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Clinical Drug Investigation

, Volume 25, Issue 1, pp 23–31 | Cite as

Effect of a Simple Dose-Escalation Schedule on Tramadol Tolerability

Assessment in the Clinical Setting
  • I. Tagarro
  • J. Herrera
  • C. Barutell
  • M. C. Díez
  • M. Marín
  • D. Samper
  • C. Busquet
  • M. J. Rodríguez
Original Research Article

Abstract

Objective: To assess the effect of a very simple dose-escalation schedule on tramadol tolerability in clinical practice. This schedule consists of starting treatment with sustained-release tramadol 50mg twice daily, and escalating the dose around 7 days later to 100mg twice daily.

Methods: Data from 1925 outpatients with non-malignant chronic pain were collected in this multicentre, prospective, comparative, non-randomised, open, observational study.

Results: A total of 1071 patients (55.6%) were included in the dose-escalation group (50mg group) and 854 patients (44.4%) in the control group (sustained-release tramadol 100mg twice daily; 100mg group). The proportion of patients who interrupted tramadol treatment due to the occurrence of adverse reactions was significantly lower in the 50mg group (5.6%) than in the 100mg group (12.6%) [p = 0.001]. In line with this, the proportion of patients who experienced at least one adverse reaction was significantly lower in the 50mg group (18.4%) than in the 100mg group (30.4%) [p = 0.001] and, interestingly, the two most frequently reported adverse reactions, nausea and dizziness, were found with a significantly lower frequency in the 50mg group (p < 0.001). Multivariate analysis showed that the risk of safety-related treatment cessations was 2.3 times higher in the 100mg group than in the 50mg group, and 2.2 times higher in females than in males. The two treatments were equally effective in reducing pain intensity (p = 0.121), measured as a reduction in pain score obtained by means of a visual analogue scale.

Conclusion: The instauration of tramadol treatment, starting with sustained-release 50mg capsules twice daily and escalating the dose some days later to 100mg twice daily, was shown to be an effective and easy way to improve tramadol tolerability in clinical practice, whilst maintaining its analgesic efficacy.

Keywords

Adverse Reaction Tramadol Visual Analogue Scale Score Treatment Interruption Treatment Cessation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

Funding for this study was provided by Viatris Pharmaceuticals SAU (formerly ASTA Medica SAU), Madrid, Spain.

References

  1. 1.
    Bamigbade TA, Langford RM. The clinical use of tramadol hydrochloride. Pain Rev 1998; 5: 155–82CrossRefGoogle Scholar
  2. 2.
    Hennies HH, Friderichs E, Schneider J. Receptor binding, analgesic and antitussive potency of tramadol and other selected opioids. Arzneimittel Forschung 1988; 38: 877–80PubMedGoogle Scholar
  3. 3.
    Raffa RB, Friderichs E, Reimann W, et al. Opioid and non-opioid components independently contribute to the mechanism of action of tramadol, an ‘atypical’ opioid analgesic. J Pharmacol Exp Ther 1992; 260: 275–85PubMedGoogle Scholar
  4. 4.
    Raber M, Hofmann S, Junge K, et al. Analgesic efficacy and tolerability of tramadol 100mg capsules in patients with moderate to severe chronic low back pain. Clin Drug Invest 1999; 17: 415–23CrossRefGoogle Scholar
  5. 5.
    Schnitzer TJ, Gray WL, Paster RZ, et al. Efficacy of tramadol in treatment of chronic low back pain. J Rheumatol 2000; 27: 772–8PubMedGoogle Scholar
  6. 6.
    Wilder-Smith CH, Hill L, Spargo K, et al. Treatment of severe pain from osteoarthritis with slow-release tramadol or dihydrocodeine in combination with NSAID’s: a randomised study comparing analgesia, antinociception and gastrointestinal effects. Pain 2001; 91: 23–31PubMedCrossRefGoogle Scholar
  7. 7.
    Pavelka K. Treatment of pain in osteoarthritis. Eur J Pain 2000; 4: 23–30PubMedGoogle Scholar
  8. 8.
    Reig E. Tramadol in musculoskeletal pain — a survey. Clin Rheumatol 2002; 21 Suppl. 1: S9–11PubMedCrossRefGoogle Scholar
  9. 9.
    Petzke F, Radbruch L, Sabatowski R, et al. Slow-release tramadol for treatment of chronic malignant pain: an open multicenter trial. Support Care Cancer 2001; 9: 48–54PubMedGoogle Scholar
  10. 10.
    Grond S, Radbruch L, Meuser T, et al. High-dose tramadol in comparison to low-dose morphine for cancer pain relief. J Pain Symptom Manage 1999; 18: 174–9PubMedCrossRefGoogle Scholar
  11. 11.
    Courtney MJ, Cabraal D. Tramadol vs diclofenac for posttonsil-lectomy analgesia. Arch Otolaryngol Head Neck Surg 2001; 127: 385–8PubMedGoogle Scholar
  12. 12.
    Collins M, Young I, Sweeney P, et al. The effect of tramadol on dento-alveolar surgical pain. Br J Oral Maxillofac Surg 1997; 35: 54–8PubMedCrossRefGoogle Scholar
  13. 13.
    Dworkin RH, Backonja M, Rowbotham MC, et al. Advances in neuropathic pain: diagnosis, mechanisms, and treatment recommendations. Arch Neurol 2003; 60: 1524–34PubMedCrossRefGoogle Scholar
  14. 14.
    Duhmke R, Cornblath D, Hollingshead J. Tramadol for neuropathic pain. Cochrane Database Syst Rev 2004; 2: CD003726PubMedGoogle Scholar
  15. 15.
    Petrone D, Kamin M, Olson W. Slowing the titration rate of tramadol HC1 reduces the incidence of discontinuation due to nausea and/or vomiting: a double-blind randomized trial. J Clin Pharm Ther 1999; 24: 115–23PubMedCrossRefGoogle Scholar
  16. 16.
    Ruoff GE. Slowing the initial titration rate of tramadol improves tolerability. Pharmacotherapy 1999; 19: 88–93PubMedCrossRefGoogle Scholar
  17. 17.
    ASTA Medica Ltd, Cambridge, UK. Summary of product characteristics. Registration Dossier Tramadol 50, 100, 150 and 200 mg sustained-release capsules, 1998; Part IB: 92-8.Google Scholar
  18. 18.
    Raber M, Schulz HU, Schurer M, et al. Pharmacokinetic properties of tramadol sustained-release capsules. 2nd communication: investigation of relative bioavailability and food interaction. Arzneimittel Forschung 1999; 49: 588–93PubMedGoogle Scholar
  19. 19.
    Raber M, Schulz HU, Schurer M, et al. Pharmacokinetic properties of tramadol sustained-release capsules. 3rd communication: investigation of relative bioavailability under steady state conditions. Arzneimittel Forschung 1999; 49: 594–8PubMedGoogle Scholar
  20. 20.
    Tran C, Knowles SR, Liu BA, et al. Gender differences in adverse drug reactions. J Clin Pharmacol 1998; 38: 1003–9PubMedCrossRefGoogle Scholar
  21. 21.
    Drici MD, Clement N. Is gender a risk factor for adverse drug reactions? The example of drug-induced long QT syndrome. Drug Saf 2001; 24: 575–85PubMedCrossRefGoogle Scholar
  22. 22.
    Bowman L, Carlstedt BC, Hancock EF, et al. Adverse drug reaction (ADR) occurrence and evaluation in elderly inpatients. Pharmacoepidemiol Drug Saf 1996; 5: 9–18PubMedCrossRefGoogle Scholar
  23. 23.
    Montastruc JL, Lapeyre-Mestre M, Bagheri H, et al. Gender differences in adverse drug reactions: analysis of spontaneous reports to a Regional Pharmacovigilance Centre in France. Fundam Clin Pharmacol 2002; 16: 343–6PubMedCrossRefGoogle Scholar
  24. 24.
    Hui-Chen L, Yang Y, Na W, et al. Pharmacokinetics of the enantiomers of trans-tramadol and its active metabolite, trans-O-demethyltramadol, in healthy male and female Chinese volunteers. Chirality 2004; 16: 112–8PubMedCrossRefGoogle Scholar
  25. 25.
    Meibohm B, Beierle I, Derendorf H. How important are gender differences in pharmacokinetics? Clin Pharmacokinet 2002; 41: 329–42PubMedCrossRefGoogle Scholar
  26. 26.
    Lintz W, Becker R, Gerloff J, et al. Pharmacokinetics of tramadol and bioavailability of enterai tramadol formulations. 4th communication: drops (without ethanol). Arzneimittel Forschung 2000; 50: 99–108PubMedGoogle Scholar
  27. 27.
    Curkovic B, Bernik N. Three-week open multi-centre study of tramadol in various pain conditions. Arzneimittel Forschung 2003; 53: 503–6PubMedGoogle Scholar

Copyright information

© Adis Data Information BV 2005

Authors and Affiliations

  • I. Tagarro
    • 1
  • J. Herrera
    • 2
  • C. Barutell
    • 3
  • M. C. Díez
    • 1
  • M. Marín
    • 4
  • D. Samper
    • 5
  • C. Busquet
    • 6
  • M. J. Rodríguez
    • 7
  1. 1.Viatris Pharmaceuticals SASan Fernando de Henares, MadridSpain
  2. 2.Hospital de ValmeSevillaSpain
  3. 3.Hospital Vall d’HebronBarcelonaSpain
  4. 4.Hospital San Juan de DiosSan SebastiánSpain
  5. 5.Hospital Germans Trias i PujolBarcelonaSpain
  6. 6.Hospital Dr. Josep TruetaGironaSpain
  7. 7.Hospital Civil de MálagaMálagaSpain

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