UKPAR Nicotinell ® / NicAid 2mg & 4mg medicated chewing gum
PL 00030/0441-2
Nicotinell® mint 2mg medicated chewing gum
NicAid mint 2mg medicated chewing gum
PL 00030/0441
&
Nicotinell® mint 4mg medicated chewing gum
NicAid mint 4mg medicated chewing gum
PL 00030/0442
(Nicotine)
UKPAR
TABLE OF CONTENTS
Lay Summary
Page 2
Scientific discussion
Page 3
Steps taken for assessment
Page 12
Steps taken after authorisation
Page 13
Summary of Product Characteristics
Page 14
Product Information Leaflet
Page 21
Labelling
Page 29
1
UKPAR Nicotinell ® / NicAid 2mg & 4mg medicated chewing gum
PL 00030/0441-2
Nicotinell® / NicAid mint 2mg medicated chewing gum
& Nicotinell® / NicAid mint 4mg medicated chewing gum
PL 00030/0441-2
(Nicotine)
LAY SUMMARY
The Medicines and Healthcare products Regulatory Agency (MHRA) granted
Novartis Consumer Health UK Ltd (trading as Novartis Consumer Health) Marketing
Authorisations (licences) for the medicinal products Nicotinell® / NicAid mint 2mg
medicated chewing gum (PL 00030/0441) and Nicotinell® / NicAid mint 4mg
medicated chewing gum (PL 00030/0442) on 9th March 2010. These medicines are
available on the General Sales List (GSL), and can be purchased at pharmacies,
supermarkets and other retail outlets without the supervision of a pharmacist.
Nicotinell medicated chewing gum is a type of nicotine replacement therapy which is
used to help you to stop smoking. It is available in two strengths (2mg and 4mg). The
chewing gum contains nicotine, which is one of the substances contained in tobacco.
When chewed, nicotine is released slowly and absorbed through the lining of the
mouth. Nicotinell chewing gum does not contain the other harmful substances found
in tobacco smoke such as tar and carbon monoxide. These medicinal products are
used to:
•
relieve some of the unpleasant nicotine withdrawal symptoms that frequently
occur when giving up smoking such as feeling ill or irritable
•
reduce your desire to smoke by providing some of the nicotine previously
inhaled form cigarettes and therefore helps your willpower to resist cigarettes.
Nicotinell 2mg gum is for smokers smoking less than 20 cigarettes per day. It can also
be used by smokers smoking between 20 and 30 cigarettes per day. Nicotinell 4mg
gum is for smokers smoking more than 30 cigarettes per day. It can also be used by
smokers smoking between 20 and 30 cigarettes per day, and by those who have
previously failed to stop smoking with the aid of nicotine replacement therapy.
These applications are duplicates of previously granted applications for Nicotinell
mint 2mg and 4mg medicated chewing gum (PL 00030/0427-8), held by Novartis
Consumer Health UK Ltd (trading as Novartis Consumer Health), and authorised in
the UK on 18th January 2007. The test and reference products are identical.
No new or unexpected safety concerns arose from these simple applications and it was
therefore judged that the benefits of Nicotinell® / NicAid mint 2mg and 4mg
medicated chewing gum outweigh the risks; hence Marketing Authorisations have
been granted.
2
UKPAR Nicotinell ® / NicAid 2mg & 4mg medicated chewing gum
PL 00030/0441-2
Nicotinell® / NicAid mint 2mg medicated chewing gum
& Nicotinell® / NicAid mint 4mg medicated chewing gum
PL 00030/0441-2
(Nicotine)
SCIENTIFIC DISCUSSION
TABLE OF CONTENTS
Introduction
Page 4
Pharmaceutical assessment
Page 6
Preclinical assessment
Page 9
Clinical assessment
Page 10
Overall conclusion and risk benefit assessment
Page 11
3
UKPAR Nicotinell ® / NicAid 2mg & 4mg medicated chewing gum
PL 00030/0441-2
INTRODUCTION
Based on the review of the data on quality, safety and efficacy, the MHRA granted
Novartis Consumer Health UK Ltd (trading as Novartis Consumer Health) Marketing
Authorisations for the medicinal products Nicotinell® / NicAid mint 2mg medicated
chewing gum (PL 00030/0441) and Nicotinell® / NicAid mint 4mg medicated
chewing gum (PL 00030/0442) on 9th March 2010. The products are available through
general supply (GSL).
These applications were submitted as simple abridged ‘informed consent’ applications
according to article 10c of Directive 2001/83/EC (as amended), cross-referring to the
Marketing Authorisations for Nicotinell mint 2mg and 4mg medicated chewing gum
(PL 00030/0427-8), granted to Novartis Consumer Health UK Ltd (trading as
Novartis Consumer Health) on 18th January 2007.
Nicotinell gum is indicated for the relief of nicotine withdrawal symptoms, as an aid
to smoking cessation. Concurrent counselling/behavioural support is recommended as
it is likely to increase the chances of a successful quit.
The 2 mg chewing gum may not be well suited to smokers with a strong or very
strong nicotine dependency. The 4 mg chewing gum is intended to be used by
smokers with a strong or very strong nicotine dependency and those who have
previously failed to stop smoking with the aid of nicotine replacement therapy.
Nicotine, the primary alkaloid in tobacco products and a naturally occurring
autonomous substance, is a nicotine receptor agonist in the peripheral and central
nervous systems and has pronounced CNS and cardiovascular effects. On
consumption of tobacco products, nicotine has proven to be addictive, resulting in
craving and other withdrawal symptoms when administration is stopped. This craving
and these withdrawal symptoms include a strong urge to smoke, dysphoria, insomnia,
irritability, frustration or anger, anxiety, concentration difficulties agitation and
increased appetite or weight gain. The gum replaces part of the nicotine that would
have been administrated via tobacco and reduces the intensity of the withdrawal
symptoms and smoking urge.
When the gum is chewed, nicotine is steadily released into the mouth and is rapidly
absorbed through the buccal mucosa. A proportion, by the swallowing of nicotine
containing saliva, reaches the stomach and intestine where it is inactivated. Nicotine is
eliminated mainly via hepatic metabolism; small amounts of nicotine are eliminated in
unchanged form via the kidneys. The plasma half-life is approximately three hours.
Nicotine crosses the blood-brain barrier, the placenta and is detectable in breast milk.
No new data were submitted nor was it necessary for these simple applications, as the
data are identical to that of the previously granted cross-reference products. As the
cross-reference products were granted prior to the introduction of current legislation,
no PAR was generated for them.
The pharmacovigilance system as described by the MAH fulfils the requirements and
provides adequate evidence that the MAH has the services of a qualified person
responsible for pharmacovigilance and has the necessary means for the notification of
4
UKPAR Nicotinell ® / NicAid 2mg & 4mg medicated chewing gum
PL 00030/0441-2
any adverse reaction suspected of occurring either in the Community or in a third
country.
The marketing authorisation holder has provided adequate justification for not
submitting a Risk Management Plan (RMP) and Environmental Risk Assessment
(ERA).
5
UKPAR Nicotinell ® / NicAid 2mg & 4mg medicated chewing gum
PL 00030/0441-2
PHARMACEUTICAL ASSESSMENT
LICENCE NUMBERS:
PL 00030/0441 & 0442
PROPRIETARY NAME:
Nicotinell® / NicAid 2mg medicated chewing gum
Nicotinell® / NicAid 4mg medicated chewing gum
ACTIVE INGREDIENTS:
Nicotine
COMPANY NAME:
Novartis Consumer Health UK Ltd (trading as
Novartis Consumer Health)
E.C. ARTICLE:
Article 10c of Directive 2001/83/EC (as amended)
LEGAL STATUS:
GSL
1.
INTRODUCTION
These are simple abridged applications, submitted under Article 10c of Directive
2001/83/EC (as amended) for Nicotinell® / NicAid 2mg and 4mg medicated chewing
gum. The proposed MA holder is Novartis Consumer Health UK Ltd (trading as
Novartis Consumer Health).
The reference products are Nicotinell mint 2mg and 4mg medicated chewing gum (PL
00030/0427-8), granted to Novartis Consumer Health UK Ltd (trading as Novartis
Consumer Health) on 18th January 2007. The test and reference products are identical.
2.
MARKETING AUTHORISATION APPLICATION FORM
2.1
Name(s)
The proposed names of the products are Nicotinell® / NicAid 2mg medicated chewing
gum and Nicotinell® / NicAid 4mg medicated chewing gum. The products have been
named in line with current requirements.
2.2
Strength, pharmaceutical form, route of administration, container and
pack sizes
Each piece of gum contains 2mg or 4mg of the active ingredient nicotine (as nicotinepolacrilin in a 1:4 ratio). The chewing gum is packed in PVC / PVdC / aluminium
blisters each containing either 2 or 12 pieces of gum. The blisters are packed in boxes
containing 2, 12, 24, 36, 48, 60, 72, 84 (2mg only) 96 108, 120 and 204 pieces of
gum. The MAH has stated that not all pack sizes may be marketed.
The approved shelf-life (2 years) and storage conditions (‘Do not store above 25oC’)
are consistent with the details registered for the cross-reference products.
2.3
Legal status
The products are GSL licensed medicines, available by supply through pharmacies,
supermarkets and other retail outlets without the need for supervision by a pharmacist.
2.4
Marketing authorisation holder / Contact Persons/Company
The proposed Marketing Authorisation holder is ‘Novartis Consumer Health UK Ltd,
Trading as Novartis Consumer Health, Wimblehurst Road, Horsham, West Sussex
RH12 5AB’.
6
UKPAR Nicotinell ® / NicAid 2mg & 4mg medicated chewing gum
PL 00030/0441-2
The QP responsible for pharmacovigilance is stated and their CV is included.
2.5
Manufacturers
The proposed manufacturing sites are consistent with those registered for the crossreference products and evidence of GMP compliance has been provided.
2.6
Qualitative and quantitative composition
The proposed compositions are consistent with the details registered for the crossreference products.
2.7
Manufacturing process
The proposed manufacturing process is consistent with the details registered for the
cross-reference products and the maximum batch sizes are stated.
2.8
Finished product / shelf-life specification
The proposed finished product specifications are in line with the details registered for
the cross-reference products.
2.9
Drug substance specification
The proposed drug substance specifications are consistent with the details registered
for the cross-reference products.
2.10
TSE Compliance
The only excipient used that contains material of animal or human origin is gelatin.
Satisfactory documentation has been provided by the gelatin supplier/s stating that the
gelatin they provide complies with the criteria described in the current version of the
monograph ‘Products with risk of transmitting agents of animal spongiform
encephalopathies’.
3.
EXPERT REPORTS
Satisfactory expert reports and curriculum vitae of experts were provided.
4.
PRODUCT NAME & APPEARANCE
See 2.1 for details of the proposed product names. The appearance of the products
(off-white, rectangular-shaped) is consistent with that of the cross-reference products.
5.
SUMMARY OF PRODUCT CHARACTERISTICS
The approved SmPCs are consistent with the details registered for the cross-reference
products.
6.
PATIENT INFORMATION LEAFLET (PIL) / CARTON
PIL
The patient information leaflets have been prepared in the user tested format and in
line with the details registered for the cross-reference products. The general text of the
PILs is identical to that approved for the reference licences (PL 00030/0427-8). The
PILs for the reference licences were included for these submissions and have been
incorporated into this report.
7
UKPAR Nicotinell ® / NicAid 2mg & 4mg medicated chewing gum
PL 00030/0441-2
Cartons
Colour mock-ups of the labelling have been provided for the reference licences (PL
00030/0427-8) and are satisfactory. The labelling for these applications is identical to
that of the reference licences, apart from the PL numbers.
7.
CONCLUSIONS
The grounds for these applications are considered adequate. Marketing Authorisations
were therefore granted.
8
UKPAR Nicotinell ® / NicAid 2mg & 4mg medicated chewing gum
PL 00030/0441-2
PRECLINICAL ASSESSMENT
These applications were submitted as simple abridged applications according to article 10c
of Directive 2001/83/EC (as amended).
No new preclinical data have been supplied with these applications and none are
required for applications of this type. A preclinical expert report has been written by a
suitably qualified person and is satisfactory.
9
UKPAR Nicotinell ® / NicAid 2mg & 4mg medicated chewing gum
PL 00030/0441-2
CLINICAL ASSESSMENT
These applications were submitted as simple abridged applications according to article 10c
of Directive 2001/83/EC (as amended).
As these are duplicate applications for PLs 00030/0427 and 0428, no new clinical data
have been supplied, and none are required for applications of this type. A clinical
expert report has been written by a suitably qualified person and is satisfactory.
10
UKPAR Nicotinell ® / NicAid 2mg & 4mg medicated chewing gum
PL 00030/0441-2
OVERALL CONCLUSION AND RISK BENEFIT ASSESSMENT
QUALITY
The data for these applications are consistent with that previously assessed for the
cross-reference products and as such has been judged to be satisfactory.
PRECLINICAL
No new preclinical data were submitted and none are required for applications of this
type.
EFFICACY
Medicinal products containing nicotine have been available in the UK for much more
than ten years. Their use is well established with recognised efficacy and acceptable
safety.
These applications are identical to the cross-reference products Nicotinell mint 2mg
and 4mg medicated chewing gum (PL 00030/0427-8), held by Novartis Consumer
Health UK Ltd (trading as Novartis Consumer Health).
No new or unexpected safety concerns arise from these applications.
PRODUCT LITERATURE
The approved SmPCs, PILs and labelling are satisfactory and consistent with those for
the cross-reference products.
The package leaflets have been evaluated via a user consultation study in accordance
with the requirements of Articles 59(3) and 61(1) of Directive 2001/83/EC. The
results show that the package leaflets meet the criteria for readability as set out in the
Guideline on the readability of the label and package leaflet of medicinal products for
human use. The Marketing Authorisation Holder (MAH) has committed to submitting
a mock-up PIL for PL 00030/0442 for assessment before packs are commercially
marketed.
Colour mock-ups of the labelling have been provided and are satisfactory. The
approved labelling artwork complies with statutory requirements.
RISK BENEFIT ASSESSMENT
The quality of the products is acceptable and no new preclinical or clinical safety
concerns have been identified. The applicant’s products are identical to the crossreference products. Extensive clinical experience with nicotine is considered to have
demonstrated the therapeutic value of the active substance. The risk: benefit ratio is,
therefore, considered to be positive.
11
UKPAR Nicotinell ® / NicAid 2mg & 4mg medicated chewing gum
PL 00030/0441-2
Nicotinell® / NicAid mint 2mg medicated chewing gum
& Nicotinell® / NicAid mint 4mg medicated chewing gum
PL 00030/0441-2
(Nicotine)
STEPS TAKEN FOR ASSESMENT
1
The MHRA received the marketing authorisation applications on 16th December
2009
2
Following standard checks and communication with the applicant the MHRA
considered the applications valid on 23rd December 2009
3
Following assessment of the application the MHRA requested further
information relating to the quality dossier on 4th March 2010
4
The applicant responded to the MHRA’s request, providing further information
for the quality sections on 9th March 2010
5
The applications were determined on 9th March 2010 and granted on 10th March
2010
12
UKPAR Nicotinell ® / NicAid 2mg & 4mg medicated chewing gum
PL 00030/0441-2
Nicotinell® / NicAid mint 2mg medicated chewing gum
& Nicotinell® / NicAid mint 4mg medicated chewing gum
PL 00030/0441-2
(Nicotine)
STEPS TAKEN AFTER AUTHORISATION
Not applicable
13
UKPAR Nicotinell ® / NicAid 2mg & 4mg medicated chewing gum
PL 00030/0441-2
SUMMARY OF PRODUCT CHARACTERISTICS
The UK Summary of Product Characteristics (SmPC) for Nicotinell® / NicAid mint
2mg and 4mg medicated chewing gum (PL 00030/0441 & 0442) is as follows –
Differences between the individual SmPCs are highlighted:
1
NAME OF THE MEDICINAL PRODUCT
Nicotinell® mint 2mg medicated chewing gum
NicAid mint 2mg medicated chewing gum
Nicotinell® mint 4mg medicated chewing gum
NicAid mint 4mg medicated chewing gum
2
QUALITATIVE AND QUANTITATIVE COMPOSITION
One piece of medicated chewing gum contains 2 mg nicotine (as 10 mg nicotine – polacrilin (1:4)).
One piece of medicated chewing gum contains 4 mg nicotine (as 20 mg nicotine – polacrilin (1:4)).
For excipients, see section 6.1
3
PHARMACEUTICAL FORM
Medicated chewing gum.
Each piece of coated chewing gum is off-white in colour and rectangular in shape.
4
CLINICAL PARTICULARS
4.1
THERAPEUTIC INDICATIONS
Nicotinell gum is indicated for the relief of nicotine withdrawal symptoms, as an aid to smoking
cessation.
Concurrent counselling/behavioural support is recommended as it is likely to increase the chances of a
successful quit.
4.2
POSOLOGY AND METHOD OF ADMINISTRATION
Adults and elderly
Users should stop smoking completely during treatment with Nicotinell gum.
One piece of Nicotinell gum to be chewed when the user feels the urge to smoke. Normally, 8-12
pieces per day can be used, up to a maximum of 25 pieces per day.
The 2 mg chewing gum may not be well suited to smokers with a strong or very strong nicotine
dependency.
The 4 mg chewing gum is intended to be used by smokers with a strong or very strong nicotine
dependency and those who have previously failed to stop smoking with the aid of nicotine replacement
therapy.
The optimal dosage form is selected according to the following table:
14
UKPAR Nicotinell ® / NicAid 2mg & 4mg medicated chewing gum
PL 00030/0441-2
Low to moderate
dependency
Moderate to strong dependency
Strong to very strong
dependency
Less than 20 cigarettes / day
From 20 to 30 cigarettes / day
Over 30 cigarettes / day
Low dose forms are
preferable
(2 mg gum)
Low (2 mg gum) or high (4 mg gum)
dose forms are acceptable depending
on patient characteristics and
preference.
High dose forms are
preferable
(4 mg gum)
Low dosage forms acceptable
High dosage forms acceptable
If an adverse event is noted when high dose forms are initiated, this should be replaced by the lower
dosage form.
The characteristics of chewing-gum as a pharmaceutical form are such that individually different
nicotine levels can result in the blood. Therefore, dosage frequency should be adjusted according to
individual requirements within the stated maximum limit.
Directions for use:
1.
One piece of gum should be chewed until the taste becomes strong.
2.
The chewing gum should be rested between the gum and cheek.
3.
When the taste fades, chewing should commence again.
4.
The chewing routine should be repeated for 30 minutes.
The treatment time is individual. Normally, treatment should continue for at least 3 months.
After three months, the user should gradually cut down the number of pieces chewed each day until
they have stopped using the product.
Treatment should be discontinued when the dose has been reduced to 1-2 pieces of gum per day. Use of
nicotine products like Nicotinell gum beyond 6 months is generally not recommended. Some exsmokers may need treatment with the gum for longer to avoid returning to smoking. Patients who have
been using oral nicotine replacement therapy beyond 9 months are advised to seek additional help and
information from health care professionals.
Nicotinell gum is sugar free.
Adolescents (aged 12-18 years of age)
The above recommendation can be used for adolescents aged between 12 and 18 years of age. As data
are limited in this age group, medical advice should be obtained should it be found necessary to use the
gum beyond 12 weeks.
Concomitant use of acidic beverages such as coffee or soda may decrease the buccal absorption of
nicotine. Acidic beverages should be avoided for 15 minutes prior to chewing the gum.
4.3
CONTRAINDICATIONS
Hypersensitivity to nicotine or any components of the gum.
Nicotinell gum should not be used by non-smokers.
15
UKPAR Nicotinell ® / NicAid 2mg & 4mg medicated chewing gum
4.4
PL 00030/0441-2
SPECIAL WARNINGS AND PRECAUTIONS FOR USE
Any risks that may be associated with nicotine replacement therapy are substantially outweighed by the
well established dangers of continued smoking.
Precautions: Users should stop smoking completely during therapy with Nicotinell gum. They should
be informed that if they continue to smoke while using the gums they may experience increased
adverse effects due to the hazards of smoking, including cardiovascular effects.
Cardiovascular disease
In stable cardiovascular disease Nicotinell gum presents a lesser hazard than continuing to smoke.
However dependant smokers currently hospitalised as a result of a recent myocardial infarction, severe
disrythmia, or recent cerebrovascular accident who are considered to be haemodynamically unstable
should be encouraged to stop smoking with non-pharmacological interventions. If this fails, Nicotinell
gum may be considered but as data on safety in this patient group are limited, initiation should only be
under medical supervision.
Diabetes mellitus
Patients with diabetes mellitus should be advised to monitor their blood sugar levels more closely than
usual when nicotine replacement therapy is initiated as catecholamines released by nicotine can affect
carbohydrate metabolism.
Allergic reactions
Angioedema and urticaria have been reported.
Gastro-intestinal disease
Swallowed nicotine may exacerbate symptoms in patients suffering from oesophagitis, gastritis, or
peptic ulcers and oral nicotine replacement therapy preparations should be used with caution in these
conditions. Ulcerative stomatitis have been reported.
Renal and or hepatic impairment
Should be used with caution in patients with moderate to severe hepatic impairment and/or severe renal
impairment as the clearance of nicotine or its metabolites may be decreased with the potential for
increased adverse effects.
Danger in small children
Doses of nicotine tolerated by adult and adolescent smokers can produce severe toxicity in small
children that may be fatal. Products containing nicotine should not be left where they may be misused,
handled or ingested by children. Nicotinell gum should be disposed of with care.
Pheochromocytoma and uncontrolled hyperthyroidism
Nicotinell gum should be used with caution in patients with uncontrolled hyperthyroidism or
pheochromocytoma as nicotine causes the release of catecholamines.
Transferred dependence
Transferred dependence is rare and is both less harmful and easier to break than smoking dependence.
Stopping smoking
Polycyclic aromatic hydrocarbons in tobacco smoke induce the metabolism of drugs catalysed by CYP
1A2 (and possibly CYP 1A1). When a smoker stops, this may result in slower metabolism and a
consequential rise in blood levels of drugs such as theophylline, tacrine, olanzaprine and clozaprine.
Other warnings
If denture wearers experience difficulty in chewing the gum, it is recommended that they use a
different pharmaceutical form of nicotine replacement therapy.
Patients with rare hereditary problems of fructose intolerance should not take this medicine.
Nicotinell 2mg gum contains sorbital (E420) 0.2g per gum, a source of 0.04g fructose. Calorific value
1.0 kcal/piece of gum.
Nicotinell 2mg gum contains sodium 11.50 mg per piece of gum.
16
UKPAR Nicotinell ® / NicAid 2mg & 4mg medicated chewing gum
4.5
PL 00030/0441-2
INTERACTION WITH OTHER MEDICINAL PRODUCTS AND OTHER FORMS OF
INTERACTION
No information is available on interactions between Nicotinell gum and other drugs. No clinically
relevant interactions between nicotine replacement therapy and other drugs has definitely been
established, however nicotine may possibly enhance the haemodynamic effects of adenosine.
4.6
PREGNANCY AND LACTATION
Pregnancy
Smoking during pregnancy is associated with risks such as intra-uterine growth retardation, premature
birth or still birth. Stopping smoking is the single most effective intervention for improving the health
of the pregnant smoker and her baby. The earlier abstinence is achieved the better.
Ideally smoking cessation during pregnancy should be achieved without nicotine replacement therapy.
For women unable to quit on their own nicotine replacement therapy may be recommended to assist a
quit attempt. The risk of using nicotine replacement therapy to the foetus is lower than that expected
with tobacco smoking, due to lower maximal plasma concentrations and no additional exposure to
polycyclic hydrocarbons and carbon monoxide.
However as nicotine passes to the foetus affecting breathing movements and has a dose-dependant
effect on placental/foetal circulation, the decision to use nicotine replacement therapy should be made
on a risk-benefit assessment as early on in pregnancy as possible with the aim of discontinuing use
after 2-3 months.
Intermittent dose products may be preferable as these usually provide a lower daily dose of nicotine
than patches. However, patches may be preferred if the woman is suffering from nausea during
pregnancy. If patches are used they should be removed before going to bed to avoid exposure
overnight when the foetus would not normally be subjected to smoke derived nicotine.
Lactation
Nicotine from smoking and nicotine replacement therapy is found in breast milk. However the
amounts of nicotine the infant is exposed to is relatively small and less hazardous than the second-hand
smoke they would otherwise be exposed to.
Using intermittent dose products, compared to patches, may minimize the amount of nicotine in the
breast milk as the time between administrations of nicotine replacement therapy and feeding can be
more easily prolonged.
4.7
EFFECTS ON ABILITY TO DRIVE AND USE MACHINES
Not applicable.
4.8
UNDESIRABLE EFFECTS
Some symptoms such as dizziness, headache and sleep disturbances may be related to the withdrawal
of nicotine associated with stopping smoking.
In principle, Nicotinell gums can cause adverse reactions similar to those associated with nicotine
administered by other means (including smoking) and these are mainly dose dependant. At
recommended doses Nicotinell gum has not been found to cause any serious adverse effects. Excessive
consumption of Nicotinell gum by those who have not been in the habit of inhaling tobacco smoke
could possibly lead to nausea, faintness or headaches.
Most of the side effects which are reported by patients occur generally during the first 3-4 weeks after
initiation of therapy.
Nicotine from gums may sometimes cause a slight irritation of the throat and increase salivation at the
start of the treatment.
The gum may stick to and in rare cases damage dentures and dental appliances.
17
UKPAR Nicotinell ® / NicAid 2mg & 4mg medicated chewing gum
PL 00030/0441-2
Common (> 1/100).
Nervous system disorders: headache, dizziness
Gastrointestinal disorders: hiccups, gastric symptoms e.g. nausea, vomiting, indigestion, heartburn,
increased salivation, irritation or sore mouth or throat
Musculoskeletal, connective and bone disorders: jaw muscle ache.
Uncommon (>1/1,000, <1/100)
Cardiac disorders: palpitations
Skin and subcutaneous tissue disorders: erythema, urticaria
Rare (<1/1,000)
Cardiac disorders: cardiac arrhythmias (e.g. atrial fibrillation)
Immune system disorders: hypersensitivity, angioneurotic oedema and anaphylactic reactions.
4.9
OVERDOSE
In overdose, symptoms corresponding to heavy smoking may be seen, however the toxicity of nicotine
cannot be directly compared with that of smoking, because tobacco smoke contains additional toxic
substances (eg. carbon monoxide and tar).
Overdose with Nicotinell gum may only occur if many pieces are chewed simultaneously. Nicotine
toxicity after ingestion will most likely be minimized as a result of early nausea and vomiting that
occur following excessive nicotine exposure. Risk of poisoning by swallowing the gum is small. Since
the release of nicotine from the gum is slow, very little nicotine is absorbed from the stomach and
intestine, and if any is, it will be inactivated in the liver.
Chronic smokers can tolerate doses of nicotine that, in a non-smoker, would be more toxic, because of
the development of tolerance.
Symptoms
The minimum lethal dose of nicotine in a non-tolerant man has been estimated to be 40-60mg.
Symptoms of acute nicotine poisoning include nausea, salivation, abdominal pain, diarrhoea, sweating,
headache, dizziness, disturbed hearing and marked weakness. In extreme cases, these symptoms may
be followed by hypotension, rapid or weak or irregular pulse, breathing difficulties, prostration,
circulatory collapse and terminal convulsions.
Management of overdose
Following overdose, symptoms may be rapid particularly in children. All nicotine intake should stop
immediately and the patient should be treated symptomatically. Artificial respiration with oxygen
should be instituted if necessary. Activated charcoal reduces the gastro-intestinal absorption of
nicotine.
5
PHARMACOLOGICAL PROPERTIES
5.1
PHARMACODYNAMIC PROPERTIES
ATC Code: N07B A01
Pharmacotherapeutic group: Drugs used in nicotine dependence
Nicotine, the primary alkaloid in tobacco products and a naturally occurring autonomous substance, is a
nicotine receptor agonist in the peripheral and central nervous systems and has pronounced CNS and
cardiovascular effects. On consumption of tobacco products, nicotine has proven to be addictive,
resulting in craving and other withdrawal symptoms when administration is stopped. This craving and
these withdrawal symptoms include a strong urge to smoke, dysphoria, insomnia, irritability, frustration
or anger, anxiety, concentration difficulties agitation and increased appetite or weight gain. The gum
replaces part of the nicotine that would have been administrated via tobacco and reduces the intensity
of the withdrawal symptoms and smoking urge.
18
UKPAR Nicotinell ® / NicAid 2mg & 4mg medicated chewing gum
5.2
PL 00030/0441-2
PHARMACOKINETIC PROPERTIES
When the gum is chewed, nicotine is steadily released into the mouth and is rapidly absorbed through
the buccal mucosa. A proportion, by the swallowing of nicotine containing saliva, reaches the stomach
and intestine where it is inactivated.
The nicotine peak plasma mean concentration after a single dose of the 2 mg coated gum is
approximately 6.4 nanograms per ml (after 45 minutes) (average plasma concentration of nicotine
when smoking a cigarette is 15-30 nanograms per ml).
Nicotine is eliminated mainly via hepatic metabolism; small amounts of nicotine are eliminated in
unchanged form via the kidneys. The plasma half-life is approximately three hours. Nicotine crosses
the blood-brain barrier, the placenta and is detectable in breast milk.
5.3
PRECLINICAL SAFETY DATA
No definite conclusion can be drawn on the genotoxic activity of nicotine in vitro. Nicotine was
negative in in-vivo tests.
Animal experiments have shown that nicotine induces post-implantation loss and reduces the growth of
foetuses.
The results of carcinogenicity assays did not provide any clear evidence of a tumorigenic effect of
nicotine.
6
PHARMACEUTICAL PARTICULARS
6.1
LIST OF EXCIPIENTS
Gum base (containing butylhydroxytoluene)
Calcium carbonate
Sorbitol (E420)
Sodium carbonate anhydrous
Sodium hydrogen carbonate
Polacrilin,
Glycerol
Purified water
Levomenthol
Peppermint oil
Eucalyptus oil
Saccharin
Sodium saccharin
Acesulfame potassium
Xylitol
Mannitol (E421)
Gelatin
Titanium dioxide (E171)
Carnauba wax
Talc.
6.2
INCOMPATIBILITIES
Not applicable.
6.3
SHELF LIFE
2 years
6.4
SPECIAL PRECAUTIONS FOR STORAGE
Do not store above 25°C.
19
UKPAR Nicotinell ® / NicAid 2mg & 4mg medicated chewing gum
6.5
PL 00030/0441-2
NATURE AND CONTENTS OF CONTAINER
The chewing-gum is packed in PVC/PVdC/aluminium blisters each containing either 2 or 12 pieces of
gum. The blisters are packed in boxes containing 2, 12, 24, 36, 48, 60, 72, 84 (PL 00030/0441 only), 96
108, 120 and 204 pieces of gum.
Not all pack sizes may be marketed.
6.6
SPECIAL PRECAUTIONS FOR DISPOSAL
No special requirements.
7
MARKETING AUTHORISATION HOLDER
Novartis Consumer Health UK Ltd
Trading as Novartis Consumer Health
Wimblehurst Road,
Horsham,
West Sussex RH12 5AB
8
MARKETING AUTHORISATION NUMBER(S)
PL 00030/0441
PL 00030/0442
9
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
09/03/2010
10
DATE OF REVISION OF THE TEXT
09/03/2010
20
UKPAR Nicotinell ® / NicAid 2mg & 4mg medicated chewing gum
PL 00030/0441-2
PATIENT INFORMATION LEAFLET
Nicotinell® / NicAid mint 2mg medicated chewing gum – PL 00030/0441
The general PIL text is identical to that shown below for the cross-referenced licence, PL 00030/0427
21
UKPAR Nicotinell ® / NicAid 2mg & 4mg medicated chewing gum
PL 00030/0441-2
22
UKPAR Nicotinell ® / NicAid 2mg & 4mg medicated chewing gum
PL 00030/0441-2
Nicotinell® / NicAid mint 4mg medicated chewing gum – PL 00030/0442
The general PIL text is identical to that shown below for the cross-referenced licence, PL 00030/0428
23
UKPAR Nicotinell ® / NicAid 2mg & 4mg medicated chewing gum
PL 00030/0441-2
24
UKPAR Nicotinell ® / NicAid 2mg & 4mg medicated chewing gum
PL 00030/0441-2
25
UKPAR Nicotinell ® / NicAid 2mg & 4mg medicated chewing gum
PL 00030/0441-2
26
UKPAR Nicotinell ® / NicAid 2mg & 4mg medicated chewing gum
PL 00030/0441-2
27
UKPAR Nicotinell ® / NicAid 2mg & 4mg medicated chewing gum
PL 00030/0441-2
28
UKPAR Nicotinell ® / NicAid 2mg & 4mg medicated chewing gum
PL 00030/0441-2
LABELLING
®
Nicotinell / NicAid mint 2mg medicated chewing gum
The labelling is identical to that shown below for the cross-referenced licence,
PL 00030/0427, apart from the PL number
Carton for blisters – pack size 12
29
UKPAR Nicotinell ® / NicAid 2mg & 4mg medicated chewing gum
PL 00030/0441-2
Carton for blisters – pack size 24
30
UKPAR Nicotinell ® / NicAid 2mg & 4mg medicated chewing gum
PL 00030/0441-2
Carton for blisters – pack size 36
31
UKPAR Nicotinell ® / NicAid 2mg & 4mg medicated chewing gum
PL 00030/0441-2
Carton for blisters – pack size 96
32
UKPAR Nicotinell ® / NicAid 2mg & 4mg medicated chewing gum
PL 00030/0441-2
Carton for blisters – pack size 120
33
UKPAR Nicotinell ® / NicAid 2mg & 4mg medicated chewing gum
PL 00030/0441-2
Carton for blisters – pack size 204
34
UKPAR Nicotinell ® / NicAid 2mg & 4mg medicated chewing gum
PL 00030/0441-2
Nicotinell® / NicAid mint 4mg medicated chewing gum
The labelling is identical to that shown below for the cross-referenced licence,
PL 00030/0428, apart from the PL number
Carton for blisters – pack size 24
35
UKPAR Nicotinell ® / NicAid 2mg & 4mg medicated chewing gum
PL 00030/0441-2
Carton for blisters – pack size 36
36
UKPAR Nicotinell ® / NicAid 2mg & 4mg medicated chewing gum
PL 00030/0441-2
Carton for blisters – pack size 96
37
UKPAR Nicotinell ® / NicAid 2mg & 4mg medicated chewing gum
PL 00030/0441-2
Carton for blisters – pack size 120
38
UKPAR Nicotinell ® / NicAid 2mg & 4mg medicated chewing gum
PL 00030/0441-2
Blister strip – 2mg gum
Blister strip – 4mg gum
39