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Nicotine Replacement Therapy : A summary of use and safety in practice Updated July 2010 In response to various queries from the sector regarding the use and safety of Nicotine Replacement Therapy, the following document “Nicotine Replacement Therapy (NRT): A summary of use and safety in practice” has been prepared by Dr Hayden McRobbie on behalf of the New Zealand Ministry of Health. As more health professionals are implementing ABC into their practice it is important that NRT is well understood as a key pharmacotherapy agent. NRT is an effective smoking cessation aid and can also be used to aid temporary abstinence (i.e. for use where people are unable to smoke, such as hospitals). However a number of practical and safety issues have come to the Ministry of Health’s attention from the implementation of the ABC project. This document aims to address some of these. This document does not constitute guidance and is not a replacement to other resources (e.g. Smoking cessation guidelines 2007, e-learning tool www.smokingcessationabc.org.nz) and should be viewed as supplementary information to increase understanding over some safety concerns. For further information please contact Dr Hayden McRobbie via e-mail: [email protected] 1 A Report on NRT prepared by Dr Hayden McRobbie on behalf of the New Zealand Ministry of Health. Nicotine Replacement Therapy (NRT) A summary of use and safety in practice June 2010 [updated 26 July 2010] Author Hayden McRobbie1, on behalf of the New Zealand Ministry of Health. Purpose The purpose of this document is to summarise some of the practical and safety issues of nicotine replacement therapy (such as lozenges, patches, gum, inhaler and microtabs) use in clinical practice. Summary Nicotine Replacement Therapy (NRT) is a safe and effective treatment for smoking cessation and doubles the chance of quitting long-term. In New Zealand the patches, gum, and lozenges are available via the Quit Card Scheme and via general sale in supermarkets and pharmacies. Other products, i.e. inhaler and sublingual tablets are not subsidised but are available for purchase in pharmacies. There are no true contraindications for NRT use in people who smoke as they are already receiving nicotine from their tobacco use. The labelling on some NRT products has recently changed, however a number of cautions for use in certain smokers (e.g. pregnant women and people with cardiovascular disease) remain. Healthcare workers should follow best practice as described in the New Zealand Smoking Cessation Guidelines and other Ministry of Health documents. NRT doses should be tailored to match the degree of tobacco dependence. Nicotine overdose associated with NRT use is rare. Underdosing is more prevalent and can lead to relapse. Smoking cessation is an integral part of best practice management for people at risk of cardiovascular and respiratory diseases. 1 Hayden McRobbie (MB ChB PhD) is a Senior Clinical Research Fellow at the Wolfson Institute of Preventive Medicine, Barts & The London School of Medicine and Dentistry, Queen Mary University of London and holds a Senior Lecturer post in the School of Public Health and Psychosocial Studies, Auckland University of Technology as well as an Honorary Senior Lectureship at The School of Population Health, The University of Auckland. He is also a consultant of Inspiring Limited. 2 A Report on NRT prepared by Dr Hayden McRobbie on behalf of the New Zealand Ministry of Health. Introduction Nicotine replacement therapy (NRT) is an effective smoking cessation treatment [1]. It roughly doubles the chances of long-term abstinence regardless of the degree of concomitant behavioural support. NRT has been available on the worldwide market for approximately 30 years and it has a good safety profile. There are currently seven products available on the worldwide market (patch, gum, lozenge, sublingual tablet, inhaler, nasal spray, and mouth spray). All products, except for the nasal and mouth sprays, are available in New Zealand and three (patches, gum, and lozenges) are currently fully subsidised via the Quit Card Scheme. Indications for use Traditionally NRT has been used primarily for smoking cessation, but more recently its use has been extended to assist smoking reduction, temporary abstinence and used in combination with other NRT products. Some brands of NRT products available in New Zealand indicate that NRT can be used for these purposes, others do not. Safety concerns There remains some concern about the safety of nicotine among consumers (people who smoke) and healthcare professionals. One such concern is the incorrect belief that nicotine is the main component in tobacco smoke responsible for smoking-related disease. Published data show that smokers believe that NRT products are just as likely as cigarettes to cause smoking related disease [2, 3]. People who have safety concerns regarding NRT are less likely to use NRT products at all or under use them [3]. Insufficient use of NRT is associated with poorer outcomes [4, 5]. A likely barrier for healthcare professionals in recommending NRT to people who smoke are the overly-cautious warnings on some NRT products. The warnings that appear on NRT product labels vary by product and manufacturer and have not always reflected best practice as described in the New Zealand Smoking Cessation Guidelines. However product labelling is slowly changing. For example use of Habitrol gum in those under the age of 18 was previously contraindicated, however the datasheets have recently been updated to allow use in smokers aged 12 years and older (see table 1). There remain some differences in labelling between NRT products. From a policy viewpoint, cigarettes are the most harmful vehicles of 3 A Report on NRT prepared by Dr Hayden McRobbie on behalf of the New Zealand Ministry of Health. nicotine delivery and yet are the most under-regulated [6]. To the contrary nicotine from NRT is much safer and yet highly regulated with contraindications, warnings, and restrictions on dose. A change of NRT regulation in the UK In 2005 the Medicine and Healthcare products Regulatory Agency (MHRA) issued a report making recommendations on regulatory changes that relaxed the control on the use of NRT products. The recommendations of the working group were [7]: “NRT is to be licensed for adolescents, pregnant and breast-feeding women and smokers with cardiovascular and other underlying diseases; some NRT products are licensed to cut down smoking as a stepping stone to stopping completely, for smokers who are currently unable to stop abruptly; the product information for NRT will be revised to provide more clear-cut, easily assimilated information for users, maximising the benefits and ensuring that any risks there may be are seen in the context of the dangers of continued smoking.” These changes have been implemented in the UK and product labelling is now more closely aligned. Recent changes have also been made to the New Zealand product labelling, for example NRT use is no longer contraindicated in pregnancy. However cautions regarding use in people with certain illnesses, young people and pregnant women remain. This is largely due to a lack of data from clinical trials of NRT in these populations. Comparison of NRT to smoking Experts agree that it is not nicotine that causes the adverse health effects associated with smoking. However health risks associated with nicotine cannot be ruled out completely. There are some data that suggest that nicotine has adverse effects in pregnancy [8] and that it might be involved in steps that increase the likelihood of some cells becoming cancerous, although there is no evidence that nicotine induces cancer [9]. The key message however is that nicotine use does not pose any additional risk to people who smoke. Smokers receive large amounts of nicotine from their tobacco every day, along with many other substances that are known to cause cancer and have adverse health effects. For the majority of smokers short-term (3-6 months) use of NRT is unlikely to have any adverse health effect. In fact in using NRT they are more likely to succeed in stopping smoking long-term and so more likely to achieve the health benefits associated with stopping smoking (e.g. reduced chance of premature death). However there are some situations where healthcare professionals are unsure whether to use NRT or not (e.g. in pregnancy 4 A Report on NRT prepared by Dr Hayden McRobbie on behalf of the New Zealand Ministry of Health. and in those with acute cardiovascular illnesses). NRT use in pregnancy: The risks of smoking in pregnancy are well documented. It is always preferable for a pregnant woman to be smoke free and nicotine free. However, for those who are struggling to become smokefree there is less risk associated with NRT use than continuing to smoke [10]. In this circumstance NRT use can be considered (see the recommendation on page 7). Short-acting or intermittent products (e.g. gum or lozenge) are preferred for use in pregnancy. However, if a patch is judged to be the most appropriate product, then it should be used during waking hours only and removed overnight [10]. NRT use following acute cardiac events or stroke: There are some data to suggest that nicotine might have a negative impact on function of some cells in the cardiovascular system [11]. However there is no evidence to show that NRT increases the risk of myocardial infarction or stroke [12-14]. There are few data from clinical trials using NRT in patients who smoke following acute cardiovascular events, but expert opinion is that the benefits of smoking cessation outweigh the risk of using NRT in these people [14, 15]. Patients that smoke who are hospitalised following acute cardiovascular events may not feel like smoking when ill. However many will experience craving and in some patients these may be strong enough to lead them to smoke. Smoking cessation medications, such as NRT alleviate these. Cessation support should also be offered with or without NRT for these patients to prevent relapse on discharge. NRT use in patients undergoing reconstructive surgery There is good evidence to show that tobacco use impairs wound healing [16, 17]. Therefore people who smoke should be strongly advised, and supported, to stop smoking as early as possible prior to surgery. It is unlikely that nicotine plays a major role in this post-operative complication, however there is concern in using nicotine (NRT) in patients who have undergone certain surgical procedures where success lies in good blood supply (e.g. flap surgery). The concern is that nicotine may cause constriction of small blood vessels resulting in reduced blood supply and tissue death. There are data to show that nicotine does reduce blood flow in cutaneous and subcutaneous blood vessels, but this reduction is limited [18]. Conversely smoking produces a significant reduction in blood flow [18]. Although there may be some risk in using NRT in the above cases, the risks of smoking far outweigh the risks of using NRT. Plasma nicotine concentrations seen in people smoking cigarettes are typically between 10 – 50 ng/ml [19]. Plasma nicotine concentrations seen in people using NRT are typically between 2-20 ng/ml [20]. Smoking is also associated with 5 A Report on NRT prepared by Dr Hayden McRobbie on behalf of the New Zealand Ministry of Health. increased COHb with decreased oxygen carrying capacity and increased blood viscosity. Obviously it is better for people undergoing surgery, such as breast reconstruction, to be both tobacco free and nicotine free. However if they cannot remain smokefree then NRT provides a better option. Oral products are preferable to patches as they provide an intermittent dose [14, 21]. If there is reservation in using NRT post-operatively then one of the non-nicotine treatments for smoking cessation should be used e.g. varenicline, bupropion, and nortriptyline. They do not provide instant withdrawal relief as they require a few days to reach steady state plasma concentration. Bupropion and nortriptyline are subsidised; varenicline is not currently subsidised. NRT and drug interactions There are no drug interactions with NRT. However, smoking tobacco causes induction of the liver enzyme cytochrome P450 (CYP1A1, CYP1A2) [22]. This is mainly the effect of the polycyclic aromatic hydrocarbons present in tobacco smoke, not an effect of the nicotine. CYP1A2 is responsible for the breakdown of several medications, and medications metabolised by this enzyme will be metabolised faster in smokers than in non-smokers. On a person’s cessation of smoking, these enzymes return to a normal level of activity, but this may mean that several medications are metabolised more slowly, so a dosage adjustment may be needed [22]. Relevant medications are shown in Table 2 (page 16). There have been case reports of clozapine toxicity following smoking cessation [2326]. However, because of genetic variation in the activity of the CYP1A2 enzyme not all smokers will show a clinically significant change in blood levels. As a general rule therapeutic drug monitoring should be carried out following smoking cessation and dosage adjustments should be made accordingly [26]. What do the New Zealand Guidelines recommend? The New Zealand Smoking Cessation Guidelines were updated in 2007 [27], and recommend: a) Offer NRT routinely as an effective medication for people who want to quit smoking tobacco b) The choice of NRT product can be guided by individual preference c) Use NRT for at least 8 weeks d) Combining two NRT products (for example, patch and gum is a popular combination) increases abstinence rates 6 A Report on NRT prepared by Dr Hayden McRobbie on behalf of the New Zealand Ministry of Health. e) NRT can be used to encourage reduction prior to quitting f) People who need NRT for longer than 8 weeks (for example, people who are highly dependent) can continue to use NRT g) NRT can be provided to people with cardiovascular disease h) Pregnant women can use NRT after they have been informed of and have weighed up the risks and benefits. Intermittent NRT (for example, gum, inhaler, microtab and lozenge) should be used in preference to patches i) NRT can be used by young people (12–18 year of age) who are dependent on nicotine (that is, it is not recommended in occasional smokers such as those who smoke on weekends only) if it is believed that the NRT may help stopping smoking Using higher doses of NRT Despite its good track record people who use NRT still have a less than 20% chance of quitting for a year or more. This may in part be due to the fact that many smokers are under-dosed. NRT products typically provide less than half the nicotine an average treatment seeking smoker receives from their tobacco [28]. Even with combination NRT treatment many smokers do not obtain blood nicotine levels comparable with their baseline smoking levels. In a trial of combined nicotine patch and inhalator blood nicotine levels were only 60% of that achieved during ad lib smoking [29]. In some smokers the standard dosing is sufficient while in others much higher doses may be needed. It is also likely that using NRT only after stopping smoking is not an optimal treatment strategy. Higher NRT doses: There are modest data to show that a higher degree of nicotine replacement is associated with greater quit rates. The Cochrane Review on NRT for smoking cessation identified six studies comparing quit rates associated with combination NRT use (e.g. patch plus a short acting NRT product) compared with single product use and one study comparing combination NRT use with no NRT.[1] Combing these studies shows a clear advantage of combination vs. single product NRT use (RR=1.35; 95%CI: 1.11-1.63). An additional seven studies compared higher dose patches (e.g. 44mg/24 hours) with standard doses (21mg/24 hours). Overall there was a small increase in long-term quit rates (RR=1.15, 95%CI: 1.01-1.30). The Cochrane Review also summarises data for two oral forms of NRT available in high and low strength (gum and lozenges). Data show that more highly dependent smokers are more likely to quit when they use high dose gum (4mg) than lower dose (2mg) gum (RR=1.85, 95%CI: 1.30-2.50) [1]. Similar results are seen with the lozenge [30]. These outcome data are supported by several trials that show that higher dose NRT is associated with better 7 A Report on NRT prepared by Dr Hayden McRobbie on behalf of the New Zealand Ministry of Health. relief of tobacco withdrawal symptoms [31-34]. Safety of higher NRT doses and using NRT while smoking: Since NRT was first introduced, some 30 years ago, extensive evidence has accumulated showing that all existing NRTs have a very good safety profile, even when used in non-smokers (nicotine patches have been used as treatment for ulcerative colitis [35] and Parkinson’s Disease [36]). Nicotine overdose associated with NRT use in smokers is uncommon. Smokers are used to very large doses of nicotine from tobacco use. Studies of high dose patches (e.g. 63mg) found nausea to be the most common adverse effect, which is easily managed by reducing the dose. Nicotine has a short half-life (around 90 minutes) and so recovery is fast. In a small (n=6) open label study of nicotine patch treatment for Parkinson’s Disease participants, all never smokers, were exposed to doses of up to 105mg/day for 17 weeks [37]. Five tolerated 105mg/day, the other needed the dose reduced to 75mg/day. Again, the most common adverse effect was nausea. There were no adverse changes to cardiovascular parameters. NRT use and concomitant smoking is also safe and well tolerated [38, 39]. Randomised placebo controlled trials of using NRT concomitantly with smoking show that symptoms that could have been related to nicotine overdose (e.g. nausea, palpitations) were uncommon and were reported equally by both groups [40, 41]. The authors of the meta-analysis of NRT use prior to quitting found no increase in adverse events in patch users compared to those on placebo [42]. Finally post-marketing surveillance does not highlight any concerns with using NRT whilst smoking [7]. Conclusions NRT is proven to help people stop smoking. It has a good safety record and can be used to help anyone who smokes to stop. Healthcare workers should follow best practice as described in the New Zealand Smoking Cessation guidelines to provide the best care for people who smoke. Acknowledgements Special thanks go tp William Allan (Chief Pharmacist, Hawke’s Bay Hospital, Hawke’s Bay DHB), Carleine Receveur (Project Manager, SmokeFree DHB, Hawke’s Bay District Health Board, Hastings and Workstream lead for secondary care - ABC project team, Tobacco Control Team, Ministry of Health) and Catherine Marshall for their very helpful comments on the draft of this summary document. References 1. STEAD, L. F., PERERA, R., BULLEN, C., MANT, D. & LANCASTER, T. (2008) Nicotine replacement therapy for smoking cessation, Cochrane Database Syst Rev, 8 A Report on NRT prepared by Dr Hayden McRobbie on behalf of the New Zealand Ministry of Health. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. CD000146. BANSAL, M. A., CUMMINGS, K. M., HYLAND, A. & GIOVINO, G. A. (2004) Stop-smoking medications: who uses them, who misuses them, and who is misinformed about them?, Nicotine Tob Res, 6 Suppl 3, S303-10. SHIFFMAN, S., FERGUSON, S. G., ROHAY, J. & GITCHELL, J. G. (2008) Perceived safety and efficacy of nicotine replacement therapies among US smokers and ex-smokers: relationship with use and compliance, Addiction, 103, 1371-8. SHIFFMAN, S. (2007) Use of more nicotine lozenges leads to better success in quitting smoking, Addiction, 102, 809-14. JACKSON, P. H., STAPLETON, J. A., RUSSELL, M. A. & MERRIMAN, R. J. (1989) Nicotine gum use and outcome in a general practitioner intervention against smoking, Addict Behav, 14, 335-41. MCNEILL, A., FOULDS, J. & BATES, C. (2001) Regulation of nicotine replacement therapies (NRT): a critique of current practice, Addiction, 96, 1757-68. MEDICINES AND HEALTHCARE PRODUCTS REGULATORY AGENCY (2005) Report of the committee on safety of medicines working group on nicotine replacement therapy (MHRA, Committee on Safety of Medicines. Available online at: http://www.mhra.gov.uk/home/idcplg?IdcService=GET_FILE&dDocName=CON2 023239&RevisionSelectionMethod=LatestReleased Accessed: 3 July 2006). BRUIN, J. E., GERSTEIN, H. C. & HOLLOWAY, A. C. (2010) Long-term consequences of fetal and neonatal nicotine exposure: a critical review, Toxicol Sci. THUNNISSEN, F. B. (2009) Acetylcholine receptor pathway and lung cancer, J Thorac Oncol, 4, 943-6. DEMPSEY, D. A. & BENOWITZ, N. L. (2001) Risks and benefits of nicotine to aid smoking cessation in pregnancy, Drug Saf, 24, 277-322. BALAKUMAR, P. & KAUR, J. (2009) Is nicotine a key player or spectator in the induction and progression of cardiovascular disorders?, Pharmacol Res, 60, 3618. KIMMEL, S. E., BERLIN, J. A., MILES, C., JASKOWIAK, J., CARSON, J. L. & STROM, B. L. (2001) Risk of acute first myocardial infarction and use of nicotine patches in a general population, J Am Coll Cardiol, 37, 1297-302. HUBBARD, R., LEWIS, S., SMITH, C., GODFREY, C., SMEETH, L., FARRINGTON, P. et al. (2005) Use of nicotine replacement therapy and the risk of acute myocardial infarction, stroke, and death, Tob Control, 14, 416-21. MCROBBIE, H. & HAJEK, P. (2001) Nicotine replacement therapy in patients with cardiovascular disease: guidelines for health professionals, Addiction, 96, 154751. JOSEPH, A. M. & FU, S. S. (2003) Smoking cessation for patients with cardiovascular disease: What is the best approach?, American Journal of Cardiovascular Drugs, 3, 339-349. SILVERSTEIN, P. (1992) Smoking and wound healing, Am J Med, 93, 22S-24S. BARTSCH, R. H., WEISS, G., KASTENBAUER, T., PATOCKA, K., DEUTINGER, M., KRAPOHL, B. D. et al. (2007) Crucial aspects of smoking in wound healing after breast reduction surgery, J Plast Reconstr Aesthet Surg, 60, 1045-9. SORENSEN, L. T., JORGENSEN, S., PETERSEN, L. J., HEMMINGSEN, U., BULOW, J., LOFT, S. et al. (2009) Acute effects of nicotine and smoking on blood flow, tissue oxygen, and aerobe metabolism of the skin and subcutis, J Surg Res, 152, 224-30. LE HOUEZEC, J. (2003) Role of nicotine pharmacokinetics in nicotine addiction and nicotine replacement therapy: a review, International Journal of Tuberculosis & Lung Disease, 7, 811-9. 9 A Report on NRT prepared by Dr Hayden McRobbie on behalf of the New Zealand Ministry of Health. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. DAUTZENBERG, B., NIDES, M., KIENZLER, J. L. & CALLENS, A. (2007) Pharmacokinetics, safety and efficacy from randomized controlled trials of 1 and 2 mg nicotine bitartrate lozenges (Nicotinell), BMC Clin Pharmacol, 7, 11. BENOWITZ, N. & DEMPSEY, D. (2004) Pharmacotherapy for smoking cessation during pregnancy, Nicotine Tob Res, 6 Suppl 2, S189-202. ZEVIN, S. & BENOWITZ, N. L. (1999) Drug Interactions with Tobacco Smoking, Clin Pharmacokinetics, 36, 425-438. DERENNE, J. L. & BALDESSARINI, R. J. (2005) Clozapine toxicity associated with smoking cessation: case report, Am J Ther, 12, 469-71. BONDOLFI, G., MOREL, F., CRETTOL, S., RACHID, F., BAUMANN, P. & EAP, C. B. (2005) Increased clozapine plasma concentrations and side effects induced by smoking cessation in 2 CYP1A2 genotyped patients, Ther Drug Monit, 27, 539-43. ZULLINO, D. F., DELESSERT, D., EAP, C. B., PREISIG, M. & BAUMANN, P. (2002) Tobacco and cannabis smoking cessation can lead to intoxication with clozapine or olanzapine, Int Clin Psychopharmacol, 17, 141-3. MEYER, J. M. (2001) Individual changes in clozapine levels after smoking cessation: results and a predictive model, J Clin Psychopharmacol, 21, 569-74. MINISTRY OF HEALTH (2007) New Zealand Smoking Cessation Guidelines (Wellington, Ministry of Health). JOHNSTONE, E., BROWN, K., SAUNDERS, C., ROBERTS, K., DRURY, M., WALTON, R. et al. (2004) Level of nicotine replacement during a quit-smoking attempt, Nicotine Tob Res, 6, 377-9. BOHADANA, A., NILSSON, F., RASMUSSEN, T. & MARTINET, Y. (2000) Nicotine inhaler and nicotine patch as a combination therapy for smoking cessation: a randomized, double-blind, placebo-controlled trial, Arch Intern Med, 160, 3128-34. SHIFFMAN, S., DRESLER, C. M., HAJEK, P., GILBURT, S. J., TARGETT, D. A. & STRAHS, K. R. (2002) Efficacy of a nicotine lozenge for smoking cessation, Arch Intern Med, 162, 1267-76. ROHSENOW, D. J., MONTI, P. M., HUTCHISON, K. E., SWIFT, R. M., MACKINNON, S. V., SIROTA, A. D. et al. (2007) High-dose transdermal nicotine and naltrexone: effects on nicotine withdrawal, urges, smoking, and effects of smoking, Exp Clin Psychopharmacol, 15, 81-92. SHIFFMAN, S., FERGUSON, S. G., GWALTNEY, C. J., BALABANIS, M. H. & SHADEL, W. G. (2005) Reduction of abstinence-induced withdrawal and craving using high-dose nicotine replacement therapy, Psychopharmacology (Berl), 1-8. TONNESEN, P., PAOLETTI, P., GUSTAVSSON, G., RUSSELL, M. A., SARACCI, R., GULSVIK, A. et al. (1999) Higher dosage nicotine patches increase one-year smoking cessation rates: results from the European CEASE trial. Collaborative European AntiSmoking Evaluation. European Respiratory Society [see comments], Eur Respir J, 13, 238-46. EBBERT, J. O., DALE, L. C., PATTEN, C. A., CROGHAN, I. T., SCHROEDER, D. R., MOYER, T. P. et al. (2007) Effect of high-dose nicotine patch therapy on tobacco withdrawal symptoms among smokeless tobacco users, Nicotine Tob Res, 9, 43-52. PULLAN, R. D., RHODES, J., GANESH, S., MANI, V., MORRIS, J. S., WILLIAMS, G. T. et al. (1994) Transdermal nicotine for active ulcerative colitis, N Engl J Med, 330, 8115. VIEREGGE, A., SIEBERER, M., JACOBS, H., HAGENAH, J. M. & VIEREGGE, P. (2001) Transdermal nicotine in PD: a randomized, double-blind, placebo-controlled study, Neurology, 57, 1032-5. VILLAFANE, G., CESARO, P., RIALLAND, A., BALOUL, S., AZIMI, S., BOURDET, C. et al. (2007) 10 A Report on NRT prepared by Dr Hayden McRobbie on behalf of the New Zealand Ministry of Health. 38. 39. 40. 41. 42. Chronic high dose transdermal nicotine in Parkinson's disease: an open trial, Eur J Neurol, 14, 1313-6. FAGERSTROM, K. O. & HUGHES, J. R. (2002) Nicotine concentrations with concurrent use of cigarettes and nicotine replacement: a review, Nicotine Tob Res, 4 Suppl 2, S73-9. BENOWITZ, N. L., ZEVIN, S. & JACOB, P., 3RD (1998) Suppression of nicotine intake during ad libitum cigarette smoking by high-dose transdermal nicotine, J Pharmacol Exp Ther, 287, 958-62. BOLLIGER, C. T., ZELLWEGER, J. P., DANIELSSON, T., VAN BILJON, X., ROBIDOU, A., WESTIN, A. et al. (2000) Smoking reduction with oral nicotine inhalers: double blind, randomised clinical trial of efficacy and safety, BMJ, 321, 329-33. WENNIKE, P., DANIELSSON, T., LANDFELDT, B., WESTIN, A. & TONNESEN, P. (2003) Smoking reduction promotes smoking cessation: results from a double blind, randomized, placebo-controlled trial of nicotine gum with 2-year follow-up, Addiction, 98, 1395-402. SHIFFMAN, S. & FERGUSON, S. G. (2008) Nicotine patch therapy prior to quitting smoking: a meta-analysis, Addiction, 103, 557-63. 11 A Report on NRT prepared by Dr Hayden McRobbie on behalf of the New Zealand Ministry of Health. Table 1: Summary of current labelling on NRT products approved for use in New Zealand These data have been compiled from the data sheets available on the Medsafe Website (http://www.medsafe.govt.nz/profs/datasheet/DSForm.asp) Product Indications Dosage Contraindications Cautions Habitrol Gum HABITROL nicotine chewing gum treatment is indicated for the relief of nicotine withdrawal symptoms, in nicotine dependency as an aid to smoking cessation. It may be used as part of a smoking reduction strategy by smokers who are unable or not ready to stop smoking abruptly as a step towards stopping completely. May be used by smokers who are unable or not ready to quit on occasions when they want to temporarily abstain from smoking. Users should stop smoking completely during treatment with HABITROL gum. HABITROL gum should not be used by non-smokers or people under 12 years of age. Dependent smokers with a recent myocardial infarction, unstable or worsening angina pectoris including Prinzmetal’s angina, severe cardiac arrhythmias, uncontrolled hypertension or recent cerebrovascular accident should be encouraged to stop smoking with non-pharmacological interventions (such as counselling). If this fails, HABITROL may be considered but as data on safety in these patient groups are limited, initiation should only be under close medical supervision. Treatment of nicotine dependence, as an aid to smoking cessation. The subject should be advised to stop smoking completely when starting treatment with HABITROL Patch. Habitrol Patch One piece of HABITROL gum to be chewed when the user feels the urge to smoke. Normally, 8-12 pieces per day, up to a maximum of 25 pieces per day for the 2 mg gum and 15 pieces for the 4 mg gum. Nicotine is excreted in breast milk in quantities that may affect the child even in therapeutic doses. Like smoking, nicotine replacement therapy should be avoided during breast-feeding. However HABITROL chewing gum may be used if necessary. Women should breastfeed just before they use the product to allow time between NRT use and feeding to be as long as possible. Swallowed nicotine may exacerbate symptoms in subjects suffering from active oesophagitis, oral and pharyngeal inflammation, gastritis or peptic ulcer. Use with caution in patients with hypertension, stable angina pectoris, cerebrovascular disease, occlusive peripheral arterial disease, heart failure, hyperthyroidism, diabetes mellitus, and renal or hepatic impairment. Counselling may help smokers to quit. HABITROL Patch should not be used for non-smokers, children under 12 years of age, or occasional smokers. For those smoking more than 20 cigarettes a day it is recommended that treatment be started with HABITROL STEP 1 Dependent smokers with a recent myocardial infarction, unstable or worsening angina pectoris including Prinzmetal’s angina, severe cardiac arrhythmias, uncontrolled hypertension or recent cerebrovascular accident should be encouraged to stop smoking with non-pharmacological interventions (such as counselling). If this fails, HABITROL may be considered but as data on safety in these patient groups are limited, initiation should only be under close medical supervision. HABITROL Patch should only be used after carefully weighing the risks with the benefits in these conditions: hypertension, stable angina pectoris, cerebrovascular disease, occlusive peripheral arterial disease, heart failure, hyperthyroidism, diabetes mellitus, Those smoking less than 12 A Report on NRT prepared by Dr Hayden McRobbie on behalf of the New Zealand Ministry of Health. Product Indications Dosage this should start with HABITROL STEP 2 Patch Contraindications Cautions renal or hepatic impairment, peptic ulcer. Such subjects should be encouraged to stop smoking without HABITROL Patch if possible. HABITROL Patch should only be considered if this proves impossible. In general any risk from the use of HABITROL Patch would be expected to be less than the risk of continued smoking. In cases of severe or persistent skin reactions, it may be advisable to discontinue treatment. Allergic reactions: Contact sensitisation was reported in a few patients using transdermal nicotine in clinical trials. Patients who develop contact sensitisation to nicotine should be cautioned that a severe reaction could occur from exposure to other nicotine containing products or smoking. Habitrol lozenge An effective aid to smoking cessation by the relief of nicotine withdrawal symptoms in nicotine dependency. Helps stop smoking, combating the unpleasant withdrawal symptoms caused by giving up smoking If you smoke less than 20 cigarettes per day it is recommended you start on the 1mg lozenge. If you smoke more than 20 cigarettes per day or if you have previously failed to quit smoking use the 2mg lozenge. Do not use HABITROL Lozenges if: hypersensitivity to nicotine or any other excipients of the lozenge. non-smoker under 12 years of age. Nicotine can stimulate the production of adrenaline. Habitrol Mint Lozenge should be used with caution in patients with uncontrolled hypertension, stable angina pectoris, cerebrovascular disease, occlusive peripheral arterial disease, heart failure, diabetes mellitus, hyperthyroidism or phaeochromocytoma and severe hepatic and/or renal impairment. Swallowed nicotine may exacerbate symptoms in patients suffering from active oesophagitis, oral and pharyngeal inflammation, gastritis or peptic ulcer. Habitrol Mint Lozenge contains aspartame which metabolises to phenylalanine, which is of relevance for patients with phenylketonuria. Initially, 1 lozenge should be taken every 1-2 hours. The usual dosage is 8-12 lozenges per day. The maximum daily dose is 25 lozenges of the 1mg lozenge and 15 lozenges of the 2mg lozenge. Pregnant smokers should try to stop smoking completely without use of nicotine replacement therapy. In pregnant smokers who have failed to stop smoking, continued smoking may pose greater hazard to the foetus as compared with the use of nicotine replacement products in a supervised smoking cessation program. Use of the lozenge by pregnant smokers should only be initiated after advice from a physician. Nicotine is excreted in breast milk in quantities that may affect the child even in therapeutic doses. Like smoking, nicotine replacement therapy should be avoided during breast-feeding. However HABITROL Lozenges may be used if necessary. Women should breastfeed just before they use the product to allow time Smokers are advised to 13 A Report on NRT prepared by Dr Hayden McRobbie on behalf of the New Zealand Ministry of Health. Product Indications Dosage quit smoking when they start using Habitrol Mint Lozenge Contraindications Cautions between NRT use and feeding to be as long as possible. NRT should only be used in adolescents 12 to 17 years after consultation with a healthcare professional and use should be restricted to 12 weeks. If treatment is required for longer than 12 weeks, this should be discussed with a healthcare professional. Do not use in children under 12 years Nicorette patch The treatment of nicotine dependence and the relief of withdrawal symptoms associated with smoking cessation. Daily treatment commences with one 15 mg patch, applied on waking (usually in the morning) and removed 16 hours later (usually at bedtime). Treatment should continue at this dose for an initial period of 8 weeks. Patients who have successfully abstained from smoking during this 8 week period should be supported through a further 4 week weaning period, using the lower strength patches. Downward titration of dose is achieved by applying one 10 mg patch daily for 2 weeks followed by one 5 mg patch daily for a further 2 weeks. Hypersensitivity to nicotine or any component of the patch. Nicorette Patch should not be administered to individuals under 18 years of age without recommendation from a physician. There is limited experience of treating this age group. Nicorette patch should only be used after consulting a physician by particular cardiovascular patient groups: those who have experienced a serious cardiovascular event, or hospitalisation for a cardiovascular complaint, in the previous 4 weeks (e.g. stroke, myocardial infarction, unstable angina, cardiac arrhythmia, coronary artery bypass graft and angioplasty) or where they suffer with uncontrolled hypertension. Nicorette patch should be used with caution in patients with severe or moderate hepatic impairment, severe renal impairment, active duodenal and gastric ulcers. Nicotine, both from nicotine replacement therapy and smoking, causes the release of catecholamines from the adrenal medulla. Therefore Nicorette patch should also be used with caution in patients with hyperthyroidism or pheochromocytoma. Patients with diabetes mellitus may require lower doses of insulin as a result of smoking cessation Pregnant or breast-feeding smokers should only use Nicorette patch after consulting a health care professional. The risks for the foetus from Nicorette patch are not fully known. The benefits of nicotine replacement therapy in pregnant women who cannot abstain without such therapy substantially outweigh the risk of continued smoking. Nicotine passes into breast milk in small quantities that may affect the infant, even at therapeutic doses. Nicorette Gum For the treatment of tobacco dependence by relieving The initial dosage should be individualised on the Hypersensitivity to nicotine or any components of the chewing 14 A Report on NRT prepared by Dr Hayden McRobbie on behalf of the New Zealand Ministry of Health. Nicorette chewing gum should not be administered to persons under 18 years of age without recommendation from a health Product Indications nicotine craving and withdrawal symptoms thus: Facilitating smoking cessation in smokers motivated to quit. Helping smokers to temporarily abstain from smoking. Facilitating smoking reduction in smokers unable or unwilling to quit. Dosage basis of the patient's nicotine dependence. Most smokers require about 8-12 pieces of the 2 mg gum or 4-6 pieces of the 4 mg gum. Not more than 20 pieces of the 2 mg gum or 10 pieces of the 4 mg gum (equivalent to a daily dose of 40 mg) should be chewed in one day. Low dependent smokers (Fagerström Test for Nicotine Dependence (FTND) < 6 or smoking ≤ 20 cigarettes/day) should begin treatment with the 2mg strength and high dependent smokers should receive the 4 mg dosage, initially Contraindications gum. Cautions care professional. There is limited experience of treating this age group with Nicorette chewing gum. Pregnant or breast-feeding smokers should only use Nicorette chewing gum after consulting a health care professional. The risks for the foetus from Nicorette chewing gum are not fully known. The benefits of nicotine replacement therapy in pregnant women who cannot abstain without such therapy substantially outweigh the risk of continued smoking. Nicotine passes into breast milk in small quantities that may affect the infant, even at therapeutic doses. To reduce the exposition to the child the Nicorette chewing gum should be used just after breast-feeding Smokers who wear dentures may experience difficulty in chewing Nicorette gum. The chewing gum may stick to, and may in rare cases damage dentures. Nicorette gum should only be used after consulting a physician by particular cardiovascular patient groups: those who have experienced a serious cardiovascular event, or hospitalisation for a cardiovascular complaint, in the previous 4 weeks (e.g. stroke, myocardial infarction, unstable angina, cardiac arrhythmia, coronary artery bypass graft and angioplasty) or where they suffer with uncontrolled hypertension. The risk of using nicotine replacement therapy should be weighed against the risk of continued smoking. Nicorette chewing gum should be used with caution in patients with severe or moderate hepatic impairment, severe renal impairment, active duodenal and gastric ulcers. Nicotine, both from nicotine replacement products and smoking, causes the release of catecholamines from the adrenal medulla. Therefore Nicorette chewing gum should also be used with caution in patients with uncontrolled hyperthyroidism or pheochromocytoma. Patients with diabetes mellitus may require lower doses of insulin as a result of smoking cessation. 15 A Report on NRT prepared by Dr Hayden McRobbie on behalf of the New Zealand Ministry of Health. Product Nicorette Inhaler Indications For the treatment of tobacco dependence by relieving nicotine craving and withdrawal symptoms, thereby: (1) facilitating smoking cessation in smokers motivated to quit, (2) helping smokers to temporarily abstain from smoking or (3) facilitating smoking reduction in smokers unable or unwilling to quit. Dosage Smoking cessation Contraindications Hypersensitivity to nicotine or any other component of the inhaler. Smoking reduction Temporary abstinence In combination nicotine patch Cautions Nicorette Inhaler should not be administered to individuals under 18 years of age without recommendation from a physician. There is no experience of treating adolescents under the age of 18 with Nicorette Inhaler. Nicorette Inhaler should only be used after consulting a physician by particular cardiovascular patient groups: those who have experienced a serious cardiovascular event, or hospitalisation for a cardiovascular complaint, in the previous 4 weeks (e.g. stroke, myocardial infarction, unstable angina, cardiac arrhythmia, coronary artery bypass graft and angioplasty) or where they suffer with uncontrolled hypertension. with Nicorette Inhaler should be used with caution in patients with severe or moderate hepatic impairment, severe renal impairment, active duodenal and gastric ulcers, chronic throat diseases and bronchospastic disease. Nicotine, both from Nicotine Replacement Therapy and smoking, causes the release of catecholamines from the adrenal medulla. Therefore Nicorette Inhaler should also be used with caution in patients with hypothyroidism or pheochromocytoma. Patients with diabetes mellitus may require lower doses of insulin as a result of smoking cessation. Some users may continue to use Nicorette Inhaler after the recommended treatment period but the potential risk of longerterm use is far less than those associated with resuming to smoking. If a child swallows, chews or sucks on the nicotine plug, (used as well as unused) there is a risk of poisoning the child. Pregnant or breast-feeding smokers should only use Nicorette Inhaler after consulting a health care professional. The risks for the foetus from Nicorette Inhaler are not fully known. The benefits of nicotine replacement therapy in pregnant women who cannot abstain without such therapy substantially outweigh the risk of continued smoking. Nicotine passes into breast milk in small quantities that may 16 A Report on NRT prepared by Dr Hayden McRobbie on behalf of the New Zealand Ministry of Health. Product Indications Dosage Contraindications 17 A Report on NRT prepared by Dr Hayden McRobbie on behalf of the New Zealand Ministry of Health. Cautions affect the infant, even at therapeutic doses. To reduce the exposition to the child the Nicorette Inhaler should be used just after breast-feeding Table 2: Drugs affected or not affected by smoking or smoking cessation Drug affected by smoking Effect of smoking Caffeine Increased clearance (by 56%) Chlorpromazine Decreased serum concentrations (by 24%) Clozapine Decreased plasma concentrations (by 28%) Estradiol Possible anti-estrogenic effects Flecainide Increased clearance (by 61%) Fluvoxamine Decreased plasma concentrations (by 47%) Haloperidol Decreased serum concentrations (by 70%) Heparin Increased clearance Imipramine Decreased serum concentrations Insulin Decreased subcutaneous absorption; possible higher insulin requirements in smokers Lidocaine Decreased oral bioavailability Olanzapine Increased clearance (by 98%) Propranolol Increased oral clearance (by 77%) Tacrine Decreased mean plasma concentrations (3-fold) Theophylline Increased metabolic clearance (by 58 to 100%); within 7 days of smoking cessation, theophylline clearance falls by 35%) Warfarin Decreased plasma concentrations (by 13%). No effect on prothrombin time Stopping smoking can result in the opposite effect to those noted above. Healthcare workers should be aware of the potential for increased blood levels of some of these medications when smoking is ceased. Blood levels of some medications (eg, clozapine, theophyline) may need to be monitored. Drugs not affected by smoking or smoking cessation Benzodiazepines (diazepam,lorazepam, midazolam, chlordiazepoxide) Bupropion Ethinyl estradiol (levonorgestrel) Glucocorticoids (prednisone, prednisolone, dexamethasone) Paracetamol Quinidine Drugs on which the effect of smoking or smoking cessation is unclear Nortriptyline Source: Adapted from S Zevin, NL Benowitz. Drug interactions with tobacco smoking. An update. Clin Pharmacokinetics 1999; 36(6): 425–38. 18