NICORAMA FRUITMINT 2 MG MEDICATED CHEWING-GUM - summary of medicine characteristics

1 NAME OF THE MEDICINAL PRODUCT

Nicorama Fruitmint 2 mg medicated chewing-gum

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Nicotine resinate 10 mg, corresponding to nicotine 2 mg.

Excipients with known effect

Xylitol, butylated hydroxytoluene and butylated hydroxyanisole.

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Medicated chewing-gum

White to off-white, round, biconvex, coated chewing-gums, which are smooth on both sides. Diameter: 15 mm and thickness: 8 mm.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

For treatment of tobacco dependence by providing relief of nicotine craving and withdrawal symptoms, and thereby facilitating smoking cessation in smokers motivated to stop smoking. Permanent cessation of tobacco use is the aim of the treatment.

Nicorama Fruitmint should preferably be used in conjugation with a behavioral support program.

4.2 Posology and method of administration

Posology

Adults and elderly:

The strength of the chewing-gum should be selected based on the patient’s nicotine dependency. For low nicotine dependency, the 2 mg chewing-gum is recommended.

For high nicotine dependency (FTND > 6 or if the patient smokes > 20 cigarettes/day) or after previous failure with 2 mg chewing-gums, the 4 mg chewing-gum is recommended.

Nicorama Fruitmint chewing-gum should be used when cigarettes normally would have been smoked or if smoke craving arise.

At the beginning of treatment, 1 chewing-gum can be taken every 1 to 2 hours. Sufficient number of gums should be used daily. The dosage is individual and should be based on the smoker’s nicotine dependency. In most cases, 8–12 chewing-gums per day are sufficient, irrespective of strength. In order to maximize the chances to succeed, it is important to avoid underdosing.

Maximum daily dose:

Nicorama Fruitmint 2 mg: 24 gums per day, corresponding to nicotine 48 mg/day.

Administration of nicotine should be stopped temporarily if any symptoms of nicotine overdose occurs. If symptoms of nicotine overdose remain, the nicotine intake should be reduced either by lowering the dosing frequency or the strength (see section 4.9).

The treatment duration is individual. Normally, treatment should continue for at least 3 months. After 3 months, the nicotine dose is gradually reduced. Treatment should be discontinued when the dose has been reduced to 1–2 chewing-gums per day. Regular use of Nicorama Fruitmint chewing-gums for more than 6 months is generally not recommended. However, some ex-smokers may need longer treatment to avoid returning to smoking. Any spare gum should be retained, as craving may suddenly occur.

Counselling and support may improve the chance to succeed.

Paediatric population

Nicorama Fruitmint chewing-gum should not be used in adolescents (12–17 years of age) unless prescribed by healthcare professionals. There is no experience in treating adolescents under the age of 18 with Nicorama Fruitmint.

Children below 12 years of age:

Nicorama Fruitmint chewing-gum should not be used in children below 12 years of age.

Renal and Hepatic impairment

Use with caution in patients with moderate to severe renal impairment and/or moderate to severe hepatic impairment as the clearance of nicotine or its metabolites maybe decreased with the potential for increased adverse effects.

Method of administration

Each Nicorama Fruitmint chewing-gum should be chewed slowly, with pauses, for 30 minutes. Nicorama Fruitmint should be chewed until the taste becomes strong or a slight burning sensation is felt, stop chewing and let the gum rest between your cheek and the gums until the taste and the burning sensation has ceased, start chewing slowly again, and repeat.

The user should not eat or drink when using the gum. Drinks lowering the pH in the oral cavity, e.g. coffee, juice and soda, may decrease the absorption of nicotine in the oral cavity. In order to reach maximal absorpion of nicotine, these drinks should be avoided for up to 15 minutes prior to using the chewing-gum.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Children below 12 years of age.

Non-smokers.

4.4 Special warnings and precautions for use

The benefits of stopping smoking outweigh any risks that may be associated with the correct treatment of nicotine replacement therapy.

A benefit/risk assessment should be performed by appropriate healthcare professional in patients with following conditions:

Cardiovascular disease: Smokers with a recent myocardial infarction, unstable or worsening angina including Prinzmetal's an­gina, severe cardiac arrhythmias, recent cerebrovascular accident and/or uncontrolled hypertension, should be encouraged to stop smoking with non-pharmacological interventions (such as counselling). If this fails, Nicorama Fruitmint chewing-gum may be considered, but as data on safety in this patient group are limited, initiation should only be under close medical supervision.

Diabetes mellitus: Patients with diabetes mellitus should be advised to monitor their blood sugar levels more closely than usual when they stop smoking and nicotine replacement therapy is initiated as a reduction in nicotine induced catecholamines release can affect carbohydrate metabolism. They may require lower insulin doses as a result of smoking cessation.

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.

Seizures: Potential risks and benefits of nicotine should be carefully evaluated before use in subjects taking anti-convulsant therapy or with a history of epilepsy as cases of convulsions have been reported in association with nicotine.

Pheochromocytoma and uncontrolled hyperthyroidism: Nicotine, both from drugs and from smoking, causes release of catecholamines from the adrenal medulla. Therefore, Nicorama Fruitmint chewing-gum should be used with caution in patients with uncontrolled hyperthyroidism or pheochromocytoma.

Gastro-intestinal disease: Nicotine may exacerbate symptoms in patients suffering from oesophagitis, gastric or peptic ulcers. Nicotine replacement therapy should be used with caution in these conditions.

Smokers wearing dentures may experience difficulties with chewing Nicorama Fruitmint. The chewing-gum may stick to, and in rare cases, damage dentures and dental bridges.

Paediatric population

Danger in small children: doses of nicotine that are tolerated by adult smokers during treatment may produce severe symptoms of poisoning in small children and may prove fatal (please see Section 4.9). Products containing nicotine should not be left where they can be misused, handled or ingested by children (see section 4.9).

Transferred dependence

Transferred dependence of Nicorama Fruitmint is rare and is both less harmful and easier to break than smoking dependence.

Nicorama Fruitmint contains xylitol, which may have a laxative effect.

Calorific value: 2.4 kcal/g xylitol, corresponding to 0.8 kcal per chewing-gum (Nicorama Fruitmint 2 mg and 4 mg).

Nicorama Fruitmint contains butylated hydroxytoluene and butylated hydroxyanisole, which may cause local skin reactions (e.g. contact dermatitis) or cause irritation to eyes and mucous membranes.

This medicine contains less than 1 mmol sodium (23 mg) per dosage unit, that is to say essentially ‘sodium-free”.

4.5 Interaction with other medicinal products and other forms of interaction Drug Interactions

No information is available on interactions between Nicorama Fruitmint and other medicinal products.

Smoking Cessation

Smoking but not nicotine is associated with increased CYP1A2 activity. After stopping smoking there may be reduced clearance of substrates for this enzyme and increased plasma levels of some medicinal products of potential clinical importance because of their narrow therapeutic window e.g. theophylline, tacrine, olanzapine and clozapine.

The plasma concentrations of other active substances metabolised by CYP1A2 e.g. caffeine, paracetamol, phenazone, phenylbutazone, pentazocine, lidocaine, benzodiazepines, warfarin, oestrogen and vitamin B12 may also increase. However the clinical significance of this effect for these active substances is unknown.

Smoking may lead to reduced analgesic effects of propoxyphene, reduced diuretic response to furosemide (frusemide), reduced effect of propranolol on blood pressure and heart rate and reduced responder rates in ulcer healing with H2-antagonists.

Smoking and nicotine may raise the blood levels of cortisol and catecholamines, i.e. may lead to a reduced effect of nifedipine or adrenergic antagonists and to an increased effect of adrenergic agonists.

Limited data indicate that the metabolism of flecainide and pentazocine may potentially also be induced by smoking.

Increased subcutaneous absorption of insulin which occurs upon smoking cessation may necessitate a reduction in insulin dose.

4.6 Fertility, pregnancy and lactation

Women of child-bearing potential/birth control in men and women

In contrast to the well-known adverse effects of tobacco smoking on human conception and pregnancy, the effects of therapeutic nicotine treatment are unknown. Thus, whilst to date no specific advice regarding the need for female contraception has been found to be necessary, the most prudent state for women intending to become pregnant is to be both non-smoking, and not using nicotine replacement therapy.

Whilst smoking may have adverse effects on male fertility, no evidence exists that particular contraceptive measures are required during nicotine replacement therapy by males.

Pregnancy

Smoking during pregnancy is associated with risks such as intra-uterine growth retardation, premature birth or stillbirth. Stopping smoking is the single most effective intervention for improving the health of both the pregnant smoker and her baby, and the earlier abstinence is achieved the better.

Nicotine passes the placenta affecting the breathing pattern and circulation of the fetus. The effect on the circulation of the fetus is dose dependent. Pregnant smokers should therefore always be advised to stop smoking completely without using any nicotine drugs. The risk of continued smoking may however be a greater risk for the fetus than the use of nicotine replacement therapy in a controlled smoking cessation program. Nicorama Fruitmint chewing-gum should only be used in pregnant women with a strong nicotine dependency on the advice of healthcare professionals.

Breastfeeding

Nicotine is excreted in human milk in quantities that may affect the child even with therapeutic doses. Nicorama Fruitmint chewing-gums should therefore be avoided during breastfeeding. If smoking cessation has not been achieved, breastfeeding smokers should only use Nicorama Fruitmint on the advice of healthcare professionals. Intermittent dose forms would minimize the amount of nicotine in breast milk and permit feeding when levels were at their lowest. Women should then take the gum immediately after breastfeeding.

Fertility

Smoking increases the risk of infertility in women and men. In vitro-studies have shown that nicotine can negatively affect sperm characteristics. Impaired sperm characteristics and reduced fertility has been shown in rats. Effects similar to those in rats have not been reported to occur in humans.

4.7 Effects on ability to drive and use machines

Nicorama Fruitmint has no or negligible influence on the ability to drive and use machines.

4.8 Undesirable effects

Nicorama Fruitmint gums may cause adverse reactions similar to those associated with nicotine administered by other means. Most of the undesirable effects reported by patients occur during the first 3–4 weeks after start of treatment. The undesirable effects of nicotine gums can predominantly be attributed to incorrect chewing technique or to the pharmacological effects of nicotine, which are dose dependent.

Mouth and throat irritation may be experienced, but most users adapt to this at continuous use.

The adverse reactions observed in patients treated with oral nicotine formulations during clinical trials and post-marketing experience are listed below by system organ class.

For the adverse reactions identified post-marketing, the frequency categories have been estimated from clinical trials.

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).

Allergic reactions (including symptoms of anaphylaxis) are rare when using Nicorama Fruitmint.

Effects of smoking cessation

Irrespective of what method is being used, a wide variety of symptoms are associated with stopping habitual use of tobacco. These include emotional or cognitive effects such as; dysphoria or depressed mood; insomnia; irritability, frustration or anger; anxiety; poor concentration and restlessness or impatience. There may also be physical effects, e.g. decreased heart rate, increased appetite or weight gain, dizziness or presyncopal symptoms, cough, constipation, gingival bleeding or aphthous ulcers or nasopharyngitis. In addition, and of clinical importance, nicotine addiction may lead to strong urge to smoke (craving).

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 Yellow Card Scheme

Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9 Overdose

Symptoms

Symptoms of nicotine overdose may occur if the patient has a low nicotine consumption before treatment or concomitanly use other nicotine sources.

Symptoms of overdose are the same as symptoms of acute nicotine poisoning such as nausea, vomiting, salivation, abdominal pain, diarrhoea, sweating, headache, dizziness, disturbed hearing and pronounced weakness. At high doses, these symptoms may be followed by hypotension, weak or irregular pulse, breathing difficulties, prostration, circulatory collapse and generalized convulsions.

Nicotine doses tolerated by adult smokers during ongoing treatment may result in serious symptoms of poisoning in children, which may prove fatal. Suspected nicotine poisoning in a child should be considered a medical emergency and treated immediately.

Treatment of overdose

All nicotine intake must be stopped immediately, and the patient should be treated symptomatically. If excessive quantities of nicotine are swallowed, activated charcoal reduces the gastrointestinal absorption of nicotine.

The acute minimum lethal dose of nicotine in human has been estimated to be 40 to 60 mg.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Drugs used in nicotine dependence, ATC code: N07BA01

Abrupt discontinuation of tobacco products after a long period of daily use may cause characteristic withdrawal symptoms including four or several of the following symptoms; depression or lowered mood, insomnia, irritability, frustration or aggression, anxiety, concentration difficulties, restlessness or impatience, decreased heart rate, increase appetite or weight gain. Craving, recognized as a clinically relevant symptom, is an important part of the withdrawal symptoms of stopping smoking.

Clinical studies have shown that nicotine replacement therapy can help smokers refrain from smoking.

Comparative efficacy studies between different formulations of Nicorama Fruitmint have not been conducted.

5.2 Pharmacokinetic properties

Absorption

The amount of released nicotine absorbed from one nicotine gum depends on the amount of nicotine released in the oral cavity and what disappears through swallowing. The majority of nicotine being released is absorbed by the oral mucosa.

Distribution

The systemic bioavailability of swallowed nicotine is lower due to first-pass elimination. The high and rapidly increasing nicotine concentrations seen upon smoking is rarely achieved with gum treatment.

Normally, approximately 1.4 mg nicotine from a 2 mg gum and approximately 3.4 mg nicotine from a 4 mg gum is released. Maximum blood concentration is reached after 30 minutes of chewing, comparable with the concentration at 2030 minutes after smoking a medium-strong cigarette.

Biotransformation

Distribution volume after intravenous administration of nicotine is approximately (2)3 L/kg and the half-life is approximately 2 hours. Nicotine is metabolized mainly in the liver with an average plasma clearance of approximately 70 L/hour. Nicotine is also metabolized in the kidneys and lungs. More than 20 metabolites have been identified, all of which are believed to be less active than nicotine. The major metabolite is cotinine, with a half-life of 15–20 hours giving approximately 10 times higher plasma concentrations than nicotine. The plasma protein binding of nicotine is less than 5%.

Other disorders or concomitant use of other medical products affecting the level of plasma proteins are not expected to have any significant effect on the kinetics of nicotine.

The major metabolites in urine are cotinine (15% of the dose) and trans-3-hydroxycotinine (45% of the dose). Approximately 10% of the nicotine is excreted unchanged in the urine. Up to 30% can be excreted with increased diuresis and acidification below pH 5.

Elimination

Severe renal impairment is likely to affect total clearance of nicotine. The pharmacokinetics of nicotine is unaffected in patients with cirrhosis with mild hepatic impairment (Child score 5) and reduced in patients with cirrhosis with moderate hepatic impairment (Child score 7).

Elevated nicotine levels have been observed in smoking haemodialysis patients.

A smaller reduction of total clearance of nicotine has been shown in healthy, elderly users, however an adjustment of the dose is not necessary.

No differences in the kinetics of nicotine has been observed between women and men.

5.3 Preclinical safety data

There are no pre-clinical safety data for nicotine gums.

As a tobacco component the toxicity of nicotine is however well documented. The most common symptoms at nicotine overdose are nausea and vomiting. The symptoms of severe acute poisoning are weak and irregular pulse, breathing difficulties and generalized convulsions.

There is no evidence of nicotine being genotoxic or mutagenic. The well-known carcinogenic properties of tobacco smoke are formed mainly by pyrolysis of tobacco. None of this occur in nicotine gums.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Chewing gum base (containing butylated hydroxytoluene [E321])

Xylitol (E967)

Silica, colloidal, hydrated

Magnesium stearate

Sodium carbonate, anhydrous

Hypromellose

Flavouring with cooling effect

Mint flavour

Sodium hydrogen carbonate

Citrus-/fruit flavour (containing butylated hydroxyanisole [E320])

Levomenthol

Macrogol

Glycerol

Titanium dioxide (E171)

Talc

Acesulfame potassium

Sucralose

Xanthan gum

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

2 years

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5 Nature and contents of container

30, 96, 105 and 204 gums in blisters.

The blister consists of PVC/PVDC film and aluminium foil.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

No special requirements.

7 MARKETING AUTHORISATION HOLDER

Enorama Pharma AB

Sodergatan 3

211 34 Malmo

Sweden

8 MARKETING AUTHORISATION NUMBER(S)

PL 52211/0003

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THEAUTHORISATION

08/06/2020