Tramadol


Description

Tramadol is a centrally acting synthetic opioid analgesic and SNRI (serotonin/norepinephrine reuptake-inhibitor) that is structurally related to [codeine] and [morphine]. Due to its good tolerability profile and multimodal mechanism of action, tramad...

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Pharmacology

Indication

Tramadol is approved for the management of moderate to severe pain in adults.[ Read more

Pharmacodynamic

Tramadol modulates the descending pain pathways within the central nervous system through the bindin... Read more

Mechanism of action

Tramadol is a centrally acting μ-opioid receptor agonist and SNRI (serotonin/norepinephrine reuptake... Read more

Absorption

**Oral Administration**

Tramadol is administered as a racemate, with both the [-] and [+] forms o...
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Protein binding

About 20% of the administered dose is found to bind to plasma proteins. Protein binding appears to b... Read more

Volume of distribution

The volume of distribution of tramadol is reported to be in the range of 2.6-2.9 L/kg.[ Read more

Clearance

In clinical trials, the clearance rate of tramadol ranged from 3.73 ml/min/kg in renal impairment pa... Read more

Half life

Tramadol reported a half-life of 5-6 hours while the M1 metabolite presents a half-life of 8 hours.[... Read more

Route of elimination

Tramadol is eliminated primarily through metabolism by the liver and the metabolites are excreted pr... Read more

Toxicity

The reported LD50 for tramadol, when administered orally in mice, is 350 mg/kg.[ Read more


Adverse Effects

Effect Regions Age Groups Incidences Evidence Type
Constipation US
  • Kind: experimental
    • Percent: 24-46%
  • Clinical Trial
    Nausea US
  • Kind: experimental
    • Percent: 24-40%
  • Clinical Trial
    Dizziness/vertigo US
  • Kind: experimental
    • Percent: 26-33%
  • Clinical Trial
    Headache US
  • Kind: experimental
    • Percent: 18-32%
  • Clinical Trial
    Somnolence US
  • Kind: experimental
    • Percent: 16-25%
  • Clinical Trial
    Vomiting US
  • Kind: experimental
    • Percent: 9-17%
  • Clinical Trial
    Hallucinations US
  • Kind: experimental
    • Percent: 7-14%
  • Clinical Trial
    Emotional Lability US
  • Kind: experimental
    • Percent: 7-14%
  • Clinical Trial
    Euphoria US
  • Kind: experimental
    • Percent: 7-14%
  • Clinical Trial
    Spasticity US
  • Kind: experimental
    • Percent: 7-14%
  • Clinical Trial
    Tremor US
  • Kind: experimental
    • Percent: 7-14%
  • Clinical Trial
    Agitation US
  • Kind: experimental
    • Percent: 7-14%
  • Clinical Trial
    Anxiety US
  • Kind: experimental
    • Percent: 7-14%
  • Clinical Trial
    Dyspepsia US
  • Kind: experimental
    • Percent: 5-13%
  • Clinical Trial
    Asthenia US
  • Kind: experimental
    • Percent: 6-12%
  • Clinical Trial
    Pruritus US
  • Kind: experimental
    • Percent: 8-11%
  • Clinical Trial
    Dry Mouth US
  • Kind: experimental
    • Percent: 5-10%
  • Clinical Trial
    Diarrhea US
  • Kind: experimental
    • Percent: 5-10%
  • Clinical Trial
    Sweating US
  • Kind: experimental
    • Percent: 6-9%
  • Clinical Trial
    Rash US
  • Kind: experimental
    • Percent: 1-<5%
  • Clinical Trial
    Visual Disturbance US
  • Kind: experimental
    • Percent: 1-<5%
  • Clinical Trial
    Menopausal Symptoms US
  • Kind: experimental
    • Percent: 1-<5%
  • Clinical Trial
    Urinary Frequency US
  • Kind: experimental
    • Percent: 1-<5%
  • Clinical Trial
    Urinary Retention US
  • Kind: experimental
    • Percent: 1-<5%
  • Clinical Trial
    Malaise US
  • Kind: experimental
    • Percent: 1-<5%
  • Clinical Trial
    Anxiety US
  • Kind: experimental
    • Percent: 1-<5%
  • Clinical Trial
    Vasodilation US
  • Kind: experimental
    • Percent: 1-<5%
  • Clinical Trial
    Coordination disturbance US
  • Kind: experimental
    • Percent: 1-<5%
  • Clinical Trial
    Confusion US
  • Kind: experimental
    • Percent: 1-<5%
  • Clinical Trial
    Miosis US
  • Kind: experimental
    • Percent: 1-<5%
  • Clinical Trial
    Euphoria US
  • Kind: experimental
    • Percent: 1-<5%
  • Clinical Trial
    Sleep Disorder US
  • Kind: experimental
    • Percent: 1-<5%
  • Clinical Trial
    Nervousness US
  • Kind: experimental
    • Percent: 1-<5%
  • Clinical Trial
    Anorexia US
  • Kind: experimental
    • Percent: 1-<5%
  • Clinical Trial
    Abdominal Pain US
  • Kind: experimental
    • Percent: 1-<5%
  • Clinical Trial
    Hypertonia US
  • Kind: experimental
    • Percent: 1-<5%
  • Clinical Trial
    Flatulence US
  • Kind: experimental
    • Percent: 1-<5%
  • Clinical Trial
    Accidental injury US
  • Kind: experimental
    • Percent: <1%
  • Clinical Trial
    Allergic Reaction US
  • Kind: experimental
    • Percent: <1%
  • Clinical Trial
    Anaphylaxis US
  • Kind: experimental
    • Percent: <1%
  • Clinical Trial
    Death US
  • Kind: experimental
    • Percent: <1%
  • Clinical Trial
    Suicidal tendency US
  • Kind: experimental
    • Percent: <1%
  • Clinical Trial
    Weight Loss US
  • Kind: experimental
    • Percent: <1%
  • Clinical Trial
    Serotonin Syndrome US
  • Kind: experimental
    • Percent: <1%
  • Clinical Trial
    Orthostatic Hypotension US
  • Kind: experimental
    • Percent: <1%
  • Clinical Trial
    Syncope US
  • Kind: experimental
    • Percent: <1%
  • Clinical Trial
    Tachycardia US
  • Kind: experimental
    • Percent: <1%
  • Clinical Trial
    Abnormal Gait US
  • Kind: experimental
    • Percent: <1%
  • Clinical Trial
    Difficulty in concentration US
  • Kind: experimental
    • Percent: <1%
  • Clinical Trial
    Depression US
  • Kind: experimental
    • Percent: <1%
  • Clinical Trial

    Contraindications

    • Regions: Canada
    • Excluded Age Groups:
      • pediatric
    • Below Age:
      • Amount: 12
      • Unit: year
    • Regions: Canada
    • Patient Conditions:
        • Name: Central nervous system depression
        • Drugbank Id: DBCOND0096632
    • Regions: Canada
    • Patient Conditions:
        • Name: Acute Head Injury
        • Drugbank Id: DBCOND0112466
    • Regions: Canada
    • With Categories Coadmin:
        • Name: Monoamine Oxidase Inhibitors
        • Drugbank Id: DBCAT001004
        • Mesh Id: D008996
    • Regions: Canada
    • Patient Conditions:
        • Name: Convulsive disorders
        • Drugbank Id: DBCOND0107830
    • Regions: Canada
    • Patient Conditions:
        • Name: Delirium Tremens (DTs)
        • Drugbank Id: DBCOND0107126
    • Regions: Canada
    • Patient Conditions:
        • Name: Acute alcoholism
        • Drugbank Id: DBCOND0107892
        • Modification Of:
          • Base:
            • Name: Alcoholism
            • Drugbank Id: DBCOND0006017
          • Severity:
            • Includes:
              • acute
    • Regions: Canada
    • Patient Conditions:
        • Name: Cor Pulmonale
        • Drugbank Id: DBCOND0042897
    • Regions: Canada
    • Patient Conditions:
        • Name: Respiratory Depression
        • Drugbank Id: DBCOND0034868
    • Regions: Canada
    • Patient Conditions:
        • Name: Severe COPD
        • Drugbank Id: DBCOND0050607
        • Modification Of:
          • Base:
            • Name: COPD
            • Drugbank Id: DBCOND0043004
          • Severity:
            • Includes:
              • severe
    • Regions: Canada
    • Patient Conditions:
        • Name: Status Asthmaticus
        • Drugbank Id: DBCOND0001831
    • Regions: Canada
    • Patient Conditions:
        • Name: Severe bronchial asthma
        • Drugbank Id: DBCOND0107864
        • Modification Of:
          • Base:
            • Name: Bronchial Asthma
            • Drugbank Id: DBCOND0031527
          • Severity:
            • Includes:
              • severe
    • Regions: Canada
    • Patient Conditions:
        • Name: Severe Hepatic Impairment
        • Drugbank Id: DBCOND0070791
        • Modification Of:
          • Base:
            • Name: Heptic Impairment
            • Drugbank Id: DBCOND0072269
          • Severity:
            • Includes:
              • severe
    • Regions: Canada
    • Patient Conditions:
        • Name: Severe Renal Impairment
        • Drugbank Id: DBCOND0045819
        • Modification Of:
          • Base:
            • Name: Renal Impairment
            • Drugbank Id: DBCOND0031781
          • Severity:
            • Includes:
              • severe
    • Regions: Canada
    • Patient Conditions:
        • Name: Suspected surgical abdomen
        • Drugbank Id: DBCOND0107886
    • Regions: Canada
    • Patient Conditions:
        • Name: Ileus
        • Drugbank Id: DBCOND0010794
    • Regions: Canada
    • Patient Conditions:
        • Name: Bowel Obstruction
        • Drugbank Id: DBCOND0031840
    • Regions: US
    • Patient Conditions:
        • Name: Intoxication
        • Drugbank Id: DBCOND0022957
    • Hypersensitivity:
      • true
    • Regions: US

    Food Interactions

    • Oral administration of tramadol hydrochloride with food does not significantly affect its rate or extent of absorption, therefore, tramadol hydrochloride can be administered without regard to food.

    Interactions

    Type in a drug name to check for interaction with Tramadol

    The metabolism of (R)-warfarin can be decreased when combined with Tramadol.
    The metabolism of (S)-Warfarin can be decreased when combined with Tramadol.
    The metabolism of Tramadol can be decreased when combined with 1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine.
    The therapeutic efficacy of Tramadol can be decreased when used in combination with 1,10-Phenanthroline.
    2,5-Dimethoxy-4-ethylamphetamine may increase the analgesic activities of Tramadol.
    2,5-Dimethoxy-4-ethylthioamphetamine may increase the analgesic activities of Tramadol.
    The metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Tramadol.
    4-Bromo-2,5-dimethoxyamphetamine may increase the analgesic activities of Tramadol.
    The metabolism of 4-hydroxycoumarin can be decreased when combined with Tramadol.
    4-Methoxyamphetamine may increase the central nervous system depressant (CNS depressant) activities of Tramadol.
    The metabolism of 5-androstenedione can be decreased when combined with Tramadol.
    The risk or severity of adverse effects can be increased when Tramadol is combined with 5-methoxy-N,N-dimethyltryptamine.
    The metabolism of Tramadol can be decreased when combined with 6-Deoxyerythronolide B.
    The metabolism of 6-O-benzylguanine can be decreased when combined with Tramadol.
    The metabolism of Tramadol can be decreased when combined with 7-ethyl-10-hydroxycamptothecin.
    7-Nitroindazole may increase the central nervous system depressant (CNS depressant) activities of Tramadol.
    The risk or severity of serotonin syndrome and seizure can be increased when 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline is combined with Tramadol.
    The metabolism of 9-aminocamptothecin can be decreased when combined with Tramadol.
    Tramadol may decrease the excretion rate of Abacavir which could result in a higher serum level.
    The metabolism of Tramadol can be increased when combined with Abatacept.

    References

    • 1 . Dayer P, Desmeules J, Collart L: [Pharmacology of tramadol]. Drugs. 1997;53 Suppl 2:18-24. [PubMed: 9190321]
    • 2 . Harati Y, Gooch C, Swenson M, Edelman S, Greene D, Raskin P, Donofrio P, Cornblath D, Sachdeo R, Siu CO, Kamin M: Double-blind randomized trial of tramadol for the treatment of the pain of diabetic neuropathy. Neurology. 1998 Jun;50(6):1842-6. [PubMed: 9633738]
    • 3 . Harati Y, Gooch C, Swenson M, Edelman SV, Greene D, Raskin P, Donofrio P, Cornblath D, Olson WH, Kamin M: Maintenance of the long-term effectiveness of tramadol in treatment of the pain of diabetic neuropathy. J Diabetes Complications. 2000 Mar-Apr;14(2):65-70. [PubMed: 10959067]
    • 4 . Gobel H, Stadler T: [Treatment of post-herpes zoster pain with tramadol. Results of an open pilot study versus clomipramine with or without levomepromazine]. Drugs. 1997;53 Suppl 2:34-9. [PubMed: 9190323]
    • 5 . Boureau F, Legallicier P, Kabir-Ahmadi M: Tramadol in post-herpetic neuralgia: a randomized, double-blind, placebo-controlled trial. Pain. 2003 Jul;104(1-2):323-31. [PubMed: 12855342]
    • 6 . Beakley BD, Kaye AM, Kaye AD: Tramadol, Pharmacology, Side Effects, and Serotonin Syndrome: A Review. Pain Physician. 2015 Jul-Aug;18(4):395-400. [PubMed: 26218943]
    • 7 . Shin HW, Ju BJ, Jang YK, You HS, Kang H, Park JY: Effect of tramadol as an adjuvant to local anesthetics for brachial plexus block: A systematic review and meta-analysis. PLoS One. 2017 Sep 27;12(9):e0184649. doi: 10.1371/journal.pone.0184649. eCollection 2017. [PubMed: 28953949]
    • 8 . Martyn-St James M, Cooper K, Kaltenthaler E, Dickinson K, Cantrell A, Wylie K, Frodsham L, Hood C: Tramadol for premature ejaculation: a systematic review and meta-analysis. BMC Urol. 2015 Jan 30;15:6. doi: 10.1186/1471-2490-15-6. [PubMed: 25636495]
    • 9 . Monteiro BP, Klinck MP, Moreau M, Guillot M, Steagall PV, Pelletier JP, Martel-Pelletier J, Gauvin D, Del Castillo JR, Troncy E: Analgesic efficacy of tramadol in cats with naturally occurring osteoarthritis. PLoS One. 2017 Apr 12;12(4):e0175565. doi: 10.1371/journal.pone.0175565. eCollection 2017. [PubMed: 28403198]
    • 10 . Stoops WW, Lofwall MR, Nuzzo PA, Craig LB, Siegel AJ, Walsh SL: Pharmacodynamic profile of tramadol in humans: influence of naltrexone pretreatment. Psychopharmacology (Berl). 2012 Oct;223(4):427-38. doi: 10.1007/s00213-012-2739-4. Epub 2012 May 24. [PubMed: 22623016]
    • 11 . Vazzana M, Andreani T, Fangueiro J, Faggio C, Silva C, Santini A, Garcia ML, Silva AM, Souto EB: Tramadol hydrochloride: pharmacokinetics, pharmacodynamics, adverse side effects, co-administration of drugs and new drug delivery systems. Biomed Pharmacother. 2015 Mar;70:234-8. doi: 10.1016/j.biopha.2015.01.022. Epub 2015 Feb 7. [PubMed: 25776506]
    • 12 . Grond S, Sablotzki A: Clinical pharmacology of tramadol. Clin Pharmacokinet. 2004;43(13):879-923. [PubMed: 15509185]
    • 13 . Wiffen PJ, Derry S, Moore RA: Tramadol with or without paracetamol (acetaminophen) for cancer pain. Cochrane Database Syst Rev. 2017 May 16;5:CD012508. doi: 10.1002/14651858.CD012508.pub2. [PubMed: 28510996]
    • 14 . Xu J, Zhang XC, Lv XQ, Xu YY, Wang GX, Jiang B, Cai L, Cai XJ: Effect of the cytochrome P450 2D6*10 genotype on the pharmacokinetics of tramadol in post-operative patients. Pharmazie. 2014 Feb;69(2):138-41. [PubMed: 24640604]
    • 15 . Arafa MH, Atteia HH: Genetic polymorphisms of cytochrome P450 2D6 (CYP2D6) are associated with long term tramadol treatment-induced oxidative damage and hepatotoxicity. Toxicol Appl Pharmacol. 2018 May 1;346:37-44. doi: 10.1016/j.taap.2018.03.019. Epub 2018 Mar 16. [PubMed: 29555325]
    • 16 . Barakat A: Revisiting Tramadol: A Multi-Modal Agent for Pain Management. CNS Drugs. 2019 May;33(5):481-501. doi: 10.1007/s40263-019-00623-5. [PubMed: 31004280]
    • 17 . Haeseler G, Foadi N, Ahrens J, Dengler R, Hecker H, Leuwer M: Tramadol, fentanyl and sufentanil but not morphine block voltage-operated sodium channels. Pain. 2006 Dec 15;126(1-3):234-44. doi: 10.1016/j.pain.2006.07.003. Epub 2006 Sep 1. [PubMed: 16949748]
    • 18 . Marincsak R, Toth BI, Czifra G, Szabo T, Kovacs L, Biro T: The analgesic drug, tramadol, acts as an agonist of the transient receptor potential vanilloid-1. Anesth Analg. 2008 Jun;106(6):1890-6. doi: 10.1213/ane.0b013e318172fefc. [PubMed: 18499628]
    • 19 . Hara K, Minami K, Sata T: The effects of tramadol and its metabolite on glycine, gamma-aminobutyric acidA, and N-methyl-D-aspartate receptors expressed in Xenopus oocytes. Anesth Analg. 2005 May;100(5):1400-5, table of contents. [PubMed: 15845694]
    • 20 . Sawynok J, Reid AR, Liu J: Spinal and peripheral adenosine A(1) receptors contribute to antinociception by tramadol in the formalin test in mice. Eur J Pharmacol. 2013 Aug 15;714(1-3):373-8. doi: 10.1016/j.ejphar.2013.07.012. Epub 2013 Jul 16. [PubMed: 23872384]
    • 21 . Dean L: Tramadol Therapy and CYP2D6 Genotype . [PubMed: 28520365]
    • 22 . Epstein DH, Preston KL, Jasinski DR: Abuse liability, behavioral pharmacology, and physical-dependence potential of opioids in humans and laboratory animals: lessons from tramadol. Biol Psychol. 2006 Jul;73(1):90-9. doi: 10.1016/j.biopsycho.2006.01.010. Epub 2006 Feb 23. [PubMed: 16497429]
    • 23 . Murray BP, Carpenter JE, Dunkley CA, Moran TP, Alfaifi M, Alsukaiti WS, Kazzi Z: Seizures in tramadol overdoses reported in the ToxIC registry: predisposing factors and the role of naloxone. Clin Toxicol (Phila). 2019 Aug;57(8):692-696. doi: 10.1080/15563650.2018.1547826. Epub 2019 Jan 24. [PubMed: 30676832]
    • 24 . Hassamal S, Miotto K, Dale W, Danovitch I: Tramadol: Understanding the Risk of Serotonin Syndrome and Seizures. Am J Med. 2018 Nov;131(11):1382.e1-1382.e6. doi: 10.1016/j.amjmed.2018.04.025. Epub 2018 May 10. [PubMed: 29752906]
    • 25 . Raffa RB, Friderichs E, Reimann W, Shank RP, Codd EE, Vaught JL, Jacoby HI, Selve N: Complementary and synergistic antinociceptive interaction between the enantiomers of tramadol. J Pharmacol Exp Ther. 1993 Oct;267(1):331-40. [PubMed: 8229760]
    • 26 . Shiraishi M, Minami K, Uezono Y, Yanagihara N, Shigematsu A, Shibuya I: Inhibitory effects of tramadol on nicotinic acetylcholine receptors in adrenal chromaffin cells and in Xenopus oocytes expressing alpha 7 receptors. Br J Pharmacol. 2002 May;136(2):207-16. [PubMed: 12010769]
    • 27 . FDA approvals [Link]
    • 28 . WHO reports [Link]
    • 29 . FDA Label - Tramadol [File]
    • 30 . Health Canada Monograph - Tramadol [File]

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