Predictors and Timing of Adverse Experiences During Transdermal Nicotine Therapy



Difficulty sleeping is arecognised tobacco withdrawal symptom, but sleep problems, like application site reactions, are commonly reported as adverse reactions to transdermal nicotine therapy. However, no studies have examined potential predictive factors associated with the occurrence of expected adverse experiences during transdermal nicotine therapy. The subject of skin tolerability among patients with a history of eczema, psoriasis or other skin disorders is of particular interest, as are the relationships between plasma concentrations of nicotine, concurrent smoking, sleep problems and nausea.


The cohort study involving 1392 participants was designed to assess the timing, severity and predictive factors of adverse experiences reported during 24-hour transdermal nicotine therapy. Data were collected on patients aged 18 to 70 years old who were smokers and who had expressed a strong desire to stop smoking. The intervention consisted of brief behavioural counselling, a booklet containing smoking cessation advice and instructions for use of the patches, and a 12-week course of decreasing transdermal nicotine doses.


Follow-up was available on 1392 out of 1481 study participants. The majority of adverse experiences were mild. Sleep problems occurred in 669 out of 1392 (48%) participants and most often commenced on the day of smoking cessation. Application site reactions occurred in 478 out of 1392 (34%) participants and most often occurred after 6 days of therapy. No predictor had an adjusted hazard ratio above 2. Statistically significant (p < 0.05) predictors of sleep problems were successfully quitting smoking and female gender. Predictors of application site reactions were psoriasis or eczema, other skin conditions, age <40 years, female gender, place of birth outside Australasia, and trade or university education level.

Substantially increased nicotine intake during therapy compared with baseline smoking occurred in 8% of participants who smoked concurrently, and 4% of participants who did not (p = 0.1). Increased nicotine intake was associated with a modest increase in the overall rate of adverse experiences (89% vs 63%, p = 0.04) and dizziness/lightheadedness (17% vs 3%, p = 0.03), but not with sleep problems or cardiovascular events.


Transdermal nicotine therapy appears to be well tolerated, even if the user smokes concurrently. Sleep disturbance during therapy appeared to be primarily associated with tobacco withdrawal rather than with nicotine excess from treatment with transdermal nicotine. Study participants with pre-existing skin disorders were somewhat more likely to report mild application site reactions than other participants.

This is a preview of subscription content, access via your institution.


  1. 1.

    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: 1304–8

    Article  Google Scholar 

  2. 2.

    Richmond RL, Harris K, de Almeida Neto A. The transdermal nicotine patch: results of a randomised placebo-controlled trial. Med J Aust 1994; 161: 130–5

    PubMed  CAS  Google Scholar 

  3. 3.

    Hurt RD, Dale LC, Fredrickson PA, et al. Nicotine patch therapy for smoking cessation combined with physician advice and nurse follow-up: one year outcome and percentage of nicotine replacement. JAMA 1994; 271: 595–600

    PubMed  Article  CAS  Google Scholar 

  4. 4.

    Gourlay SG, Forbes A, Marriner T, et al. A randomised clinical trial of a second course of transdermal nicotine therapy. BMJ 1995; 311: 363–6

    PubMed  Article  CAS  Google Scholar 

  5. 5.

    Campbell IA, Prescott RJ, Tjeder-Burton SM. Transdermal nicotine plus support in patients attending hospital with smoking-related diseases: a placebo-controlled study. Respir Med 1996; 90: 47–51

    PubMed  Article  CAS  Google Scholar 

  6. 6.

    Sachs DP, Säwe U, Leischow SJ. Effectiveness of a 16-hour transdermal nicotine patch in a medical practice setting, without intensive group therapy. Arch Intern Med 1993; 153: 1881–90

    PubMed  Article  CAS  Google Scholar 

  7. 7.

    Jorenby DE, Smith SS, Fiore MC, et al. Varying nicotine patch dose and type of smoking cessation counseling. JAMA 1995; 274: 1347–52

    PubMed  Article  CAS  Google Scholar 

  8. 8.

    Transdermal nicotine study group. Transdermal nicotine for smoking cessation. JAMA 1991; 266: 3133–8

    Article  Google Scholar 

  9. 9.

    Gourlay SG, Forbes A, Marriner T, et al. A prospective study of factors predicting smoking cessation using transdermal nicotine therapy. BMJ 1994; 309: 842–6

    PubMed  Article  CAS  Google Scholar 

  10. 10.

    Gourlay SG, Benowitz NL, Forbes A, et al. Determinants of plasma concentrations of nicotine and cotinine during smoking and transdermal nicotine treatment. Eur J Clin Pharmacol 1997; 51(5): 407–14

    PubMed  Article  CAS  Google Scholar 

  11. 11.

    Gourlay SG, McNeil JJ. Antismoking products. Med J Aust 1990; 153: 699–707

    PubMed  CAS  Google Scholar 

  12. 12.

    Dwyer CM, Forsyth A. Allergic contact dermatitis from methacrylates in a nicotine transdermal patch. Contact Dermatitis 1994; 30: 309–10

    PubMed  Article  CAS  Google Scholar 

  13. 13.

    Bircher AJ, Howald H, Rufli T. Adverse skin reactions to nicotine in a transdermal therapeutic system. Contact Dermatitis 1991; 25: 230–6

    PubMed  Article  CAS  Google Scholar 

  14. 14.

    Smith EW, Smith KA, Maibach HI, et al. The local side effects of transdermally absorbed nicotine. Skin Pharmacol 1992; 5: 69–76

    PubMed  Article  CAS  Google Scholar 

  15. 15.

    Hogan DJ, Maibach HI. Adverse dermatological reactions to transdermal drug delivery systems. J Am Acad Dermatol 1992; 22: 811–4

    Article  Google Scholar 

  16. 16.

    Greenland S, Satterfield MH, Lanes SF. A meta-analysis to assess the incidence of adverse effects associated with the trans-dermal nicotine patch. Drug Safety 1998; 18: 297–308

    PubMed  Article  CAS  Google Scholar 

  17. 17.

    Wolter TD, Hauri PJ, Schroeder DR, et al. Effects of 24-hr nicotine replacement on sleep and daytime activity during smoking cessation. Prev Med 1996; 25: 601–10

    PubMed  Article  CAS  Google Scholar 

  18. 18.

    Davila DG, Hurt RD, Offord KP, et al. Acute effects of trans-dermal nicotine on sleep architecture, snoring, and sleep-disordered breathing in nonsmokers. Am J Respir Crit Care Med 1994; 150: 469–74

    PubMed  CAS  Google Scholar 

  19. 19.

    Silagy C, Mant D, Fowler G, et al. Metaanalysis on efficacy of nicotine replacement therapies in smoking cessation. Lancet 1994; 343: 139–42

    PubMed  Article  CAS  Google Scholar 

  20. 20.

    Benowitz NL, Chan K, Denaro CP, et al. Stable isotope method for studying transdermal drug absorption. Clin Pharm Ther 1991; 50: 286–93

    Article  CAS  Google Scholar 

  21. 21.

    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: 311–5

    PubMed  Article  CAS  Google Scholar 

  22. 22.

    Russell MAH, Stapleton JA, Feyerabend C, et al. Targeting heavy smokers in general practice: randomised controlled trial of transdermal nicotine patches. Br J Med 1993; 306: 1308–12

    Article  CAS  Google Scholar 

  23. 23.

    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. Arch Fam Med 1993; 2: 417–23

    PubMed  Article  CAS  Google Scholar 

  24. 24.

    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: 41–7

    PubMed  Article  CAS  Google Scholar 

  25. 25.

    Benowitz NL, Gourlay SG. The cardiovascular safety of nicotine: implications for nicotine replacement therapy. JACC 1997; 29: 1422–31

    PubMed  CAS  Google Scholar 

  26. 26.

    Working Group for the Study of Transdermal Nicotine in Patients With Coronary Artery Disease. NRT for patients with coronary artery disease. Arch Intern Med 1994; 154: 989–95

    Article  Google Scholar 

  27. 27.

    Joseph AM, Norman SM, Ferry LH, et al. The safety of trans-dermal nicotine as an aid to smoking cessation in patients with cardiac disease. N Engl J Med 1996; 335: 1792–8

    PubMed  Article  CAS  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to Dr Steven G. Gourlay.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Gourlay, S.G., Forbes, A., Marriner, T. et al. Predictors and Timing of Adverse Experiences During Transdermal Nicotine Therapy. Drug-Safety 20, 545–555 (1999).

Download citation


  • Nicotine
  • Adis International Limited
  • Smoking Cessation
  • Sleep Problem
  • Nicotine Replacement Therapy