Champix pills 1mg, 28pcs

Composition

Active ingredient:

varenicline – 1 mg (as varenicline tartrate 1.71 mg)

Auxiliary substances:

cellulose microcrystalline – 125.13 mg,

calcium hydrogen phosphate – 66.66 a mg,

croscarmellose sodium – 4.00 mg,

silicon dioxide colloid -1,00 mg,

magnesium stearate – 1,50 mg;

film shell: Opadry transparent YS-2-19114-And (contains hypromellose and triacetin) – 1,00 mg; Opadry blue 03 90547 (contains hypromellose. titanium dioxide, macrogol and aluminum varnish based on indigo carmine) – 8.00 mg

Pharmacological action

Pharmacotherapy group:

nicotine addiction treatment.

ATX Code: N07BA03

Pharmacodynamics

Varenicline binds with high affinity and selectivity to the a4p2 nicotinic acetylcholine receptors of the brain, for which it is both a partial agonist (but to a lesser extent than nicotine) and an antagonist in the presence of nicotine. Electrophysiological studies in vitro and neurochemical studies in vivo have shown that varenicline binds to the a4p2 nicotinic acetylcholine receptors and stimulates them, but to a much lesser extent than nicotine. Nicotine competitively binds to the same site of the receptor to which varenicline has a higher affinity. Thus, varenicline effectively blocks the ability of nicotine to stimulate receptors and activate the mesolimbic dopamine system – a neuronal mechanism that underlies the implementation of mechanisms for the formation of nicotine addiction (getting pleasure from smoking). Varenicline is highly selective and binds more strongly to the a4p2 receptor subtype than to other nicotinic receptor subtypes (AZP4, a7, afub) or other receptors and transport proteins. The effectiveness of varenicline as a drug for the treatment of nicotine addiction is due to its partial agonism against a4 [} 2 nicotine receptors, binding to which reduces cravings for smoking and facilitates the manifestation of “withdrawal” syndrome, while simultaneously leading to a decrease in the feeling of pleasure from smoking (antagonism in the presence of nicotine).

When used in adult patients, varenicline showed a reduction in smoking cravings and withdrawal symptoms. Increasing the duration of varenicline use to 24 weeks (an additional 12 weeks to the standard course) led to an increase in its effectiveness. Varenicline was also effective for quitting smoking when used repeatedly in patients who had previously stopped smoking with varenicline. Varenicline was also effective when the patient chose their own smoking cessation date (“flexible” course of use).

Varenicline was effective for smoking cessation in patients with chronic obstructive pulmonary disease, including long-term follow – up (52 weeks from the start of treatment), in cardiological patients with acute and chronic cardiovascular diseases (including those hospitalized with acute coronary syndrome-unstable angina and myocardial infarction with and without ST-segment elevation), both for complete smoking cessation and for reducing the number of cigarettes smoked. 11. the efficacy and safety of varenicline for smoking cessation in patients with a history of psychiatric diseases was demonstrated.

Pharmacokinetics

Suction

The maximum concentration of varenicline (Cm; iX) in blood plasma, as a rule, is reached 3-4 hours after oral use. At subsequent doses in healthy volunteers, the equilibrium state was reached within 4 days. The drug is almost completely absorbed after oral use and has a high systemic bioavailability, not related to food intake and time of use during the day. After a single dose of 0.1 mg to 3 mg or repeated dose of 1 mg/day to 3 mg/day, the pharmacokinetics of varenicline were linear.

Distribution

Varenicline is distributed in the tissues and penetrates the blood-brain barrier, entering the brain. The degree of binding to plasma proteins is low ( The apparent volume of distribution at equilibrium is 415 liters. In rodents, varenicline penetrates into breast milk and passes through the placental barrier.

Metabolism

Varenicline undergoes minimal transformation: 92% of the dose is excreted unchanged by the kidneys and less than 10% – in the form of metabolites. Among varenicline metabolites, varenicline N-carbamylglucuronide and hydroxyvarenicline were detected in the urine. In the blood plasma, varenicline circulates by 91% unchanged. Varenicline N-carbamylglucuronide and N-glucosylvarenicline were found among the circulating metabolites. In vitro studies have shown that varenicline does not inhibit cytochrome P450 iso enzymes (inhibitory concentration 50 > 6400 ng / ml). The following cytochrome P 450 isoenzymes were tested: 1 A 2.2 A 6,2 B 6,2 C 8.2 C 9,2CI9.2D6.2 E 1, and FOR 4/5. It was also shown in vitro in human hepatocytes that varenicline does not induce the activity of cytochrome P450 isoenzymes IA2 and ZA4. Thus, it is unlikely that varenicline will affect drugs that are primarily metabolized by cytochrome P450 isoenzymes. Deduction

The elimination half-life (T’/;) of varenicline is about 24 hours. Excretion of varenicline by the kidneys is mainly carried out by glomerular filtration in combination with active tubular secretion by organic cationic proteins of OST-2 transporters.

Linearity / non-linearity

of varenicline pharmacokinetics The pharmacokinetics of varenicline are linear with single (0.1 to 3 mg) and multiple (I to 3 mg/day) use. Pharmacokinetics in special groups

Pharmacokinetic studies and population-based pharmacokinetic analysis have shown that the pharmacokinetics of varenicline do not significantly depend on age, race, gender, smoking status, or concomitant therapy. Renal impairment

The pharmacokinetics of varenicline were unchanged in patients with mild renal impairment (creatinine clearance > 50 ml / min and > In patients with moderate renal insufficiency (creatinine clearance > 30 ml/min and >< 50 ml/min), the AUC of varenicline increased 1.5-fold compared to that in patients with normal renal function (creatinine clearance > 80 ml/min). In patients with severe renal impairment (creatinine clearance In patients with end-stage renal failure, varenicline was effectively removed by hemodialysis.

Impaired liver function

Given the absence of pronounced metabolism of varenicline in the liver, the pharmacokinetics of varenicline should not change in patients with impaired liver function.

Elderly patients

Pharmacokinetics of varenicline in elderly patients with normal renal function (age 65 to 75 years) it doesn’t change. Recommendations for the use of varenicline in elderly patients with impaired renal function are indicated in the section “Dosage and use”.

Indications

Champix® is intended for use as a smoking cessation aid in adults from the age of 18 years and beyond, without age restriction.

Use during pregnancy and lactation

Adequate and strictly controlled studies on the safety of Champix during pregnancy have not been conducted, so the use of the drug is contraindicated.

It is not known whether varenicline is excreted in human breast milk. If it is necessary to use the drug during lactation, breastfeeding should be discontinued.

Contraindications

Hypersensitivity to any component of the drug.

Age up to 18 years (insufficient clinical data on the effectiveness and safety of the drug in this age group).

Pregnancy and lactation. End-stage renal failure.

Use during pregnancy and lactation

Pregnancy

A moderate amount of data was obtained on pregnant women (results of assessing the outcomes of 300-1000 pregnancies), which indicated that there was no toxic effect of varenicline on the fetus/newborn, leading to malformations of physical development.

In the course of animal studies, toxic effects on the reproductive sphere were revealed. As a precautionary measure, use during pregnancy is contraindicated.

Breast-feeding

There is no information about the excretion of varenicline in breast milk in women. Animal studies have shown that varenicline is excreted in breast milk. As a precautionary measure, use during breastfeeding is contraindicated.

Fertility

There are no clinical data on the effect of varenicline on fertility. Preclinical studies have shown that there is no negative effect of varenicline on fertility in standard rat studies. Women of childbearing age should refrain from planning pregnancy during varenicline treatment.

Side effects

Smoking cessation, both during therapy and without it, is accompanied by various symptoms, in particular, there was a decrease in mood and dysphoria, insomnia, irritability, feelings of displeasure and anger, anxiety, impaired concentration, motor restlessness, a decrease in heart rate, increased appetite or weight gain. Smoking cessation with or without medication was also accompanied by an exacerbation of concomitant mental disorders.When developing the design of clinical trials of Champix 1 and analyzing their results, no distinction was made between adverse events that may be associated with the use of the drug under study and those actually associated with nicotine withdrawal syndrome. Adverse reactions are based initially on the evaluation of registration studies and supplemented with data from 18 placebo-controlled registration and post-marketing studies, which included about 5,000 patients taking varenicline.

According to the results of clinical studies, adverse reactions usually appeared in the first week after the start of treatment, were usually mild or moderate, and their frequency did not depend on the age, race or gender of the patient.

In patients who received Champix at the recommended dose of 1 mg twice daily after the titration period, the most frequent reported side effects were nausea (28.6%). In most cases, nausea occurred in the early stages of therapy, was mild or moderate, and rarely required discontinuation of the drug. Against the background of taking Champix, the following reactions from organs and systems are also possible (frequency assessment criteria: very frequent > 10%; frequent – from >>1% to >><10%; infrequent – from > 0.1% to <10%; infrequent – from >< 1%; rare-from > 0.01% to < 1%; rare – from >< 0.1%, very rare – from:

Infectious and parasitic diseases: very common – nasopharyngitis: common -bronchitis, sinusitis; infrequent – fungal infections, viral infections.

Disorders of the blood and lymphatic system: rare – low platelet count.

Metabolic and nutritional disorders: frequent – weight gain, decreased appetite, increased appetite; infrequent – hyperglycemia; rare-diabetes mellitus, polydipsia.

Mental disorders: very frequent-unusual dreams, insomnia; infrequent – suicidal behavior, aggressiveness, panic reaction, thinking disorders, anxiety, mood swings, depression*, states of fear*, hallucinations*, increased libido, decreased libido; rare-psychosis, somnambulism, behavioral abnormalities, dysphoria, bradyphrenia.

Nervous system disorders: very frequent – headaches; frequent -drowsiness, dizziness, dysgeusia; infrequent – convulsive seizures, tremor, lethargy, hypesthesia; rare-stroke, hypertension, dysarthria, coordination disorders, hypogeusia, sleep and wake rhythm disorders.

Visual disturbances: infrequent-conjunctivitis, eye pain; rare-scotoma, scleral discoloration, mydriasis, photophobia, myopia, increased lacrimation.

Hearing disorders and labyrinth disorders: infrequent-ear noise.

Cardiac disorders: infrequent – myocardial infarction, angina pectoris, tachycardia, palpitations, increased heart rate; rare – atrial fibrillation, ST interval depression on the ECG. reduced amplitude of T waves on the ECG.

Vascular disorders: infrequent – high blood pressure, hot flashes.

Respiratory, thoracic and mediastinal disorders:frequent – shortness of breath, cough; infrequent-upper respiratory tract inflammation, airway hyperemia, dysphonia, allergic rhinitis, pharyngeal irritation, maxillary sinus mucosal edema, upper respiratory tract cough syndrome, rhinorrhea; rare-laryngeal pain, snoring.

Disorders of the gastrointestinal tract: very frequent – nausea; frequent -gastro-esophageal reflux, vomiting, constipation, diarrhea, gas, abdominal pain, toothache, dyspepsia, bloating, dry mouth; infrequent – hematocheia, gastritis, violations of the usual rhythm of bowel movement, belching, aphthous stomatitis, pain in the gums; rare-vomiting with blood, changes in the stool, covered tongue.

Skin and subcutaneous tissue disorders: common-rash, pruritus of the skin; infrequent-erythema, acne, hyperhidrosis, night sweating; rare-severe skin reactions, including Stevens Johnson syndrome and erythema multiforme, angioedema.

Musculoskeletal and connective tissue disorders: common -arthralgia, myalgia, back pain; infrequent-muscle spasms, chest pains related to skeletal muscles; rare-ankylosis, chondritis of the rib.

Kidney and urinary tract disorders: infrequent – gullakiuria, nocturia; rare-glucosuria, polyuria.

Genital and breast disorders: infrequent – menorrhagia; rare-leucorrhoea, sexual functional disorders.

General disorders and disorders at the injection site: frequent – chest pain, fatigue; infrequent-complaints about the chest, a disease with symptoms similar to flu symptoms, fever, pyrexia. asthenia, malaise; rare-feeling of cold, cyst.

Influence on the results of laboratory and instrumental studies: frequent -deviation from the norm of biochemical parameters of liver function; rare-deviation from the norm of seminal fluid analysis results, increased content of C-reactive protein, low level of calcium in the blood.

* Frequency estimation based on data from a post-marketing observational study in cohorts.

Interaction

Based on pharmacological properties and clinical data, varenicline has no clinically significant drug interactions. No dose adjustment of varenicline or the drugs listed below is required for concomitant use.

In vitro studies have shown that active renal secretion of varenicline is mediated by the human organic cation transporter (OST 2). When used concomitantly with OST 2 inhibitors, no dose adjustment of varenicline is required. since no significant increase in systemic exposure to varenicline tartrate is expected. In vitro studies indicate that varenicline does not alter the pharmacokinetics of drugs that are metabolized by cytochrome P450 isoenzymes. Since varenicline clearance is less than 10% due to metabolism, it is unlikely that substances that affect the activity of cytochrome P45o isoenzymes can affect the pharmacokinetics of varenicline, and therefore no dose adjustment is required.

Varenicline in therapeutic concentrations does not inhibit renal protein transport in humans. Therefore, varenicline should not affect the pharmacokinetics of drugs that are cleared by renal secretion (in particular, metformin-see below). Metforminvarenicline does not affect the pharmacokinetics of metformin. Metformin does not alter the pharmacokinetics of varenicline.

Cimetidine cimetidine causes a 29% increase in varenicline AUC due to a decrease in its renal clearance. No dose adjustment is required in patients with normal renal function or in patients with mild to moderate renal insufficiency. Concomitant use of cimetidine and varenicline should be avoided in patients with severe renal insufficiency.

Digoxinv Arenicline does not affect the pharmacokinetics of digoxin at steady state.

Warfarin Varenicline does not alter the pharmacokinetics of warfarin and does not affect prothrombin time (MHO). Smoking cessation alone may lead to changes in the pharmacokinetics of warfarin.

Alcohol

Data on concomitant use of varenicline and alcohol are limited. Cases of increased toxic effects of alcohol have been reported during post-marketing use of varenicline. A causal relationship between these cases and the use of varenicline has not been established.

Use in combination with other anti-smoking agents

Bupropion

Varenicline does not affect the pharmacokinetics of bupropion at steady state.

Nicotine replacement therapy

Concomitant use of varenicline and nicotine-containing patches in smokers for 12 days revealed a statistically significant decrease in mean systolic blood pressure (by 2.6 mm Hg) on the last day of the study. At the same time, the incidence of nausea, headache, vomiting, dizziness, dyspepsia, and fatigue with combination therapy was higher than with NRT alone.

The safety and efficacy of varenicline in combination with other anti-smoking agents have not been studied.

How to take, course of use and dosage

The likelihood of successful treatment with a smoking cessation drug increases in patients who are motivated to quit smoking, who are provided with additional counseling and support.

Champix” is taken orally, swallowing the tablets whole and washed down with water, regardless of the meal. The recommended dose of the drug is 1 mg twice a day with titration of the dose according to the following scheme:

First, the patient must choose a date to stop smoking. Treatment with Champix should usually be started 1-2 pedels before the selected date. The total duration of Champix treatment should be 12 weeks.

Patients who successfully quit smoking by the end of the 12th week of treatment may be recommended an additional 12-week course of varenicline therapy at a dose of 1 mg twice a day to maintain smoking cessation.

For patients who are unable or unwilling to stop smoking abruptly, a gradual approach with varenicline therapy may be considered. In this case, you should reduce the intensity of smoking during the first 12 weeks of therapy, with complete cessation of smoking by the end of this period. After that, patients should take varenicline for another 12 weeks, so that the total treatment period is 24 weeks.

Patients with appropriate motivation, but who failed to quit smoking during the previous course of varenicline treatment. or who relapse after successful completion of treatment, may be re-treated with varenicline, provided that the reasons for the failure of the first attempt have been established and measures have been taken to eliminate them.

Patients who do not tolerate taking Champix due to adverse reactions may need to reduce the dose to 0.5 mg twice a day temporarily or permanently.

The risk of smoking recurrence is increased in individuals who have recently completed smoking cessation therapy.

Elderly patients

Dose adjustment of Champix in elderly patients is not required. Elderly people are more likely to have reduced kidney function, so it is advisable to evaluate it before starting treatment. Impaired renal function

Changes in the dose of Champix in patients with mild renal impairment (creatinine clearance > 50 ml / min and >< 80 ml / min) and moderate renal insufficiency (creatinine clearance > 30 ml / min and < 80 ml / min) and moderate renal insufficiency (creatinine clearance > In patients with moderate renal insufficiency who do not tolerate adverse reactions to Champix*, the daily dose can be reduced to 1 mg once a day. In patients with severe renal impairment (creatinine clearance Treatment begins with a dose of 0.5 mg once a day, which after 3 days is increased to 1 mg once a day. Since clinical data on the use of Champix in patients with end-stage renal failure are limited, the drug is not recommended for such patients (see the section “Contraindications”).

Impaired liver function

Dose adjustment of Champix in patients with impaired liver function is not required.

Children

Champix* is not recommended for use in children and adolescents under 18 years of age, as information on its safety and effectiveness in this age group is insufficient.

Overdose

No cases of varenicline overdose have been reported in registered clinical trials. In case of overdose, symptomatic therapy should be used. Varenicline is eliminated by hemodialysis in patients with severe renal impairment, but there is no experience of using hemodialysis in overdose.

Special instructions

Effects of smoking cessation: Physiological changes associated with smoking cessation while taking Champix or without treatment may cause pharmacokinetic or pharmacodynamic disturbances in certain medications, which may require a change in their dose (for example, theophylline, warfarin and insulin). Smoking causes an increase in CYP1A2 activity, so stopping smoking can lead to an increase in plasma levels of CYP1A2 substrates. Smoking cessation with or without pharmacotherapy has been associated with an increase in psychiatric illnesses (e. g., depression). Caution should be exercised in patients with a history of psychiatric disorders. Patients should be warned about the possibility of exacerbation of such diseases when stopping smoking. There is no experience of using Champix in patients with epilepsy. Discontinuation of Champix after treatment was associated with increased irritability, smoking cravings, depression, and/or insomnia in 3% of patients. The doctor should inform the patient about the possible occurrence of such reactions and consider the possibility of gradually reducing the dose.

Influence on the ability to drive a car and use Technicalchampix has a small or moderate impact on the ability to drive a car and use complex equipment. Champix can cause dizziness and drowsiness and, consequently, affect the ability to drive a car and use complex equipment. Patients are advised not to drive a car, use complex machinery, or perform other potentially dangerous tasks until they have assessed their response to the medication.

Form of production

Film-coated tablets

Storage conditions

At a temperature of 15-30 °C

Shelf life

2 years

Active ingredient

Vareniklin

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Smoking Cessation