Drug Interactions With Smoking

Lisa A. Kroon, Pharm.D


Am J Health Syst Pharm. 2007;64(18):1917-1921. 

In This Article

Pharmacodynamic Drug Interactions

Figure 1 also lists the pharmacodynamic drug interactions with smoking. The most clinically significant interaction occurs with combined hormonal contraceptives. The use of oral contraceptives increases the risk of cardiovascular adverse effects, specifically thromboembolism (e.g., venous thrombosis, pulmonary embolism), ischemic stroke, and myocardial infarction (MI), but the risk is lower than that associated with the higher-dose oral contraceptives used in the past.[26,27,28] Smoking increases the risk of arterial adverse events (i.e., ischemic stroke and MI) associated with oral contraceptive use.[26] The risk for cardiovascular events with oral contraceptive use substantially increases in older women who are heavy smokers. For women who use low-dose oral contraceptives (20-50 µg of estrogen), the absolute risk of death from cardiovascular disease in nonsmoking women ages 15-34 years is 0.65 per 100,000 and 6.21 per 100,000 for women ages 35-44 years.[29] This risk greatly increases in women who smoke: 3.3 per 100,000 women ages 15-34 years versus 29.4 per 100,000 women ages 35-44 years. In a case-control study assessing the risk of a first nonfatal MI in oral contraceptive users younger than 45 years, the odds ratio among heavy smokers (≥25 cigarettes a day) was 2.5 (95% confidence interval, 0.9-7.5) and close to 1.0 among light smokers and nonsmokers.[30] The use of oral contraceptives is contraindicated in women age 35 years or older who smoke 15 or more cigarettes daily.[31,32] Practitioners should target smoking-cessation interventions toward women in this high-risk population. If unsuccessful, an alternative form of contraception should be recommended, such as a progestin-only contraceptive.[33,34] Of note, the clinical efficacy of hormonal contraceptives is not reduced in smokers.

Labeling for the Ortho Evra (Ortho-McNeil) contraceptive patch (containing ethinyl estradiol and norelgestromin) was revised in 2005 to indicate that the patch results in 60% higher estrogen levels compared with levels achieved using an oral contraceptive containing 35 µg of estrogen.[35] While the published data on this increased cardiovascular risk mainly deal with oral contraceptives, this risk is presumed to be associated with other dosage forms of hormonal contraceptives, such as a patch and ring. The labeling for Ortho Evra and NuvaRing (Organon) warns against use in women over age 35 years who smoke 15 or more cigarettes daily.[35,36] Women who use combined hormonal contraceptives of any kind should be strongly advised to quit smoking or use an alternative form of contraception if they cannot quit.

The efficacy of inhaled corticosteroids may be reduced in patients with asthma who smoke. In patients with mild asthma receiving 1000 µg daily of inhaled fluticasone (as two puffs twice daily with a metered-dose inhaler), the increase in peak expiratory flow at three months was significantly greater in nonsmokers (27 L/ min), compared with a decrease of 5 L/min in smokers (p = 0.006).[37] Another study of patients with mild, persistent asthma demonstrated significantly less improvement in morning peak expiratory function in smokers taking low-dose inhaled beclomethasone (400 µg daily) than in nonsmokers (p = 0.019).[38] However, these differences were not significant in patients receiving 2000 µg daily of inhaled beclomethasone (p = 0.661).[38] Practitioners should be aware that patients with chronic asthma may be less responsive to inhaled corticosteroids and should be a targeted priority for smoking-cessation interventions.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.