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All Wales Guide:
Pharmacotherapy for
Smoking Cessation

July 2014



This guidance has been prepared by Rosemary Allgeier, Principal Pharmacist in Public Health, Public Health Wales, with support from the All Wales Prescribing Advisory Group (AWPAG) and the All Wales Therapeutics and Toxicology Centre (AWTTC), and has subsequently been endorsed by the All Wales Medicines Strategy Group (AWMSG). Please direct any queries to AWTTC: All Wales Therapeutics and Toxicology Centre University Hospital Llandough Penlan Road Llandough Vale of Glamorgan CF64 2XX 029 2071 6900 This document should be cited as: All Wales Medicines Strategy Group. All Wales Guide: Pharmacotherapy for Smoking Cessation. July 2014. All Wales Guide: Pharmacotherapy for Smoking Cessation
CONTENTS
Page 1 of 16
All Wales Medicines Strategy Group
1.0 INTRODUCTION

Both behavioural support and pharmacotherapies are effective in helping people to stop
smoking. Combining both treatment approaches is recommended where possible1.
Pharmacotherapy should normally be prescribed/supplied as part of an abstinent-
contingent treatment, in which the smoker makes a commitment to stop smoking on or
before a particular date (target quit date)2.
Nicotine replacement therapy (NRT), varenicline and bupropion are the three forms of
pharmacotherapy that are licensed for use in the UK to assist with smoking cessation. A
Cochrane network meta-analysis concluded that each of these improves the chances of
quitting. Combination NRT (the use of an immediate-release formulation plus patches) is
as effective as varenicline, and more effective than single types of NRT3.
Clinical suitability and patient preference are important in guiding the choice of
pharmacotherapy4. NRT, bupropion or varenicline should not be prescribed/supplied
together in any combination.
The ultimate responsibility for the prescribing of pharmacotherapy lies with the prescriber
who signs the prescription. Where patients are supplied smoking cessation
pharmacotherapy as part of a community pharmacy enhanced stop smoking service, the
ultimate responsibility for supply lies with the community pharmacist making that supply.
The supply of NRT, varenicline or bupropion should be sufficient to last no more than two
weeks after the target quit date2. Subsequent supplies should be given only to people who
have demonstrated, on re-assessment (e.g. by carbon monoxide testing), that their quit
attempt is continuing2.
Phased prescribing/supply enables ongoing review of the suitability of the formulation and
dosage in order to more closely target the individual's needs during their quit attempts and
reduce the potential for wastage.
Locally commissioned NHS community pharmacy stop smoking services supply
pharmacotherapy at weekly intervals during the first few weeks of a quit attempt followed
by two-weekly intervals thereafter. This is in accordance with local arrangements with their
health board.
The Stop Smoking Wales communications to healthcare practitioners have been revised
so that they are consistent with the supply intervals for pharmacotherapy recommended in
this guide. Stop Smoking Wales advisors do not assess patients' clinical suitability for
pharmacotherapy.
Tobacco smoking increases the metabolism of some medicines by stimulating the hepatic
enzyme CYP1A2. When smoking is discontinued, the dose of these medicines, in
particular theophylline, cinacalcet, ropinirole, and some antipsychotics (including
clozapine, olanzapine, chlorpromazine and haloperidol), may need to be reduced5.
Regular monitoring for adverse effects is advised.
A Summary of cautions in the use of pharmacotherapy in special populations is
provided in Appendix I.
A Summary dosage and supply guide for smoking cessation pharmacotherapy is
provided in Appendix II.
Healthcare practitioners should refer to the latest edition of the and
manufacturers'
(SPCs) for further guidance and
prescribing information.

Page 2 of 16
All Wales Guide: Pharmacotherapy for Smoking Cessation
1.1 Assessing nicotine dependence
The Fagerström test is widely used to assess nicotine dependence. How soon a person
smokes after waking seems to be the most important indicator of dependence6. Smoking
within 30 minutes of waking is a reliable indicator of nicotine dependence. Smoking within
5 minutes of waking indicates a higher level of dependence.
The number of cigarettes smoked per day is less predictive. Dependence is more likely if
more than 10 cigarettes are smoked per day.
The level of nicotine dependence is a predictor of withdrawal symptoms and the intensity
of treatment required. Cravings and withdrawal symptoms experienced in previous quit
attempts can also be a useful guide.
2.0 NICOTINE REPLACEMENT THERAPY

In the context of this guide, the term NRT refers to its use in place of cigarettes after
abrupt cessation of smoking.
The aim of using NRT is to reduce withdrawal symptoms by providing some of the nicotine
that would be obtained from cigarettes, without providing the harmful chemicals present in
tobacco smoke. NRT delivers nicotine to the body but at a lower dose and slower rate
compared with smoking.
2.1 Choice of NRT formulation
There are eight different types of NRT formulations available (patches, gum, lozenges,
sublingual tablets, inhalator, oral spray, oral films, and nasal spray) and a variety of
strengths. This offers a variety of approaches to best match individual smokers' needs
and preferences.
Patches provide slower, sustained-release delivery of nicotine, while oral and nasal
formulations provide faster release of nicotine as intermittent doses.
All formulations of NRT have similar effectiveness. Therefore, the choice of NRT depends
largely on:
• Patient preference • Previous patient experience of the type of formulation(s), if any, tried before • Contraindications, cautions and the potential for adverse effects
Patients with a high level of nicotine dependence, or those who have failed with NRT
previously, may benefit from using combination NRT through use of an immediate-release
preparation and patches to achieve abstinence.
Table 1. Some advantages and disadvantages of different NRT formulations

Formulation
Discreet and easy to use. Long-acting. Doesn't mimic the highs and lows associated with smoking. Allows good control of nicotine dose. Unsuitable for people who use dentures. Discreet, flexible, good dose control. Sublingual tablet
Discreet, flexible, good dose control. Inhalator
May be useful for people who miss the hand-to-mouth movements of smoking. Oral spray
Rapid delivery of nicotine. Oral film
Rapid delivery of nicotine, discreet. Nasal spray
Rapid delivery of nicotine similar to smoking cigarettes. Page 3 of 16
All Wales Medicines Strategy Group
2.2 Clinical suitability
Most of the health warnings associated with NRT also apply to continued smoking, but the
risks of continued tobacco smoking outweigh any risks of using NRT preparations in
virtually all situations5.
NRT can be considered for all people attempting to quit smoking, including pregnant and
breast-feeding women, and young people aged 12 to 18 years old2. All forms of NRT can
be used by patients with stable cardiovascular disease, but should be used with caution in
those in hospital for acute cardiovascular events.
The use of NRT in pregnancy is considered preferable to the continuation of smoking, but
should be used only if smoking cessation without NRT fails5,7. Intermittent therapy is
preferable to patches, but avoid liquorice-flavoured products. Patches may be appropriate
if pregnancy-related nausea and vomiting is a problem. If patches are used they should be
removed at night before going to bed5,7. Intermittent therapy is preferable for breast-
feeding women5.
Specific cautions for individual preparations are usually related to the local effect of
nicotine. Examples are provided in Table 2.
2.3 Adverse effects
Most adverse effects experienced with NRT are not serious and are similar to the effects
experienced from nicotine obtained by smoking8.
Minor adverse effects are common with NRT use, particularly in patients using high-
strength formulations. They usually improve with time but treatment may need to be
reviewed if they continue or become troublesome.
However, patients may confuse the side effects of NRT with nicotine withdrawal
symptoms. Common symptoms of nicotine withdrawal include malaise, headache,
dizziness, sleep disturbance, coughing, influenza-like symptoms, depression, irritability,
increased appetite, weight gain, restlessness, anxiety, drowsiness, mouth ulcers,
decreased heart rate, and impaired concentration.
Common adverse effects of NRT include headache, dizziness, coughing, and
gastrointestinal disturbances. Palpitations may occur and, rarely, allergic reactions
(including angioedema) and (very rarely) reversible atrial fibrillation.
Mild local reactions are common on initiation of NRT because of the irritant effect of
nicotine. Mouth ulcers have also been reported. Examples of cautions and adverse effects
which may be related to formulation type are provided in Table 2.


Page 4 of 16
All Wales Guide: Pharmacotherapy for Smoking Cessation
Table 2. Examples of cautions and adverse effects which may be related to formulation type

Cautions
Adverse effects
formulation
Minor skin irritation at the application site(s). If the skin reaction becomes more severe or more widespread, treatment with patches should be discontinued. Nicotine patches should not be placed on broken skin and should be used with Dry mouth, sleep disturbances including abnormal caution in patients with skin disorders. dreams. Chest pain, sweating, myalgia and arthralgia have been reported. Caution in use with oesophagitis, oral or pharyngeal inflammation, gastritis, or gastric/peptic ulcers. Gastrointestinal disturbances are common and Oral NRT in
Due to the potential for reduced may be caused by swallowed nicotine; nausea, absorption of nicotine through buccal vomiting, dyspepsia, and hiccupping occur most mucosa, patients should generally avoid: • Acidic beverages for 15 minutes before • Eating or drinking while using oral NRT The gum may stick to and damage Increased salivation, and sore mouth or throat. Dry mouth, increased salivation, mouth ulcers, and sore mouth or throat. Less commonly: thirst, taste disturbance, gingival bleeding, and halitosis. Sublingual
Dry mouth, sore mouth or throat, burning sensation in the mouth, rhinitis, coughing. Care should be taken with the inhalation Mild local reactions such as irritation of the throat cartridges in patients with obstructive Inhalator
and mouth, and coughing occur in about 40% of lung disease, chronic throat disease, or people using a nicotine inhalator. bronchospastic disease. Dry mouth, increased salivation, mouth ulcers, burning lips, taste disturbance, toothache, oral soft tissue pain and paraesthesia. Oral spray
Less commonly: watery eyes. Sweating and myalgia have been reported. Pharyngitis, coughing, pharyngolaryngeal pain, Oral film
dry mouth, mouth ulcers, oral discomfort. Nasal irritation as sneezing, running nose, watering eyes, and cough occur in nearly all The nasal spray can cause worsening of (94%) of people using a nicotine nasal spray bronchial asthma. Use of the spray in Nasal spray
during the first 2 days of therapy. Both the patients with hyperreactive airways is not frequency and severity are likely to decline with continued use. Nose bleeds, gastrointestinal disorders. Page 5 of 16
All Wales Medicines Strategy Group
2.4 Prescribing/supply notes for NRT
• Prescribing/supply of NRT should not commence until the patient has decided on a
target quit date. • The initial prescription/supply should be sufficient to last a maximum of 2 weeks after the target quit date. (Quantity guide in Table 3.) • Emphasise the importance of using NRT regularly at first, and at an adequate dose to reduce the symptoms of nicotine withdrawal sufficiently. (Dosage guide in Table 4.) • Further prescriptions/supplies should only be issued if the quit attempt is continued. • Prescribing/supplying for a maximum of 14-day intervals can help to tailor the NRT formulation and dosage to the individual patient's needs and to avoid potential waste. (Quantity guide in Table 3 and dosage guide in Table 4.) • Treatment is recommended for 8 to 12 weeks, unless otherwise stated in the product • If continued longer and abstinence is not achieved after 6 to 9 months, treatment should be reviewed. • Where NRT is added to repeat prescribing systems this should be for short-term use
Table 3. Quantity of NRT: First and further prescription(s)
Formulation
First prescription
Further prescription(s)
Appropriate quantity to last 2 weeks based 1 or 2-week supply at maximum daily Single NRT
on actual usage and any remaining NRT from previous prescription. 2-week supply (14) patches plus an
1 or 2-week supply (7 or 14) patches appropriate quantity of one immediate- plus half the suggested maximum daily
Combination NRT
release NRT, to last 2 weeks based on dose quantity of one immediate- actual usage and any remaining NRT from previous prescription. Patch (single or 1 or 2-week supply (7 or 14 patches).
2-week supply (14 patches). combination NRT)
Page 6 of 16
All Wales Guide: Pharmacotherapy for Smoking Cessation
Table 4. Dosage guide for NRT formulations

Relative
2-week supply
Strength
More than 10 cigarettes daily
Fewer than 10 cigarettes daily
(transdermal patches)
(max dose)
• Specify the patch strength (mg) and duration (16 or • Specify the patch strength (mg) and duration (16 or • Start with a high-strength patch daily for the first 6 • Start with a medium-strength patch daily for the first • Follow with a medium-strength patch for 2 weeks. • Follow with a low-strength patch for the final 2 to 4 • Then a low-strength patch for the final 2 weeks. • 24-hour patches may be more suitable if patients have strong cravings for cigarettes on waking. • Sleep disturbances may be helped by removing the patches before bed (changing from a 24-hour patch to a 16-hour patch). Additional information
• If abstinence is not achieved, or if withdrawal symptoms are experienced, maintain or increase the strength of the patch until the patient is stabilised. If patients using a high-strength patch experience excessive side effects that do not resolve within a few days, change to a medium-strength patch for the remainder of the initial period, and then a low-strength patch for 2 to 4 weeks. Gum (medicated
chewing gum sugar-
Strength
More than 20 cigarettes daily
Fewer than 20 cigarettes daily
• Start with lower-strength gum (2 mg). • Start with higher-strength gum (4 mg). • Up to 15 pieces of gum daily. • Maximum 15 pieces of gum daily. • If patient uses more than 15 pieces of 2 mg gum Consider starting with higher strength if the first daily, change to the higher-strength (4 mg) gum cigarette of the day is smoked within 30 minutes of Consider starting with lower strength if the first waking up. cigarette of the day is smoked more than 30 minutes after waking up. Strength
More than 20 cigarettes daily
Fewer than 20 cigarettes daily
4 mg (mini or standard), • Start with lower-strength (1 mg) standard or (1.5 mg) mini lozenge. Start with higher-strength (2 mg or 4 mg) standard • Up to 30 standard (1 mg) or 15 mini (1.5 mg) or (4 mg) mini lozenge. Maximum 15 higher-strength standard or mini • Change to higher-strength (2 mg) standard or (4 mg) mini lozenges if insufficient effect at maximum Consider starting with a higher strength if the first dose of lower strength. cigarette of the day is smoked within 30 minutes of Consider starting with a lower strength if the first waking up. cigarette of the day is smoked more than 30 minutes after waking up. Page 7 of 16
All Wales Medicines Strategy Group

Table 4. Dosage guide for NRT formulations (continued)

Sublingual tablets
Relative
2-week supply
More than 20 cigarettes daily
Fewer than 20 cigarettes daily
(max dose)
• Start with lower dosage: 1 tablet each hour. • Start with higher dosage: 2 tablets each hour. • Increase to 2 tablets each hour if necessary. (cyclodextrin complex) • Maximum 40 tablets daily. • Maximum 40 tablets daily. Inhalator
All dependency levels
(inhalation cartridges)
• Maximum 6 cartridges of the 15 mg strength daily. Oral spray
All dependency levels
(oromucosal spray sugar-free)
• Maximum 2 sprays per episode (up to 4 sprays every hour). (150 sprays per 13.2 ml) • Maximum of 64 sprays daily. Oral film
First cigarette of the day smoked more than 30 minutes after waking up
(orodispersible film sugar-free)
• Maximum 15 films daily. Nasal spray
All dependency levels
500 micrograms per dose • Use one spray in each nostril, up to twice every hour for 16 hours daily. (200 sprays per 10 ml) • Maximum 64 sprays daily. Page 8 of 16
All Wales Guide: Pharmacotherapy for Smoking Cessation
3.0 VARENICLINE

Varenicline is a selective nicotine-receptor partial agonist. It reduces the severity of
cravings and withdrawal symptoms, while simultaneously reducing the rewarding
effects of nicotine9. It should normally be prescribed/supplied only as part of a
programme of behavioural support.
3.1 Clinical suitability
Varenicline is licensed for use with all smokers except those under 18 or pregnant
women. It should be avoided in breast-feeding women due to a lack of safety data and
is contraindicated in those with hypersensitivity to varenicline or any of the excipients in
the formulation10.
Care should be taken when considering prescribing varenicline to patients with a
history of psychiatric illness. Where a decision is taken to prescribe varenicline to such
patients, they should be closely monitored.
Caution is recommended for use in patients with cardiovascular disease, or
predisposition to seizures (including conditions that lower seizure threshold). Dosage
may need to be adjusted in moderate or severe renal impairment. Treatment with
varenicline is not recommended for use in patients with end-stage renal disease.
To date, there are no known clinically meaningful drug interactions with varenicline.
3.2 Adverse effects
Varenicline is a black triangle medicine ( ) subject to intensive monitoring and all suspected adverse reactions should be reported to the Medicines and Healthcare Products Regulatory Agency (MHRA) through the Yellow Card Scheme. Nausea is the most common adverse effect of varenicline (almost 30% of patients). Very commonly reported adverse effects include headache, insomnia, abnormal dreams and nasopharyngitis. Whilst these side effects are generally not serious, there have been reports of more serious suspected side effects associated with the use of varenicline. Changes in behaviour or thinking, anxiety, psychosis, mood swings, aggressive behaviour, depression, suicidal thoughts, suicide attempts and completed suicides have been reported in patients attempting to quit smoking with varenicline. Some of the patients had no known pre-existing psychiatric condition and some continued to smoke. The BNF highlighted MHRA/Commission on Human Medicines (CHM) advice on the risk of suicidal thoughts and behaviour with varenicline5: MHRA/CHM advice
Suicidal behaviour and varenicline

Patients should be advised to discontinue treatment and seek prompt medical advice if they develop
agitation, depressed mood or suicidal thoughts.
Patients with a history of psychiatric illness should be monitored closely whilst taking varenicline.
Varenicline may also affect a patient's ability to drive or use machines: patients should not drive or operate complex machinery, or take part in potentially hazardous activities until they know how varenicline affects them. Page 9 of 16
All Wales Medicines Strategy Group
3.3 Dose and duration of treatment
The recommended duration of treatment with varenicline is 12 weeks. Review every 2
weeks.
The 12-week course can be repeated in abstinent individuals to reduce the risk of
relapse.
Table 5. Dosage guide for varenicline

Relative cost = £££
Start 1 to 2 weeks before target quit date (up to maximum of 5 weeks before target quit date). Adults over 18 years
500 micrograms once daily for 3 days, increase to 500 micrograms twice daily for 4 days, then 1 mg twice daily for 11 weeks. Reduce dose to 500 micrograms twice daily if not tolerated. Severe renal impairment (eGFR
500 micrograms once a day for the first 3 days, then increase to 1 mg < 30 ml/min/1.73 m2). Avoid in
end-stage renal disease

Stopping varenicline is associated with an increase in irritability, urge to smoke,
depression and/or insomnia in up to 3% of patients. Dose tapering should be
considered at the end of a 12-week course to prevent symptoms and reduce the risk of
relapse.
Table 6. Prescribing/supply intervals and quantities for varenicline

Varenicline
Duration
Quantity
11 x 500 microgram tablets and 14 x 1 mg tablets 2 weeks (starter pack) 1 mg x 28 tablets 2nd, 3rd, 4th, 5th & 6th
(500 microgram x 28 tablets if using lower dose) Page 10 of 16
All Wales Guide: Pharmacotherapy for Smoking Cessation
4.0 BUPROPION

Bupropion is a non-nicotine aid to smoking cessation that reduces the urge to smoke
and withdrawal symptoms. It has dopaminergic and noradrenergic effects that can aid
smoking cessation. Bupropion was originally developed as an antidepressant.
4.1 Clinical suitability
Bupropion is licensed for use with all smokers except those under 18 or pregnant
women. It should be avoided in breast-feeding women due to a lack of safety data and
is contraindicated in those with hypersensitivity to bupropion or any of the excipients in
the formulation11.
Bupropion is associated with a dose-related risk of seizure. The incidence of seizures
is approximately 1 in 1,000 at doses up to 150 mg twice daily.
Bupropion is contraindicated in patients with: a current seizure disorder or any history
of seizures, central nervous system (CNS) tumour, acute alcohol or benzodiazepine
withdrawal, eating disorders, severe hepatic cirrhosis, bipolar disorder, or use of
monoamine oxidase inhibitors (MAOIs).
The risk of seizures is increased in the presence of predisposing factors. Prescribe
bupropion only if the potential benefit clearly outweighs risks. Risk factors for seizures
include: alcohol misuse, history of head trauma, diabetes, and concomitant use of any
medicine known to lower seizure threshold. Reduced dosage should be considered if
prescribing for patients with risk factors for seizures.
Bupropion may be used with caution in patients with hepatic impairment and in the
elderly. Reduced dosage is recommended for these patients.
Bupropion inhibits the CYP2D6 pathway. Medicines predominantly metabolised by
CYP2D6 (including certain antidepressants, antipsychotics, beta-blockers, and anti-
arrhythmics) should be started at the lower end of the dose range in patients taking
bupropion. If bupropion is prescribed to a patient already taking such a medicine, the
need to decrease the dose of that medicine should be considered. The expected
benefits of treatment with bupropion should be weighed against the potential risks.
Bupropion is metabolised primarily by CYP2B6, and medicines which affect this
enzyme such as substrates (e.g. cyclophosphamide) or inhibitors (e.g. orphenadrine or
clopidogrel) may alter levels of bupropion and its metabolites. The clinical effect of this
is unknown.
Since bupropion is extensively metabolised, medicines that inhibit its metabolism (e.g.
valproate) or induce metabolism (e.g. carbamazepine and phenytoin), may affect its
clinical effects.
4.2 Adverse effects
Bupropion causes insomnia very commonly. This can be reduced by avoiding bedtime
doses, provided there is at least 8 hours between doses. Common adverse effects
include: hypersensitivity reactions (e.g. urticaria), dry mouth, gastrointestinal disorders,
taste disturbance, agitation, anxiety, tremor, dizziness, depression, headache, impaired
concentration, rash, pruritus, sweating, and fever.
Seizures are a rare but clinically important adverse effect of bupropion. At doses up to
150 mg twice daily, the incidence of seizures is approximately 0.1% (1 in 1,000).
Treatment with bupropion should be stopped if a patient has a seizure while taking it.
Page 11 of 16
All Wales Medicines Strategy Group
Hypertension, in some cases severe, has been reported in patients taking bupropion.
This has been observed in patients with and without pre-existing hypertension. Blood
pressure should be measured at the start of treatment and monitoring undertaken.
Depression and, very rarely, suicide attempts have been reported during treatment with
bupropion.
Patients should exercise caution before driving or using machinery until they are
reasonably certain bupropion does not adversely affect their performance.
4.3 Dose and duration of treatment
The recommended duration of treatment with bupropion is 7 to 9 weeks. Review every
2 weeks.

Table 7. Dosage guide for bupropion

Relative cost = £££
Start 1 to 2 weeks before target quit date. 150 mg daily for 6 days then 150 mg twice daily (max. single dose 150 Adults over 18 years
mg, max. daily dose 300 mg; minimum 8 hours between doses). Period of treatment 7–9 weeks; discontinue if abstinence not achieved at 7 weeks. Max.150 mg once a day. Hepatic impairment. (Avoid in
Reduce dose to 150 mg once a day. severe hepatic cirrhosis.)
Renal impairment
Reduce dose to 150 mg once a day. Predisposition to seizures
Consider a maximum dose of 150 mg daily.
Although discontinuation reactions are unlikely on stopping bupropion, a tapering off
period may be considered 1 to 2 weeks before stopping if the patient prefers.
Table 8. Prescribing/supply intervals and quantities for bupropion

Bupropion
Duration
Quantity
22 x 150 mg tablets (provides 2-week supply at standard initiation dose) 28 x 150 mg tablets (14 x 150 mg tablets if using lower dose) Up to 3 weeks (to complete the Up to 42 x 150 mg tablets course of treatment) (Up to 21 x 150 mg tablets if using lower dose) Page 12 of 16
All Wales Guide: Pharmacotherapy for Smoking Cessation
APPENDIX I: SUMMARY OF CAUTIONS IN THE USE OF PHARMACOTHERAPY IN SPECIAL POPULATIONS

Special population
Varenicline
Bupropion
NRT use in pregnancy is preferable to the continuation of smoking, but should only be used if smoking cessation without NRT fails. Intermittent therapy is preferable to patches. Avoid Pregnant women
Avoid – lack of safety data. Avoid – lack of safety data. liquorice-flavoured NRT. Patches are useful, however, if the patient is experiencing pregnancy-related nausea and vomiting. If patches are used, they should be removed before bed. Nicotine from NRT is present in breast milk; however, the amount to which the infant is exposed is small and less Avoid – lack of safety data. Present in breast Breast-feeding women
Avoid – lack of safety data. hazardous than second-hand smoke. Intermittent therapy is Caution in use with haemodynamically unstable patients hospitalised with severe arrhythmias, myocardial infarction, or Measure blood pressure before and during cerebrovascular accident. Initiation should only be under Caution in use with history of Cardiovascular disease
treatment, especially with pre-existing medical supervision. If there is a clinically significant increase in cardiovascular disease. cardiovascular or other effects attributable to nicotine, the dose should be reduced or discontinued. Care in use in patients with diabetes mellitus. Blood glucose No specific cautions. However, blood glucose concentrations may be more variable when Diabetes mellitus
concentration should be monitored closely while using NRT. stopping smoking and should be monitored closely. Reduce dose to 150 mg daily. Avoid in Hepatic impairment
Caution in use with moderate to severe hepatic impairment. severe hepatic cirrhosis. If eGFR less than 30 ml/minute/1.73 m2, initial dose 500 micrograms once daily, Caution in use with renal insufficiency. Renal impairment
Caution in use with severe renal impairment. increased after 3 days to 1 mg once daily. Reduce dose to 150 mg daily. Avoid in end-stage renal disease. Care should be taken with patients with a Psychiatric illness
history of psychiatric illness. Prescribe only if benefit clearly outweighs Potential risks and benefits of NRT should be considered before risks. Risks include the concomitant use of use in patients taking anti-convulsant therapy or with a history of Caution in use, including conditions that Predisposition to seizures
medicines and/or presence of other epilepsy as cases of convulsions have been reported in may lower seizure threshold. conditions that may lower seizure threshold. association with nicotine. Consider a maximum dose of 150 mg daily. Uncontrolled hyperthyroidism
All NRT preparations are licensed for adolescents over 12 years Children and adolescents (12
old (with the exception of Nicotinell™ lozenges which are Not licensed for use in those under 18 Not licensed for use in those under 18 years to 18 years)
licensed for those under 18 years old only when recommended years old. Maximum dose of 150 mg once a day. Page 13 of 16
All Wales Medicines Strategy Group
APPENDIX II: SUMMARY DOSAGE AND SUPPLY GUIDE FOR SMOKING CESSATION PHARMACOTHERAPY

Relative
2-week supply
More than 10 cigarettes daily
Fewer than 10 cigarettes daily
(max. dose)
Strength
• Specify the patch strength (mg) and duration (16 or 24 • Specify the patch strength (mg) and duration (16 or 24 Start with a high-strength patch daily for the first 6 to 8 Start with a medium-strength patch daily for the first 6 to 8 Follow with a medium-strength patch for 2 weeks. Follow with a low-strength patch for the final 2 to 4 weeks. Then a low-strength patch for the final 2 weeks. Strength
More than 20 cigarettes daily
Fewer than 20 cigarettes daily
• Start with lower-strength gum (2 mg). • Start with higher-strength gum (4 mg). • Up to 15 pieces of gum daily. • Maximum 15 pieces of gum daily. • If patient uses more than 15 pieces of 2 mg gum daily, Consider starting with higher strength if the first cigarette of change to the higher-strength (4 mg) gum. the day smoked within 30 minutes of waking up. Consider starting with lower strength if the first cigarette of the day smoked more than 30 minutes after waking up. Strength
More than 20 cigarettes daily
Fewer than 20 cigarettes daily
• Start with lower-strength (1 mg) standard or (1.5 mg) mini Start with higher-strength (2 mg or 4 mg) standard or (4 mg) Up to 30 standard (1 mg) or 15 mini (1.5 mg) lozenges daily. • Maximum 15 higher-strength standard or mini lozenges • Change to higher-strength (2 mg) standard or (4 mg) mini lozenges if insufficient effect at maximum dose of lower • Consider starting with a higher strength if the first cigarette of the day is smoked within 30 minutes of waking up. Consider starting with a lower strength if the first cigarette of the day is smoked more than 30 minutes after waking up. Sublingual tablets
More than 20 cigarettes daily
Fewer than 20 cigarettes daily
Start with lower dosage: 1 tablet each hour. • Start with higher dosage: 2 tablets each hour. • Increase to 2 tablets each hour if necessary. (cyclodextrin complex) • Maximum 40 tablets daily. • Maximum 40 tablets daily. 560 tablets Higher dose Inhalator
All dependency levels
• Maximum 6 cartridges of the 15 mg strength daily. Oral spray
All dependency levels
• Maximum 2 sprays per episode (up to 4 sprays every hour). (150 sprays per 13.2 ml) • Maximum of 64 sprays daily. Oral film
First cigarette of the day smoked more than 30 minutes after waking up
• Maximum 15 films daily. Nasal spray
All dependency levels
500 micrograms per dose • Use one spray in each nostril, up to twice every hour for 16 hours daily. (200 sprays per 10 ml) • Maximum 64 sprays daily. Page 14 of 16
All Wales Guide: Pharmacotherapy for Smoking Cessation
ADDITIONAL INFORMATION
NRT

Formulation
First prescription
Further prescription(s)
Appropriate quantity to last 2 weeks based on actual Single NRT
1 or 2-week supply at maximum daily dose. usage and any remaining NRT from previous prescription. 2-week supply (14) patches plus an appropriate
1 or 2-week supply (7 or 14) patches plus half
quantity of one immediate-release NRT, to last 2 Combination NRT
the suggested maximum daily dose quantity of weeks based on actual usage and any remaining one immediate-release NRT. NRT from previous prescription. (single or
1 or 2-week supply (7 or 14 patches) 2-week supply (14 patches) combination NRT)
NRT patches
24-hour patches may be more suitable if patients have strong cravings for cigarettes on waking. Sleep disturbances may be helped by removing the patches before bed (changing from a 24-hour patch to a 16-hour patch). If abstinence is not achieved, or if withdrawal symptoms are experienced, maintain or increase the strength of the patch until the patient is stabilised. • If patients using a high-strength patch experience excessive side effects that do not resolve within a few days, change to a medium-strength patch for the remainder of the initial period, then a low-strength patch for 2 to 4 weeks.
Varenicline

Relative cost = £££
Start 1 to 2 weeks before target quit date (up to maximum of 5 weeks before target quit date). Adults over 18 years
500 micrograms once daily for 3 days, increase to 500 micrograms twice daily for 4 days, then 1 mg twice daily for 11 weeks. Severe renal impairment (eGFR < 30
Reduce dose to 500 micrograms twice daily if not tolerated. ml/min/1.73 m2). Avoid in end-stage renal
500 micrograms once a day for the first 3 days, then increase to 1 mg once Varenicline
Duration
Quantity
2 weeks (starter pack) 11 x 500 microgram tablets and 14 x 1 mg tablets (starter pack) 1 mg x 28 tablets 2nd, 3rd, 4th, 5th & 6th
(500 microgram x 28 tablets if using lower dose)
Bupropion

Relative cost = £££
Start 1 to 2 weeks before target quit date. 150 mg daily for 6 days then 150 mg twice daily (max. single dose 150 mg, Adults over 18 years
max. daily dose 300 mg; minimum 8 hours between doses). Period of treatment 7–9 weeks; discontinue if abstinence not achieved at 7 weeks. Max.150 mg once a day. Hepatic impairment. (Avoid in severe hepatic
Reduce dose to 150 mg once a day. cirrhosis.)
Renal impairment
Reduce dose to 150 mg once a day. Predisposition to seizures
Consider a maximum dose of 150 mg daily. Bupropion
Duration
Quantity
22 x 150 mg tablets (provides 2-week supply at standard initiation dose) 28 x 150 mg tablets (14 x 150 mg tablets if using lower dose) Up to 3 weeks (to complete Up to 42 x 150 mg tablets the course of treatment) (Up to 21 x 150 mg tablets if using lower dose) Page 15 of 16
All Wales Medicines Strategy Group
REFERENCES

1 Stead LF, Lancaster T. Combined pharmacotherapy and behavioural
interventions for smoking cessation. Cochrane Database of Systematic Reviews 2012; (10). Available at 2 National Institute for Health and Care Excellence. Public Health Guidance 10. Smoking cessation services. 2008. Available at Accessed Mar 2014. 3 Cahill K, Stevens S, Perera R et al. Pharmacological interventions for smoking cessation: an overview and network meta-analysis (Review). Cochrane Database of Systematic Reviews 2013; (5). Available atjsessionid=CD9CFE63D2C6065A836E0D534D37E06D.d01t01. 4 Zwar NA, Mendelsohn CP, Richmond RL. Supporting smoking cessation. British Medical Journal 2014. Available at 5 British Medical Association, Royal Pharmaceutical Society. British National Formulary. No 67. 2014. 6 Fagerström K. Time to first cigarette; the best single indicator of tobacco dependence? Monaldi Archives for Chest Disease 2003; 59 (1): 91-4. Available at 7 National Institute for Health and Care Excellence. Public Health Guidance 26. Quitting smoking in pregnancy and following childbirth. 2010. Available at Accessed Jul 2014. 8 Medicines and Healthcare Products Regulatory Agency, Committee on Safety of Medicines. New advice on use of nicotine replacement therapy (NRT): wider access in at-risk populations. 2005. Available at Accessed Mar 2014. 9 National Institute for Health and Care Excellence. Technology Appraisal 123. Varenicline for smoking cessation. 2007. Available at Accessed Mar 2014. 10 Pfizer Limited. Champix® 0.5 mg and 1 mg film-coated tablets. Summary of Product Characteristics. 2014. Available at Accessed Mar 2014. 11 GlaxoSmithKline UK. Zyban® 150 mg prolonged release film-coated tablets. 2013. Available at Accessed Mar 2014. Page 16 of 16

Source: http://www.awmsg.org/docs/awmsg/medman/All%20Wales%20Guide%20-%20Pharmacotherapy%20for%20Smoking%20Cessation.pdf

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