4.1. Therapeutic indications

Smoking cessation and reduction of nicotine cravings in smokers who are willing to stop smoking. The treatment goal of Cytisinicline is the permanent cessation of the nicotine‑containing products use.

4.2. Posology and method of administration

Posology

One package of Cytisinicline (100 tablets) is sufficient for a complete treatment course.

The duration of therapy is 25 days.

Cytisinicline should be taken according to the following schedule:

Days of treatment

Recommended dosing

Maximum daily dose

From the 1st to the 3rd day

1 tablet every 2 hours

6 tablets

From the 4th to the 12th day

1 tablet every 2.5 hours

5 tablets

From the 13th to the 16th day

1 tablet every 3 hours

4 tablets

From the 17th to the 20th day

1 tablet every 5 hours

3 tablets

From the 21st to the 25th day

1-2 tablets a day

to 2 tablets

Smoking should be stopped no later than on the 5th day of treatment. Smoking should not be continued during treatment as this may aggravate adverse reactions (see section 4.4). In case of treatment failure, the treatment should be discontinued and may be resumed after 2 to 3 months.

Special population (renal impairment, hepatic impairment)

There is no clinical experience of Cytisinicline in patients with renal or hepatic impairment, therefore the drug product is not recommended for use in this patient population.

Elderly population

Due to limited clinical experience, Cytisinicline is not recommended for use in elderly patients over 65 years of age.

Paediatric population

The safety and efficacy of Cytisinicline in persons under 18 years of age have not been established. Cytisinicline is not recommended for use in persons under 18 years of age.

Method of administration

Cytisinicline should be taken orally with a suitable amount of water.

4.3. Contraindications

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

Unstable angina,

A history of recent myocardial infarction,

Clinically significant arrhythmias,

A history of recent stroke,

Pregnancy and breastfeeding.

4.4. Special warnings and precautions for use

Cytisinicline should be taken only by those with a serious intention of weaning off nicotine. Patient should be aware, that the simultaneous administration of the drug and smoking or use of products containing nicotine could lead to aggravated adverse reactions of nicotine.

Cytisinicline should be taken with caution in case of ischemic heart disease, heart failure, hypertension, pheochromocytoma, atherosclerosis and other peripheral vascular diseases, gastric and duodenal ulcer, gastroesophageal reflux disease, hyperthyroidism, diabetes and schizophrenia.

Effect of smoking cessation: Polycyclic aromatic hydrocarbons in tobacco smoke induce the metabolism of drugs metabolised by CYP 1A2 (and possibly by CYP 1A1). When a smoker stops smoking, this may result in slower metabolism and a consequent rise in blood levels of such drugs. This is of potential clinical importance for products with a narrow therapeutic window, e.g. theophylline, tacrine, clozapine and ropinirole.

The plasma concentration of other medicinal products metabolised in part by CYP1A2 e.g. imipramine, olanzapine, clomipramine and fluvoxamine may also increase on cessation of smoking, although data to support this are 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.

Depressed mood, rarely including suicidal ideation and suicide attempt, may be a symptom of nicotine withdrawal. Clinicians should be aware of the possible emergence of serious neuropsychiatric symptoms in patients attempting to quit smoking with or without treatment.

History of psychiatric disorders Smoking cessation, with or without pharmacotherapy, has been associated with exacerbation of underlying psychiatric illness (e.g. depression).

Care should be taken with patients with a history of psychiatric illness and patients should be advised accordingly.

Women of childbearing potential

Women of childbearing potential must use highly effective contraception while taking Cytisinicline (see section 4.5 and 4.6).

4.5. Interaction with other medicinal products and other forms of interaction

Cytisinicline should not be used with anti-tuberculosis drugs. No other clinical data on significant interaction with other drugs.

Patient should be aware, that the simultaneous administration of the drug and smoking or use of products containing nicotine could lead to aggravated adverse reactions of nicotine (see section 4.4).

Hormonal contraceptives

It is currently unknown whether Cytisinicline may reduce the effectiveness of systemically acting hormonal contraceptives, and therefore women using systemically acting hormonal contraceptives should add a second barrier method.

4.6. Fertility, pregnancy and lactation

Pregnancy

There are no or limited amount of data from the use of cytisinicline in pregnant women.

Animal studies are insufficient with respect to reproductive toxicity (see section 5.3).

Cytisinicline is contraindicated during pregnancy (see section 4.3).

Breastfeeding

Cytisinicline is contraindicated during breast-feeding (see section 4.3).

Fertility

No data on the effects of Cytisinicline on fertility.

Women of childbearing potential

Women of childbearing potential must use highly effective contraception while taking Cytisinicline (see section 4.5 and 4.4). Women using systemically acting hormonal contraceptives should add a second barrier method.

4.7. Effects on ability to drive and use machines

Cytisinicline has no influence on the ability to drive and use machines.

4.8. Undesirable effects

The clinical studies and previous experience with use of cytisinicline-containing product indicate a good tolerability of cytisinicline. The proportion of patients who discontinued treatment because adverse reactions was 6-15,5% and in controlled studies it was comparable to the proportion of patients who discontinued treatment in the placebo group. Mild to moderate adverse reactions have usually been observed, most frequently concerning the gastrointestinal tract. The majority of adverse reactions occurred at the beginning of the therapy and resolved during treatment. These symptoms could also be the result of smoking cessation, rather than the use of drug product.

All adverse reactions by system organ class and frequency of occurrence in clinical trials are listed below. The frequency of occurrence is defined as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data).

Metabolism and nutrition disorders:

very common: change in appetite (mainly increase), weight gain

Nervous system disorders:

very common: dizziness, irritability, mood changes, anxiety, sleep disorders (insomnia, drowsiness, lethargy, abnormal dreams, nightmares), headaches

common: difficulty in concentration

uncommon: feeling of heaviness in the head, decreased libido

Eye disorders:

uncommon: lacrimation

Cardiac disorders:

very common: tachycardia

common: slow heart rate

Vascular disorders:

very common: hypertension

Respiratory, thoracic and mediastinal disorders:

uncommon: dyspnea, increased sputum

Gastrointestinal disorders:

very common: dry mouth, diarrhea, nausea, changes flavour, heartburn, constipation, vomiting, abdominal pain (especially in the upper abdomen)

common: abdominal distension, burning tongue

uncommon: excessive salivation

Skin and subcutaneous tissue disorders:

very common: rash

uncommon: sweating, decreased elasticity of the skin

Musculoskeletal and connective tissue disorders:

very common: myalgia

General disorders and administration site conditions:

very common: fatigue

common: malaise

uncommon: tiredness

Investigations:

uncommon: increase in serum transaminase levels

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:

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 of nicotine intoxication are observed in Cytisinicline overdose. Symptoms of overdose include malaise, nausea, vomiting, increased heart rate, blood pressure fluctuations, breathing disorders, visual disturbances, clonic convulsions. In all cases of overdose, standard procedure should be taken as in acute poisoning; gastric lavage should be performed and the diuresis should be controlled with infusion fluids and diuretics. The anti-epileptic drugs, acting on the cardiovascular system and stimulating the respiration may be used, if necessary. Breathing, blood pressure and heart rate should be monitored.