Products
Tramadol is commercially available in the form of tablets, capsules, melting tablets, drops, effervescent tablets, suppositories, and as a solution for injection. (Tramal, generic). Fixed combinations with acetaminophen are also available (Zaldiar, generic). Tramadol was developed by Grünenthal in Germany in 1962 and has been approved in many countries since 1977 and in the United States since 1995.
Structure and properties
Tramadol (C16H25NO2, Mr = 263.38 g/mol) is a cyclohexanolamine and is present in drugs as tramadol hydrochloride, a white crystalline powder that is readily soluble in water. It is a racemate and both enantiomers and a metabolite are involved in its action. Tramadol is structurally closely related to the SSNRI venlafaxine.
Effects
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 by inhibiting neurotransmitter reuptake, thus affecting pain perception. Thus, it can be seen as a combination of an opioid and a reuptake inhibitor such as venlafaxine. The -desmethyl metabolite M1, rather than the parent compound, is thought to be responsible for the opioid effect.
Indications
Tramadol is used to treat moderate-to-severe persistent pain when nonopioid analgesics, such as the nonsteroidal anti-inflammatory drugs NSAIDs and acetaminophen, are not sufficiently effective. According to a Cochrane review, like some antidepressants, it is also useful for treating neuropathic pain. It is also used for pain relief in fibromyalgia.
Abuse
Like other opioids, tramadol can be abused as a narcotic, becoming addictive and causing withdrawal symptoms.
Contraindications
- Hypersensitivity
- Intoxication with alcohol, hypnotics, painkillers, opioids, and psychotropic drugs
- Concurrent or 14 days prior treatment with MAO inhibitors.
- Epilepsy
- Tramadol must not be used for drug substitution.
Full precautions can be found in the SmPC.
Interactions
Tramadol is biotransformed and glucuronidated by CYP3A4 and CYP2D6 to – and -desmethyl metabolites. -Desmethyltramadol (M1), formed via CYP2D6, is active as an opioid. Therefore, interactions with CYP inducers such as carbamazepine and CYP inhibitors such as azole antifungals or macrolides are possible. Combination with MAO inhibitors is contraindicated and potentially potentially life-threatening. Because tramadol is serotonergic, combination with other serotonergic drugs may result in serotonin syndrome (see Serotonin Syndrome). Centrally depressant drugs, such as sleeping pills and sedatives, and alcohol may increase the depressant effect of tramadol. When vitamin K antagonists such as phenprocoumon are used, bleeding time should be monitored. Because tramadol may cause seizures, it should not be administered concomitantly with drugs that lower the seizure threshold. Opioid antagonists may attenuate the effects of tramadol. Full details of interactions can be found in the SmPC.
Adverse effects
The most common adverse effect is nausea. Headache, drowsiness, vomiting, constipation, dry mouth, sweating, and fatigue are common. Occasionally, there are disturbances in circulatory regulation with palpitations, low blood pressure, and collapse, as well as skin reactions. Withdrawal symptoms may occur after discontinuation.
