In this study, we observed that among ST users who used 3 cans/week, standard dose (21 mg/day) nicotine patch therapy resulted in a mean “under-replacement” of serum nicotine concentrations achieved during ad lib ST use. We also found that the 63 mg/day dose of the nicotine patch frequently resulted in “over-replacement” of nicotine and that subjects receiving this dose had more reports of toxicity. The 42 mg/day dose achieved nearly 100% replacement of the ad lib steady-state serum nicotine concentrations and was associated with minimal toxicity.
Nicotine concentrations observed in the current study at 1600 hours with the nicotine patch were similar to steady-state nicotine concentrations achieved in abstinent cigarette smokers receiving similar nicotine patch doses in previous studies (Lawson et al., 1998
). Higher doses of nicotine patch therapy for smokers have been observed to increase the percentage of cotinine replacement, decrease withdrawal symptoms (Dale et al., 1995
) and increase tobacco abstinence rates (Silagy et al., 2002
). We were underpowered in this study for an assessment of increased treatment efficacy with higher nicotine patch doses in ST users.
Several strengths to our study exist. First, the inpatient GCRC setting for this study provided the ability to obtain frequent blood samples among ST users wearing different nicotine patch doses in a controlled research environment designed to eliminate the chances for concomitant tobacco use. Second, the randomized, placebo-controlled trial design may have prevented early subject discontinuation of the nicotine patch therapy resulting from knowledge of treatment assignment. Third, the design allowed us to collect serum nicotine measurements during ad lid
ST use. Fourth, our study provides novel information on the percentage replacement of serum nicotine concentrations among ST users using ≥ 3 cans/week and the use of nicotine patch doses up to 63 mg/day. Finally, our findings have important implications for the treatment of ST users seeking treatment who, in previously published studies, have a reported average ST use rate of over 3 cans per week (Dale et al., 2002
; Hatsukami et al., 2000
; Hatsukami et al., 1996
; Howard-Pitney et al., 1999
The major weakness of this study relates to the fact that enrolled ST users were required to be using ≥ 3 cans/pouches per week. While this was necessary in order to ensure subject safety with the doses of nicotine patch therapy, the results do not apply to all ST users. Another weakness of this study is the small sample size as only 42 patients were enrolled. The small sample-size precludes drawing any definitive conclusions regarding the association between the use of 63 mg/day and nicotine toxicity.
Nicotine replacement therapy should be guided by the principles of maximization of symptom relief and minimization of toxicity. We have observed that higher doses of nicotine patch therapy resulted in improved relief of withdrawal symptoms (Ebbert et al., In press
). Since we identified clinical adverse events associated with “over-replacement” of serum nicotine concentrations in the 63 mg/day patch dose, we submit that this may not be the optimal starting dose for ST users who consume ≥ 3 cans/week. Our data support the initial dose of nicotine patch for heavier ST users should be 42 mg/day. We conclude that in a clinical setting in which serum tobacco alkaloids are not typically measured, heavier ST users (≥ 3 cans/week) can safely be treated with nicotine patch doses of 42 mg/day with dose-titration based upon clinical response. Careful clinical monitoring of response is recommended due to the wide inter-individual variation in serum nicotine concentrations between ST users.