Interactions : אינטראקציות

4.5 Interaction with other medicinal products and other forms of interaction
Concomitant use is contraindicated with:


•   Non-selective MAO Inhibitors
Risk of serotonergic syndrome: diarrhoea, tachycardia, hyperhidrosis, trembling, confusional state, even coma.

•   Selective-A MAO Inhibitors
Extrapolation from non-selective MAO inhibitors
Risk of serotonergic syndrome: diarrhoea, tachycardia, hyperhidrosis, trembling, confusional state, even coma.
•   Selective-B MAO Inhibitors
Central excitation symptoms evocative of a serotonergic syndrome: diarrhoea, tachycardia, hyperhidrosis, trembling, confusional state, even coma.
In case of recent treatment with MAO inhibitors, a delay of two weeks should occur before treatment with tramadol

Concomitant use is not recommended with:

•   Alcohol
Alcohol increases the sedative effect of opioid analgesics.
The effect on alertness can make driving of vehicles and the use of machines dangerous. Avoid intake of alcoholic drinks and of medicinal products containing alcohol.

•   Carbamazepine and other enzyme inducers
Risk of reduced efficacy and shorter duration due to decreased plasma concentrations of tramadol.

•   Opioid agonists-antagonists (buprenorphine, nalbuphine, pentazocine) Decrease of the analgesic effect by competitive blocking effect at the receptors, with the risk of occurrence of withdrawal syndrome.

Concomitant use which needs to be taken into consideration:

•   Tramadol can induce convulsions and increase the potential for selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, antipsychotics and seizure threshold-lowering medicinal products (such as bupropion, mirtazapine, tetrahydrocannabinol) to cause convulsions.
•    Concomitant therapeutic use of tramadol and serotonergic drugs such as selective serotonin re-uptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), MAO inhibitors (see section 4.3), tricyclic antidepressants and mirtazapine may cause serotonin syndrome, a potentially life-threatening condition (see sections 4.4 and 4.8).
•       Other opioid derivatives (including antitussive drugs and substitutive treatments) Increased risk of respiratory depression which can be fatal in cases of overdose.
•       Other central nervous system depressants, such as other opioid derivatives (including antitussive drugs and substitutive treatments), other anxiolytics, hypnotics, sedative antidepressants, sedative antihistamines, neuroleptics, centrally-acting antihypertensive drugs, thalidomide and baclofen.
These drugs can cause increased central depression. The effect on alertness can make driving of vehicles and the use of machines dangerous.
•       Sedating medicinal products such as benzodiazepines or related substances: 
The concomitant use of opioids with sedative medicines such as benzodiazepines or related drugs increases the risk of sedation, respiratory depression, coma and death because of additive CNS depressant effects. The dose and duration of the concomitant use should be limited (see section 4.4).

•         As medically appropriate, periodic evaluation of prothrombin time should be performed when Zaldiar and warfarin like compounds are administered concurrently due to reports of increased INR.
•         In a limited number of studies, the pre- or postoperative application of the antiemetic 5HT3 antagonist ondansetron increased the requirement of tramadol in patients with postoperative pain.


• Caution should be taken when paracetamol is used concomitantly with flucloxacillin, as concurrent intake has been associated with high anion gap metabolic acidosis, especially in patients with risk factors (see section 4.4).