Download Summary of current labelling on NRT products

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]
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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.
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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
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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
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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
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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
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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
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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.
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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