Tramadol drug interactions
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Authored by: Km39 14:32, 22 March 2007 (PDT) | |||
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Drug-drug interactions
Severity level | Drug and description of interaction |
| 4 | monoamine oxidase inhibitors (MAOIs), rasagiline, selegiline: The risk of serotonin syndrome and seizures is increased when tramadol is co-administered with these drugs. 14 days should elapse before starting tramadol after discontinuing the use of MAOIs.[1][2][3] |
| 3 | amitriptyline, bupropion: CYP 2D6 inhibitors may lead to lower concentrations of the active metabolite, M1, and thus, altered pain-relieving effects (likely lowered efficacy).[1]
carbamazepine: Carbamazepine is an inducer of tramadol metabolism leading to decreased analgesic efficacy of tramadol.[1] citalopram, duloxetine, escitalopram, linezolid, meperidine, nefazodone, paroxetine, procarbazine, selective norepinephrine reuptake inhibitors (SNRIs), selective serotonin reuptake inhibitors (SNRIs), sertraline, venlafaxine: The risk of serotonin syndrome and seizures is increased when tramadol is co-administered with these drugs.[1][3][4][5][6][7] clozapine, phenothiazines, sodium phosphate monobasic monohydrate/sodium phosphate dibasic anhydrous: The risk of seizures is increased when tramadol is co-administered with these medications.[1] fluoxetine: The risk of serotonin syndrome and seizures is increased when tramadol is co-administered with fluoxetine. Fluoxetine is also a CYP 450 inhibitor which can lead to inhibition of the metabolism of tramadol.[8] opiate agonists: The risk of CNS and respiratory depression and seizures is increased when tramadol is co-administered with opiate agonists.[1] warfarin: May increase prothrombin times and thus the risk for bleeding. A case report of a 65 year old man found an INR increase from 2.5 to 6.14 within 6 days of starting tramadol 100 mg/day. Tramadol was continued and the warfarin dosage was decreased by 30%. Based on this case report, the authors recommednd empiric dosage reduction of 25-30% in warfarin or keeping the same dose of warfarin, and rechecking the INR in three days.[1][9] |
| 2 | amiodarone, chloroquine, gefitinib, haloperidol, imatinib, propafenone, propoxyphene, quinacrine, quinidine, quinine, ranolazine, ritonavir, terbinafine: CYP 2D6 inhibitors may lead to lower concentrations of the active metabolite, M1, and thus, altered pain-relieving effects (likely lowered efficacy).[1]
amoxapine, mirtazapine, tricyclic antidepressants (TCAs): The risk of serotonin syndrome and seizures is increased when tramadol is co-administered with these drugs.[1] anxiolytics, hypnotics, sedatives: The risk of respiratory and CNS depression is increased when co-administering tramadol and these drugs.[1] buprenorphine, butorphanol, entacapone, first generation antihistamines, nabilone, nalbuphine, pentazocine, pramipexole, pregabalin, ropinirole, skeletal muscle relaxants, tolcapone: The risk of CNS depression is increased when co-administering tramadol and these drugs.[1][10][11] chlorpheniramine, diphenhydramine: The risk of respiratory and CNS depression is increased when co-administering tramadol and these drugs. These drugs are also inhibitors of CYP 2D6 which can lead to inhibition of the metabolism of tramadol.[8] cyclobenzaprine, maprotiline, opiate antagonists: The risk of seizures is increased when tramadol is co-administered with these drugs.[1][12] digoxin: Tramadol may increase the concentrations of digoxin, leading to digoxin toxicity.[1] droperidol: A study of ondansetron and droperidol in mice treated with tramadol found antagonism between tramadol and the two antiemetics for analgesia and inhibition of gastrointestinal transit of tramadol.[13] erythromycin, ketoconazole: CYP 3A4 inhibitors may increase serum concentrations of tramadol, which may lead to adverse reactions or toxicity.[1] ondansetron: A study of ondansetron and droperidol in mice treated with tramadol found antagonism between tramadol and the two antiemetics for analgesia and inhibition of gastrointestinal transit of tramadol.[13] Ondansetron and tramadol are both metabolized by CYP2D6, thus there may be an interaction leading to decreased production of the active M1 metabolite of tramadol, leading to decreased analgesia.[14] rifampin: CYP 3A4 inducers may decrease the plasma concentrations of tramadol due to CYP3A4 induction. The positive enantiomer of tramadol undergoes N-demethylation, by CYP3A4 and CYP2B6.[1] |
| 1 | None known |
Drug-food/drug-herb interactions
| Severity level | Drug and description of interaction |
| 4 | None known |
| 3 | ethanol: The risk of seizures is increased when tramadol is co-administered with alcohol. The risk of respiratory depression is increased if the patient is acutely intoxicated with alcohol.[1] |
| 2 | St. John's Wort: Increased risk of serotonin syndrome. Additionally, St. John's Wort is an inducer of CYP3A4 which may lead to decreased concentrations of tramadol.[1] |
| 1 | None known |
References
- ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 1.16 Ortho-McNeil Pharmaceutical INC. Ultram (tramadol hydrochloride tablets) prescribing information. 2004.
- ↑ Emsam® (selegiline transdermal system) package insert. In: Somerset Pharmaceuticals I, editor. Tampa, FL; 2006.
- ↑ 3.0 3.1 Gillman PK. Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity. British journal of anaesthesia. 2005 Oct;95(4):434-41.
- ↑ Mahlberg R, Kunz D, Sasse J, Kirchheiner J. Serotonin syndrome with tramadol and citalopram. The American journal of psychiatry. 2004 Jun;161(6):1129.
- ↑ Mason BJ, Blackburn KH. Possible serotonin syndrome associated with tramadol and sertraline coadministration. The Annals of pharmacotherapy. 1997 Feb;31(2):175-7.
- ↑ Egberts AC, ter Borgh J, Brodie-Meijer CC. Serotonin syndrome attributed to tramadol addition to paroxetine therapy. International clinical psychopharmacology. 1997 May;12(3):181-2.
- ↑ Houlihan DJ. Serotonin syndrome resulting from coadministration of tramadol, venlafaxine, and mirtazapine. The Annals of pharmacotherapy. 2004 Mar;38(3):411-3.
- ↑ 8.0 8.1 Kesavan S, Sobala GM. Serotonin syndrome with fluoxetine plus tramadol. Journal of the Royal Society of Medicine. 1999 Sep;92(9):474-5.
- ↑ Dumo PA, Kielbasa LA. Successful anticoagulation and continuation of tramadol therapy in the setting of a tramadol-warfarin interaction. Pharmacotherapy. 2006 Nov;26(11):1654-7.
- ↑ Cesamet(nabilone) package insert. Costa Mesa, CA: Valeant Pharmaceuticals International; 2006 May.
- ↑ Frampton JE, Foster RH. Pregabalin: in the treatment of postherpetic neuralgia. Drugs. 2005;65(1):111-8; discussion 9-20.
- ↑ Spiller HA, Gorman SE, Villalobos D, Benson BE, Ruskosky DR, Stancavage MM, et al. Prospective multicenter evaluation of tramadol exposure. Journal of toxicology. 1997;35(4):361-4.
- ↑ 13.0 13.1 Dursteler C, Mases A, Fernandez V, Pol O, Puig MM. Interaction between tramadol and two anti-emetics on nociception and gastrointestinal transit in mice. European journal of pain (London, England). 2006 Oct;10(7):629-38.
- ↑ Stamer UM, Stuber F. Analgesic efficacy of tramadol if coadministered with ondansetron. Anesthesia and analgesia. 2001 Dec;93(6):1626.
