Recognize that nicotine replacement is safe in most patients, that bupropion carries some risk of adverse effects in some patients with comorbid conditions or on other drugs, varenicline was safe and well-tolerated in clinical trials that enrolled primarily healthy participants, and that the role of these agents is unclear in pregnancy.

• Nicotine Replacement Therapy
  • Despite the theoretical concern of using nicotine replacement therapy in patients with ischemic heart disease, it appears to be safe in persons with stable coronary disease
• Bupropion
  • Bupropion is contraindicated in persons with a recent history of seizures, bulimia, or anorexia nervosa as it lowers seizure threshold
  • The two forms of bupropion, Zyban© and Wellbutrin SR©, should not be administered together
  • Patients who are currently using or have used a monoamine oxidase inhibitor within the previous 14 days should not receive bupropion
  • Patients should be advised that anaphylaxis has been reported at a rate of 1 to 3 per 1000 patients enrolled in clinical trials
  • Blood pressure should be monitored in patients using bupropion as it has been associated with hypertension requiring treatment.
• Varenicline
  • Nausea is the most common side effect with varenicline (30%). Symptoms are generally mild and decrease with continued treatment (52; 53).
  • Varenicline is excreted by the kidneys and should be used with caution in patients with renal failure. Doses should not exceed 0.5 mg twice daily in patients with substantial renal dysfunction (creatinine clearance <30 mL/min or 0.5 mg per day) in patients on hemodialysis (see manufacturer's label).

Evidence:

• Nicotine Replacement Therapy
  • Two randomized trials of nicotine replacement therapy in patients with stable ischemic heart disease found no increase in adverse cardiac events (62; 63)
  • A meta-analysis examining the incidence of adverse effects in individuals using the nicotine patch found no excess of cardiovascular outcomes in participants treated with the patch (64)
  • There have been a few case reports of myocardial infarction and atrial fibrillation in persons who have used nicotine replacement therapy, although causation remains unclear (65; 66)
• Bupropion
  • Bupropion is known to reduce seizure thresholds, with a seizure rate of about 1 per 1000 subjects treated. Patients with seizures, bulimia or anorexia nervosa, and others with lowered seizure thresholds should avoid its use. Anaphylaxis has been reported at a rate of 1 to 3 per 1000 patients enrolled in clinical trials. Drug interactions with antipsychotics and MAO inhibitors have been reported. Contraindications are listed in the product monograph (50; 67)

Comments:

• Use of nicotine replacement therapy in patients with unstable coronary disease (e.g., post myocardial infarction) requires consideration of the potential adverse effects of the drug vs. the risks associated with smoking.
• At this time, the risks vs. benefits of nicotine replacement therapy in pregnancy is unclear. Further studies examining this issue are required before a definite statement of risk vs. benefit can be made.
• Bupropion is classified as a Category B drug for pregnancy and should be considered only if behavioral therapy or educational materials are unsuccessful.
• Current guidelines suggest that pregnant women attempt non-drug means of cessation first. If these fail, clinicians can suggest nicotine replacement therapy, recognizing that the benefits and harms of this therapy in pregnant women are not known (1).