Tramadol Drug interactions that can affect the efficiency of the drug

Drug interactions change how the medications work or can result in severe side effects too. This article will help you discover some Tramadol drug interactions. Firstly, make a list of other medications that you are using currently apart from Tramadol. You can show this list to your doctor to know about various drug interactions. Your doctor can help you know about possible Tramadol interactions with the medications you are using currently.

Drugs that affect seizure threshold

Parallel use of Tramadol enhances the risk of seizures in patients taking SNRI/SSRI antidepressants or TCA antidepressants, anorectics and other tricyclic compounds, other opioids, neuroleptics or any other medications that reduce the seizure threshold.

CYP3A4 and/or CYP2D6 inhibitors

Tramadol is processed by CYP2D6 to build active metabolite- O-desmethyl tramadol (M1). The studies indicate that using CYP2D6 inhibitors like Amitriptyline, fluoxetine and paroxetine can lead to some obstruction in Tramadol metabolism process.

Tramadol is also processed by CYP3A4 and using CYP3A4 inhibitors like erythromycin, ketoconazole with Tramadol hydrochloride (extended release) can influence the process of tramadol metabolism resulting in changed tramadol exposure.


Based on mechanism of Tramadol and prospective of serotonin syndrome, extra caution should be taken when using Tramadol hydrochloride (extended release) with Triptans. The patient should be carefully monitored especially during the initial stages of treatment or dose increase.

Serotonergic drugs

The studies indicate the risk of serotonin syndrome in case of combined use of tramadol and SNRIs/SSRIs or a2-adrenergic blockers and MAOIs. Extra caution needs to be taken when tramadol hydrochloride (extended release) is taken with other drugs that can impact the serotonergic neurotransmitter system like MAOIs, triptans, SSRIs, lithium, linezolid, or St. John’s Wort. During the treatment when patient is treated with tramadol hydrochloride (extended release) and other medications that influence serotonergic neurotransmitter system, extra caution should be taken during initial stages of treatment and increment of dose.

CNS depressants

Tramadol hydrochloride (extended release) needs to be taken with extra caution and in low doses when given to the patients using CNS depressants like narcotics, anesthetic agents, opioids, sedative hypnotics, tranquilizers or phenothiazines. Tramadol hydrochloride (extended release) enhances the risk of respiratory and CNS depression in patients.

Warfarins and Digoxin

Some reports have indicated adjustment of warafin and digoxin toxicity effect including increase in prothrombin times.


Quinidine is a powerful inhibitor of CYP2D6. As per studies related to drug interactions, Tramadol doesn’t have any effect on metabolism of quinidine.

CYP3A4 Inducers

Patients using carbamazepine (CYP3A4 inducer) with Tramadol can have less analgesic effect of Tramadol as carbamazepine enhances metabolism of Tramadol and due to risk of seizures linked to tramadol, parallel use of tramadol hydrochloride(extended release)   and carbamazepine is not advised.

Do not take alcohol with tramadol and also let your doctor know if you are taking other medicines for allergy, cold, cough, anxiety, sleep, muscle relaxants, pain relievers (narcotic) psychiatric medicines etc., your doctor can help you know about the drug interactions and how to avoid them. He can recommend a dose change or other alternative medicines that can help you avoid risks associated with drug interactions.

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