Drugs and Diseases Interacting with Cigarette Smoking in US Prescription Drug Labelling

Abstract

The US Food and Drug Administration (FDA) draft guidance for industry on drug interaction studies recommends, but does not mandate, that both cigarette smokers and non-smokers can be used to study drug metabolism in clinical trials, and that important results related to smoking should be included in drug labelling to guide medication usage. This study aimed to provide a comprehensive review of drugs or diseases interacting with smoking, as presented in all US drug labelling. The 62,857 drug labels deposited in the FDA Online Label Repository were searched using the keywords 'smoke', 'smoker(s)', 'smoking', 'tobacco' and 'cigarette(s)' on 19 June 2014. The resultant records were refined to include only human prescription drug labelling, for manual examination. For 188 single-active-ingredient drugs and 36 multiple-active-ingredient drugs, the labelling was found to contain smoking-related information. The pharmacokinetics of 29 and 21 single-active-ingredient drugs were affected and unaffected, respectively, by smoking. For the remaining drugs, the provided information related to smoking affecting efficacy, safety or diseases but not pharmacokinetics. Depending on the nature of specific drugs, the perturbation in pharmacokinetic parameters in smokers ranged from 13 to 500%, in comparison with non-smokers. Dosage modifications in smokers are necessary for four drugs and may be necessary for six drugs, but are unnecessary for seven drugs although the pharmacokinetic parameters of four of them are affected by smoking. Cigarette smoking is a risk factor for 16 types of diseases or adverse drug reactions. For one single-active-ingredient contraceptive drug and 10 multiple-active-ingredient contraceptive drugs, a black box warning (the FDA's strongest safety warning) is included in the labelling for increased risks of heart attacks and strokes in female smokers, and "women are strongly advised not to smoke" when using these drugs. This study presents the first comprehensive overview of cigarette smoking interacting with drugs and/or diseases, as presented in US drug labelling.

Alteration of human hepatic drug transporter activity and expression by cigarette smoke condensate

“…Previous studies have demonstrated that cigarette smoke can regulate detoxifying enzymes in hepatic and extra-hepatic tissues, thus causing alteration of pharmacokinetics and drug interactions (Kroon 2007;Li and Shi 2015). The data reported in the present work demonstrate that CSC can alter activity and/or expression of hepatic drug transporters (See Table 1 for a summary of the effects of CSC towards transporter activity and expression), thus fully highlighting that drug transporters also constitute molecular targets for cigarette smoke chemicals.…”

“…By this way, tobacco smoke is recognized as one leading preventable cause of death (Jha 2009). In addition, smoking cause alterations of pharmacokinetics and drug interactions (Kroon 2007;Li and Shi 2015;Smith 2009). This has been primarily related to induction of liver detoxifying enzymes, including cytochrome P-450 (CYP) 1A1, CYP1B1, CYP1A2, CYP2B6 and glutathione S-transferases, by cigarette smoke chemicals (Chang et al 2003;Eke and Iscan 2002;Schrenk et al 1998;Washio et al 2011).…”

Smoking Cessation, Version 1.2016, NCCN Clinical Practice Guidelines in Oncology

“…Drugs whose metabolisms are known to be affected include erlotinib, irinotecan, and bendamustine. [2][3][4][5][6] • Smoking increases risk of radiation therapy (RT)-associated treatment complications during RT and may decrease treatment response. [7][8][9] • Smoking is associated with increased rates of postoperative complications and mortality after cancer surgery.…”

“…The American Heart Association, AACR, and ASCO recognize the potential for ENDS to alter existing smoking behaviors, as well as the lack of defi nitive data regarding associated benefi ts and harms. 1,2 However, ENDS are not recommended by these associations because of the insuffi cient data on effi cacy and safety. According to the US Preventative Services Task Force (USPSTF), "Current evidence is insuffi cient to recommend electronic nicotine delivery systems (ENDS) for tobacco cessation in adults, including pregnant women.…”

Effect of overnight smoking abstinence on a marker for microglial activation: a [11C]DAA1106 positron emission tomography study

“…For example, cigarette smoking has been shown to reduce numbers of resident microglial cells (Shi et al 2009), which would presumably lead to less radiotracer binding. Cigarette smokers are also known to have higher metabolism of some medications than non-smokers (Li and Shi 2015), which (if applicable to [ 11 C]DAA1106) would be expected to lessen radiotracer uptake and binding. In addition, cigarette smoking may result in inflammation in parts of the body other than brain (Rom et al 2013), which could lead to sequestration of the radiotracer and less binding in brain.…”