Advertisement

Drug Safety

, Volume 18, Issue 4, pp 297–308 | Cite as

A Meta-Analysis to Assess the Incidence of Adverse Effects Associated with the Transdermal Nicotine Patch

  • Sander Greenland
  • Margaret H. Satterfield
  • Stephan F. Lanes
Original Research Article

Summary

To estimate the frequency of adverse effects associated with the use of the transdermal nicotine patch, we abstracted and analysed data from 47 reports of 35 clinical trials. The meta-analysis presented here represents a synthesis of data from 41 groups of nicotine patch recipients totalling 5501 patients, and 33 groups of placebo recipients totalling 3752 patients. Smoking abstinence was the primary outcome in 32 of the trials, and relief of colitis symptoms was the primary outcome in 2 of the trials; 1 study of contact sensitisation was included in the skin irritation analysis. The patch was clearly effective as an aid to smoking abstinence. Despite the large number of patients in the analysis, few adverse cardiovascular outcomes (myocardial infarction, stroke, tachycardia, arrhythmia, angina) were reported, and no excess of these outcomes was detected among patients assigned to nicotine-patch use. The incidences of several minor adverse effects were clearly elevated among the nicotine-patch groups, especially sleep disturbances, nausea or vomiting, localised skin irritation and respiratory symptoms, but the background rates and risk ratios varied considerably across studies. The incidence of nausea or vomiting appeared to be lowest when the patch dose was tapered. The results of this meta-analysis indicate that very large studies would be needed to assess the effect of the patch, if any, on serious, rare outcomes. These results also suggest that the rate of minor adverse effects might be lowered by modifying patch-use protocols.

Keywords

Nicotine Adis International Limited Smoking Cessation Risk Ratio Skin Irritation 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Abelin T, Buehler A, Muller P, et al. Controlled trial of transdermal nicotine patch in tobacco withdrawal. Lancet 1989; I: 7–10CrossRefGoogle Scholar
  2. 2.
    Abelin T, Ehrsam R, Buhler-Reichert A, et al. Effectiveness of a transdermal nicotine system in smoking cessation studies. Methods Find Exp Clin Pharmacol 1989; 11: 205–14PubMedGoogle Scholar
  3. 3.
    Abelin T, Ehrsam R, Imhof PR, et al. Clinical experience with a transdermal nicotine system in healthy nicotine-dependent smokers. In: Wilhelmsen L, editor. Smoking as a cardiovascular risk factor — new strategies for smoking cessation. Lewiston NY: Hogrefe & Huber, 1991: 35–46Google Scholar
  4. 4.
    Muller P, Abelin T, Ehrsam R, et al. The use of transdermal nicotine in smoking cessation. Lung 1990; 168: 445–53PubMedCrossRefGoogle Scholar
  5. 5.
    Allen SS, Matsukami D, Gorsline J. Cholesterol changes in smoking cessation using the transdermal nicotine system. Prev Med 1994; 23: 190–6PubMedCrossRefGoogle Scholar
  6. 6.
    Transdermal Nicotine Study Group. Transdermal nicotine for smoking cessation: six-month results from two multicenter controlled clinical trials. JAMA 1991; 266: 3133–8CrossRefGoogle Scholar
  7. 7.
    Daughton DM, Heatley SA, Prendergast JJ, et al. Effect of transdermal nicotine delivery as an adjunct to low-intervention smoking cessation therapy. Arch Intern Med 1991; 151: 749–52PubMedCrossRefGoogle Scholar
  8. 8.
    Daughton DM, Heatley SA, Prendergast JJ, et al. Effects of transdermal nicotine as an adjunct in smoking cessation therapy: a double-blind randomized study controlled with placebo. Arch Monaldi Mal Torace 1992; 47: 17–29PubMedGoogle Scholar
  9. 9.
    Ehrsam R, Buehler A, Muller P, et al. Transdermal nicotine as an aid towards abstinence in young smokers. Schweiz Rundsch Med Prax 1991; 80: 145–50PubMedGoogle Scholar
  10. 10.
    Foulds J, Stapleton J, Hayward M, et al. Transdermal nicotine patches with low-intensity support to aid smoking cessation in outpatients in a general hospital: a placebo-controlled trial. Arch Fam Med 1993; 2: 417–23PubMedCrossRefGoogle Scholar
  11. 11.
    Hilleman DE, Mohiuddin SM, Delcore MG. Comparison of fixed-dose transdermal nicotine, tapered-dose transdermal nicotine, and buspirone in smoking cessation. J Clin Pharmacol 1994; 34: 222–4PubMedGoogle Scholar
  12. 12.
    Hurt RD, Dale LC, Fredrickson PA, et al. Nicotine patch therapy for smoking cessation combined with physician advice and nurse follow-up. JAMA 1994; 271: 595–600PubMedCrossRefGoogle Scholar
  13. 13.
    Imperial Cancer Research Fund General Practice Research Group. Effectiveness of a nicotine patch in helping people stop smoking: results of a randomised trial in general practice. BMJ 1993; 306: 1304–8CrossRefGoogle Scholar
  14. 14.
    Jorenby DE, Smith SS, Fiore MC, et al. Varying nicotine patch dose and type of smoking cessation counselling. JAMA 1995; 274: 1347–52PubMedCrossRefGoogle Scholar
  15. 15.
    Kornitzer M, Boutsen M, Dramaix M, et al. Combined use of nicotine patch and gum in smoking cessation: a placebo-controlled clinical trial. Prev Med 1995; 24: 41–7PubMedCrossRefGoogle Scholar
  16. 16.
    Kornitzer M, Boutsen M, Thijs J, et al. Efficiency and safety of combined use of nicotine patches and nicotine gum in smoking cessation: a placebo controlled double-blind trial [abstract]. Eur Respir J 1993; 6: 630sGoogle Scholar
  17. 17.
    Merz P-G, Keller-Stanislawski B, Huber T, et al. Transdermal nicotine in smoking cessation and involvement of non-specific influences. Int J Clin Pharmacol Ther Toxicol 1993; 31: 476–82PubMedGoogle Scholar
  18. 18.
    Westman EC, Levin ED, Rose JE. The nicotine patch in smoking cessation: a randomized trial with telephone counseling. Arch Intern Med 1993; 153: 1917–23PubMedCrossRefGoogle Scholar
  19. 19.
    Westman EC, Rose JE. Effectiveness of a transdermal nicotine patch in smoking cessation: a double-blind, randomized, placebo-controlled tiral [abstract]. Clin Res 1991; 39: 887AGoogle Scholar
  20. 20.
    Rennard SI, Daughton DM, Fortmann S, et al. Transdermal nicotine enhances smoking cessation in coronary artery disease patients [abstract]. Chest 1991; 100: 5SGoogle Scholar
  21. 21.
    Working Group for the Study of Transdermal Nicotine in Patients with Coronary Artery Disease. Nicotine replacement therapy for patients with coronary artery disease. Arch Intern Med 1994; 154: 989–95CrossRefGoogle Scholar
  22. 22.
    Richmond RL, Harris K, de Almeida Neto A. The transdermal nicotine patch: results of a randomised placebo-controlled trial. Med J Aust 1994; 161: 130–5PubMedGoogle Scholar
  23. 23.
    Russell MAH, Stapleton J, Feyerabend C, et al. Targeting heavy smokers in general practice: randomised controlled trial of transdermal nicotine patches. BMJ 1993; 306: 1308–12PubMedCrossRefGoogle Scholar
  24. 24.
    Stapleton J, Russell MAH, Feyerabend C, et al. Dose effects and predictors of outcome in a randomized trial of transdermal nicotine patches in general practice. Addiction 1995; 90: 31–42PubMedCrossRefGoogle Scholar
  25. 25.
    Sachs DPL, Sawe U, Leischow SJ. Effectiveness of a 16-hour transdermal nicotine patch in a medical practice setting, without intensive group counseling. Arch Intern Med 1993; 153: 1881–90PubMedCrossRefGoogle Scholar
  26. 26.
    Tonnesen P, Norregaard J, Simonsen K, et al. A double-blind trial of a 16-hour transdermal nicotine patch in smoking cessation. N Engl J Med 1991; 325: 311–5PubMedCrossRefGoogle Scholar
  27. 27.
    Tonnesen P, Norregaard J, Simonsen K, et al. A double-blind trial of nicotine patches in smoking cessation. Ugeskr Laeger 1992; 154: 251–4PubMedGoogle Scholar
  28. 28.
    Tonnesen P, Norregaard J, Simonsen K, et al. The effects of a 16-hour nicotine patch in smoking cessation with a 2-year follow-up [abstract]. Eur Respir J 1991; 4: 504sGoogle Scholar
  29. 29.
    Buchkremer G, Bents H, Horstmann M, et al. Combination of behavioural smoking cessation with transdermal nicotine substitution. Addict Behav 1989; 14: 229–38PubMedCrossRefGoogle Scholar
  30. 30.
    Buchkremer G, Bents H, Minneker E, et al. Longterm effects of smoking cessation therapy combining behavior therapy and transdermal nicotine substitution. Nervenarzt 1988; 59: 488–90PubMedGoogle Scholar
  31. 31.
    Fiore MC, Kenford SL, Jorenby DE, et al. Two studies of the clinical effectiveness of the nicotine patch with different counseling treatments. Chest 1994; 105: 524–33PubMedCrossRefGoogle Scholar
  32. 32.
    Foulds J, Stapleton J, Feyerabend C, et al. Effect of transdermal nicotine patches on cigarette smoking: a double blind crossover study. Psychopharmacology 1992; 106: 421–7PubMedCrossRefGoogle Scholar
  33. 33.
    Hurt RD, Lauger GG, Offord KP, et al. Nicotine-replacement therapy with use of a transdermal nicotine patch - a randomized double-blind placebo-controlled trial. Mayo Clin Proc 1990; 65: 1529–37PubMedGoogle Scholar
  34. 34.
    Krumpe P, Malani N, Adler J, et al. Efficacy of transdermal nicotine administration as an adjunct for smoking cessation in heavily nicotine addicted smokers [abstract]. Am Rev Respir Dis 1989; 139: A337Google Scholar
  35. 35.
    Levin ED, Westman EC, Stein RM, et al. Nicotine skin patch treament increases abstinence, decreases withdrawal symptoms, and attenuates rewarding effects of smoking. J Clin Psychopharmacol 1994; 14: 41–9PubMedCrossRefGoogle Scholar
  36. 36.
    Mulligan SC, Masterson JG, Devane JG, et al. Clinical and pharmacokinetic properties of a transdermal nicotine patch. Clin Pharmacol Ther 1990; 47: 331–7PubMedCrossRefGoogle Scholar
  37. 37.
    Pullan RD, Ganesh S, Mani V, et al. Transdermal nicotine treatment for ulcerative colitis: a controlled trial [abstract]. Gut 1993; 34: S48CrossRefGoogle Scholar
  38. 38.
    Pullan RD, Rhodes J, Ganesh S, et al. Transdermal nicotine for active ulcerative colitis. N Engl J Med 1994; 330: 811–5PubMedCrossRefGoogle Scholar
  39. 39.
    Rose JE, Levin ED, Behm FM, et al. Transdermal nicotine facilitates smoking cessation. Clin Pharmacol Ther 1990; 47: 323–30PubMedCrossRefGoogle Scholar
  40. 40.
    Thomas GAO, Rhodes J, Mani V, et al. Transdermal nicotine as maintenance therapy for ulcerative colitis. N Engl J Med 1995; 332: 988–92PubMedCrossRefGoogle Scholar
  41. 41.
    Fagerstrom KO, Schneider NG, Lunell E. Effectiveness of nicotine patch and nicotine gum as individual versus combined treatments for tobacco withdrawal symptoms. Psychopharmacology 1993; 111: 271–7PubMedCrossRefGoogle Scholar
  42. 42.
    Gourlay SG, Forbes A, Marriner T, et al. Double blind trial of repeated treatment with transdermal nicotine for relapsed smokers. BMJ 1995; 311: 363–6PubMedCrossRefGoogle Scholar
  43. 43.
    Campbell I. Double-blind study of the efficacy of transdermal administration of nicotine (TTS) versus placebo in tobacco withdrawal in patients with chronic chest disease or cardiovascular risk. 1994; Basle: Ciba-Geigy Ltd. NI/ET2Google Scholar
  44. 44.
    Menard P, La Grue D. Double-blind trial versus placebo on the tolerability of transdermal nicotine application (TTS) in the cessation of smoking in patients at risk. 1994; Basle: Ciba-Geigy Ltd. NI/ET1Google Scholar
  45. 45.
    Tzivoni D, Kelen A. Nicotinell TTS in patients with coronary artery disease: double-blind, between-patient randomized trial of the tolerability of transdermal nicotine (Nicotinell TTS) in comparison with placebo administered for 2 weeks during a smoking cessation program: using ambulatory ECG (Holter) monitoring in patients with coronary artery disease. 1995; Basle: Ciba-Geigy Ltd. IL/T 02Google Scholar
  46. 46.
    Bertocchi F, Francucci BM. Randomized, placebo-controlled, within-patient study to evaluate the effect of repeated administration of nicotine TTS 30 cm2, placebo and cigarette smoking on cardiovascular sympathetic control, both in normotensive and hypertensive smokers. 1995; Basle: Ciba-Geigy Ltd. TNSI01Google Scholar
  47. 47.
    Jordan WP. Clinical evaluation of the contact sensitization potential of a transdermal nicotine system (Nicoderm). J Fam Pract 1992; 34: 709–12PubMedGoogle Scholar
  48. 48.
    Joseph AM, Norman SM, Ferry LH, et al. The safety of transdermal nicotine as an aid to smoking cessation in patients with cardiac disease. N Engl J Med 1996; 335: 1792–8PubMedCrossRefGoogle Scholar
  49. 49.
    Hughes JR. Risk-benefit assessment of nicotine preparations in smoking cessation. Drug Saf 1993; 8: 49–56PubMedCrossRefGoogle Scholar
  50. 50.
    Henningfield JE. Nicotine medications for smoking cessation. N Engl J Med 1995; 333: 1196–203PubMedCrossRefGoogle Scholar
  51. 51.
    Fiore MC, Smith SS, Jorenby DE, et al. The effectiveness of the nicotine patch for smoking cessation: a meta-analysis. JAMA 1994; 271: 1940–7PubMedCrossRefGoogle Scholar
  52. 52.
    Dickersin K. The existence of publication bias and risk factors for its occurrence. JAMA 1990; 263: 1385–9PubMedCrossRefGoogle Scholar
  53. 53.
    Greenland S, Rothman KJ. Modern epidemiology. 2nd ed. Philadelphia: Lippincott, 1998: 253–79Google Scholar
  54. 54.
    Berry G, Armitage P. Mid-P confidence intervals: a brief review. The Statistician 1995; 44: 417–23CrossRefGoogle Scholar
  55. 55.
    Greenland S, Robins JM. Estimation of a common effect parameter from sparse follow-up data. Biometrics 1985; 41: 55–68PubMedCrossRefGoogle Scholar
  56. 56.
    Breslow NE, Day NE. The design and analysis of cohort studies. Lyon: IARC, 1987Google Scholar
  57. 57.
    Stijnen T, Houwelingen HC. Relative risk, risk difference, and rate difference models for sparse stratified data: a pseudolikelihood approach. Stat Med 1993; 12: 2285–303PubMedCrossRefGoogle Scholar
  58. 58.
    McIntosh MW. The population at risk as an explanatory variable in research synthesis of clinical trials. Stat Med 1996; 15: 1713–28PubMedCrossRefGoogle Scholar
  59. 59.
    Greenland S. Second-stage least squares versus penalized quasi-likelihood for fitting hierarchical models in epidemiologic analyses. Stat Med 1997; 15: 515–26CrossRefGoogle Scholar
  60. 60.
    McCullagh P, Nelder JA. Generalized linear models. 2nd ed. New York: Chapman and Hall, 1989Google Scholar

Copyright information

© Adis International Limited 1998

Authors and Affiliations

  • Sander Greenland
    • 1
  • Margaret H. Satterfield
    • 2
  • Stephan F. Lanes
    • 2
  1. 1.Department of EpidemiologyUCLA School of Public HealthLos AngelesUSA
  2. 2.Epidemiology Resources Inc.Newton Lower FallsUSA

Personalised recommendations