Zonnic Pepparmint
SUMMARY OF PRODUCT CHARACTERISTICS
1. NAME OF THE MEDICINAL PRODUCT
Zonnic Pepparmint 1mg/spraying, oromucosal spray
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
0.07 ml contains 1 mg nicotine, which corresponds to 1 mg nicotine per spraying.
Excipient with known effect: ethanol
For the full list of excipients, see section 6.1.
3. PHARMACEUTICAL form
Oromucosal spray
A clear solution with a faint scent of peppermint.
4. Clinical particulars
4.1 Therapeutic indications
For the treatment of tobacco dependence by relieving nicotine craving and withdrawal symptoms, thereby facilitating smoking cessation in smokers motivated to quit or to facilitate smoking reduction in smokers who are not able or willing to quit smoking.
4.2 Posology and method of administration
Posology
The patient should not eat or drink while using the oromucosal spray. Drinks, which lower the pH in the mouth, e.g. coffee, fruit juice or sodas, may reduce the buccal absorption of nicotine. To achieve the maximum absorption of nicotine, these drinks should be avoided up to 15 minutes prior to using the oromucosal spray.
Adults and elderly
The oromucosal
spray should be sprayed 1-2 times between the cheek and the teeth.
The spray nozzle should be turned to the side and thereafter direct
the oromucosal spray between the cheek and the teeth. Spray 1-2
times and alter between the left and right cheek. Initially the
oromucosal spray can be taken every 1-2 hours. The usual dosage is
spraying 1-2 times for 8-12 times a day. The maximum daily dose is
a total of 30 sprayings (eg. spraying twice, 15 times a
day).
Paediatric population
Zonnic Pepparmint should not be administered to adolescents below 18 years of age without recommendations from a physician.
There is no experience in treating adolescents below 18 years of age with Zonnic Pepparmint.
Smoking cessation
The duration of treatment is individual. Normally, the treatment should continue for at least 3 months.
Gradually weaning from the oromucosal spray should then be initiated. Treatment should be discontinued when the dose is reduced to 1-2 sprayings per day. Regular use of Zonnic Pepparmint for more than six months is generally not recommended. In some cases a longer treatment period might be necessary in order to avoid relapse. Any spare oromucosal spray should be retained, as craving may suddenly occur.
Counselling may help smokers to quit.
Smoking reduction
Zonnic Pepparmint is used between periods of smoking in order to extend the smoking –free intervals and with regard to reduce smoking as much as possible. Professional help should be consulted if a decrease in number of cigarettes has not been achieved after 6 weeks of treatment.
An attempt to quit smoking should be made as soon as the smoker is motivated, however no later than 6 months after treatment start. Professional help should be consulted if there is no possibility to perform a serious attempt to quit smoking within 9 months. Regular use of Zonnic Pepparmint for more than 1 year is generally not recommended. Some ex- smokers may need treatment with the oromucosal spray for a longer period in order to avoid relapse. Any spare oromucosal spray should be retained, as craving may suddenly occur.
Renal and hepatic impairment
See section 4.4
4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Recent myocardial infarction (within 3 months).
Unstable and progressive angina pectoris.
Prinzmetal’s variant angina.
Severe cardiac arrhythmias.
Stroke in
acute phase.
4.4 Special warnings and precautions for use
Zonnic Pepparmint should be used with caution in patients with severe cardiovascular diseases (e.g. occlusive peripheral arterial disease, cerebrovascular disease, stable angina pectoris and uncompensated heart failure), vasospasm, uncontrolled hypertension, severe/moderate hepatic impairment, severe renal impairment, active duodenal- and gastric ulcers. The risk with continuing smoking is always a greater danger than the usage of Zonnic Pepparmint.
Nicotine both from nicotine replacement therapy and smoking, cause release of catecholamines from adrenal medulla. Therefore Zonnic Pepparmint should also be used with caution in patients with hyperthyroidism or phaeochromocytoma.
Patients with diabetes mellitus may require lower dosage of insulin as a result of smoking cessation.
Continued nicotine dependence may occur but to a lower extent. The use of nicotine itself is however less harmful than smoking/use of tobacco.
4.5 Interaction with other medicinal products and other forms of interaction
Smoking, (but not nicotine), is associated with increased activity of CYP1A2. After smoking cessation, reduced clearance of substrates for this enzyme may occur. This may lead to an increase in plasma levels for some medicinal products. The increase may have a potential clinical importance for products with a narrow therapeutic window, e.g. theophylline, tacrine, clozapine, and ropinirole.
The plasma concentration of other drugs metabolised in part by CYP1A2 e.g. imipramine, olanzapine, clomipramine and fluvoxamine may also increase on cessation of smoking. Data to support this are although lacking and the possible clinical significance of this effect for these drugs is unknown.
Limited data indicate that the metabolism of flecainide and pentazocine may also be induced by smoking.
4.6 Fertility, pregnancy and lactation
Pregnancy
Smoking during pregnancy is associated with risks such as intra-uterine growth retardation, premature birth or stillbirth, which seem to be correlated with the quantity of cigarettes smoked and the period of pregnancy, since such effects are observed when smoking is continued in the third trimester. Stopping smoking is the single most effective intervention for improving the health of both pregnant smoker and her baby and most important is to achieve stopping smoking before the first trimester of pregnancy. The earlier abstinence is achieved the better.
Nicotine passes to the foetus and affects its breathing movements and circulation. The effect on the circulation is dose-dependent.
Therefore the pregnant smoker should always be advised to stop smoking completely without use of nicotine replacement therapy. The risk of continued smoking may pose greater hazard to the foetus as compared with the use of nicotine replacement products in a supervised smoking cessation programme. Use of Zonnic Pepparmint by the pregnant highly dependent smoker should only be initiated after advice from a physician.
Lactation
Nicotine passes freely into breast milk in quantities that may affect the child even with therapeutic doses. Zonnic Pepparmint should therefore be avoided during breastfeeding.
Should smoking withdrawal not be achieved, use of Zonnic Pepparmint by breastfeeding smokers should only be initiated after advice from a physician. Where nicotine replacement therapy is used whilst breast-feeding, Zonnic Pepparmint should be taken just after breastfeeding and not during the two hours before breastfeeding.
4.7 Effects on ability to drive and use machines
Zonnic Pepparmint has no or negligible influence on the ability to drive and use machines.
Undesirable effects
Zonnic Pepparmint may cause adverse reactions similar to those associated with nicotine administered by other means and are dose dependent. Most of undesirable effects reported by the patient usually occur during the first 3-4 weeks after treatment start.
Very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1 000, <1/100);
rare (≥1/10 000, <1/1 000); very rare (<1/10 000), not known (cannot be estimated from the available data).
|
Body system |
Undesirable effects |
|
Nervous system disorders |
|
|
Common |
Dizziness, headache |
|
Cardiac disorders |
|
|
Uncommon |
Palpitations |
|
Rare |
Atrial fibrillation |
|
Skin and subcutaneous tissue disorders |
|
|
Uncommon |
Erythema, hives |
|
Gastrointestinal disorders |
|
|
Common |
Gastrointestinal discomfort, hiccups, nausea, vomiting. |
|
General disorders and administration site conditions |
|
|
Common |
Irritated mouth or throat |
|
Rare |
Allergic reaction such as e.g. angio-oedema |
Some symptoms, such as dizziness, headache and sleeplessness may be related to withdrawal symptoms associated with abstinence from smoking. Increased frequency of aphtous ulcer may occur after abstinence from smoking. The causality is unclear.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in
[To be completed nationally]
4.9 Overdose
Symptoms of overdose with nicotine may occur in patients with low pre-treatment nicotine intake or if other sources of nicotine are used concomitantly.
Symptoms of overdose are those of acute nicotine poisoning and include nausea, salivation, abdominal pain, diarrhoea, sweating, headache, dizziness, disturbed hearing and marked weakness. At high doses, these symptoms may be followed by hypotension, weak and irregular pulse, breathing difficulties, prostration, circulatory collapse and general convulsions.
Doses of nicotine that are tolerated by adult smokers during treatment may produce severe symptoms of poisoning in small children and may prove fatal.
Management of overdose: Administration of nicotine must be stopped immediately and the patient should be treated symptomatically. Activated charcoal reduces the gastrointestinal absorption of nicotine.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Drugs used in nicotine dependence
ATC code: N07BA01
Abrupt
cessation of the use of tobacco-containing products following a
prolonged period of daily use results in a characteristic
withdrawal syndrome that includes four or more of the following:
dysphoria or depressed mood; insomnia; irritability, frustration or
anger; anxiety; difficulty concentrating, restlessness or
impatience; decreased heart rate; and increased appetite or weight
gain. Nicotine craving, which is recognised as a clinically
relevant symptom, is also an important element in nicotine
withdrawal.
Clinical
studies have shown that nicotine replacement products can help
smokers abstain from smoking by relieving these withdrawal
symptoms.
Compared with nicotine gum or nicotine lozenge, the absorption of nicotine from the oromucosal spray is more rapid (section 5.2).
In an open-label, single-dose crossover craving study in 48 healthy smokers it was observed that one and two sprays of 1 mg Zonnic oromucosal spray reduced the urge to smoke significantly more than nicotine lozenge 4 mg, at 1 minute after administration. It has not been shown that the properties of the spray formulation made any difference with respect to quitting smoking.
5.2 Pharmacokinetic properties
Absorption
The amount of released nicotine being absorbed from a nicotine oromucosal spray depends on the amount of nicotine released in the oral cavity and the amount thereof that is swallowed. The main part of nicotine released is absorbed through the buccal mucosa. The systemic bioavailability of swallowed nicotine is lower due to first- passage elimination.
In normal case approximately 1 mg of nicotine is released from one dose of oromucosal spray.
Nicotine uptake from the oral nicotine spray was detected at 4 min, the first timepoint tested. In the same study, nicotine was not detected at 4 min after nicotine lozenge administration. The median Tmax was 30 minutes (range 4 to 120 minutes) after administration of a 1 or 2 mg dose of the spray. The maximum plasma concentration was 3.1 and 5.2 ng/ml and AUCinf was 10 and 17 h*ng/ml after a 1 and 2 mg dose, respectively.
Distribution
The volume of distribution following i.v. administration of nicotine is about (2-) 3l/kg and its half-life is about 2 hours. Other diseases or concomitant use of other drugs which influence levels of plasma proteins are not expected to have any significant effect on the kinetics of nicotine.
Biotransformation
Nicotine is
metabolized mainly in the liver and plasma clearance is in average
about 70 l/ hour. Nicotine is metabolized also in kidneys and
lungs. More than 20 metabolites are identified whereof all are
believed to be less active than nicotine. The primary metabolite of
nicotine is cotinine which has a half-life 15-20 hours and which
give plasma concentrations that exceed nicotine by 10-fold. Plasma
protein binding is less than 5 %.
Elimination
The major metabolites in urine are cotinine (15 % of the dose) and trans-3-hydroxycotinin (45% of the dose). About 10% of nicotine is excreted unchanged in the urine. As much as 30% of nicotine may be excreted in the urine at increased diuresia and acidification of the urine below pH 5.
Special populations
Heavily impaired kidney function is assumed to exert influence on total clearance of nicotine.
The pharmacokinetics of nicotine is unaffected in cirrhotic patients with mild liver impairment (Child score 5) and decreased in liver cirrhosis patients with moderately liver impairment (Child score 7). Increased nicotine levels have been observed in smoking haemodialysis patients.
Minor reduction of total clearance of nicotine has been demonstrated in healthy, elderly users, however, adjusting of the dose is not necessary.
No differences in nicotine kinetics have been observed between males and females.
5.3 Preclinical safety data
Nicotine was positive in some in vitro genotoxicity tests but there are also negative results with the same test systems. 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
Sucralose
Mint flavour
Ethanol
Glycerol
Potassium dihydrogen phosphate
Sodium hydroxide
Water
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
2 years
6.4 Special precautions for storage
Do not store above 25°C. Store in the original package.
Nature and contents of container
Vial of glass or plastic (PET) with accuator made of polypropylene. Each vial contains 3 ml (40 sprayings) or 15 ml (200 sprayings).
Package sizes:
40 sprayings
200 sprayings
400 (2 x 200) sprayings
6.6 Special precautions for disposal and other handling
No special requirements.
7. MARKETING AUTHORISATION HOLDER
Niconovum AB
Järnvägsgatan 13
252 24 Helsingborg
8. MARKETING AUTHORISATION NUMBER(S)
25810
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
2008-06-26/2013-06-26
10. DATE OF REVISION OF THE TEXT
2015-03-11
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