Nicorette® with fresh fruit flavor

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT NICO RETTE® FRESH FRUIT FLAVOUR (NICORETTE® FRESHFRUIT)

Composition:

Active substance: nicotine; 3-(1-methyl-2-pyrrolidinyl)pyridine;

One therapeutic chewing gum contains a nicotine-polymer complex – 11.0 mg or 22.0 mg, corresponding to nicotine 2 mg or 4 mg;

Excipients: Core: gum base, xylitol, peppermint oil, anhydrous sodium carbonate, sodium bicarbonate (only in the 2 mg dosage), potassium acesulfame, levomenthol, light magnesium oxide, quinoline yellow (E 104) (only in the 4 mg dosage); Sub-coating: Tutti-frutti QL84441, hypromellose, sucrose, polysorbate 80; Hard coating: xylitol, acacia resin, titanium dioxide (E 171), Tutti-frutti QL84441, carnauba wax, quinoline yellow (E 104) (only in the 4 mg dosage).

Pharmaceutical form. Therapeutic chewing gum.

Main physicochemical properties: White (for 2 mg) or light yellow (for 4 mg) coated square tablets, approximately 15×15×6 mm in size.

Pharmacotherapeutic group. Medicinal product for the treatment of nicotine dependence.

ATC code N07BA01.

Pharmacological Properties

Pharmacodynamics

Sudden cessation of nicotine-containing products after a prolonged period of daily use leads to a characteristic withdrawal syndrome: dysphoria or depression; insomnia; irritability; frustration or aggression; restlessness; difficulty concentrating; impatience; cardiovascular disturbances; increased appetite or weight gain. Nicotine dependence is also a prominent clinical symptom observed during withdrawal syndrome.

Nicorette® with fresh fruit flavor helps prevent the development of withdrawal syndrome in individuals who have stopped smoking; it assists in avoiding the development of nicotine dependence.

Nicorette® with fresh fruit flavor, when used at the appropriate dose, helps control body weight after smoking cessation.

Pharmacokinetics

The amount of nicotine absorbed depends on the quantity of nicotine released and that lost due to swallowing. During chewing, nicotine is slowly released and absorbed through the oral mucosa. Systemic bioavailability of swallowed nicotine is low due to its hepatic metabolism via the so-called "first-pass effect." Rapid attainment of high nicotine concentrations, as observed during smoking, is unlikely with the use of Nicorette®.

Typically, 1.4 mg of nicotine is released from the 2 mg gum, or 3.4 mg of nicotine from the 4 mg gum.

Maximum blood concentration is reached after 30 minutes of chewing and at that point is comparable to the concentration achieved 20–30 minutes after smoking a cigarette of average strength.

Clinical characteristics.

Indications.

Treatment of tobacco dependence by reducing the need for nicotine and alleviating withdrawal symptoms; facilitating smoking cessation when there is motivation; assisting smokers who are unable to completely quit nicotine dependence to reduce the number of cigarettes smoked.

Contraindications.

Nicorette® with fresh fruit flavor is contraindicated in the following cases:

1. Hypersensitivity to nicotine or to any component of the product;
2. Recent myocardial infarction (within the last 3 months);
3. Unstable or progressing angina pectoris;
4. Prinzmetal's angina;
5. Severe cardiac arrhythmias;
6. Acute stroke.

Interaction with other medicinal products and other forms of interaction.

Smoking (but not nicotine itself) is associated with increased CYP1A2 enzyme activity. After smoking cessation, a decrease in the clearance of substrates of this enzyme may occur. This may lead to increased plasma levels of certain medicinal products; this effect may also be clinically significant for drugs with a narrow therapeutic window, such as theophylline, tacrine, clozapine, and ropinirole.

Plasma concentrations of some other medicinal products metabolized by CYP1A2 may also increase after smoking cessation; for example, this phenomenon may occur with imipramine, olanzapine, clomipramine, and fluvoxamine, but data confirming this effect are insufficient, and potential clinical consequences have not been studied.

Limited data suggest that the metabolism of flecainide and pentazocine may also be altered by smoking.

Nicotine may enhance the hemodynamic effects of adenosine, such as increased blood pressure and heart rate, as well as intensify pain response (chest pain resembling angina) caused by adenosine administration.

Special precautions for use.

In smokers who wear removable dentures, difficulties may occur when chewing Nicorette® Fresh Fruit flavored gum. The chewing gum may adhere to dental prostheses and occasionally damage them.

Nicorette® Fresh Fruit flavored chewing gum should be used with caution in patients with severe cardiovascular diseases: peripheral arterial occlusive disease, cerebrovascular disorders, decompensated heart failure, stable angina pectoris, vasospasm, uncontrolled hypertension.

The physician should carefully weigh the risks and benefits in patients with the following conditions.

Smokers dependent on tobacco who have recently suffered a myocardial infarction (˂ 4 weeks), unstable or progressing angina, including Prinzmetal's angina, severe cardiac arrhythmias, uncontrolled arterial hypertension, or recent stroke should be encouraged to quit smoking without pharmacological treatment (e.g., through psychotherapy). If this approach fails, use of Nicorette® Fresh Fruit flavored chewing gum may be considered. Since safety data in this patient group are limited, the use of Nicorette® Fresh Fruit flavored chewing gum should be strictly under close medical supervision.

Nicorette® Fresh Fruit flavored chewing gum should be used with caution in patients with moderate or severe hepatic impairment or severe renal impairment, as clearance of nicotine or its metabolites may be reduced, increasing the risk of adverse effects.

Nicotine may exacerbate symptoms in patients with esophagitis, gastric or peptic ulcers; therefore, Nicorette® Fresh Fruit flavored chewing gum should be used with caution in such patients. Cases of ulcerative stomatitis have been reported.

Nicotine, whether from chewing gum or from smoking, promotes the release of catecholamines by the adrenal glands. Therefore, Nicorette® Fresh Fruit flavored chewing gum should be used cautiously in patients with uncontrolled hyperthyroidism or pheochromocytoma.

Patients with diabetes who are quitting smoking and starting nicotine replacement therapy should be monitored more closely than usual for blood glucose levels, since reduced nicotine-induced catecholamine release may affect carbohydrate metabolism.

Cessation of smoking may necessitate a reduction in insulin dosage in patients with diabetes.

Some patients continue to use Nicorette® Fresh Fruit flavored gum beyond the recommended duration; however, the potential risk of prolonged gum use is significantly lower than the continued risk of smoking.

Nicorette® Fresh Fruit flavored chewing gum contains xylitol, which may have a laxative effect.

Caloric content: 2.4 kcal/g of xylitol, corresponding to 1.5 kcal and 1.4 kcal per piece (Nicorette® Fresh Fruit flavored 2 mg and 4 mg, respectively).

Special precautions for the combination of Nicorette® Fresh Fruit flavored chewing gum and Nicorette® transdermal patch are the same as for each product individually (see the medical instructions for Nicorette® transdermal patch).

Seizures: Caution is advised in patients receiving anticonvulsant therapy or with a history of epilepsy, as seizures have been reported in association with nicotine use.

Potential for dependence: Dependence on nicotine-containing medications may occur. However, it is rare, less harmful to health than tobacco-related nicotine dependence, and easier to overcome.

Use during pregnancy or breastfeeding

Nicotine crosses the placenta and affects fetal respiration and circulation. The circulatory effect is dose-dependent. Smoking during pregnancy may lead to low birth weight and increases the risk of pregnancy complications and perinatal mortality.

Cessation of nicotine use is the single most effective measure to improve the health of a pregnant smoker and her child; the earlier this occurs, the better.

Pregnant women should be advised to quit smoking without using nicotine replacement therapy. However, if a pregnant woman cannot quit smoking without pharmacological support (or this is considered unlikely), nicotine replacement therapy may be used, as the risk to the fetus is lower than that associated with continued smoking.

For nicotine replacement therapy in pregnancy, intermittent-dose nicotine formulations are preferred due to the possibility of reducing nicotine exposure. However, in the presence of nausea and/or vomiting, transdermal patches may be necessary, which, if possible, should be removed at night when the fetus is usually not exposed to nicotine.

Smoking may cause significant harm to the fetus or infant and should be discontinued. The risk to the fetus from using Nicorette® has not been fully studied. Continuing to smoke poses a greater threat to the fetus than using nicotine replacement therapy.

Nicorette® chewing gum may be used during pregnancy only in cases of very high nicotine dependence and only under a physician's recommendation.

Nicotine freely passes into breast milk in amounts that may adversely affect the infant, even when used at therapeutic doses. Therefore, breastfeeding women should be advised to quit smoking without using nicotine replacement therapy. If this is not possible, use of Nicorette® Fresh Fruit flavored chewing gum may be considered only on a physician’s recommendation after careful risk-benefit assessment.

Nicotine intake should be avoided during breastfeeding. The relatively small amount of nicotine found in breast milk during nicotine replacement therapy is less dangerous to the infant than passive smoking. Intermittent-dose nicotine formulations may minimize nicotine levels in breast milk and allow breastfeeding during periods of lowest nicotine concentration.

The product should be taken as soon as possible after breastfeeding.

Tobacco smoking in women delays conception and reduces the success rate of in vitro fertilization, significantly increasing the risk of infertility.

In men, tobacco smoking reduces sperm production, increases oxidative stress, and damages DNA. Spermatozoa from smokers have reduced fertilizing capacity.

There are no reliable data on the effects of nicotine on human reproductive function.

Effect on reproductive function

Unlike the well-known adverse effects of tobacco smoking on conception and pregnancy in humans, the corresponding effects of nicotine used for therapeutic purposes are unknown. Currently, there are no specific recommendations regarding the need for female contraception in such cases. It is more advisable for women trying to conceive to abstain from both tobacco smoking and nicotine replacement therapy. Although tobacco smoking may negatively affect male fertility, there is no evidence supporting the need for contraceptive use by men during nicotine replacement therapy.

Effect on the ability to drive or operate machinery

Caution is advised when driving or operating machinery, as the use of Nicorette® may occasionally cause dizziness.

Dosage and method of application.

Nicorette® 2 mg chewing gum can be used as monotherapy or in combination with Nicorette® transdermal patch.

Nicorette® 4 mg chewing gum is used as monotherapy.

Do not eat or drink while chewing the gum. Beverages that lower the pH of the oral cavity, such as coffee, juice, or mineral water, may reduce nicotine absorption in the mouth. To achieve maximum nicotine absorption, avoid consuming these beverages for 15 minutes before using the gum.

Adults and elderly patients

Use of Nicorette® Fresh Fruit Flavour Chewing Gum as monotherapy.

Each piece of Nicorette® Fresh Fruit Flavour Chewing Gum should be slowly chewed for approximately 30 minutes, with pauses. Chew the gum until a strong taste of nicotine or a moderate tingling sensation is felt; then stop chewing, place the gum between the gum and cheek until the taste and tingling disappear, then slowly chew again and repeat the procedure.

Depending on the intensity of smoking dependence, chewing gum with different active substance concentrations may be used. For mild dependence, use 2 mg chewing gum. For heavy smokers (Fagerström test for nicotine dependence ≥ 6 points, or those who smoke more than 20 cigarettes per day, or who smoke their first cigarette within 30 minutes after waking up), or patients who cannot quit smoking using 2 mg Nicorette® Fresh Fruit Flavour Chewing Gum, it is recommended to start treatment with the 4 mg dosage form.

At the beginning of treatment, one piece every 2 hours may be used. Usually, 8–12 chewing gums per day are sufficient. Do not use more than 24 pieces per day (for the 4 mg dosage) or more than 30 pieces per day (for the 2 mg dosage).

Complete smoking cessation

Treatment duration is individual. After complete smoking cessation, continue using Nicorette® for at least 3 months. Then gradually reduce the number of chewing gums used. Discontinue the product when daily consumption decreases to 1–2 pieces.

Regular use of Nicorette® Fresh Fruit Flavour Chewing Gum for more than 12 months is not recommended, although some former smokers may require longer treatment to prevent relapse. Keep several pieces of chewing gum available in case of sudden cravings.

Psychological counseling and support generally help achieve success.

Smoking reduction

If smoking cessation is achieved gradually by reducing the number of cigarettes smoked, chew the gum between smoking episodes, immediately when an irresistible urge to smoke arises, in order to maximize the intervals between smoking episodes and thereby reduce daily cigarette consumption. If reduction in the number of smoked cigarettes is not achieved within 6 weeks, reassess the therapeutic approach.

An attempt to quit smoking should be made when the patient feels ready, but no later than 6 months after starting treatment. If significant smoking cessation is not achieved within 9 months of starting treatment, reassess the treatment regimen.

Regular use of Nicorette® Fresh Fruit Flavour Chewing Gum for more than 12 months is not recommended, although some former smokers may require longer treatment to prevent relapse. Keep several pieces of chewing gum available in case of sudden cravings.

Psychological counseling and support generally help achieve success.

Temporary abstinence

To prevent symptoms of temporary abstinence, it is recommended to use Nicorette® chewing gum during periods when the patient does not smoke, for example, in smoke-free zones or in other situations when the patient is unable to smoke and experiences sudden cravings.

Use of 2 mg Nicorette® Fresh Fruit Flavour Chewing Gum in combination with Nicorette® transdermal patch

Patients who still experience cravings despite using nicotine-containing medications, or who have not succeeded with Nicorette® chewing gum alone, may use Nicorette® transdermal patch together with Nicorette® Fresh Fruit Flavour Chewing Gum to rapidly relieve sudden cravings.

Initial combination therapy

Begin treatment with one 25 mg/16 hours patch per day in combination with 2 mg Nicorette® Fresh Fruit Flavour Chewing Gum. Use at least 4 pieces of 2 mg chewing gum per day. In most cases, 5–6 pieces per day are sufficient. Do not use more than 24 pieces per day. Treatment usually lasts 6–12 weeks. Then gradually reduce the nicotine dose.

Apply the patch in the morning and remove it before bedtime. Apply the patch to a dry, clean, hairless, and undamaged area of skin on the torso, arms, or thighs.

To reduce the risk of local irritation, apply the Nicorette® transdermal patch alternately to different skin areas.

After applying the patch, wash hands thoroughly to avoid eye irritation from residual nicotine on fingers.

Discontinuation of nicotine medications

Two possible regimens are available (see table below).

1. Regimen with continued use of transdermal patch. Use a lower-strength patch, i.e., 15 mg/16 hours for 3–6 weeks, followed by a 10 mg/16 hours patch for another 3–6 weeks, in combination with the initial dose of 2 mg Nicorette® Fresh Fruit Flavour Chewing Gum. Then gradually reduce the number of chewing gum pieces over 12 months.
2. Regimen without continued use of transdermal patch. Discontinue the patch and gradually reduce the number of chewing gum pieces over 12 months.

Table of recommended dosages:

Time period	Transdermal patch	2 mg chewing gum
First 6-12 weeks	1 patch with a strength of 25 mg/16 hours per day	As needed. Recommended: 5-6 pieces per day
Scheme 1. Scheme with subsequent use of transdermal patch.
Next 3-6 weeks	1 patch with a strength of 15 mg/16 hours per day	Continue using chewing gum as needed.
Further 3-6 weeks	1 patch with a strength of 10 mg/16 hours per day	Continue using chewing gum as needed.
Up to 12 months	----	Gradual reduction in the number of chewing gum pieces.
Scheme 2. Scheme without subsequent use of transdermal patch.
Up to 12 months	----	Gradual reduction in the number of chewing gum pieces.

Children. Experience with the use of NICORETTE®** in children is lacking. Nicotine chewing gum should not be used in individuals under 18 years of age without medical supervision.**

Overdose.

Overdose may occur if the patient has very low tolerance to nicotine at the beginning of treatment or simultaneously receives nicotine from other sources (e.g., continued smoking). It is known that nicotine dependence, such as in smokers, leads to increased tolerance compared to non-smokers. The acute lethal dose of nicotine is 40–60 mg in children (in cases of tobacco ingestion from cigarettes into the oral cavity) and 0.8 to 1.0 mg/kg in non-smoking adults.

Excessive use of nicotine through chewing gum and/or continued smoking may cause symptoms of overdose. The risk of poisoning from swallowing chewing gum is very low, since without chewing, absorption is very slow and incomplete.

Symptoms of overdose are the same as those observed in acute nicotine poisoning: nausea, increased salivation, abdominal pain, diarrhea, sweating, headache, dizziness, hearing disturbances, and pronounced general weakness. With high doses of nicotine, in addition to the above symptoms, arterial hypotension, weak and irregular pulse, labored breathing, prostration, vascular collapse, and generalized seizures may occur.

Nicotine doses that are well tolerated by adult smokers during treatment may cause severe poisoning symptoms in young children, potentially leading to fatal outcomes.

Management in case of overdose

Nicotine administration should be stopped immediately, and symptomatic treatment should be initiated. Activated charcoal reduces nicotine absorption in the gastrointestinal tract.

Adverse Reactions

Possible consequences of smoking cessation: these include emotional and cognitive effects such as dysphoria or depressed mood, nocturnal awakenings, insomnia, irritability or aggression, frustration or anger, anxiety, restlessness, difficulty concentrating, and arousal. Physical effects of smoking cessation may also occur, such as decreased heart rate, increased appetite or weight gain, dizziness or pre-syncope symptoms, cough, constipation, gum bleeding or aphthous ulcers, or nasopharyngitis. In addition, clinically significant nicotine craving may lead to frequent urges to smoke.

Nicorette® Fresh Fruit Flavour may cause adverse reactions similar to those caused by nicotine from other sources.

Excessive use of Nicorette® Fresh Fruit Flavour chewing gum by non-smokers may lead to nausea, weakness, or headache. Excessive swallowing of dissolved nicotine may initially cause hiccups.

Nicotine contained in the chewing gum may sometimes cause mild throat irritation at the beginning of treatment; however, most patients adapt to this with continued use.

Increased salivation may occur during use of the product.

Allergic reactions (including symptoms of anaphylactic shock) may rarely occur during use of Nicorette® Fresh Fruit Flavour chewing gum.

Individuals prone to digestive problems may initially experience mild gastrointestinal discomfort or heartburn when using the 4 mg dose of Nicorette® Fresh Fruit Flavour chewing gum. These symptoms usually resolve with slower chewing and switching to the 2 mg dose of Nicorette® Fresh Fruit Flavour chewing gum (used more frequently, if needed).

The likelihood and severity of adverse reactions are dose-dependent.

Most adverse reactions occur within the first 3–4 weeks after initiation of treatment. Adverse effects of nicotine chewing gum mainly arise from incorrect chewing technique or dose-dependent pharmacological effects of nicotine.

Adverse events were reported with the following frequency: 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, frequency not known (cannot be estimated based on available data).

Psychiatric disorders: uncommon – sleep disturbances, including unusual dreams.

Nervous system disorders: common – dizziness, headache, burning sensation at application site; uncommon – paraesthesia, oral paraesthesia, oral hypaesthesia, hot flushes, hyperhidrosis, fatigue, asthenia, malaise, eye disorders, dysphonia, dysgeusia; frequency not known – seizures*.

Cardiovascular disorders: uncommon – palpitations, tachycardia, hypertension, shortness of breath, hot flushes; very rare – reversible atrial fibrillation.

Respiratory system disorders: very common – mouth or throat pain, throat irritation; common – cough; uncommon – bronchospasm, sneezing, chest pain and discomfort, nasal congestion, shortness of breath, dysphonia, sensation of throat tightness, oropharyngeal pain.

Gastrointestinal disorders: common – increased salivation, discomfort, hiccups, nausea, vomiting, heartburn, digestive disturbances, abdominal pain, dry mouth sensation, flatulence, stomatitis, dyspepsia, diarrhea; uncommon – dysphagia, belching, vomiting urges, burning sensation, glossitis, blistering and desquamation of oral mucosa, oral paraesthesia; rare – oral hypaesthesia, vomiting urges; frequency not known – dry throat sensation, gastrointestinal discomfort, lip pain.

Eye disorders: frequency not known – blurred vision, increased lacrimation.

Skin and subcutaneous tissue disorders: uncommon – erythema, urticaria, hyperhidrosis, skin rash, pruritus.

General disorders and administration site conditions: common – oral and pharyngeal mucosal ulcers, jaw muscle pain, fatigue; uncommon – chest discomfort and pain, asthenia, malaise; rare – allergic reactions, including angioedema, oral pain, dry mouth, throat tightness, glossitis, blistering of oral mucosa, stomatitis; frequency not known – lip pain.

Immune system disorders: anaphylactic reactions, hypersensitivity reactions, including allergic reactions such as rash and pruritus.

Musculoskeletal and connective tissue disorders: uncommon – jaw pain; frequency not known – muscle tension.

Some of these symptoms, such as dizziness, headache, irritability, aggression, dysphoria, depressed mood, restlessness, poor concentration, intolerance, increased appetite, weight gain, intense desire to smoke, decreased heart rate, and sleep disturbances, may be manifestations of withdrawal syndrome caused by smoking cessation.

The frequency of aphthous stomatitis may increase. A causal link between this symptom and chewing gum use has not been established.

The chewing gum may adhere to dentures and bridges and, in rare cases, may damage them.

Adverse effects associated with combination therapy (chewing gum and transdermal patch) differ only by the local adverse reactions related to the dosage form. The frequency of adverse effects is described in the instructions for medical use of the respective medicinal products.

*Seizures have been reported in patients receiving anticonvulsant therapy or with a history of epilepsy.

Reporting of Adverse Reactions

Reporting suspected adverse reactions after medicine authorization is of great importance. It allows continuous monitoring of the benefit-risk balance of the medicine. Healthcare professionals and patients, or their legal representatives, should report any suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua.

Shelf life. 3 years.

Storage conditions. Store at temperatures not exceeding 25 °C, in a place inaccessible to children.

Packaging. 15 chewing gums per blister; 2 blisters per cardboard pack.

Prescription status. Over-the-counter.

Manufacturer.

McNeil AB, Sweden.

Manufacturer's address and location of operations.

Norrbroplatsen 2, Helsingborg, 25442, Sweden.

Marketing Authorization Holder.

McNeil AB, Sweden.

Address of Marketing Authorization Holder.

Box 941, Helsingborg, 25109, Sweden.

Representative of the Marketing Authorization Holder.

LLC "Johnson & Johnson Ukraine", Ukraine.

Address of the Representative.

32/2, Knyaziv Ostrozkykh St., Kyiv, 01010, Ukraine.

In case of adverse reactions, please contact:

+38 (044) 498 0888

+38 (044) 498 7392