Active ingredients: Varenicline
HAMPIX 0.5 mg film-coated tablets
CHAMPIX 1 mg film-coated tablets
Why is Champix used? What is it for?
CHAMPIX contains the active substance called varenicline. CHAMPIX is a medicine used in adults to help them stop smoking.
CHAMPIX can help you relieve the symptoms of craving and withdrawal associated with smoking cessation.
Although it is recommended not to smoke after the smoking cessation date, CHAMPIX can also reduce the enjoyment of cigarettes if you smoke during treatment (the quit date is the day of the second week of treatment when you will stop smoking. , see paragraph 3).
Contraindications When Champix should not be used
Do not use CHAMPIX:
- if you are allergic to varenicline tartrate or any of the other ingredients of this medicine (listed in section 6).
Precautions for use What you need to know before taking Champix
Talk to your doctor or pharmacist before taking CHAMPIX.
Cases of depression, suicidal ideation and behavior, and suicide attempts have been reported in patients taking CHAMPIX. If you are taking CHAMPIX and develop agitation, depressed mood and changes in behavior that cause concern to you, your family or your doctor, or if you develop suicidal ideation or behavior, you should stop treatment and contact your doctor immediately.
Effects of smoking cessation
The effects of the changes in your body that result from quitting smoking, with or without treatment with CHAMPIX, can alter the way other medicines work. Therefore, a dose adjustment may be necessary in some cases. For further details see the section below "Other medicines and CHAMPIX".
In some people, stopping smoking, with or without treatment, has been associated with an increased risk of changes in thinking or behavior, feelings of depression and anxiety and may be associated with worsening of psychiatric illness. a history of psychiatric illness talk to your doctor or pharmacist.
Depressed mood may occur in the smoking cessation phase, with or without treatment. Depression, rarely associated with suicidal thoughts and suicide attempts, has been reported in patients being treated for smoking cessation. . These sensations have also been reported in patients who have tried to quit smoking with CHAMPIX. If these symptoms persist when you stop taking CHAMPIX, your doctor will need to keep monitoring you closely until you feel better.
Cardiovascular symptoms
Especially in people who already have cardiovascular problems, new or worsening heart or blood vessel (cardiovascular) problems have been reported. Tell your doctor if you experience any changes in symptoms during treatment with CHAMPIX. If you have symptoms of a heart attack or stroke, seek emergency medical help immediately.
Seizures
Before starting treatment with CHAMPIX, tell your doctor if you have had fits or if you suffer from epilepsy. Some people have experienced seizures during treatment with CHAMPIX.
Discontinuation of treatment with CHAMPIX
When you stop taking CHAMPIX, you may temporarily report an increase in irritability, an urge to smoke, depression and / or sleep disturbances. Your doctor may decide to gradually reduce the dose of CHAMPIX at the end of the treatment.
Children and adolescents
The use of CHAMPIX in children or adolescents under the age of 18 is not recommended as safety and efficacy in this age group have not been established.
Interactions Which drugs or foods can modify the effect of Champix
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
The effects of the changes in your body that result from quitting smoking, with or without treatment with CHAMPIX, can alter the way other medicines work. Therefore, a dose adjustment may be necessary in some cases. These include theophylline (a medicine to treat breathing problems), warfarin (a medicine used to reduce blood clots) and insulin (a medicine for diabetes). If in doubt, consult the doctor or pharmacist.
If you have severe kidney disease you should avoid taking cimetidine (a medicine for stomach disorders) while taking CHAMPIX, as this may cause the blood levels of CHAMPIX to rise.
Using CHAMPIX with other smoking cessation therapies
The safety and benefits of using CHAMPIX in combination with other smoking cessation medicines have not been studied. Therefore, the use of CHAMPIX together with other smoking cessation therapies is not recommended.
CHAMPIX with food and drink
CHAMPIX can be taken with or without food.
Warnings It is important to know that:
Pregnancy and breastfeeding
You should not use CHAMPIX if you are pregnant.
Talk to your doctor if you plan to become pregnant. If you want to start treatment with CHAMPIX, the timing of your treatment should be set in order to complete the course of treatment before becoming pregnant.
Although it has not been studied, CHAMPIX may pass into breast milk. Ask your doctor or pharmacist for advice before taking CHAMPIX.
Driving and using machines
CHAMPIX can cause dizziness and sleepiness. You should not drive, operate complex machinery or perform any other potentially dangerous activities until you know if this medicine affects your ability to perform these activities.
Dose, Method and Time of Administration How to use Champix: Posology
They are more likely to be able to quit smoking if motivated. Your doctor or pharmacist can provide you with advice, support and further information to help you make your attempts to quit smoking successful.
Always take this medicine exactly as your doctor has told you. If in doubt, consult your doctor or pharmacist.
Before starting the course of treatment with CHAMPIX, you should usually set a date of the second week of treatment (between the 8th and 14th day) to stop smoking. If you do not want or are unable to set a date in to quit within the first 2 weeks, you can choose your individual quit date within 5 weeks of starting treatment. He has to write this date on the package to remember it.
CHAMPIX tablets should be swallowed whole with water.
CHAMPIX is available as white tablets (0.5 mg) and light blue tablets (1 mg). You start with the white tablet and then usually switch to the light blue tablet. See the table below for instructions on the usual doses you should follow from day 1.
After 12 weeks of treatment, if you have stopped smoking, your doctor may recommend an additional 12-week course of CHAMPIX 1 mg film-coated tablets twice a day to help prevent you from smoking again.
If you are unable or unwilling to stop smoking immediately, you should reduce smoking during the first 12 weeks of treatment and quit by the end of that period. You should then continue taking CHAMPIX 1 mg film-coated tablets twice a day for an additional 12 weeks, for a total of 24 weeks of treatment.
If adverse events occur that you cannot tolerate, your doctor may decide to reduce the dose temporarily or permanently to 0.5 mg twice a day.
If you have kidney problems, you should talk to your doctor before taking CHAMPIX. You may need a lower dose.
During the course of smoking cessation therapy, the risk of resuming smoking may be high in the period immediately following the end of treatment. The doctor may decide to gradually reduce the dose of CHAMPIX at the end of treatment.
Overdose What to do if you have taken too much Champix
If you take more CHAMPIX than you should
If you accidentally take more CHAMPIX than you were told to, you should see your doctor or go to the nearest emergency department. Take the pack of tablets with you.
If you forget to take CHAMPIX
Do not take a double dose to make up for a forgotten tablet. It is important that you take your CHAMPIX tablet regularly at the same time each day. If you forget to take a dose, take it as soon as you remember it. If it is almost time for your next dose, do not take the forgotten tablet.
If you stop taking CHAMPIX
In clinical studies, it has been shown that taking all doses of the medicine at the right time and for the recommended treatment duration described above will increase the likelihood of quitting smoking. Therefore, unless your doctor tells you to stop. treatment, it is important to continue taking CHAMPIX following the instructions described in the table above.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
Side Effects What are the side effects of Champix
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Quitting smoking, with or without treatment, can cause a variety of symptoms. These can include mood changes (such as feeling depressed, irritated, frustrated or anxious), insomnia, difficulty concentrating, decreased heart rate and increased "appetite or weight gain.
If you are taking CHAMPIX and develop agitation, depressed mood, changes in behavior or thoughts of suicide you should stop treatment and contact your doctor immediately.
Very common side effects which may affect more than 1 in 10 people:
- Inflammation of the nose and throat, altered dreams, difficulty sleeping, headache.
- Nausea.
Common side effects that may affect up to 1 in 10 people:
- Chest infections, sinusitis.
- Weight gain, appetite decrease, appetite increase.
- Somnolence, dizziness, taste disturbances.
- Shortness of breath, cough.
- Heartburn, vomiting, constipation, diarrhea, bloating, abdominal pain, toothache, indigestion, intestinal gas, dry mouth.
- Skin rash, itching.
- Joint pain, muscle pain, back pain.
- Chest pain, fatigue.
Uncommon side effects which may affect up to 1 in 100 people:
- Fungal infection, viral infection.
- Feeling of panic, difficulty thinking, restlessness, mood swings, depression, anxiety, hallucinations, changes in sexual impulses.
- Seizures, tremors, feeling of apathy, loss of sensitivity to touch.
- Conjunctivitis, eye pain.
- Ringing in the ears.
- Angina, rapid heartbeat, palpitations, increased heart rate.
- Increased blood pressure, hot flashes.
- Inflammation of the nose, sinuses and throat, congestion of the nose, throat and chest, hoarse voice, hay fever, throat irritation, congested sinuses, excess mucus in the nose causing cough, runny nose.
- Red blood in stool, stomach irritation, change in bowel habits, belching, mouth ulcers, gum pain.
- Skin redness, acne, increased sweating, night sweats.
- Muscle spasms, chest wall pain.
- Frequent urine abnormally, nocturnal urine.
- Increased menstrual flow.
- Chest discomfort, flu-like syndrome, fever, feeling weak or unwell.
Rare side effects which may affect up to 1 in 1,000 people:
- Excessive thirst.
- Feeling uneasy or unhappy, slow thinking.
- Stroke.
- Increased muscle tension, difficulty speaking, difficulty with coordination, decreased sense of taste, altered sleep rhythm.
- Visual disturbances, ocular globe discolouration, dilated pupils, sensitivity to light, nearsightedness, profuse lacrimation.
- Irregular heartbeat or heart rhythm disturbances.
- Sore throat, snoring.
- Presence of blood in the vomit, altered stools, impaned tongue.
- Stiffness in the joints, pain in the ribs.
- Glucose in the urine, increased urine volume and frequency.
- Vaginal discharge, impaired sexual performance.
- Feeling cold, cyst.
Other side effects have occurred in a small number of people who have tried to quit smoking with CHAMPIX, but their exact frequency is unknown: heart attack episodes, suicidal thoughts, loss of contact with reality and inability to think o Make clear judgments (psychosis), changes in thinking or behavior (such as aggression and abnormal behavior), sleepwalking, diabetes and high blood sugar. There have also been reports of serious skin reactions including Erythema Multiforme (a type of rash) and Stevens-Johnson Syndrome (a serious disease with blistering of the skin, mouth, around the eyes or genitals) and severe allergic reactions including angioedema (swelling of the face, mouth or throat. You should stop using CHAMPIX and contact your doctor immediately if you notice peeling or blistering of the skin, or if you experience swelling of the face, mouth or throat.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton or carton. The expiry date refers to the last day of the month.
Blisters: Store below 30 ° C.
Bottle: This medicine does not require any special storage conditions.
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Composition and pharmaceutical form
What CHAMPIX contains
- The active ingredient is 0.5 mg varenicline and 1 mg varenicline respectively
- The excipients are:
What CHAMPIX looks like and contents of the pack
- CHAMPIX 0.5 mg film-coated tablets are white in modified capsule shape and engraved with "Pfizer" on one side and "CHX 0.5" on the other.
- CHAMPIX 1 mg film-coated tablets are light blue in a modified capsule shape and engraved with "Pfizer" on one side and "CHX 1.0" on the other.
CHAMPIX is available in the following packs:
Not all pack sizes may be marketed.
- Treatment initiation pack containing 2 blisters; 1 clear blister of 11 film-coated tablets of CHAMPIX 0.5 mg and 1 clear blister of 14 film-coated tablets of CHAMPIX 1 mg contained in a secondary carton.
- Treatment initiation pack containing 2 blisters; 1 clear blister of 11 film-coated tablets of CHAMPIX 0.5 mg and 14 film-coated tablets of CHAMPIX 1 mg and 1 clear blister of 28 film-coated tablets of CHAMPIX 1 mg contained in a secondary carton.
- Maintenance pack containing 2 clear blisters of 14 film-coated tablets of CHAMPIX 1 mg in a secondary carton.
- Maintenance pack containing 2 clear blisters of 28 film-coated tablets of CHAMPIX 1 mg in a secondary carton.
- Maintenance pack containing 2 clear blisters of 14 film-coated tablets of CHAMPIX 0.5 mg in a secondary carton.
- Maintenance pack containing 2 clear blisters of 28 film-coated tablets of CHAMPIX 0.5 mg in a secondary carton. Document made available by AIFA on 01/04/2015 93
- Treatment initiation pack containing 2 blisters; 1 clear blister of 11 film-coated tablets of CHAMPIX 0.5 mg and 1 clear blister of 14 film-coated tablets of CHAMPIX 1 mg contained in a carton.
- Maintenance pack containing 2 clear blisters of 14 film-coated tablets of CHAMPIX 1 mg in a carton.
- Maintenance pack containing 4 clear blisters of 14 film-coated tablets of CHAMPIX 1 mg in a carton.
- Maintenance pack containing 8 clear blisters of 14 film-coated tablets of CHAMPIX 1 mg in a carton.
- Maintenance pack containing 10 clear blisters of 14 film-coated tablets of CHAMPIX 1 mg in a carton.
- Pack containing 1 blue-white sealed HDPE bottle with child resistant closure containing 56 tablets of CHAMPIX 1 mg in a carton.
- Pack containing 1 blue-white sealed HDPE bottle with child resistant closure containing 56 tablets of CHAMPIX 0.5 mg in a carton.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
CHAMPIX TABLETS COATED WITH FIM
▼ Medicinal product subject to additional monitoring. This will allow the rapid identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 for information on how to report adverse reactions
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each film-coated tablet contains 0.5 mg of varenicline (as tartrate)
Each film-coated tablet contains 1 mg of varenicline (as tartrate)
Excipients with known effects:
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Film-coated tablets.
0.5 mg film-coated tablets: White, capsule-shaped, biconvex tablets with the imprint "Pfizer" engraved on one side and "CHX 0.5" on the other.
1 mg film-coated tablets: light blue, capsule-shaped, biconvex tablets with the imprint "Pfizer" engraved on one side and "CHX 1.0" on the other.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
CHAMPIX is indicated for the cessation of smoking in adults.
04.2 Posology and method of administration
Dosage
The recommended dose of varenicline is 1 mg twice daily after one week of dose increases made according to the following schedule:
The patient must set a date to quit smoking. Treatment with CHAMPIX should generally start 1-2 weeks before this date (see section 5.1).
In patients who cannot tolerate the adverse reactions of CHAMPIX the dose can be temporarily or permanently reduced to 0.5 mg twice daily.
Patients should be treated with CHAMPIX for 12 weeks.
For patients who have successfully quit smoking at the end of the 12th week, an additional 12-week course of treatment with CHAMPIX at a dose of 1 mg twice daily may be considered (see section 5.1).
Patients who are motivated but have not been able to stop smoking during previous CHAMPIX therapy, or who have resumed smoking after treatment, may benefit from another CHAMPIX quit attempt (see section 5.1).
Smoking cessation therapies are more likely to be successful in patients who are motivated to quit and receive additional and supportive counseling.
During the course of smoking cessation therapy, the risk of relapse is high in the period immediately following the end of treatment. In patients at high risk of relapse, a gradual reduction of the dose may be considered (see section 4.4 ).
Patients with renal impairment
No dosage adjustment is necessary in patients with mild (creatinine clearance> 50 ml / min and ≤ 80 ml / min) to moderate (creatinine clearance ≥ 30 ml / min and ≤ 50 ml / min) renal impairment.
In patients with moderate renal impairment presenting with intolerable adverse reactions the dose can be reduced to 1 mg once daily.
In patients with severe renal impairment (creatinine clearance
Patients with hepatic impairment
No dosage adjustment is necessary in patients with hepatic impairment (see section 5.2).
Elderly patients
No dosage adjustment is necessary in elderly patients (see section 5.2). Since decreased renal function is more likely in elderly patients, the prescribing physician should consider the renal condition of elderly patients.
Pediatric population.
The safety and efficacy of CHAMPIX in children or adolescents below 18 years of age have not been established. Currently available information is described in section 5.2, but no posology can be recommended.
Method of administration
CHAMPIX is for oral use and the tablets should be swallowed whole with water.
CHAMPIX can be taken on a full or empty stomach.
04.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
04.4 Special warnings and appropriate precautions for use
Effect of smoking cessation
Physiological changes resulting from smoking cessation, with or without treatment with CHAMPIX, may alter the pharmacokinetics or pharmacodynamics of some medicinal products for which dosage adjustment may be required (eg theophylline, warfarin and insulin). Since smoking induces cytochrome CYP1A2, cessation of smoking may lead to increased plasma levels of CYP1A2 substrates.
Neuropsychiatric symptoms
Changes in behavior or thinking, anxiety, psychosis, mood swings, aggressive behavior, depression, suicidal ideation and suicidal behavior, and suicide attempts have been reported in patients who attempted to quit smoking with CHAMPIX in the post-marketing phase. Not all patients had quit smoking when symptoms occurred, and not all patients had pre-existing psychiatric conditions. Physicians should be aware of the possible onset of significant depressive symptoms in patients trying to quit smoking and should Consequently, inform patients. Champix treatment should be stopped immediately if agitation, depressed mood, or changes in behavior or thinking are observed that concern the doctor, patient, family or caregivers, or if the patient develops suicidal thoughts or a compo suicidal rtamento. In many of the cases occurring in the post-marketing phase, resolution of symptoms has been reported after discontinuation of varenicline treatment, although persistence of symptoms has been observed in some cases; therefore, continuous follow-up of the patient has to be performed. patient until symptoms resolve.
Depressed mood, rarely associated with suicidal ideation and suicide attempts, may be a symptom of nicotine withdrawal. Furthermore, cessation of smoking, with or without drug therapy, has been associated with an exacerbation of pre-existing psychiatric conditions. (and for example depression).
Cardiovascular events
In a clinical study in patients with stable cardiovascular disease (CVD), some cardiovascular events were reported more frequently in patients treated with CHAMPIX (see section 5.1). A meta-analysis of 15 clinical trials, including the smoking cessation study in patients with stable cardiovascular disease, yielded similar results (see section 5.1). Patients taking CHAMPIX should be aware that they should inform their physician of new symptoms. worsening of the cardiovascular system and that, in the event of signs and symptoms of myocardial infarction or stroke, they should seek immediate medical assistance.
History of psychiatric diseases
Studies of Champix on smoking cessation provided data in patients with major depression and limited data in patients with stable schizophrenia or schizoaffective disorder (see section 5.1). Caution should be exercised in patients with a history of psychiatric illness and patients should be advised accordingly.
Seizures
Seizures have been reported in patients treated with CHAMPIX, with or without a history of seizures, in clinical trials and in the post-marketing setting. CHAMPIX should be used with caution in patients with a history of seizures or other conditions that may lower the seizure threshold.
Discontinuation of treatment
At the end of treatment, discontinuation of CHAMPIX was associated with increased irritability, compulsive desire to smoke, depression and / or insomnia in up to 3% of patients.Accordingly, the prescribing physician should inform the patient and discuss or consider the need for a gradual dose reduction.
Hypersensitivity reactions
Cases of hypersensitivity reactions including angioedema have been reported in the post-marketing setting in patients treated with varenicline. Clinical signs included swelling of the face, mouth (tongue, lips and gums), neck (throat and larynx) and extremities. Cases of angioedema that were life-threatening for the patient and required urgent medical attention due to respiratory compromise have been reported. Patients experiencing these symptoms should stop varenicline treatment and contact a healthcare professional immediately.
Skin reactions
There have also been reports of rare but serious skin reactions, including Stevens-Johnson Syndrome and erythema multiforme, in patients receiving varenicline in the post-marketing setting.
As these skin reactions can be life-threatening for the patient, patients should stop treatment at the first appearance of skin rash symptoms or skin reactions and contact a healthcare professional immediately.
04.5 Interactions with other medicinal products and other forms of interaction
Based on the characteristics of varenicline and the clinical experience available to date, CHAMPIX does not exhibit clinically significant interactions with other medicinal products. No dosage adjustment of CHAMPIX or the co-administered medicinal products listed below is recommended.
Studies in vitro indicate that varenicline is unlikely to alter the pharmacokinetics of compounds that are primarily metabolised by cytochrome P450 enzymes.
Furthermore, since the metabolism of varenicline accounts for less than 10% of its clearance, drugs known to affect the cytochrome P450 system are unlikely to alter the pharmacokinetics of varenicline (see section 5.2) and therefore no adjustment of the dosage of CHAMPIX.
Studies in vitro show that varenicline at therapeutic concentrations does not inhibit renal transport proteins in humans. Therefore, varenicline is unlikely to alter the effect of drugs excreted via renal secretion (eg metformin - see below).
Metformin: Varenicline did not alter the pharmacokinetics of metformin. Metformin had no effect on varenicline pharmacokinetics.
Cimetidine: Concomitant administration of cimetidine and varenicline increased the systemic exposure of varenicline by 29% due to a decrease in renal clearance of varenicline. No dosage adjustment is recommended when co-administered with cimetidine in subjects with normal renal function or in patients with mild to moderate renal impairment. In patients with severe renal impairment, concomitant use of cimetidine and varenicline should be avoided.
Digoxin: Varenicline did not alter the pharmacokinetics of digoxin allo steady-state.
Warfarin: Varenicline did not alter the pharmacokinetics of warfarin. Prothrombin time (INR) was not altered by varenicline. Smoking cessation itself may lead to alterations in the pharmacokinetics of warfarin (see section 4.4).
Alcoholic: Clinical data on a potential interaction between alcohol and varenicline are limited.
Use with other smoking cessation therapies:
Bupropion: Varenicline did not alter the steady-state pharmacokinetics of bupropion.
Nicotine Replacement Therapy (NRT): When varenicline and transdermal NRT were administered together with smokers for 12 days, a statistically significant reduction in mean systolic blood pressure (mean 2.6 mmHg) measured on the last day of the study was observed. In this study, the incidence of nausea, headache, vomiting, dizziness, dyspepsia and fatigue was higher for the varenicline and NRT combination than for NRT alone.
The safety and efficacy of CHAMPIX in combination with other smoking cessation therapies have not been studied.
04.6 Pregnancy and lactation
Pregnancy
There are no adequate data on the use of CHAMPIX in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. CHAMPIX should not be used during pregnancy. .
Feeding time
It is not known whether varenicline is excreted in human milk. Animal studies suggest that varenicline is excreted in breast milk. A decision on whether to continue / discontinue breast-feeding or to continue / discontinue CHAMPIX therapy must be made taking into account the benefit of breast-feeding for the child and the benefit of CHAMPIX therapy for the woman.
Fertility
There are no clinical data on the effects of varenicline on fertility.
Non-clinical data show no risk for humans based on standard male and female fertility studies performed in mice (see section 5.3).
04.7 Effects on ability to drive and use machines
CHAMPIX may have a negligible or minor influence on the ability to drive and use machines. CHAMPIX may cause dizziness and somnolence and therefore may affect the ability to drive and use machines. Patients are advised not to drive, operate complex machinery or engage in potentially hazardous activities until it is known whether this medicine impairs the ability to perform these activities.
04.8 Undesirable effects
Summary of the safety profile
Smoking cessation with or without treatment is associated with several symptoms. For example, dysphoric moods or depressed mood have been reported in patients trying to quit smoking; insomnia, irritability, frustration or anger; anxiety, difficulty concentrating; restlessness; reduced heart rate; increased appetite or weight gain. No attempt was made either with respect to study design or analysis of studies with CHAMPIX to distinguish adverse reactions associated with study drug treatment from those possibly associated with nicotine suspension.
Clinical studies included approximately 4,000 patients treated with CHAMPIX for a treatment period of up to 1 year (mean exposure of 84 days). In general, when adverse reactions occurred, onset was in the first week of therapy; severity was generally mild to moderate, and there was no age difference in the incidence of adverse reactions. race or gender.
In patients treated with the recommended dose of 1 mg BID, after an initial period of tapering the dose the most commonly reported adverse event was nausea (28.6%). In the majority of cases, nausea occurred in the The initial phase of the treatment period was mild to moderate in severity and rarely resulted in treatment discontinuation.
The discontinuation rate due to adverse reactions was 11.4% for varenicline versus 9.7% for placebo. In this group, the discontinuation rates due to the most common adverse reactions in patients on treatment with varenicline were the following: nausea (2.7% versus 0.6% for placebo), headache (0.6% versus 1.0% for placebo), insomnia (1.3% versus 1.2% for placebo) and altered dream activity (0.2% versus 0.2% for placebo).
Tabular summary of adverse reactions
In the table below, all adverse reactions that occurred with an incidence greater than placebo are listed by system organ class and frequency (very common (≥1 / 10), common (≥1 / 100 to
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous 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.
04.9 Overdose
No cases of overdose have been reported in pre-marketing clinical studies.
In the event of an overdose, necessary standard supportive measures should be initiated.
Varenicline has been shown to be dialysable in patients in the terminal stage of renal disease (see section 5.2); however, there is no experience with dialysis following overdose.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: OTHER MEDICINES OF THE CENTRAL NERVOUS SYSTEM; drugs used in nicotine addiction, ATC code: NO7BA03
Mechanism of action
Varenicline binds with high affinity and selectivity to the neuronal nicotinic receptors of acetylcholine α4β2, where it acts as a partial agonist, a compound that possesses both agonist activity, with an intrinsic efficacy lower than that of nicotine, and antagonist activity in the presence of nicotine.
Studies of electrophysiology in vitro and neurochemical studies in vivo showed that varenicline binds to neuronal nicotinic acetylcholine α4β2 receptors and stimulates receptor-mediated activity, but to a significantly lesser extent than nicotine. Nicotine competes for the same α4β2 nAChR binding site for which varenicline has a higher affinity. Thus, varenicline can effectively block nicotine's ability to fully activate α4β2 receptors and the mesolimbic dopaminergic system, the neuronal mechanism underlying the reinforcement and gratification experienced with smoking. Varenicline is highly selective and binds. to the subtype of the α4β2 receptor (Ki = 0.15 nM) to a more potent extent than the other common nicotinic receptors (α3β4 Ki = 84 nM, α7 Ki = 620 nM, α1βγ δ Ki = 3,400 nM), or to non-receptors and transporters nicotinics (Ki> 1mcM, with the exception of 5-HT3 receptors: Ki = 350 nM).
Pharmacodynamic effects
The efficacy of CHAMPIX in smoking cessation is the result of the partial agonist activity of varenicline at the level of the α4β2 nicotinic receptor where its binding produces an effect sufficient to relieve the symptoms of compulsive craving and withdrawal (agonist activity ), causing at the same time a reduction in the effects of gratification and reinforcement of the smoking habit, preventing the nicotinic binding to the α4β2 receptors (antagonist activity).
Clinical efficacy and safety
The efficacy of CHAMPIX in smoking cessation was demonstrated in 3 clinical studies involving chronic smokers (≥10 cigarettes per day). Two thousand six hundred nineteen (2,619) patients were treated with CHAMPIX 1 mg BID (dose escalation during the first week), 669 patients received bupropion 150 mg BID (also gradually increased), and 684 patients received placebo.
Comparative clinical studies
Two identical double-blind prospective clinical trials compared the efficacy of CHAMPIX (1 mg twice daily), prolonged-release bupropion (150 mg twice daily) and placebo in smoking cessation. In these 52-week studies, patients received treatment for 12 weeks, followed by a 40-week treatment-free phase. The primary endpoint of the two studies was the 4-week Continuous Cessation Rate (4 week Continuous Quit Rate - 4W-CQR) from the 9th to the 12th week, confirmed by the level of carbon monoxide (CO). The primary endpoint for CHAMPIX demonstrated statistical superiority over bupropion and placebo.
After the 40-week treatment-free phase, a key secondary endpoint for both studies was Continuous Abstinence Rate (Continuous Abstinence Rate - CA) at week 52. AC was defined as the proportion of all treated subjects who did not smoke (not even one puff) from week 9 to week 52 and who did not have an exhaled CO measurement> 10 ppm.
The 4W-CQR (9th to 12th week) and CA percentage (9th through 52nd week) for studies 1 and 2 are included in the following table:
Patients who have reported effects on compulsive craving, abstinence and smoking reinforcement
Across Studies 1 and 2 during active treatment, compulsive craving and abstinence from smoking were significantly reduced in patients randomized to treatment with CHAMPIX compared to placebo. CHAMPIX also significantly reduced the smoking reinforcement effects that may perpetuate smoking behavior in patients who smoke during treatment compared to placebo. smoking was not measured during the long-term follow-up phase without treatment.
Study on the maintenance of abstinence
The third study evaluated the benefit of an additional 12-week treatment period with CHAMPIX on maintenance of abstinence. Patients in this study (n = 1,927) received open-label CHAMPIX at a dose of 1 mg twice daily for 12 Patients who quit smoking by week 12 were then randomized to treatment with CHAMPIX (1 mg twice daily) or placebo for an additional 12 weeks for a total study duration of 52 weeks.
The primary endpoint of the study was the CO-confirmed continuous abstinence rate from week 13 to week 24 in the double-blind treatment phase. A key secondary endpoint was the continuous abstinence rate (CA) from week 13 to week 52. This study demonstrated the benefit of an additional 12-week treatment period with CHAMPIX 1 mg twice daily versus placebo for maintaining smoking cessation.The likelihood of maintaining abstinence at week 24 after an additional 12-week treatment period with CHAMPIX was 2.47 times that of placebo (p
The key findings are summarized in the following table:
Experience with CHAMPIX in the African American population is currently limited to determine its clinical efficacy. Flexible termination date between 1st and 5th week
The efficacy and safety of varenicline were evaluated in smokers who were given the flexibility to cease treatment between weeks 1 and 5 of treatment. In this 24-week study, there was a treatment period on the 12-week patients, followed by a 12-week treatment-free follow-up phase. The 4-week continuous cessation rate (4W-CQR) at week 9-12 for varenicline and placebo was 53.9% and 19.4%, respectively (difference = 34.5%, 95% CI: 27 , 0% - 42.0%) and the continuous abstinence (CA) rate at week 9-24 was 35.2% (varenicline) vs. 12.7% (placebo) (difference = 22.5%, 95% CI: 15.8% - 29.1%). Patients who are unwilling or unable to set their quit date within weeks 1-2 may be offered to start treatment and then choose their individual quit date by week 5.
Study in subjects re-treated with CHAMPIX:
CHAMPIX was evaluated in a double-blind, placebo-controlled study in 494 patients who had previously attempted to quit smoking with CHAMPIX but were unable to quit or resumed smoking after treatment. Subjects who experienced an adverse event of concern during previous treatment were excluded. Subjects were randomized in a 1: 1 ratio to receive CHAMPIX 1 mg twice daily (N = 249) or placebo (N = 245) for 12-week treatment and then followed for 40 weeks after treatment. Patients included in this study had taken CHAMPIX in the past to try to quit smoking (for a total duration of at least two weeks of treatment), at least three months prior to study entry and had smoked for at least four weeks. with CHAMPIX had a higher rate of CO-confirmed abstinence from week 9 to 12 (45.0%) compared to subjects treated with placebo (11.8%) (odds ratio 7.08; 95% CI 4.34 -11.55; p
The key findings are summarized in the table below:
Subjects with cardiovascular disease
CHAMPIX was evaluated in a randomized, double-blind, placebo-controlled clinical study in patients with stable cardiovascular disease (other than hypertension or in addition to hypertension) who had been diagnosed for more than 2 months. Patients were randomized to treatment with CHAMPIX 1 mg twice daily (n = 353) or placebo (n = 350) for 12 weeks, and followed for 40 weeks after treatment. The 4-week continuous cessation rate (4W-CQR) for varenicline and placebo was 47.3% and 14.3%, respectively, and the continuous abstinence (CA) rate at week 9-52 was 19. 8% for varenicline vs 7.4% for placebo.
Deaths and serious cardiovascular events were assigned by a blinded committee. The following assigned events occurred with a frequency ≥ 1% in both treatment groups during treatment (or within 30 days after treatment): non-fatal myocardial infarction (1.1% vs. 0.3% respectively for CHAMPIX and placebo) and hospitalization for angina pectoris (0.6% vs. 1.1%). During the post-treatment follow-up period of up to 52 weeks, assigned events included the need for coronary revascularization (2.0% vs. 0.6%), hospitalization for angina pectoris (1.7% vs. 1.1 %) and new diagnosis of peripheral vascular disease (PVD) or hospitalization for a PVD procedure (1.4% vs. 0.6%). Some patients who required coronary revascularization underwent the procedure as part of the management of non-fatal myocardial infarction and hospitalization for angina. Over the course of the 52-week study, cardiovascular death occurred in 0.3 % of patients in the CHAMPIX arm and 0.6% of patients in the placebo arm.
A meta-analysis of 15 clinical studies, with treatment duration ≥ 12 weeks, in 7,002 patients (4,190 with CHAMPIX, 2,812 with placebo), to systematically determine the cardiovascular safety of CHAMPIX. The meta-analysis also includes the study described above, conducted on patients with stable cardiovascular disease.
The key cardiovascular safety analysis includes determining the manifestation and time of onset of a composite endpoint represented by serious adverse cardiovascular events (MACE - Major Adverse Cardiovascular Events), defined as cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. These events included in the endpoint were assigned by a blinded independent committee. Overall, the occurrence of a limited number of MACE was detected during treatment in the clinical trials covered by the meta-analysis (CHAMPIX 7 [0.17%]; placebo 2 [0.07%]). In addition, the onset of a limited number of MACEs in the 30 days following the end of treatment was noted (CHAMPIX 13 [0.31%]; placebo 6 [0.21%]).
The meta-analysis demonstrated that exposure to CHAMPIX led to a MACE hazard ratio of 2.83 (95% confidence interval, 0.76 to 10.55, p = 0.12) for ongoing patients. treatment and 1.95 (95% confidence interval, 0.79 to 4.82, p = 0.15) for patients in the 30 days following the end of treatment. These results represent an increase in exposure of 6.5 MACE events and 6.3 MACE events per 1,000 patient-years, respectively. The risk ratio of MACE was higher in patients with cardiovascular risk factors other than smoking compared to that found in patients with no cardiovascular risk factors other than smoking. In the meta-analysis, the rates of all-cause mortality (CHAMPIX 6 [0.14%]; placebo 7 [0.25%]) and cardiovascular mortality (CHAMPIX 2 [0.05%]; placebo 2 [0.07%]) were similar in the CHAMPIX groups compared to the placebo groups.
People with mild or moderate chronic obstructive pulmonary disease COPD
The safety and efficacy of CHAMPIX (1 mg twice daily) for smoking cessation in subjects with mild to moderate COPD were demonstrated in a double-blind, randomized, placebo-controlled clinical study. In this 52-week study, patients received treatment for 12 weeks, followed by a 40-week no-treatment follow-up phase. The primary endpoint of the study was the 4-week Continuous Cessation Rate (4W-CQR) from week 9 to 12, and a secondary endpoint was the Continuous Abstinence (AC) Rate from week 9 to week 52. safety of varenicline was comparable to that found in other clinical trials in the general population, including pulmonary safety. Results for 4W-CQR (9th to 12th week) and percentage of CA (9th to 52nd week) are highlighted in the following table:
Study in subjects with a history of major depression
The efficacy of varenicline was confirmed by a randomized, placebo-controlled study of 525 subjects with a history of major depression within the previous two years or on stable treatment. The percentage of these patients who quit smoking was similar to that reported. for the general population. Continuous abstinence rate was 35.9% in the varenicline-treated patient group versus 15.6% in the group of patients treated with placebo between 9th and 12th week (OR 3.35 (95% CI 2.16-5.21)) and between 9th and 52nd week was 20.3% versus 10.4% respectively (OR 2.36 (95% CI 1.40-3.98)). The most common adverse events (≥ 10%) in subjects taking varenicline were nausea (27.0% vs 10.4% with placebo), headache (16.8% vs 11.2%), abnormal dreams (11.3% vs 8.2%), insomnia (10.9% vs 4.8%) and irritability (10.9% vs 8.2%). The psychiatric scores showed no difference between the varenicline-treated patient group and the placebo-treated patient group and no overall worsening of depression during the study in either patient group.
Study in patients with stable schizophrenia or schizoaffective disorder
The safety and tolerability of varenicline were evaluated in a double-blind study of 128 smokers with stable schizophrenia or schizoaffective disorder, receiving antipsychotics, randomized in a 2: 1 ratio to varenicline (1 mg twice daily). ) or placebo for 12 weeks, with 12 weeks of drug-free follow-up.
In patients taking varenicline, the most common adverse events were nausea (23.8% vs. 14.0% with placebo), headache (10.7% vs. 18.6% with placebo) and vomiting (10, 7% vs. 9.3% with placebo). Among the reported neuropsychiatric adverse events, insomnia was the only event reported in both treatment groups in ≥ 5% of patients, at a higher rate in the varenicline group than placebo (9.5% vs 4.7%).
In general, there was no worsening of schizophrenia, as measured by psychiatric scales, in either treatment group, and no general changes in extrapyramidal signs occurred.
In the varenicline group compared to placebo, a greater percentage of patients reported suicidal ideation or behavior prior to enrollment (past history) and after the end of the active treatment period (days 33 to 85 after the last dose of the drug). During the active treatment period, the incidence of suicide-related events was similar between varenicline-treated and placebo-treated patients (11 vs. 9.3%, respectively). The percentage of patients with suicide-related events in the active-treatment phase versus the post-treatment phase remained unchanged in the varenicline group; in the placebo group this percentage was lower in the post-treatment phase. Although there were no completed suicides, a suicide attempt did occur in a patient on varenicline whose past history included several similar attempts. The limited data available from this single smoking cessation study do not allow definitive conclusions on safety in patients with schizophrenia or schizoaffective disorder.
05.2 Pharmacokinetic properties
Absorption
Maximum plasma concentrations of varenicline are generally reached within 3-4 hours after oral administration. Following multiple dose oral administration in healthy volunteers, steady-state conditions are achieved within 4 days. Absorption following oral administration is virtually complete and systemic availability is high. The oral bioavailability of varenicline is not affected by food or the time of administration.
Distribution
Varenicline is distributed in tissues, including the brain. The apparent volume of distribution averaged 415 liters (% CV = 50) at steady-state. The plasma protein binding of varenicline is low (≤ 20%) and is independent of both age and renal function. In rodents, varenicline is transferred across the placenta and excreted in breast milk.
Biotransformation
Varenicline undergoes minimal metabolism with 92% of the dose excreted unchanged in the urine and less than 10% eliminated as metabolites. Minor metabolites in urine include varenicline N-carbamoyl-glucuronide and hydroxy-varenicline. Circulating varenicline represents 91% of drug-related material. Minor circulating metabolites include varenicline N-carbamoyl-glucuronide and N-glucosylvarenicline.
Studies in vitro show that varenicline does not inhibit cytochrome P450 enzymes (IC50> 6,400 ng / ml). The P450 enzymes tested for inhibition are: 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4 / 5. Also, in human hepatocytes in vitro Varenicline has been shown not to induce the activity of cytochrome P450 enzymes 1A2 and 3A4. Therefore, varenicline is unlikely to alter the pharmacokinetics of compounds that are primarily metabolised by cytochrome P450 enzymes.
Elimination
The elimination half-life of varenicline is approximately 24 hours. Renal elimination of varenicline occurs primarily via glomerular filtration together with active tubular secretion via the organic cation transporter OCT2 (see section 4.5).
Linearity / non-linearity
Varenicline exhibits linear kinetics when administered as a single dose (0.1 to 3 mg) or in repeated doses (1 to 3 mg / day).
Pharmacokinetics in particular patient populations
There are no clinically significant differences in varenicline pharmacokinetics with respect to age, race, gender, smoking habits or concomitant drug use, as demonstrated by specific pharmacokinetic studies and population pharmacokinetic analyzes.
Patients with hepatic impairmentDue to the absence of significant hepatic metabolism, the pharmacokinetics of varenicline should not be changed in patients with hepatic impairment (see section 4.2).
Patients with crenal impairment: The pharmacokinetics of varenicline were unchanged in subjects with mild renal impairment (creatinine clearance> 50 ml / min and ≤ 80 ml / min). In patients with moderate renal impairment (creatinine clearance ≥ 30 mL / min and ≤ 50 mL / min), varenicline exposure is increased 1.5-fold compared to subjects with normal renal function (creatinine clearance> 80 mL / min). min) In subjects with severe renal impairment (hemodialysis creatinine clearance (see section 4.2)
Senior citizens: The pharmacokinetics of varenicline in elderly patients with normal renal function (age 65-75 years) are similar to that of younger adult subjects (see section 4.2). For elderly patients with impaired renal function, please refer to section 4.2.
Pediatric population:
Single-dose and multiple-dose varenicline pharmacokinetics were studied in pediatric patients aged 12-17 years (inclusive) and were found to be nearly dose proportional over the studied daily dose range of 0.5 mg to 2 mg. Systemic exposure to steady state in adolescent patients weighing> 55 kg, as assessed by AUC (0-24), it was comparable to that observed at the same doses in the adult population. After administration of 0.5 mg BID, daily exposure to steady state varenicline was, on average, higher (by approximately 40%) in adolescent patients with body weight ≤ 55 kg compared to that found in the adult population. Efficacy and safety in the pediatric population below 18 years of age have not been demonstrated and no dosage advice can be given (see section 4.2).
05.3 Preclinical safety data
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, fertility and embryo-fetal development. In male rats treated with varenicline for 2 years, a dose-related increase in the incidence of hibernoma (brown fat tumor) was observed. Reductions in fertility and increases in startle response were observed in the offspring of pregnant rats treated with varenicline. to acoustic stimulus (see section 4.6). These effects were observed only at exposures deemed sufficiently above the maximum human exposure indicating little relevance to clinical use. Non-clinical data indicate that varenicline possesses strengthening properties despite having a lower potency than nicotine. In human clinical studies, varenicline showed a low potential for abuse.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Inside of the tablets
0.5 mg and 1 mg tablets
Microcrystalline cellulose
Calcium hydrogen phosphate anhydrous
Croscarmellose sodium
Anhydrous colloidal silica
Magnesium stearate
Tablet coating
0.5 mg tablets
Hypromellose
Titanium dioxide (E171)
Macrogol
Triacetin
1 mg tablets
Hypromellose
Titanium dioxide (E171)
Indigo carmine aluminum lake (E132)
Macrogol
Triacetin
06.2 Incompatibility
Not relevant.
06.3 Period of validity
Blister: 3 years.
06.4 Special precautions for storage
Store below 30 ° C.
06.5 Nature of the immediate packaging and contents of the package
Treatment initiation packs
PCTFE / PVC blister with aluminum foil backing containing one clear blister of 11 x 0.5 mg film-coated tablets and a second clear blister of 14 x 1 mg film-coated tablets in secondary heat sealed carton packaging.
PCTFE / PVC blister with aluminum foil backing containing one clear blister of 11 x 0.5 mg film-coated tablets and a second clear blister containing 14 x 1 mg film-coated tablets contained in a carton.
PCTFE / PVC blister with aluminum foil backing containing one clear blister of 11 0.5 mg film-coated tablets and 14 1 mg film-coated tablets and a second clear blister containing 28 1 mg film-coated tablets in carton secondary in heat-sealed cardboard.
PVC blister with aluminum foil backing containing one clear blister of 11 x 0.5 mg film-coated tablets and a second clear blister containing 14 x 1 mg film-coated tablets in secondary heat sealed carton packaging.
PVC blister with aluminum foil backing containing one clear blister of 11 x 0.5 mg film-coated tablets and a second clear blister containing 14 x 1 mg film-coated tablets in a carton.
PVC blister with aluminum foil liner containing one clear blister of 11 0.5 mg film-coated tablets and 14 1 mg film-coated tablets and a second clear blister containing 28 1 mg film-coated tablets in secondary packaging of heat-sealed cardboard.
Not all pack sizes may be marketed.
06.6 Instructions for use and handling
No special instructions.
07.0 MARKETING AUTHORIZATION HOLDER
Pfizer Limited
Ramsgate Road
Sandwich
Kent
CT13 9NJ
UK
08.0 MARKETING AUTHORIZATION NUMBER
Treatment initiation packs:
EU / 1/06/360/003
037550035
EU / 1/06/360/008
037550086
EU / 1/06/360/012
037550112
EU / 1/06/360/014
037550148
EU / 1/06/360/019
037550199
EU / 1/06/360/023
037550237
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Date of first authorization: September 26, 2006
Date of the last renewal: June 7, 2011
10.0 DATE OF REVISION OF THE TEXT
June 2014
