Advertisement

Clinical Drug Investigation

, Volume 17, Issue 6, pp 415–423 | Cite as

Analgesic Efficacy and Tolerability of Tramadol 100mg Sustained-Release Capsules in Patients with Moderate to Severe Chronic Low Back Pain

  • Marc Raber
  • S. Hofmann
  • K. Junge
  • H. Momberger
  • D. Kuhn
Clinical Use

Abstract

Objective: To investigate the analgesic efficacy, tolerability and therapeutic equivalence of a newly developed tramadol sustained-release (SR) capsule compared with a tramadol immediate-release (IR) capsule in patients with moderate to severe chronic low back pain.

Design: Randomised, multicentre, double-blind, parallel-group study.

Setting: Patients were provided with a diary card into which they recorded by use of a visual analogue scale (VAS) the intensity of pain immediately before every intake of study medication during the 9 treatment days. Besides pain intensity, secondary efficacy parameters included a sleep questionnaire, a functional capacity score and the patient’s global assessment of efficacy.

Patients: 247 patients of either gender, aged 18 to 75 years, with moderate to severe chronic low back pain were included in the study.

Interventions: 125 patients were treated with tramadol SR capsules twice daily (2 × 100 mg/day) and 122 patients with tramadol IR capsules 4 times daily (4 × 50 mg/day) over a period of 9 (+3) days.

Results: The mean (±SD) baseline pain intensity values on the 100mm VAS scale were 55.6mm (± 10.6mm) and 53.3mm (± 10.6mm) in the IR group and the SR group, respectively. The mean baseline VAS value decreased substantially in both treatment groups during the first 2 days and decreased continuously throughout the treatment period. At treatment day 8, the mean difference to baseline VAS value for tramadol IR was −24.7 (±20.1)mm and for tramadol SR−25.1(±19.9)mm. The corresponding 90% confidence interval was calculated as [−4.18; +5.09]mm, which fell completely within the predefined equivalence range of ±10mm VAS. The two 1-sided t-test method showed strong evidence for the equivalence of treatment groups (p < 0.001) regarding the VAS pain assessment. The secondary efficacy parameters also confirmed the therapeutic equivalence of the two formulations. The predominant adverse events, headache and nausea, were reported more frequently by patients treated with tramadol IR. With the IR formulation the incidence of headache and nausea was 29 and 21%, respectively, compared with 18 and 11% with the SR formulation. For the symptom nausea, the difference was statistically significant (p = 0.03). There were no clinically relevant changes in vital signs or laboratory parameters in either treatment group.

Conclusions: The results confirmed therapeutic equivalence of tramadol SR 100mg capsules twice daily and tramadol IR 50mg capsules four times daily. At the same time the study demonstrated that tramadol provides adequate pain relief in patients with chronic low back pain. Moreover, tramadol administered as sustained-release capsules was better tolerated than the reference product.

Keywords

Visual Analogue Scale Adis International Limited Tramadol Analgesic Efficacy Clin Drug Invest 
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.

References

  1. 1.
    Hennies HH, Friderichs E, Schneider J. Receptor binding analgesic and antitussive potency of tramadol and other selected opioids. Arzneimittel Forschung 1988; 38(7): 877–80PubMedGoogle Scholar
  2. 2.
    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(1): 275–85PubMedGoogle Scholar
  3. 3.
    Driessen B, Reimann W. Interaction of the central analgesic tramadol, with the uptake and release of 5-hydroxytryptamine in the rat brain in vitro. Br J Pharmacol 1992; 105: 147–51PubMedCrossRefGoogle Scholar
  4. 4.
    Raffa RB, Nayak RK, Liao S, et al. The mechanisms of action and pharmacokinetics of tramadol hydrochloride. Rev Contemp Pharmacother 1995; 6: 485–97Google Scholar
  5. 5.
    Liao S, Hill JF, Nayak RK. Pharmacokinetics of tramadol following single and multiple oral doses in man. Pharm Res 1992; 9 Suppl.: 308Google Scholar
  6. 6.
    Liao S, Hill JF, Stubbs RJ. The effect of food on the bioavailability of tramadol. Pharm Res 1992; Suppl. 9/19: S308Google Scholar
  7. 7.
    Lee CR, McTavish D, Sorkin FM. Tramadol — a preliminary review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in acute and chronic pain states. Drugs 1993; 46(2): 113–40CrossRefGoogle Scholar
  8. 8.
    Temmler Pharma GmbH. Investigation of the pharmacokinetics of tramadol following single oral administrations of the same galenic formulation differing in their content of the active constituent in healthy human volunteers. Internal Report Study No. T358 BV02. November 1996Google Scholar
  9. 9.
    Temmler Pharma GmbH. Investigation on the relative bioavailability of tramadol from a galenic sustained-release formulation referenced with an instant release formulation under steady-state conditions in healthy male volunteers. Internal Report Study No. T358 BV04. November 1996Google Scholar
  10. 10.
    Temmler Pharma GmbH. Investigation on the relative bioavailability, food-interaction and bioequivalence with tramadol-containing sustained-release formulations. Internal Report Study No. T358 BV03. November 1996Google Scholar
  11. 11.
    Ellis BW, Johns BW, Lancaster R, et al. The St Mary’s Sleep Questionnaire: a study of reliability. Sleep 1981; 4: 93–7PubMedGoogle Scholar
  12. 12.
    Liftman GS, Walker BR, Schneider BE. Reassessment of verbal and visual analogue ratings in analgesic studies. Clin Pharm Ther 1985; 38: 16–23CrossRefGoogle Scholar
  13. 13.
    Abel SR. Tramadol — an alternative analgesic to traditional opioids and NSAIDs. J Pharm Care Pain Symptom Control 1995; 3: 5–29CrossRefGoogle Scholar
  14. 14.
    Budd K. The efficacy of tramadol hydrochloride in the treatment of acute and chronic pain. Rev Contemp Pharmacother 1995; 6: 507–12Google Scholar
  15. 15.
    Sorge J. Chronischer Rückenschmerz — Dosierung und Effektivität einer dreiwöchigen Behandlung. In: Tramai® long 100 — das Basis-Opioid in Retardform — Klinische Anwendung — Ergebnisse aus klinischen Studien mit Tramai® long 100 Retardtabletten. 19. Jahrestagung der Deutschen Gesellschaft zum Studium des Schmerzes e.V. in Dresden: 21. Oktober 1994Google Scholar
  16. 16.
    Zech D. Wirksamkeit und Verträglichkeit der Therapie chronischer Tumorschmerzen. In: Tramai® long 100 — das Basis-Opioid in Retardform — Klinische Anwendung — Ergebnisse aus klinischen Studien mit Tramai® long 100 Retardtabletten. 19.Jahrestagung der Deutschen Gesellschaft zum Studium des Schmerzes e.V. in Dresden: 21. Oktober 1994Google Scholar
  17. 17.
    Carey TS, Evans AT, Hadler NM, et al. Acute severe back pain — a population-based study of prevalence and care-seeking. Spine 1996; 21: 339–44PubMedCrossRefGoogle Scholar
  18. 18.
    Dreyer SJ, Dreyfuss PH. Low back pain and the zygapophysial (facet) joints. Arch Phys Med Rehabil 1996; 77: 290–300PubMedCrossRefGoogle Scholar
  19. 19.
    Price PM, Budd K. Tramadol in the treatment of spinal pain: a short report based on the results of a survey of 50 patients. Br J Med Econ 1995; 9: 17–20Google Scholar
  20. 20.
    Sorge J, Stadler TH. Comparison of the analgesic efficacy and tolerability of tramadol 100mg sustained-release tablets and tramadol 50mg capsules for the treatment of chronic low back pain. Clin Drug Invest 1997; 14(3): 157–64CrossRefGoogle Scholar
  21. 21.
    Rauws G. Wie sinnvoll sind magensaftresistent überzogene Arzneiformen? Pharm Ztg 1992; 6: 319Google Scholar
  22. 22.
    Cossmann M, Kohnen C. General tolerability and adverse event profile of tramadol hydrochloride. Rev Contemp Phar- macother 1995; 6: 513–31Google Scholar
  23. 23.
    Radbruch L, Grond S, Lehmann KA. A risk-benefit assessment of tramadol in the management of pain. Drug Saf 1996; 15: 8–29PubMedCrossRefGoogle Scholar
  24. 24.
    Anonymous. Therapie bei chronischen Schmerzen des Bewegungsapparates. Aktuelle Rheumatol 1994; 19: M34-M35Google Scholar
  25. 25.
    Peikert A, Egbert R, Flock K, et al. Systemische Pharmakotherapie bei Kreuzschmerz — Indikationen und praktische Anwendung. Fortschr Med 1989; 107: 403–6Google Scholar
  26. 26.
    Sunshine A. New clinical experience with tramadol. Drugs 1994; 47Suppl. 1: 8–18PubMedCrossRefGoogle Scholar
  27. 27.
    Bechgaard H, Benzon A. Critical factors influencing gastrointestinal absorption — what is the role of pellets? Acta Pharm Technol 1982; 28: 149Google Scholar
  28. 28.
    Bechgaard H, Nielsen GH. Controlled-release multiple-units and single-unit doses. Drug Develop Indust Pharm 1978; 4(1): 53–67CrossRefGoogle Scholar
  29. 29.
    Katz WA. The role of tramadol in the management of musculoskeletal pain. Today’s Ther Trends 1995; 13(3): 177–86Google Scholar
  30. 30.
    Cossmann M, Wilsmann KM. Behandlung länger andauernder Schmerzsyndrome (treatment of prolonged severe pain). Münch Med Wochenschr 1987; 129(46): 851–4Google Scholar
  31. 31.
    Cossmann M, Wilsmann KM. Wirkung und Begleitwirkung von Tramadol — Offene Phase TV-Prüfung an 7198 Patienten. Therapiewoche 1987; 37: 3475–85Google Scholar
  32. 32.
    Goroll D. Tropfenform eines stark wirksamen Analgetikums in der Doppelblindprüfung. Med Klin Prax 1983; 78: 40–2Google Scholar
  33. 33.
    Lehmann KA. Tramadol for the management of acute pain. Drugs 1994; 47Suppl. 1: 19–32PubMedCrossRefGoogle Scholar
  34. 34.
    Lehmann KA, Jung C, Hoeckle W. Tramadol und Pethidin zur postoperativen Schmerz-therapie. Eine randomisierte Doppelblindstudie unter den Bedingungen der intravenösen On-Demand-Analgesie. Schmerz-Pain-Douleur 1985; 3: 88–100Google Scholar
  35. 35.
    Mackin GA. Medical and pharmacologic management of upper extremity neuropathic pain syndromes. J HandTher 1997; 10: 96–109CrossRefGoogle Scholar

Copyright information

© Adis International Limited 1999

Authors and Affiliations

  • Marc Raber
    • 1
  • S. Hofmann
    • 2
  • K. Junge
    • 3
  • H. Momberger
    • 4
  • D. Kuhn
    • 1
  1. 1.Medical DepartmentTemmler Pharma GmbHMarburgGermany
  2. 2.Medical DepartmentASTA Medica AGFrankfurtGermany
  3. 3.Department of BiostatisticsASTA Medica AGFrankfurtGermany
  4. 4.Galenical DepartmentTemmler Pharma GmbHMarburgGermany

Personalised recommendations