Varenicline - instructions for use, dose, side effects, contraindications

Clinical and pharmacological group: & nbsp

Means for correcting disorders in alcoholism, toxic and drug addiction

Included in the formulation

Champix®

pills inwards

Pfizer Inc. USA

АТХ:

N.07.B.A Drugs used in nicotine addiction

N.07.B.A.03 Varenicline

Pharmacodynamics:

Means for the treatment of nicotine addiction. Varenicline with high affinity and selectivity binds to α4β2 n-cholinergic receptors, for which it is a partial nicotine agonist, that is, simultaneously exhibits agonist activity (but to a lesser extent than nicotine) and antagonism in the presence of nicotine.

Electrophysiological studies in vitro and neurobiochemical studies in vivo showed that varenicline binds to α4β2 n-cholinergic receptors and stimulates them, but to a much lesser extent than nicotine. Nicotine competitively binds to the same receptor site to which varenicline has a higher affinity. In this way, varenicline effectively blocks the ability of nicotine to stimulate α4β2 n-cholinergic receptors and activate the mesolimbic dopamine system, the neuronal mechanism that underlies the mechanisms of the formation of nicotine addiction (getting pleasure from smoking).

The effectiveness of varenicline as a means for treating nicotine dependence is due to its partial agonism with respect to α4β2 n-cholinergic receptors,binding with them reduces the craving for smoking and facilitates the manifestation of withdrawal syndrome (agonist activity) and simultaneously leads to a decrease in the sense of pleasure from smoking (antagonism in the presence of nicotine).

Pharmacokinetics:

C_maxin blood plasma is usually achieved 3-4 hours after ingestion. With subsequent administration in healthy volunteers, the equilibrium state was achieved within 4 days. Virtually completely absorbed after ingestion and has a high systemic bioavailability, not related to eating and taking time during the day. After a single dose of 0.1 mg to 3 mg or repeated dose of 1 mg per day to 3 mg per day, the pharmacokinetics of varenicline were linear.

Varenicline is distributed in tissues and penetrates through blood-brain barrier, getting into the brain. Binding to plasma proteins is low (<20%) and does not depend on the age and function of the kidneys.

Varenicline undergoes minimal transformation: 92% of the dose is excreted by the kidneys unchanged and less than 10% - in the form of metabolites. Among the metabolites of varenicline in urine are found N-carbamyl glucuronide varenicline and hydroxyvarieniclin. In the blood plasma varenicline 91% circulates unchanged.Among circulating metabolites, N-carbamylglucuronid varenicline and N-glucosylvarenicline have been found.

The half-life of varenicline is about 24 hours. The excretion of varenicline by the kidneys is carried out, mainly, by glomerular filtration in combination with active tubular secretion.

In patients with moderate renal insufficiency (creatinine clearance> 30 mL / min and ≤ 50 mL / min), the varenicline AUC increased 1.5-fold compared with that in patients with normal renal function (creatinine clearance> 80 mL / min). In patients with severe renal dysfunction (creatinine clearance <30 ml / min), AUC varenicline increased 2.1 times. In patients with terminal stage of renal failure varenicline effectively removed during hemodialysis.

Indications:

Nicotine dependence in adults.

ICD-10

V.F10-F19.F17 Mental and behavioral disorders caused by tobacco use

Contraindications:

Terminal stage of renal failure; children and adolescents under 18; pregnancy, lactation (breastfeeding); increased sensitivity to varenicline.

Carefully:No data.

Pregnancy and lactation:

Due to the fact that adequate controlled trials of the use of varenicline in pregnant women have not been conducted, the use of the drug during pregnancy is contraindicated.

Information about the isolation of varenicline with breast milk in women is not. If you need to use the drug during lactation, breastfeeding should be discontinued.

Dosing and Administration:

Is taken internally. The initial dose is 500 mcg once a day. The dose is titrated according to a special scheme. The recommended dose is 1 mg 2 times a day.

The course of treatment is 12 weeks. Patients who successfully stopped smoking by the end of the 12th week are recommended an additional course of treatment with the drug at a dose of 1 mg twice a day for 12 weeks.

Patients who do not manage to stop smoking during the initial 12-week course of treatment or who have a relapse after treatment should be encouraged to make another attempt, provided that the reasons for the failure of the first attempt have been established and steps have been taken to address them.

For patients with severe renal insufficiency (creatinine clearance <30 mL / min), the recommended dose is 1 mg 1 time per day.Treatment begins with a dose of 500 mcg once a day, which after 3 days is increased to 1 mg 1 time per day.

Side effects:

Most often: nausea (28.6%).

From the digestive system: very often - nausea; often - vomiting, constipation, diarrhea, bloating, discomfort in the stomach, indigestion, flatulence, dry mouth; rarely - vomiting with blood, blood stench in the stool, gastritis, gastroesophageal reflux disease, abdominal pain, intestinal disorders, stool, eructation, aphthous stomatitis, soreness of the gums, swollen tongue, changes in liver function.

From the nervous system: very often - unusual dreams, insomnia, headache; often - drowsiness, dizziness, dysgeusia; rarely - panic reaction, bradyphrenia, disturbance of thinking, mood swings, tremor, coordination disorder, dysarthria, motor anxiety, dysphoria, hypoesthesia, apathy.

From the side of metabolism: often - increased appetite; rarely - anorexia, decreased appetite, polydipsia, weight gain, decreased calcium concentration in the blood.

From the cardiovascular system: rarely - increased blood pressure,depression of the ST segment on the ECG, a decrease in the amplitude of the T wave on the ECG, an increase in the heart rate, atrial fibrillation, palpitations.

From the sense organs: rarely - scotoma, scleral discoloration, pain in the eyeball, pupil dilated, photophobia, myopia, increased lachrymation, tinnitus, decreased taste sensations.

From the respiratory system: rarely - shortness of breath, cough, hoarseness, pain in the pharynx and larynx, irritation of the pharynx, congestion in the airways, congestion in the paranasal sinuses, exudation in the nasopharynx, rhinorrhea, snoring.

Dermatological reactions: rarely - generalized rash, erythema, pruritis, acne, hyperhidrosis, increased sweating at night.

From the musculoskeletal system: rarely - joint stiffness, muscle spasms, pain in the chest wall, bone chondrite.

From the urinary system: rarely - Glucosuria, nocturia, polyuria.

On the part of the reproductive system: rarely - menorrhagia, vaginal discharge, sexual dysfunction, increased libido, decreased libido, sperm change.

Infections: rarely - bronchitis, nasopharyngitis, sinusitis, fungal infections, viral infections.

Other: often fatigue; rarely - chest discomfort, chest pain, fever, sensation of cold, asthenia, disturbed circadian rhythm of sleep, malaise, cyst, decrease in the number of platelets, increase in the level of C-reactive protein.

Overdose:

No cases of a varenicline overdose have been reported.

Treatment: symptomatic.

Varenicline is excreted in hemodialysis in patients with severe renal dysfunction, but there is no experience with hemodialysis in case of an overdose.

Interaction:

Clinically significant interactions of varenicline with other drugs have not been identified. Correction of a dose of varenicline or the drugs listed below with simultaneous application is not required.

Research in vitro evidence that varenicline does not change the pharmacokinetics of drugs that are metabolized by cytochrome P450 isoenzymes. Since the varenicline clearance is less than 10% due to metabolism, it is unlikely that substances that affect the activity of cytochrome P450 isoenzymes can affect the pharmacokinetics of varenicline, and therefore correction of its dose is not required.

Varenicline in therapeutic concentrations does not inhibit renal protein transport in humans. Consequently, varenicline should not affect the pharmacokinetics of drugs, the clearance of which is due to renal secretion (in particular metformin).

Metformin. Varenicline does not affect the pharmacokinetics of metformin. Metformin does not cause a change in the pharmacokinetics of varenicline.

Cimetidine causes an increase in AUC varenicline by 29% due to a decrease in its renal clearance.

Digoxin. Varenicline does not affect the pharmacokinetics of digoxin in the equilibrium state.

Warfarin. Varenicline does not change the pharmacokinetics of warfarin and does not affect prothrombin time (INR). Cessation of smoking itself can lead to a change in the pharmacokinetics of warfarin.

Application in combination with other anti-smoking agents

Bupropion. Varenicline does not affect the pharmacokinetics of bupropion in the equilibrium state.

Nicotine replacement therapy. With the simultaneous use of varenicline smokers and patches containing nicotine, within 12 days, a statistically significant decrease in the average SAD was observed (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 was higher with combined therapy than with one nicotine-replacement therapy.

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

Special instructions:

Physiological changes that occur after quitting smoking with or without varenicline therapy can affect the pharmacokinetics or pharmacodynamics of some drugs, which may require correction of their dose (for example, theophylline, warfarin and insulin).

The completion of treatment with varenicline in 3% of patients was accompanied by increased irritability, cravings for smoking, depression and / or insomnia.

During the post-marketing use of the drug, there were reports of psycho-neurological symptoms, including behavioral disorders, agitation, depressive mood, suicidal tendencies and suicidal behavior in patients attempting to quit using varenicline. The doctor should explain to patients trying to quit using varenicline,the possibility of developing psychoneurological symptoms and take into account the possibility of a gradual dose reduction. Patients, members of their families or caregivers should be informed of the need to stop taking the drug and seek immediate medical attention if there is a behavioral disorder, agitation or depressive mood that was not previously characteristic of the patient, as well as a suicidal mood or behavior. Before starting treatment, patients should be advised to report any mental disorders that they had before.

Influence on the ability to drive and use machinery. Given that varenicline may cause dizziness and drowsiness, patients are not advised to drive, use complicated equipment or perform other potentially dangerous tasks until they evaluate their reaction to the drug.

Instructions

Varenicline (Vareniclinum)