1. Produced in association with McNeil Products Limited – the makers of nicorette ® How we can get the most out of NRT: a review and update on nicotine replacement therapy Date of preparation: May 2011. Prescribing Information can be found at the end of this presentation nicotine Dr Hayden McRobbie MB ChB PhD hayden.mcrobbie@inspiringlimited.com Date of preparation: May 2011 Prescribing Information can be found at the end of the presentation 06993

2. The risks of smoking are LARGE Smoking kills 1 in 2 smokers will die as a direct consequence of smoking 1 Helping people stop smoking is a life-saving intervention NRT is effective in helping people stop smoking 2 1 Doll, R., et al., British Medical Journal 2007; 328: 1519 2 Stead, L.F., et al., Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev, 2008(1): p. CD000146

3. NRT Is tried and tested 3 Chewing gum Skin patches Nasal spray Inhalator Microtab (sublingual tablet) Lozenges Mouthspray

4. Widely used Is the most widely used medicine for smoking cessation e.g. 64% of NHS-SSS patients using NRT last year on prescription 1 Typically started when a person stops smoking and a standard dose is used for 8-12 weeks and then stopped 1. The Health and Social Care Information Centre. Statistics on NHS Stop Smoking Services: England, April 2009 - March 2010: NHS, 2009

5. NRT is effective Stead LF, Perera R, Bullen C, Mant D, Lancaster T. Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev 2008(1)

6. …but is not a magic cure Despite NRTs significant effectiveness Versus a placebo, quitting figures are not as high as they could be. This may in part be due to Incorrect use Insufficient use

7. Reasons for NRT failure Unrealistic expectations Incorrect use Not used for long enough Nicotine is often seen as the dangerous element in cigarette smoke Safety concerns can be a barrier to use Encouraging compliance is important

8. Under-dosing? Depending on patch strength NRT patch may provide less than half the nicotine a smoker receives from their tobacco 1 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 15mg patch and inhalator, blood nicotine levels were only 60% of that achieved during ad lib smoking at week 6 2 1.Johnstone E, Brown K, Saunders C, Roberts K, Drury M, Walton R, et al. Level of nicotine replacement during a quit- smoking attempt. Nicotine Tob Res 2004;6(2):377-9 2.Bohadana A, Nilsson F, Rasmussen T, Martinet Y. Nicotine inhaler and nicotine patch as a combination therapy for smoking cessation: a randomized, double-blind, placebo-controlled trial. Arch Intern Med 2000;160(20):3128-34

9. Nicotine delivery Rates Short half life of nicotine requires smokers to regularly smoke to maintain levels 1 Situations linked to smoking such as at home, watching TV, driving the car and socialising may make it difficult to quit 2 Smokers become accustomed to the regular hand to mouth activity 1.Royal College of Physicians, Nicotine Addiction in Britain, 2000 2.Van Gucht D, et. al. J Behav Ther & Exp Psychiat 2010; 41: 172-177 Adapted from Royal College of Physicians, 2000 1 Nasal

10. Standard treatment regimens For many smokers the standard dosing is sufficient In others different (higher) doses may be needed It is also possible that using NRT only from the quit day is not an optimal treatment strategy Benowitz et al (1998) J Pharmacology & Experimental Therapeutics, 287: 958-962

11. Individualised treatment There has traditionally been a one size fits all approach with dosing of NRT This is at odds with the disease where people exhibit varying degrees of tobacco dependence There is very little individualisation of treatment for tobacco dependence as there is in the management of other chronic diseases.

12. Optimizing treatment Encouraging compliance with use Higher NRT dosing Aiding reduction prior to quitting Continuing NRT after lapse Combining NRT with other medicines

13. A quick refresher on NRT

14. Patches 16hr and 24hr The Cochrane review has failed to detect a difference in efficacy 1 Sleep disturbance is a recognized symptom of nicotine withdrawal 2 16hr patch does not add to the insomnia that occurs as a result of nicotine withdrawal 3 Different strengths Medium and low strengths are for lighter smokers and weaning 4 Skin redness and itchiness is common Place a new patch on a different site each day 4 1.Stead LF, Perera R, Bullen C, Mant D, Lancaster T. Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev 2008(1) 2.Nicotine addiction in Britain: A report of the Tobacco Advisory Group of the Royal College of Physicians. London: Royal college of physicians, 2001. 3.Tonnesen P et al. Eur Resp J 1999; 13:238-246. 4.Invisipatch SPC

15. Oral products Gum, microtabs, inhalator, lozenges Different strengths of gum and lozenges Higher dose product for more dependent smokers Nicotine from the inhalator is absorbed from the buccal mucosa (not inhaled) Best to use these as and when cravings occur Prepare smokers for the fact that they dont taste very pleasant (at least initially)

16. Nasal spray Fast acting Good for highly dependent smokers When first used format can be rejected due to usage experience Instruct how to use correctly and reassure people that they will get to like it

17. Nicotine Nasal Spray Sutherland et al (1992) Lancet 340: 324-329 RR=2.61 (95%CI: 1.52-4.47)

18. Fast Acting NRT Nicotine replacement treatments (NRT) deliver nicotine slowly when compared to nicotine delivered via smoking a cigarette Faster delivery systems may improve withdrawal relief and abstinence rates

19. Fast acting formats: Nicotine mouth spray In an effort to create an effective NRT product to be taken at the moment craving emerges, a nicotine spray for use in the mouth has been developed. This spray allows a rapid transmucosal uptake of nicotine.

20. Rapid absorption of nicotine Kraiczi H, et al. Single-Dose Pharmacokinetics of nicotine with a novel mouth spray form of nicoitine replacement therapy. Poster POS3-50 presented at SRNT, Feb 16-19 th, 2011, Toronto, Canada.

21. Short and long term efficacy with nicotine mouth spray 1.Tonnesen P, et al. efficacy and safety of a novel nicotine mouth spray in smoking cessation. A randomised, placebo controlled, double blind, multi-centre study with a 52 week follow-up. Poster POS2-38 presented at SRNT, Feb 16-19 th, 2011, Toronto, Canada. 2. Data on file - 001

22. Safety and tolerability Most adverse events were mild to moderate 2 and similar in type to other oral NRTs 1 The majority of hiccups were reported as mild 1 No serious drug related adverse events reported 2 1 Data on file - 003 2 Tonnesen P, et al. efficacy and safety of a novel nicotine mouth spray in smoking cessation. A randomised, placebo controlled, double blind, multi-centre study with a 52 week follow-up. Poster POS2-38 presented at SRNT, Feb 16-19 th, 2011, Toronto, Canada.

23. Nicotine mouth spray acts fast on cravings 1. Hansson A et al. Craving relief with a novel nicotine mouthspray form of nicotine replacement therapy. Poster POS3-45 presented at SRNT, Feb 16-19 th 2011, Toronto, Canada.

24. Using enough NRT 1030 smokers who quit for at least 2 weeks in a trial of nicotine lozenges 28-day continuous abstinence at 6-week follow- up was positively correlated with increased NRT use Each one additional active lozenge used increased the odds of quitting by 10% (P<0.001) Shiffman. Addiction 2007, 102(5) 809-14

25. Longer-term use of NRT Some people may require NRT for longer than 12 weeks < 10% of patients on oral NRT and <15% on nasal spray use NRT for a 1 year The chances of long-term use are related to speed of nicotine absorption Long-term users are mostly smokers whose chance of success would be otherwise small Hajek P, McRobbie H, Gillison F (2007) Preventive Medicine, 44, 230-234

26. Choosing an NRT product Explanation of the different products is usually adequate However one study found that NRT preferences based on explanations changed after sampling 1 NRT sampling may lead to better choice and treatment compliance Schneider at al. NTR (2008), 10, 179-186

27. How do you decide on the dose? Cigarette consumption is not always a good guide* Most people can start on full strength patches * note: cigarette consumption is used to determine the strength of patch and gum

28. Higher nicotine dosing There is data to show that a higher degree of nicotine replacement with patch is associated with an increase in long term success in smoking cessation 1 More highly dependent smokers are more likely to quit when they use high dose gum (4mg) versus lower dose (2mg) gum Similar results are seen with the lozenge 3 1.Tønnesen P, et al. Higher dosage nicotine patches increase one-year smoking cessation rates: results from the European CEASE trial. Eur Respir J 1999; 13: 238-246 2.Stead LF, Perera R, Bullen C, Mant D, Lancaster T. Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev 2008(1) 3.Shiffman S, Dresler CM, Hajek P, Gilburt SJ, Targett DA, Strahs KR. Efficacy of a nicotine lozenge for smoking cessation. Arch Intern Med 2002;162(11):1267-76

29. Combining NRT products 6 trials comparing 2 types of NRT with single NRT, and 1 trial comparing 2 types of NRT to no NRT show the advantage of combination use Mechanism of Action: Higher dose of nicotine Better control of urges to smoke Patch - provides background craving relief Intermittent dosing product - for control of breakthrough craving + 1.Stead LF, Perera R, Bullen C, Mant D, Lancaster T. Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev 2008(1)

30. Blondal et al. BMJ 1999 n=237 * * * * Significant difference between groups Patch and nasal spray (119)(118) Not significant

31. Combination Safety Profile Combination Therapy is well tolerated in large-scale studies & has a comparable safety profile to monotherapy 1-3 Smokers are adept at titrating their nicotine intake to get the nicotine they need 4 Consider offering a combination of nicotine patches and another form of NRT... To people who show a high level of dependence of nicotine or who have found single forms of NRT inadequate in the past NICE, PH10 Guidance 1.Kornitzer et al. Preventative Medicine 1995; 24: 41-47 2.Bohadana A et al. Arch Intern Med 2000; 160:3128-3134 3.Puska et al. Tobacco control1995; 4: 231-235 4.Benowitz NL et al. N Engl J Med 1983; 309:139-142

32. Cut down then stop Nicotine gum, inhalator, microtab and mouth spray are licensed for use prior to stopping smoking For smokers not intending to stop immediately The goal is to reduce cigs-per-day by 50% over up to 6-months Follow this by stopping smoking

33. The logic of cut down then stop 70% of smokers intend to stop smoking at some time, but only 12% are ready to stop in the next month NRT aids them to cut down smoking and facilitates quitting Cutting down without NRT may lead to compensatory smoking Cutting down with NRT can have some positive effects Moore D, Aveyard P, Connock M, Wang D, Fry-Smith A, Barton P. Effectiveness and safety of nicotine replacement therapy assisted reduction to stop smoking: systematic review and meta-analysis. Bmj 2009;338:b1024

34. NRT assisted reduction in people who dont want to quit abruptly Systematic review of seven RCTs involving 2767 smokers not willing or able to stop abruptly 1 Conducted a study into smoking reduction with smoking cessation as a secondary outcome 1 NRT-assisted reduction results in increased quitting and reduction compared to placebo 1 OutcomesWeighted Event RatesRBI (95% CI)NNT (CI) Smoking abstinence for 6 months 6.8% vs. 3.3%106% (34-215)29 (15-90) Sustained smoking reduction, week 6 to study end 6.1% vs. 1.6%284% (132-535)23 (12-48) 1.Moore D, Aveyard P, Connock M, Wang D, Fry-Smith A, Barton P. Effectiveness and safety of nicotine replacement therapy assisted reduction to stop smoking: systematic review and meta-analysis. Bmj 2009;338:b1024 2.Therapeutics Review: nicotine replacement therapy as assisted reduction-to-stop reduces smoking and sustains abstinence in smokers. EBM Oct 2009 Vol 14 No. 5 Adapted from EBM, Oct 2009 2

35. NRT as a safer alternative to smoking New measures to support those smokers who are unwilling or unable to quit tobacco A Smokefree Future. A Comprehensive Tobacco Control Strategy for England. Department of Health. February 2010.

36. Safer Option to Smoking Strategy Indications for use now include: To aid smokers wishing to quit To aid smokers to reduce the amount of cigarettes they smoke prior to quitting To assist smokers who are unwilling or unable to quit smoking by replacing some cigarettes with NRT licensed for a safer option to smoking Nicorette® Inhalator SPC

37. Public perception of NRT US national survey, 3,203 current and former smokers 66% agreed that NRT is just as harmful as cigarettes or were unsure if true Those who had safety concerns were less likely to use NRT and if used, used less and for a shorter time Public education is needed Shiffman et al. 2008, Addiction 103, 1371-1378

38. Conclusions NRT is effective in helping people to quit smoking NRT is well tolerated and has a good safety profile Different options for using NRT to aid smoking cessation are available Paying attention to the individual needs of smokers may be a way to improve quit rates

39. Thank You

40. Prescribing Information