CHAMPIX

Active material: Varenicline
When ATH: N07BA03
CCF: Drug for the treatment of nicotine addiction
ICD-10 codes (testimony): F17
When CSF: 02.17
Manufacturer: PFIZER MANUFACTURING DEUTSCHLAND GmbH (Germany)

PHARMACEUTICAL FORM, COMPOSITION AND PACKAGING

Pills, Film-coated white or nearly white, kapsulovidnye, lenticular, Engraved “Pfizer” on one side and “CHX 0.5” – another.

Excipients: microcrystalline cellulose, calcium hydrogen phosphate, Croscarmellose sodium, colloidal silicon dioxide, magnesium stearate.

The composition of the coating film: opadraj white YS-1-18202-A (gipromelloza, Titanium dioxide, macrogol), opadraj transparent YS-2-19114-A (gipromelloza, triacetine).

Pills, Film-coated light blue, kapsulovidnye, lenticular, Engraved “Pfizer” on one side and “CHX 1.0” – another.

Excipients: microcrystalline cellulose, calcium hydrogen phosphate, Croscarmellose sodium, colloidal silicon dioxide, magnesium stearate.

The composition of the coating film: opadraj blue 03B90547 (gipromelloza, Titanium dioxide, macrogol, aluminium lacquer based on indigokarmina), opadraj transparent YS-2-19114-A (gipromelloza, triacetine).

Primary packaging.

11 PC. (tab. 500 g) – blisters.
11 PC. (tab. 500 g) and 14 PC. (tab. 1 mg) – blisters.
14 PC. (tab. 1 mg) – blisters.
28 PC. (tab. 1 mg) – blisters.
56 PC. (tab. 1 mg) – Polyethylene cans.

Secondary packaging.

Packaging for dose titration.
11 PC. (tab. 500 g) in 1 blister and 14 PC. (tab. 1 mg) in 1 blister – packing cardboard combination.

Packaging for maintenance therapy.
11 PC. (tab. 500 g) and 14 PC. (tab. 1 mg) in 1 blister, and 28 PC. (tab. 1 mg) in 1 blister – packing cardboard combination.
14 PC. (tab. 1 mg) – blisters (1) – packs cardboard.
14 PC. (tab. 1 mg) – blisters (2) – packs cardboard.
14 PC. (tab. 1 mg) – blisters (4) – packs cardboard.
14 PC. (tab. 1 mg) – blisters (8) – packs cardboard.
14 PC. (tab. 1 mg) – blisters (2) – packing cardboard combination.
28 PC. (tab. 1 mg) – blisters (2) – packing cardboard combination.
56 PC. (tab. 1 mg) – Polyethylene cans (1) – packs cardboard.

Pharmacological action

Drug for the treatment of nicotine addiction. Varenicline with high affinity and selectivity binds to α4β2 n-holinoretseptorami, in respect of which it is a partial agonist nicotine, ie. at the same time exhibits agonističeskuû activity (but less, than nicotine) and antagonism in the presence of nicotine.

Electrophysiological studies in vitro and in vivo studies neyrobiohimicheskie shown, that varenicline binds to α4β2 n-holinoretseptorami and stimulates their, but to a much lesser extent, than nicotine. Nicotine competitively binds to the same receptor plot, to which varenicline has higher affinity. Thus, varenicline blocks nicotine's ability to effectively stimulate and activate the receptors a4r2 mezolimbičeskuû dofaminovu system – Neuronal mechanism, that underlies the mechanisms of formation of nicotine addiction (getting pleasure from smoking).

Effectiveness of varenicline as a means to treat nicotine addiction caused by partial agonizmom Nicotinic α4β2 receptor in relation, linking which reduces cravings for smoking and facilitate the manifestation of the syndrome (agonist activity) and at the same time leads to a decrease in feelings of pleasure from smoking (antagonism in the presence of nicotine).

Pharmacokinetics

Varenicline is characterized by linear farmakokinetika one-time ( 0.1-3 mg) and repeated (1-3 mg / day) the application of the.

Absorption

After intake of varenicline is almost completely absorbed from the digestive tract. C_max plasma is usually achieved within 3-4 no . Bioavailability high and does not depend on the meals or time dose. After repeated admission healthy volunteers equilibrium is achieved within 4 days.

Distribution

Varenicline is distributed in the tissues, penetrates the Geb and enters the brain. Plasma protein binding is low (≤ 20%) and does not depend on age and renal function.

Metabolism and excretion

Varenicline undergoes minimal metabolism. Excreted in the urine 92% dose unaltered, less 10% – as metabolites. In the urine detected varenicline (N)-karbamoilglûkuronid and gidroksivareniklin. In the blood of varenicline circulates in an unmodified form (91%) and as metabolites – N-karbamoilglûkuronid and N-glûkozilvareniklin varenicline.

T_1/2 is about 24 no. Excretion kidneys is carried out mainly by clubockova filtering in combination with active kanalzeva secretion.

Pharmacokinetics in special clinical situations

Varenicline pharmacokinetics are not significantly depends on the age of the, race, gender, status of smoking or concomitant therapy.

Unchanged varenicline pharmacokinetics in patients with slight impairment of renal function (CC > 50 mL/min and ≤ 80 ml / min). In patients with moderate renal insufficiency (CC > 30 mL/min and ≤ 50 ml / min) AUC of varenicline increased 1.5 compared with that in patients with normal renal function (CC > 80 ml / min). In patients with severe renal impairment (CC < 30 ml / min) AUC of varenicline increased 2.1 times. In patients with end stage renal failure varenicline effectively removed with hemodialysis.

Given the lack of expressed metabolism in liver, It is unlikely to change the pharmacokinetics of varenicline in patients with impaired liver function.

Varenicline pharmacokinetics in elderly patients with normal renal function (age 65-75 years) not changed.

Testimony

-nicotine addiction in adults.

Dosage regimen

The likelihood of a successful drug therapy for smoking cessation is increased in patients, motivated on quitting smoking, which provides additional advice and support.

The drug is taken orally with or without food. The tablets should be swallowed whole with water and.

Treatment Čampiksom^® to start over 1 week before selected a patient smoking cessation date. The recommended dose is 1 mg 2 times/day, dose titration according to the scheme, given in table.

At bad portability side effects Čampiksa^® dose can be reduced temporarily or further reception.

Course of treatment 12 Sun. Patients, who successfully stopped smoking by the end of 12 of the week, It is recommended that an additional course of drug treatment in the dose 1 mg 2 times / day for 12 Sun.

Patients, that cannot stop smoking during the initial 12-week course of treatment or relapse occurs after treatment, should be encouraged to take another try, provided, What were the causes of failure of the first attempt and the measures taken to address them.

To patients with mild renal insufficiency (CC > 50 mL/min and ≤ 80 ml / min) and moderately (CC > 30 mL/min and ≤ 50 mL/min) dose adjustment is required.

To patients with severe renal insufficiency (CC < 30 ml / min) the recommended dose of Čampiksa^® is 1 mg 1 time / day. Treatment is initiated with a dose of 500 g 1 time / day, that through 3 the day increased to 1 mg 1 time / day.

Patients with impaired liver function correction dose not required.

Elderly patients correction dose not required. It should be taken into account, This category of patients have the likelihood of kidney function above, It is therefore advisable to assess before treatment.

Čampiks^® nor should appoint children and adolescents up to 18 years, because information about the safety of the drug in this age group is not enough.

Side effect

Reaction, associated with smoking cessation (Nicotine withdrawal), with or without therapy Čampiksom^®: depressed mood and dysphoria, insomnia, irritability, feeling of displeasure and anger, alarm, impaired concentration, restlessness, a decrease in heart rate, increased appetite or weight gain, possible worsening of psychiatric comorbidity.

Nor when developing schemes for clinical research Čampiksa^®, nor in the analysis of their results no attempt to distinguish between adverse events, related to study medication, and adverse reactions, perhaps, associated itself with nicotine withdrawal symptoms.

According to the results of clinical studies unwanted reactions usually appear in the first week after starting treatment, We were, usually, mild or moderate and their frequency does not depend on the age, race or sex of the patient. Patients, receiving Čampiks^® at the recommended dose 1 mg 2 times / day after a period of titration, the most frequent of the reported adverse reactions were nausea (28.6%). In the majority of cases nausea occurred early in therapy, It expressed mild to moderate, discontinuation of the drug is rarely needed.

The frequency of discontinuation due to adverse events was 11.4% in Group, poluchavshey and varenicline 9.7% to placebo. The frequency of discontinuation due to adverse reactions in the main group, receiving varenicline and placebo, respectively: nausea - 2.7% and 0.6%; headache - 0.6% and 1.0%; Insomnia - 1.3% and 1.2%; unusual dreams - 0.2% and 0.2%.

Determination of the frequency of adverse reactions: Often (≥ 1/10); often (≥ 1/100 but < 1/10); rarely (≥ 1/1000, but < 1/100).

Infection: rarely – bronchitis, nazofaringit, sinusitis, fungal infections, viral infections.

Metabolism: often – increased appetite; rarely – anorexia, decreased appetite, polydipsia, weight gain, lowering blood calcium.

From the central and peripheral nervous system: Often – unusual dreams, insomnia, headache; often – drowsiness, dizziness, disgevziya; rarely – panic reaction, bradyphrenia, aphronia, mood swings, tremor, incoordination, dysarthria, restlessness, disforija, gipesteziya, apathy.

Cardio-vascular system: rarely – increased blood pressure, ST-segment depression on ECG, decrease in the amplitude of the T wave on the ECG, increase in heart rate, Atrial fibrillation, heartbeat.

From the senses: rarely – scotoma, discoloration of sclera, pain in the eyeball, mydriasis, photophobia, myopia, increased lacrimation, noise in ears, decrease in sense of taste.

The respiratory system: rarely – breathlessness, cough, hoarseness, pain in the throat and larynx, throat irritation, congestion in the airways, stagnation in the paranasal sinuses, exudation in the nasopharynx, rhinorrhea, snoring.

From the digestive system: very often - nausea; often – vomiting, constipation, diarrhea, abdominal distention, stomach discomfort, dyspepsia, flatulence, dry mouth; rarely – vomiting blood, blood in the stool, gastritis, gastroesophageal reflux disease, stomach ache, intestinal disorders, violation of the chair, belching, thrush, sore gums, coated tongue, changes in liver function tests.

Dermatological reactions: rarely – generalized rash, эritema, prurit, acne, hyperhidrosis, increased sweating at night.

On the part of the musculoskeletal system: rarely – joint stiffness, muscle spasms, pain in the chest wall, costochondritis.

From the urinary system: rarely – glycosuria, nocturia, polyuria.

Reproductive system: rarely – menorragija, vaginal discharge, sexual dysfunction, increased libido, decreased libido, changes in sperm.

Other: often – fatigue; rarely – chest discomfort, chest pain, fever, rhigosis, asthenia, circadian rhythm sleep, malaise, cyst, decrease in the number of platelets, elevated levels of C-reactive protein.

Smoking cessation therapy with or without accompanied by the development of nicotine withdrawal symptoms and the exacerbation of psychiatric comorbidity.

In the course of postregistracionnyh research patients, background: quit smoking using Čampiksa^®, recorded cases of depressed mood, ažitacii, behavioral disturbances, suicidal thoughts and suicide attempts. Since these events are recorded on the results of voluntary reporting population of uncertain size, not always possible to accurately set their frequency or a causal relationship to drug action. Not all patients, described in these reports, had a history of mental illness and not all of them have stopped smoking. Role Čampiksa^® in the development of responses, described in these reports, unknown. Also recorded cases of allergic reactions – angioneurotic edema and swelling of the face.

Contraindications

- End-stage renal failure;

- Up to 18 years (insufficient clinical data on the efficacy and safety of the drug in this age group);

- Pregnancy;

- Lactation (breast-feeding);

- Hypersensitivity to the drug.

Pregnancy and lactation

Adequate and well-controlled studies on the safety of Čampiksa^® during pregnancy was conducted, therefore, use of the drug is contraindicated.

Unknown, whether varenicline is allocated with breast milk in humans. If necessary, use during lactation should stop breastfeeding.

Cautions

Physiological changes, that arise after quitting amid or without drug treatment Čampiks^®, may alter the pharmacokinetics or pharmacodynamics of some drugs, which may require dose adjustment (eg, theophylline, warfarin and insulin).

Completion of treatment of varenicline in 3% patients accompanied by increased irritability, cravings, depression and / or insomnia.

During post-marketing use of the drug were reported occurrence of neuropsychiatric disorders, including breach of conduct, ažitaciû, depressed mood, suicidal thoughts and suicidal behavior in patients, receiving Čampiks^® with the aim of giving up smoking. The physician should explain to patients, receiving the drug, the possibility of neuropsychiatric symptoms and the need for a gradual reduction of the dose. Patients, members of their families or caregivers of persons should be informed of the need to stop taking Čampiksa^® and immediate treatment to a doctor with the appearance of misconduct, agitation or depressive mood, who previously were not specific to the patient, as well as in the event of suicidal thoughts or behavior. Prior to treatment you should find out, whether the patient had any previous psychiatric disorders.

Effects on ability to drive vehicles and management mechanisms

Čampiks^® may cause dizziness and drowsiness, so patients are not recommended to drive, use of sophisticated technology or perform other potentially dangerous tasks to assess individual response to the drug.

Overdose

No cases of overdose varenicline registered.

Treatment: the holding of symptomatic and supportive therapy. Varenicline appear in hemodialysis patients with severe renal impairment, However, experience with dialysis in overdose is not.

Drug Interactions

Clinically significant interactions with other drugs varenicline is not revealed. No dose adjustment of varenicline or the following preparations, while the application is not required.

In vitro studies suggest that, that varenicline does not change the pharmacokinetics of drugs, are metabolized by the action of cytochrome P450 isozymes. Since varenicline clearance less than 10% at the expense of metabolism, unlikely, that substance, affecting the activity of the enzyme system, may affect the pharmacokinetics of varenicline, in this connection the need for dose adjustment Čampiksa^® not required.

Varenicline at therapeutic concentrations does not inhibit renal transport proteins in humans. Hence, Varenicline should not affect the pharmacokinetics of medicinal products, which are derived by renal secretion (in particular, metformin).

While the application is not required correction doses of the drug Čampiks^® and the following drugs.

Metformin. Varenicline affecting farmakokinetiku metformin. Metformin does not cause changes in the pharmacokinetics of varenicline.

Cimetidine. Cimetidine causes an increase in the AUC of varenicline 29% by reducing its renal clearance.

Digoxin. Varenicline did not cause changes in the pharmacokinetics of digoxin at steady state.

Warfarin. Varenicline did not alter the pharmacokinetics of warfarin had no effect on prothrombin time (MHO). Smoking cessation itself may result in changes in the pharmacokinetics of warfarin.

Use in combination with other anti-smoking

Bupropion. Varenicline did not cause changes in the pharmacokinetics of bupropion in the equilibrium state.

Nikotinzamestitelynaya therapy (NZT). With simultaneous use of varenicline and plasters, nicotine containing, during 12 days in smokers was statistically significant decrease in average systolic blood pressure (on 2.6 mm Hg. Art.) the last day of the study. The frequency of nausea, headache, vomiting, dizziness, dyspepsia and fatigue on the combined therapy were higher, than on the background of one of NRT.

The safety and efficacy of Čampiksa^® in combination with other means of tobacco has not been studied.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored out of reach of children, at a temperature from 15 ° to 30 ° C.. Shelf life – 2 year.