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Expert Commentary on Combination Therapy with Nicotine Replacement Therapy (NRT)

OMD - Expert commentary on Combination Therapy with Nicotine Replacement Therapy (NRT) - News


Community-based pharmacists are ideally placed to assist customers who smoke. They are a respected source of health information and have a high rate of contact with customers over an extended period of time. Pharmacists have the product knowledge and counselling skills to help smokers quit, and research has shown that their intervention can significantly increase quit rates1.

Australian smoking cessation guidelines advise that all health professionals, including pharmacists, should systematically identify smokers, assess their smoking status and offer them advice and cessation treatment2. All smokers should be advised to quit in a clear, personalised and non-confrontational way at every opportunity2.

Best practice intervention consists of a combination of counselling and pharmacotherapy2. Professional counselling includes providing information, building motivation, teaching the smoker practical quitting skills, and providing support and follow-up visits2.

Pharmacotherapy eases the physical discomfort of nicotine withdrawal, reduces cravings and is recommended for all nicotine-dependent smokers (those who smoke their first cigarette within 30 minutes of waking) who are ready to quit2.

75% of Australian smokers want to quit and 40% try at least once every year3. However, nicotine dependence is a powerful substance use disorder and less than one in twenty unassisted quit attempts are successful4. On the other hand, with professional support and best practice treatment, quit rates of 20-30% can be achieved5.


Smoking is the single greatest preventable cause of death and illness in adult Australians6. Smokers live on average 10 years less than non-smokers and up to 2 out of every 3 continuing smokers will be killed prematurely by their habit7. Tobacco affects almost every part of the body, with the main causes of death being lung cancer, COPD and acute myocardial infarction6.

The good news is that the risk of death and disease due to smoking starts to decline immediately after quitting. The increased risk of a heart attack halves after about 3-4 years and continues to fall over time8. The risk of lung cancer falls by about 50% after 10 years9. Ex-smokers typically report having more energy, sleeping better and feeling more relaxed.

Smokers should be advised to stop smoking at the earliest opportunity. Smokers lose 3 months of life expectancy for every year they continue to smoke after the age of 35 years10. Quitting at any age results in years of life gained — it is never too late to quit.


Combination NRT — combining the nicotine patch with an oral form of NRT, such as gum or lozenge — increases quit rates by 34–54% 11, 12 compared to using a single form of NRT. Combination NRT triples quit rates compared to placebo and is as effective as varenicline in helping smokers to quit13.

Smokers attempting to quit experience a combination of moderate, steady cravings for cigarettes, as well as acute intermittent craving episodes14. The combination of slower and faster nicotine delivery products provides protection against both types of cigarette cravings. The nicotine patch relieves the background cravings due to low nicotine levels after quitting. Oral forms, such as the nicotine gum, lozenge and mouth spray give quick, flexible relief for breakthrough cravings as a result of smoking triggers, such as alcohol or the smell of smoke14.

Combination NRT also provides higher doses of nicotine than monotherapy and provides better relief of withdrawal symptoms15. Combination NRT is well tolerated and has a good safety profile11. Adverse effects and adherence are similar to monotherapy11.

Many smoking cessation experts now recommend combination NRT for all nicotine-dependent smokers using nicotine replacement, rather than monotherapy2.


I advise most patients to start with a nicotine patch. The Australian guidelines recommend using a full strength nicotine patch (25mg/16 hours or 21mg/24 hours) if the patient smokes 10 or more cigarettes per day and is over 45kg in weight2. The patch maintains a fairly constant level of nicotine to reduce nicotine withdrawal symptoms and urges to smoke.

For most patients, I also recommend a quick-acting oral nicotine product to be used for breakthrough cravings as needed. Fast-acting products, such as the nicotine mouth spray or oral strips, can be used when cravings occur, and start to relieve urges within 60 seconds16, 17.

Nicotine gum, lozenges and the inhalator take longer to work, but can provide effective relief if taken in advance of cravings or on a regular basis, such as hourly.

1. Saba M, Diep J, Saini B, Dhippayom T. Meta-analysis of the effectiveness of smoking cessation interventions in community pharmacy. J Clin Pharm Ther. 2014; 39(3): 240-247.
2. Zwar N, Richmond R, Borland R, et al. Supporting smoking cessation: a guide for health professionals. Melbourne: The Royal Australian College of General Practitioners. 2014. Available at Accessed 28 May 2015.
3. Cooper J, Borland R, Yong HH. Australian smokers increasingly use help to quit, but number of attempts remains stable: findings from the International Tobacco Control Study 2002-09. Aust N Z J Public Health. 2011; 35(4): 368-376.
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5. Fiore M, Jaen C, Baker T, et al. Treating tobacco use and dependence: 2008 update. Rockville MD: USDHHS, U.S. Public Health Service. 2008.
6. Begg S, Vos T, Barker B, et al. The burden of disease and injury in Australia 2003. PHE 82. Canberra: AIHW. 2007.
7. Banks E, Joshy G, Weber MF, et al. Tobacco smoking and all-cause mortality in a large Australian cohort study: findings from a mature epidemic with current low smoking prevalence. BMC Med. 2015; 13: 38.
8. Teo KK, Ounpuu S, Hawken S, et al. Tobacco use and risk of myocardial infarction in 52 countries in the INTERHEART study: a case-control study. Lancet. 2006; 368(9536): 647-658.
9. Fry JS, Lee PN, Forey BA, Coombs KJ. How rapidly does the excess risk of lung cancer decline following quitting smoking? A quantitative review using the negative exponential model. Regul Toxicol Pharmacol. 2013; 67(1): 13-26.
10. Jha P, Ramasundarahettige C, Landsman V, et al. 21st-century hazards of smoking and benefits of cessation in the United States. N Engl J Med. 2013; 368(4): 341-350.
11. Stead LF, Perera R, Bullen C, et al. Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev. 2012; 11: CD000146.
12. Shah SD, Wilken LA, Winkler SR, Lin SJ. Systematic review and meta-analysis of combination therapy for smoking cessation. J Am Pharm Assoc (2003). 2008; 48(5): 659-665.
13. Cahill K, Stevens S, Perera R, Lancaster T. Pharmacological interventions for smoking cessation: an overview and network meta-analysis. Cochrane Database Syst Rev. 2013; 5: CD009329.
14. Shiffman S, Hughes JR, Di Marino ME, Sweeney CT. Patterns of over-the-counter nicotine gum use: persistent use and concurrent smoking. Addiction. 2003; 98(12): 1747-1753.
15. Carpenter MJ, Jardin BF, Burris JL, et al. Clinical strategies to enhance the efficacy of nicotine replacement therapy for smoking cessation: a review of the literature. Drugs. 2013; 73(5): 407-426.
16. Hansson A, Hajek P, Perfekt R, Kraiczi H. Effects of nicotine mouth spray on urges to smoke, a randomised clinical trial. BMJ Open. 2012; 2(5).
17. Du D, Nides M, Borders J, et al. Comparison of nicotine oral soluble film and nicotine lozenge on efficacy in relief of smoking cue-provoked acute craving after a single dose of treatment in low dependence smokers. Psychopharmacology (Berl). 2014; 231(22): 4383-4391.

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