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Nicotine replacement therapy

Nicotine replacement therapy
Nicoderm.JPG
A nicotine patch is applied to the left arm
Clinical data
Trade namesNicoderm, Commit, Nicorette, Nicotrol, others[1]
AHFS/Drugs.comMonograph
Pregnancy
category
  • US: D (Evidence of risk) [1]
Identifiers
CAS Number
PubChem CID
ChemSpider

Nicotine replacement therapy (NRT) is a medically-approved way to take nicotine by means other than tobacco.[2] It is used to help with quitting smoking or stopping chewing tobacco.[1][3] It increases the chance of quitting smoking by about 55%.[4] Often it is used along with other behavioral techniques.[1] NRT has also been used to treat ulcerative colitis.[1] Types of NRT include the adhesive patch, chewing gum, lozenges, nose spray, and inhaler.[1] The use of multiple types of NRT at a time may increase effectiveness.[5][6]

Common side effects depend on the formulation of nicotine.[1] Common side effects with the gum include nausea, hiccups, and irritation of the mouth.[1] Common side effects with the patch include skin irritation and a dry mouth while the inhaler commonly results in a cough, runny nose, or headaches.[1] Serious risks include nicotine poisoning and continued addiction.[1] They do not appear to increase the risk of heart attacks.[4] There are possible harms to the baby if used during pregnancy.[1][7] Nicotine replacement therapy works by reducing cravings caused by nicotine addiction.[1][8]

They were first approved for use in 1984, in the United States.[1] Nicotine replacement products are on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[9] They are available as generic medication.[1] In the United States a month of patches or gum is between US$100 and US$200 while the other forms are more expensive.[10]

Medical uses

Nicotine pastilles
An oral nicotine spray

Nicotine replacement therapy, in the form of gum, patches, nasal spray, inhaler and lozenges all improve the ability of people trying to quit tobacco products.[4] Studies have shown that nicotine replacement therapy is as effective as medications, such as bupropion, in helping people quit smoking for at least 6 months.[11] Studies have also shown that all forms of nicotine replacement therapy, including nicotine gum, patches, nasal spray, inhalers, and lozenges, have similar success rates in terms of helping people stop smoking. However, the likelihood that someone will stick to a certain treatment varies, with compliance being the highest with nicotine patches, followed by nicotine gum, inhalers, and nasal sprays.[12] Using a few different nicotine replacement methods in combination may improve success rates in stopping tobacco use.[11][13] Additionally, using nicotine replacement with counseling has been proven to improve tobacco abstinence rates.[14][15] These other strategies include: creating a plan to quit and utilizing quit programs, a quit phone line, or app that provides tips and inspiration to help quit.[13]

Using nicotine replacement therapy to quit smoking should be considered for people who are severely dependent on nicotine.[16] People who are severely dependent include those who smoke: more than 1 pack per day, within 5 minutes of awakening, while ill, when they wake up in the middle of the night, to ease withdrawal signs and symptoms.[16]

Nicotine replacement products are most beneficial for heavy smokers who smoke more than 15 cigarettes per day. There are not enough studies to show whether NRT helps those who smoke fewer than 10 cigarettes per day.[15]

Effectiveness

Evaluation of NRT in real-world studies produces more modest outcomes than efficacy studies conducted by the industry-funded trials. The National Health Service (NHS) in England has a smoking cessation service based on pharmacotherapy in combination with counseling support. An Action on Smoking and Health (UK) (ASH) report claims that the average cost per life year gained for every smoker successfully treated by these services is less than £1,000 (below the NICE guidelines of £20,000 per QALY (quality-adjusted life year). However, the investment in NHS stop smoking services is relatively low. A comparison with treatment costs for illicit drug users shows that £585 million is committed for 350,000 problem drug users compared to £56 million for 9 million users of tobacco. This is £6.20 for each smoker, compared to £1,670 per illegal drug user.[17]

The claims for high efficacy and cost-effectiveness of NRT have not been substantiated in real-world effectiveness studies.[18][19][20] Pierce and Gilpin (2002) stated their conclusion as follows: “Since becoming available over the counter, NRT appears no longer effective in increasing long-term successful cessation” (p. 1260).[20] Efficacy studies, which are conducted using randomized controlled trials, do not transfer very well to real-world effectiveness. Bauld, Bell, McCullough, Richardson and Greaves (2009) reviewed 20 studies on the effectiveness of intensive NHS treatments for smoking cessation published between 1990 and 2007.[21] Quit rates showed a dramatic decrease between 4-weeks and one year. A quit rate of 53% at four weeks fell to only 15% at 1 year. Younger smokers, females, pregnant smokers and more deprived smokers had lower quit rates than other groups.

Pregnancy

Nicotine is not safe to use in any amount during pregnancy.[22] Nicotine crosses the placenta and is found in the breast milk of mothers who smoke as well as mothers who inhale passive smoke.[23] There are possible harms to the baby if NRT is used during pregnancy.[1][7] Thus, pregnant women and those who are breastfeeding should also consult a physician before initiating NRT.[24] The gum, lozenge, and nasal spray are pregnancy category C. The transdermal patch is pregnancy category D. The transdermal patch is considered less safe for the fetus because it delivers continuous nicotine exposure, as opposed to the gum or lozenge, which delivers intermittent and thus lower nicotine exposure.[25][26]

Strong evidence suggests that nicotine cannot be regarded as a safe substance of cigarette use.[27] Nicotine itself could be at least partly responsible for many of the adverse after birth health results related to cigarette use while the mother was pregnant.[27] There is evidence that nicotine negatively affects fetal brain development and pregnancy outcomes.[28] There is also risk of stillbirth and pre-term birth.[29] Nicotine use will probably harm fetal neurological development.[30] Risks to the child later in life from nicotine exposure during pregnancy include type 2 diabetes, obesity, hypertension, neurobehavioral defects, respiratory dysfunction, and infertility.[31] Nicotine exposure during pregnancy can result in attention deficit hyperactivity disorder (ADHD) and learning disabilities in the child.[citation needed] It also puts the child at increased risk for nicotine addiction in the future.[25]

Pregnant women should consider behavioral therapy before NRT is considered.[1]

Youth

In people under the age of 18, a physician is often consulted before starting NRT.[24] The evidence suggests that exposure to nicotine between the ages of 10 and 25 years causes lasting harm to the brain and cognitive ability.[32] Most tobacco users are under-eighteens when they start, and almost no-one over the age of 25 starts using.[33]

Cardiovascular conditions

While there is no evidence that NRT can increase the risk of heart attacks,[4] individuals with pre-existing cardiovascular conditions or recent heart attacks should consult a physician before initiating NRT.[24]

Smoking is known to cause cardiovascular disease such as coronary heart disease, hypertension, heart attack, stroke, and peripheral artery disease. Cigarette smoking is the cause of 20% of all cardiovascular deaths in the United States, which is the leading cause of mortality.[34]

Other conditions

Nicotine replacement therapies should be used cautiously in individuals with the following condition: diabetes (insulin-dependent), gastrointestinal disease (esophagitis, active gastric or peptic ulcer disease), liver problems, hyperthyroidism, pheochromocytoma, and renal impairment.[35]

Side effects

Possible side effects of nicotine.[36]

Some side effects are caused by the nicotine, and are common to NRT products.[37][31] Other common side effects depend on the formulation of nicotine.[1] Common side effects with the gum include nausea, hiccups, and irritation of the mouth.[1] Common side effects with the patch include skin irritation and a dry mouth while the inhaler commonly results in a cough, runny nose, or headaches.[1] The nicotine patch can also cause strange dreams if worn while asleep.[15] Nasal sprays commonly cause nasal irritation, watering eyes, and coughing.[37]

Serious risks include nicotine poisoning, which includes symptoms like visual disturbances, hyper-salivation, nausea, and vomiting; and continued addiction to nicotine products.[1] Other symptoms of nicotine overdose include headache, pale skin and mouth, belly pain, weakness, diarrhea, tremors or seizures, agitation, confusion, restlessness, high or low blood pressure, fast or irregular heartbeat, fast breathing, and cold sweats.[16]

Limited evidence exists regarding long-term NRT use, and concerns exist that long-term NRT use could raise cancer risk, due in part to the generation of carcinogens.[38]

Mechanism of action

Nicotine replacement therapy works by reducing cravings due to nicotine addiction.[1][8] Smoking cigarettes releases high doses of nicotine to the brain in a matter of seconds as opposed to low doses released over a period of minutes to hours by the various forms of nicotine replacement therapy.[39] Nicotine from NRT does not reach as high a concentration in the blood as does nicotine from smoke inhalation due to different absorption methods. NRT relies on systemic venous absorption, whereas nicotine from cigarettes reaches the arterial system.[39] Nicotine replacement products vary in the time it takes for the nicotine to enter the body and the total time nicotine stays in the body.[14] The more quickly a dose of nicotine is delivered and absorbed, the higher the addiction risk.[40] It is possible to become dependent on some NRTs.[41]

Nicotine patches are applied to the skin and continuously administer a stable dose of nicotine slowly over 16–24 hours.[14][26] Nicotine gum, nicotine sprays, nicotine toothpicks, nicotine sublingual tablets, and nicotine lozenges administer nicotine orally with quicker nicotine uptake into the body but lasting a shorter amount of time.[42] Nicotine inhalers are metered-dose inhalers[citation needed] that administer nicotine through the lungs and mucous membranes of the throat quickly but lasting a short amount of time. For example, blood nicotine levels are the highest 5–10 minutes after using the nicotine nasal spray, 20 minutes after using a nicotine inhaler or chewing nicotine gum, and 2–4 hours after using a nicotine patch.[14][43]

Society and culture

NRT products were first approved for use in the United States in 1984.[1] Nicotine replacement products are on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[9] They are available as generic medication.[1] In the United States a month of patches or gum is between US$100 and US$200 while the other forms are more expensive.[10]

Formulations

Availability in the United States [13]
NRT Types Availability How it works[44]
Patch Over-the-Counter Steadily administers a low dose of nicotine through a patch placed on the skin
Lozenge Over-the-Counter Slowly dissolves to releases nicotine through a hard candy
Gum Over-the-Counter Chewing the gum releases nicotine
Inhaler Prescription Inhaling through the mouthpiece administers nicotine
Nasal Spray Prescription Spraying a pump bottle into nose administers nicotine

In 2015, the United States Public Health Service listed seven agents for the stopping of tobacco, which included 5 nicotine replacement treatments (nicotine patches, gum, lozenges, inhalers, and nasal sprays) and 2 oral medications (bupropion and varenicline). Other NRT options are available, including nicotine mouth sprays and sublingual tablets.[45]

Trade names include Nicotex, Nicorette, Nicoderm, Nicogum, Nicotinell, Thrive and Commit Lozenge.

Dosing

The dose of nicotine replacement therapy products is generally based on if the user is considered a heavy, average, or light smoker.[16]

General guideline[16]
Type of User Dose of NRT Amount of cigarettes Amount of smokeless tobacco
Light Lower <10 cigarettes daily <2 snuff cans or tobacco pouches weekly
Average Moderate 10-20 cigarettes daily 2-3 snuff cans or tobacco pouches weekly
Heavy Higher 1 or more pack of cigarettes daily >3 snuff cans or tobacco pouches weekly

A cigarette delivers an average of 1 mg to 3 mg of the nicotine contained in it. NRT products typically aim to parallel this, but the amount of nicotine absorbed by the user is less than the original dose. Nicotine nasal sprays are formulated in doses of lowest strength, they are made in strengths of 0.5 mg and 1 mg. Nicotine lozenges deliver doses as low as 1 mg up to 4 mg.

Nicotine gum is available in doses of 2 mg and 4 mg. Using 4 mg nicotine gum versus 2 mg gum increases the likelihood of successful smoking cessation.[46]

Nicotine inhalers come in 10 mg and 15 mg cartridge strengths and typically deliver around 4 mg in one dose.[47]

Transdermal patches deliver between 5 mg and 52.5 mg of nicotine which result in plasma levels similar to that of heavy smokers. Combining nicotine patch treatment with a faster nicotine-delivery means, like nicotine gum or spray, improves the likelihood of treatment success.[46][4]

Economics

In the United States, a month of patches or gum is between US$100 and US$200 as of 2015 while the other forms are more expensive;[10] in the UK lozenges are the cheapest. In the United States, a month of patches is about US$170.[1]

Average wholesale cost[48]
Formulation Brand name Generic Strength Package size Average wholesale price (USD)
Patch Nicoderm CQ Yes 7 mg/24 hours 14 patches $23.99
14 mg/24 hours
21 mg/24 hours
Lozenge Nicorette Yes 2 mg 20 lozenges $10.92
4 mg
Gum Nicorette Yes 2 20 lozenges $8.99
4
Intranasal Nicotrol NS No 10 mg/1 mL 10 mL $524.87
Inhaler Nicotrol inhaler No 4 mg/ 1 actuation 168 actuations $499.87

Not approved as NRTs

Snus and nasal snuff also allow for nicotine administration outside of tobacco smoking.[49]

Nicotine infused toothpicks are another product that has been available in the United States since at least 2013. They can have a total nicotine delivery that is comparable to that of nicotine gum.[42] Nicotine toothpicks generally are infused with food-grade flavorings and 3 mg of nicotine which is similar to that of other oral products and what some cigarettes deliver.[50][51] In spite of these similarities, as of 2018 they have been a subject of controversy. News outlets have expressed the concern that these products have high appeal to minors wanting to experiment with nicotine due to the multitude of sweet flavors, ease of use, speed of use, and discrete nature.[52][53][54]

In 2015, NRT sales fell for the first time since 2008 while sales for e-cigarettes continued to increase at a substantial rate. This had led to speculation that UK smokers are trying to quit with e-cigarettes rather than NRT methods.[55]

E-cigarettes are often, although not always, designed to look and feel like cigarettes. They have been marketed as less harmful alternatives to cigarettes,[56] but very few are as yet approved as NRTs in any jurisdiction. Some electronic cigarettes have coarsely adjustable nicotine levels. Some healthcare groups have hesitated to recommend e-cigarettes for quitting smoking, because of limited evidence of effectiveness and safety.[57]

The U.S. Food and Drug Administration (FDA) has a list of additional tobacco products they are seeking to regulate, including electronic cigarettes.[58] Most approved NRT products have been approved for over 20 years,[59] however the FDA has also approved nicotine inhalers as a form of NRT.[60][61]

See also

References

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External links