HIGH-DOSE TRANSDERMAL NICOTINE THERAPY FOR HEAVY SMOKERS - SAFETY, TOLERABILITY AND MEASUREMENT OF NICOTINE AND COTININE LEVELS

Transdermal nicotine has been shown to relieve nicotine withdrawal and to double smoking cessation rates compared to placebo in clinical tri als. A 21 or 22 mg/day dose provides a steady state serum nicotine tha t is less than obtained from smoking. Limited information is available about higher nicotine patch doses. To define better the optimal dosin g of nicotine patch therapy, we undertook an open-label study to deter mine the safety and tolerability of 44 mg/day dose for smoking cessati on in subjects smoking greater than or equal to 20 cigarettes per day. Forty smokers received 44 mg/day of transdermal nicotine for 4 weeks followed by 4 weeks of 22 mg/day. Of the 40 subjects enrolled, 38 (95% ) completed the 4 weeks of 44 mg patch therapy and 36 (90%) completed the entire 8 weeks of patch therapy. Non-smokers at week 4 had a mean serum nicotine level of 23.4 +/- 11.7 ng/ml and cotinine of 152.2 +/- 87.3 ng/ml. Percent replacement was calculated by dividing the steady state level at week 4 by the baseline level while the subjects were sm oking their usual number of cigarettes. Percent nicotine replacement f or non-smokers at week 4 (while on 44 mg nicotine patch) averaged 158% +/- 108.4, and for cotinine was 112.0 +/- 73.8. For nicotine, 33% of non-smokers at week 4 had less than or equal to 100% nicotine replacem ent and for cotinine 63% less than or equal to 100% replacement. Bioch emically confirmed point prevalence smoking cessation rates were 65% a nd 55% at weeks 4 and 8 of patch therapy, respectively, and self-repor ted smoking cessation at 3 months was 50%. The most common effect was skin irritation at the patch site. A single subject was admitted for m yocardial infarction following step-down from 44 to 22 mg of replaceme nt nicotine. The subject was not smoking and the adverse event was dee med to be not related to the patch therapy. Sleep complaints were repo rted in 33% of subjects during the 44 mg phase. Other complaints were infrequent. We conclude that 44 mg per 24-h nicotine patch therapy in heavy smokers is safe, tolerable, and without significant adverse even ts.