Is there an interaction between codeine and tramadol?

Codeine and tramadol are two minor opioid pain relievers. Codeine, or methylmorphine, is found naturally in opium (it is an opiate), while tramadol does not exist naturally and is only obtained synthetically. Tramadol is not chemically an opiate, but it acts on opioid receptors and is therefore also considered an opioid drug.

Both are used to relieve moderate to moderately severe pain, but with important differences. Codeine is metabolized in the liver and turned into morphine. The rate of metabolism is very low and therefore its analgesic effect is much less than that of morphine. To improve analgesic action, it is usually used in association with other analgesics, mainly NSAIDs, such as paracetamol. It is also widely used as an antitussive.

Tramadol is an agonist of µ, δ and κ opioid receptors, with greater affinity for the µ type, but this action is weak and its analgesic action is mainly due to the inhibition of norepinephrine reuptake and increased serotonin release.

Both being opioid receptor agonists and being metabolized with the intervention of the cytochrome P450 system, they have important interactions and should not be taken at the same time unless prescribed and under medical supervision.

most notable interactions

The main interactions are due to the fact that both have the same side effects and can be intensified if taken at the same time. Among the most serious interactions is increased sedation and drowsiness, which in turn increases the risk of respiratory depression. Tramadol has a lower risk than codeine in respiratory depression, but when administered concomitantly, this risk is greater, especially in patients with previous respiratory problems.

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Another of the most serious interactions is an increased risk of seizures due to its epileptogenic activity. Tramadol lowers the seizure threshold in predisposed patients. Codeine has the same effect, but much less. However, together, they can increase the effect and lower the seizure threshold, putting even patients without predisposition at risk.

It also increases the risk of moderate side effects such as dizziness, nausea and constipation, side effects common to the entire opioid drug family. Furthermore, in patients with previous opioid dependence, both drugs can restart physical dependence.

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