonists can make tramadol less effective. The full information on interactions can be found in the information for healthcare professionals.

unwanted effects

The most common adverse effect is nausea. Headache, drowsiness, vomiting, constipation, dry mouth, sweating, and exhaustion are common. Occasionally there are disorders of the circulatory regulation with palpitations, low blood pressure and collapse, as well as skin reactions. Withdrawal symptoms may occur after discontinuation.

see also

Opioids, serotonin syndrome, venlafaxine, tapentadol, tramadol and paracetamol

  • Medicinal product information (CH, EMA)
  • Cepeda M.S., Camargo F., Zea C., Valencia L. Tramadol for osteoarthritis: a systematic review and metaanalysis. J Rheumatol, 2007, 34 (3), 543-55 Pubmed
  • Cepeda M.S., Camargo F., Zea C., Valencia L. Tramadol for osteoarthritis. Cochrane Database Syst Rev, 2006, CD005522 Pubmed
  • European Pharmacopoeia PhEur
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  • Hollingshead J., Dühmke R.M., Cornblath D.R. Tramadol for neuropathic pain. Cochrane Database Syst Rev, 2006, CD003726 Pubmed
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  • Leppert W. Tramadol as an analgesic for mild to moderate cancer pain. Pharmacol Rep. 2009, 61 (6), 978-92 Pubmed
  • Raffa R.B. Basic pharmacology relevant to drug abuse assessment: tramadol as example. J Clin Pharm Ther, 2008, 33 (2), 101-8 Pubmed

Conflicts of Interest: None / Independent. The author has no relationships with the manufacturers and is not involved in the sale of the products mentioned.

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This article was last changed on April 15, 2020.
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