Cycotin® is

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT CYCOTINE® IS

Composition:

Active substance: cytisine;

1 tablet contains 1.5 mg of cytisine;

Excipients: lactose monohydrate, microcrystalline cellulose, sodium croscarmellose, hypromellose (hydroxypropylmethylcellulose), talc, magnesium stearate, polyethylene glycol (macrogol), titanium dioxide (E 171), yellow iron oxide (E 172).

Pharmaceutical form. Film-coated tablets.

Main physicochemical characteristics: yellow, round, biconvex film-coated tablets.

Pharmacotherapeutic group.

Medicinal products used in nicotine dependence. ATC code N07BA04.

Pharmacological properties.

Pharmacodynamics.

The use of the medicinal product gradually reduces nicotine dependence by alleviating symptoms of nicotine withdrawal syndrome.

The active substance of the medicinal product is the plant alkaloid cytisine (cytisinecine), which is contained, in particular, in the seeds of the plant Laburnum, genus Laburnum. Chemically, cytisine is structurally similar to nicotine. It acts on nicotinic cholinergic receptors. The mechanism of action of cytisine is similar to that of nicotine, but the effect of cytisine is less pronounced. Cytisine competitively inhibits the interaction of nicotine with its corresponding receptors and, due to stronger binding, gradually displaces nicotine from them. Cytisine has partial agonist activity at nicotinic cholinergic receptors, particularly high affinity for the α4β2 subtype. Cytisine penetrates the central nervous system (CNS) to a lesser extent than nicotine. It is believed that cytisine affects the mechanism of nicotine dependence and the release of neurotransmitters in the CNS. Cytisine prevents nicotine-dependent full activation of the mesolimbic dopaminergic system and moderately increases dopamine levels in the brain, thereby alleviating central symptoms of nicotine withdrawal syndrome. In the peripheral nervous system, cytisine stimulates autonomic ganglia, causes reflex stimulation of respiration and secretion of catecholamines by the adrenal medulla, increases arterial pressure, and prevents peripheral symptoms of nicotine withdrawal syndrome.

Pharmacokinetics.

The pharmacokinetic profile of cytisine was studied in a trial involving 36 healthy volunteers who received a single 1.5 mg oral dose of cytisine.

Absorption

After oral administration, cytisine was rapidly absorbed from the gastrointestinal tract. The mean peak plasma concentration of 15.55 ng/mL was reached within 0.92 hours.

Metabolism

Cytisine undergoes partial biotransformation.

Elimination

64% of the administered dose of cytisine was excreted unchanged in urine within 24 hours. The mean elimination half-life was approximately 4 hours. The mean residence time was approximately 6 hours.

There are no data on the use of cytisine in patients with impaired renal and/or hepatic function.

The effect of food on cytisine exposure is unknown.

Clinical characteristics.

Indications.

Cytotin® IS is used for the treatment of nicotine dependence.

The medicinal product is indicated for use in patients who have a strong intention to quit smoking, to gradually reduce nicotine dependence and to stop smoking without experiencing withdrawal symptoms. The ultimate goal of treatment with the medicinal product is complete cessation of nicotine-containing products.

Contraindications.

Hypersensitivity to cytisine or to any excipient of the medicinal product, unstable angina, recent myocardial infarction, clinically significant arrhythmias, recent stroke, pregnancy and breastfeeding period.

Interaction with other medicinal products and other forms of interaction.

Concomitant use of cytisine with anti-tuberculosis medicinal products is not recommended. There are no other data on clinically significant interactions of cytisine with other medicinal products.

Patients should be informed that concomitant use of cytisine with smoking or consumption of nicotine-containing products may lead to an increased incidence of adverse reactions associated with nicotine.

Hormonal contraceptives

It is currently unknown whether cytisine may reduce the efficacy of systemic hormonal contraceptives; therefore, women using systemic hormonal contraceptives should use an additional barrier method of contraception.

Special precautions for use.

The medicinal product should be used only in patients who have a serious intention to quit nicotine. Concurrent use of the medicinal product and smoking or consumption of products containing nicotine may lead to an exacerbation of adverse reactions associated with nicotine.

Cytisine should be used with caution in patients with ischemic heart disease, heart failure (see section "Contraindications"), arterial hypertension, pheochromocytoma, atherosclerosis and other peripheral vascular diseases, gastric and duodenal ulcer, gastroesophageal reflux disease, hyperthyroidism, diabetes mellitus, and schizophrenia.

Smoking cessation

Polycyclic aromatic hydrocarbons present in tobacco smoke induce the metabolism of medicinal products metabolized by cytochrome CYP1A2 (and possibly also CYP1A1). Cessation of smoking may result in reduced metabolism of these medicinal products and, consequently, increased blood concentrations. This has potential clinical significance for medicinal products with a narrow therapeutic window, such as theophylline, tacrine, clozapine, and ropinirole.

It is hypothesized that plasma concentrations of other medicinal products partially metabolized by CYP1A2, such as imipramine, olanzapine, clomipramine, and fluvoxamine, may increase after smoking cessation, although there is no evidence to confirm this hypothesis, and the potential clinical significance of these effects for the aforementioned medicinal products is unknown.

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

Depressed mood may be a symptom of nicotine withdrawal, which rarely may be accompanied by suicidal thoughts and suicide attempts. Physicians should be aware of the possibility of serious neuropsychiatric symptoms occurring in patients attempting to quit smoking, regardless of whether they are receiving treatment for nicotine dependence.

History of psychiatric disorders

Cessation of smoking, with or without pharmacotherapy, may be associated with exacerbation of underlying psychiatric disorders (e.g., depression).

Patients attempting to quit smoking who have a history of psychiatric disorders should be informed of the need for caution.

Women of reproductive age

Women of reproductive age undergoing treatment with cytisine should use highly effective contraceptive methods (see sections "Interaction with other medicinal products and other forms of interaction" and "Use during pregnancy or breastfeeding").

Due to the presence of lactose, the medicinal product should not be administered to patients with rare hereditary problems of galactose intolerance, lactase deficiency, or glucose-galactose malabsorption.

Use during pregnancy or breastfeeding.

Pregnancy

There are no clinical data on the use of cytisine in pregnant women.

Animal studies are insufficient to assess the reproductive toxicity of cytisine.

The use of the medicinal product during pregnancy is contraindicated.

Breastfeeding

The use of the medicinal product during breastfeeding is contraindicated.

Fertility

The effect of cytisine on fertility is unknown.

Women of reproductive age

Women of reproductive age undergoing treatment with cytisine should use highly effective contraceptive methods (see sections "Interaction with other medicinal products and other forms of interaction" and "Special precautions for use"). Women using systemically acting hormonal contraceptives should also use an additional barrier method of contraception.

Ability to influence reaction speed when driving or operating machinery.

Cytisine has no effect or has a negligible effect on the ability to drive or operate machinery.

Method of administration and dosage.

One package of the medicinal product (100 tablets) is sufficient for completing a full course of treatment.

Duration of the treatment course – 25 days.

The medicinal product should be taken orally, swallowed with an adequate amount of water.

The medicinal product should be used according to the following regimen:

Smoking should be discontinued no later than the 5th day from the start of treatment. Smoking should not be continued during treatment, as this may intensify the occurrence of adverse reactions (see sections "Interaction with other medicinal products and other forms of interaction" and "Special precautions for use"). If the therapeutic outcome is unsatisfactory, treatment should be discontinued and resumed after 2–3 months.

Patients who have stopped smoking should exercise willpower and refrain from smoking even a single cigarette. The duration of the achieved therapeutic effect depends on this.

Special patient groups

Patients with renal or hepatic impairment

There is no clinical experience with the use of cytisine in patients with impaired renal or hepatic function; therefore, the use of cytisine in these patient populations is not recommended.

Elderly patients

Due to limited clinical experience, the use of cytisine is not recommended in patients aged over 65 years.

Children

The medicinal product should not be used in children (under 18 years of age) due to lack of data on safety and efficacy of cytisine in this patient group.

Overdose

In case of cytisine overdose, symptoms typical of nicotine poisoning (nicotine intoxication) occur.

Symptoms of overdose: malaise, nausea, vomiting, tachycardia, fluctuations in arterial pressure, respiratory disorders, visual disturbances, clonic seizures.

Treatment. In all cases of overdose, standard measures for acute poisoning should be implemented; gastric lavage should be performed and diuresis monitored using infusion solutions and diuretics. Anticonvulsants, cardiotonics, and analeptics may be used if necessary. Respiratory function, arterial pressure, and heart rate should be closely monitored.

Adverse reactions.

Data from clinical studies and accumulated medical experience with cytisine-containing medicinal products indicate good tolerability of cytisine. The percentage of patients who discontinued treatment with cytisine due to adverse reactions was 6.0–15.5% and in controlled studies was comparable to the percentage of patients who discontinued treatment in the placebo group. Adverse reactions are usually mild or moderate in intensity and most commonly related to the gastrointestinal tract. Most adverse reactions occur at the beginning of treatment and resolve during the course of treatment. Adverse reactions may be caused by smoking cessation, rather than by treatment with cytisine.

The list of adverse reactions provided below is classified by organ systems and frequency of occurrence in patients during clinical trials. Frequencies are defined as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10,000 to < 1/1000), very rare (< 1/10,000), frequency not known (cannot be estimated from available data).

Nervous system disorders: very common – dizziness, irritability, mood changes, anxiety, sleep disorders (insomnia, somnolence, lethargy, abnormal dreams, nightmares), headache; common – decreased concentration; uncommon – feeling of heaviness in the head, decreased libido.

Eye disorders: uncommon – lacrimation.

Skin and subcutaneous tissue disorders: very common – rash; uncommon – increased sweating, decreased skin elasticity.

Musculoskeletal and connective tissue disorders: very common – myalgia.

Cardiac disorders: very common – tachycardia, increased blood pressure; common – bradycardia.

Vascular disorders: very common – hot flushes.

Gastrointestinal disorders: very common – dry mouth, diarrhea, nausea, taste disturbances, heartburn, constipation, vomiting, abdominal pain (mainly in the upper part); common – bloating, burning sensation of the tongue; uncommon – excessive salivation.

Metabolism and nutrition disorders: very common – appetite changes (mainly increased), weight gain.

Respiratory, thoracic and mediastinal disorders: uncommon – dyspnea, increased sputum production.

General disorders and administration site conditions: very common – fatigue; common – malaise; uncommon – increased tiredness.

Investigations: uncommon – increased serum transaminase levels.

Reporting of suspected adverse reactions

Healthcare professionals and patients or their legal representatives are requested to report any suspected adverse reactions and lack of drug effect via the Automated Pharmacovigilance Information System at the website https://aisf.dec.gov.ua to monitor the benefit-risk balance of the medicinal product.

Shelf life.

2 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach and sight of children.

Packaging.

20 tablets in a blister; 5 blisters in a carton.

Prescription status.

Over-the-counter.

Manufacturer.

Limited liability company "INTERKHIM".

Manufacturer's address and place of business.

40-A, 21st km of Starokyivska Road, Odesa, Ukraine, 65025.