Champix · 4.3 Contraindications · 1

HOS-094390 · has-adverse-reaction-information · PDF-Seite 7

Summary of the safety profile Smoking cessation with or without treatment is associated with various symptoms. For example, dysphoric or depressed mood; insomnia, irritability, frustration or anger; anxiety; difficulty concentrating; restlessness; decreased heart rate; increased appetite or weight gain have been reported in patients attempting to stop smoking. No attempt has been made in either the design or the analysis of the CHAMPIX studies to distinguish between adverse reactions associated with study drug treatment or those possibly associated with nicotine withdrawal. Adverse drug reactions are based on evaluation of data from pre-marketing phase 2-3 studies and updated based on pooled data from 18 placebo-controlled pre- and post-marketing studies, including approximately 5,000 patients treated with varenicline. In patients treated with the recommended dose of 1 mg twice daily following an initial titration period the adverse event most commonly reported was nausea (28.6%). In the majority of cases nausea occurred early in the treatment period, was mild to moderate in severity and seldom resulted in discontinuation. Tabulated summary of adverse reactions In the table below all adverse reactions, which occurred at an incidence greater than placebo are listed by system organ class and frequency (very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100) and rare (≥ 1/10,000 to < 1/1,000)). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. System Organ Adverse Drug Reactions Class Infections and infestations Very common Nasopharyngitis Common Bronchitis, sinusitis Uncommon Fungal infection, viral infection Blood and lymphatic system disorders Rare Platelet count decreased Metabolism and nutrition disorders Common Weight increased, decreased appetite, increased appetite Uncommon Hyperglycaemia Rare Diabetes mellitus, polydipsia Psychiatric disorders Very common Abnormal dreams, insomnia Uncommon Suicidal ideation, aggression, panic reaction, thinking abnormal, restlessness, mood swings, depression*, anxiety*, hallucinations*, libido increased, libido decreased Rare Psychosis, somnambulism, abnormal behaviour, dysphoria, bradyphrenia Nervous system disorders Very common Headache C

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HOS-094402 · has-adverse-reaction-information · PDF-Seite 51

Summary of the safety profile Smoking cessation with or without treatment is associated with various symptoms. For example, dysphoric or depressed mood; insomnia, irritability, frustration or anger; anxiety; difficulty concentrating; restlessness; decreased heart rate; increased appetite or weight gain have been reported in patients attempting to stop smoking. No attempt has been made in either the design or the analysis of the CHAMPIX studies to distinguish between adverse reactions associated with study drug treatment or those possibly associated with nicotine withdrawal. Adverse drug reactions are based on evaluation of data from pre-marketing phase 2-3 studies and updated based on pooled data from 18 placebo-controlled pre- and post-marketing studies, including approximately 5,000 patients treated with varenicline. In patients treated with the recommended dose of 1 mg twice daily following an initial titration period the adverse event most commonly reported was nausea (28.6%). In the majority of cases nausea occurred early in the treatment period, was mild to moderate in severity and seldom resulted in discontinuation. Tabulated summary of adverse reactions In the table below all adverse reactions, which occurred at an incidence greater than placebo are listed by system organ class and frequency (very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100) and rare (≥ 1/10,000 to < 1/1,000)). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. System Organ Adverse Drug Reactions Class Infections and infestations Very common Nasopharyngitis Common Bronchitis, sinusitis Uncommon Fungal infection, viral infection Blood and lymphatic system disorders Rare Platelet count decreased Metabolism and nutrition disorders Common Weight increased, decreased appetite, increased appetite Uncommon Hyperglycaemia Rare Diabetes mellitus, polydipsia Psychiatric disorders Very common Abnormal dreams, insomnia Uncommon Suicidal ideation, aggression, panic reaction, thinking abnormal, restlessness, mood swings, depression*, anxiety*, hallucinations*, libido increased, libido decreased Rare Psychosis, somnambulism, abnormal behaviour, dysphoria, bradyphrenia Nervous system disorders Very common Headache C

Auszug; vollständigen Abschnitt im Original lesen.

HOS-094396 · has-adverse-reaction-information · PDF-Seite 29

Summary of the safety profile Smoking cessation with or without treatment is associated with various symptoms. For example, dysphoric or depressed mood; insomnia, irritability, frustration or anger; anxiety; difficulty concentrating; restlessness; decreased heart rate; increased appetite or weight gain have been reported in patients attempting to stop smoking. No attempt has been made in either the design or the analysis of the CHAMPIX studies to distinguish between adverse reactions associated with study drug treatment or those possibly associated with nicotine withdrawal. Adverse drug reactions are based on evaluation of data from pre-marketing phase 2-3 studies and updated based on pooled data from 18 placebo-controlled pre- and post-marketing studies, including approximately 5,000 patients treated with varenicline. In patients treated with the recommended dose of 1 mg twice daily following an initial titration period the adverse event most commonly reported was nausea (28.6%). In the majority of cases nausea occurred early in the treatment period, was mild to moderate in severity and seldom resulted in discontinuation. Tabulated summary of adverse reactions In the table below all adverse reactions, which occurred at an incidence greater than placebo are listed by system organ class and frequency (very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100) and rare (≥ 1/10,000 to < 1/1,000)). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. System Organ Adverse Drug Reactions Class Infections and infestations Very common Nasopharyngitis Common Bronchitis, sinusitis Uncommon Fungal infection, viral infection Blood and lymphatic system disorders Rare Platelet count decreased Metabolism and nutrition disorders Common Weight increased, decreased appetite, increased appetite Uncommon Hyperglycaemia Rare Diabetes mellitus, polydipsia Psychiatric disorders Very common Abnormal dreams, insomnia Uncommon Suicidal ideation, aggression, panic reaction, thinking abnormal, restlessness, mood swings, depression*, anxiety*, hallucinations*, libido increased, libido decreased Rare Psychosis, somnambulism, abnormal behaviour, dysphoria, bradyphrenia Nervous system disorders Very common Headache C

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HOS-094386 · has-contraindication-information · PDF-Seite 3

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

HOS-094398 · has-contraindication-information · PDF-Seite 47

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

HOS-094392 · has-contraindication-information · PDF-Seite 25

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

HOS-094391 · has-indication-information · PDF-Seite 24

CHAMPIX is indicated for smoking cessation in adults.

HOS-094385 · has-indication-information · PDF-Seite 2

CHAMPIX is indicated for smoking cessation in adults.

HOS-094397 · has-indication-information · PDF-Seite 46

CHAMPIX is indicated for smoking cessation in adults.

HOS-094388 · has-interaction-information · PDF-Seite 5

Based on varenicline characteristics and clinical experience to date, CHAMPIX has no clinically meaningful drug interactions. No dosage adjustment of CHAMPIX or co-administered medicinal products listed below is recommended. In vitro studies indicate that varenicline is unlikely to alter the pharmacokinetics of compounds that are primarily metabolised by cytochrome P450 enzymes. Furthermore since metabolism of varenicline represents less than 10% of its clearance, active substances known to affect the cytochrome P450 system are unlikely to alter the pharmacokinetics of varenicline (see section 5.2) and therefore a dose adjustment of CHAMPIX would not be required. In vitro studies demonstrate that varenicline does not inhibit human renal transport proteins at therapeutic concentrations. Therefore, active substances that are cleared by renal secretion (e.g., metformin - see below) are unlikely to be affected by varenicline. Metformin Varenicline did not affect the pharmacokinetics of metformin. Metformin had no effect on varenicline pharmacokinetics. Cimetidine Co-administration of cimetidine, with varenicline increased the systemic exposure of varenicline by 29% due to a reduction in varenicline renal clearance. No dosage adjustment is recommended based on concomitant cimetidine administration in subjects with normal renal function or in patients with mild to moderate renal impairment. In patients with severe renal impairment, the concomitant use of cimetidine and varenicline should be avoided. Digoxin Varenicline did not alter the steady-state pharmacokinetics of digoxin. Warfarin Varenicline did not alter the pharmacokinetics of warfarin. Prothrombin time (INR) was not affected by varenicline. Smoking cessation itself may result in changes to warfarin pharmacokinetics (see section 4.4). 5 Alcohol There are limited clinical data on any potential interaction between alcohol and varenicline. There have been post marketing reports of increased intoxicating effects of alcohol in patients treated with varenicline. A causal relationship between these events and varenicline use has not been established. Use with other therapies for smoking cessation Bupropion Varenicline did not alter the steady-state pharmacokinetics of bupropion. Nicotine replacement therapy (NRT) When varenicline and transdermal NRT were co-administered to smokers for 12 days, there was a statistically significant decrease

Auszug; vollständigen Abschnitt im Original lesen.

HOS-094400 · has-interaction-information · PDF-Seite 49

Based on varenicline characteristics and clinical experience to date, CHAMPIX has no clinically meaningful drug interactions. No dosage adjustment of CHAMPIX or co-administered medicinal products listed below is recommended. In vitro studies indicate that varenicline is unlikely to alter the pharmacokinetics of compounds that are primarily metabolised by cytochrome P450 enzymes. Furthermore since metabolism of varenicline represents less than 10% of its clearance, active substances known to affect the cytochrome P450 system are unlikely to alter the pharmacokinetics of varenicline (see section 5.2) and therefore a dose adjustment of CHAMPIX would not be required. In vitro studies demonstrate that varenicline does not inhibit human renal transport proteins at therapeutic concentrations. Therefore, active substances that are cleared by renal secretion (e.g., metformin - see below) are unlikely to be affected by varenicline. Metformin Varenicline did not affect the pharmacokinetics of metformin. Metformin had no effect on varenicline pharmacokinetics. Cimetidine Co-administration of cimetidine, with varenicline increased the systemic exposure of varenicline by 29% due to a reduction in varenicline renal clearance. No dosage adjustment is recommended based on concomitant cimetidine administration in subjects with normal renal function or in patients with mild to moderate renal impairment. In patients with severe renal impairment, the concomitant use of cimetidine and varenicline should be avoided. 49 Digoxin Varenicline did not alter the steady-state pharmacokinetics of digoxin. Warfarin Varenicline did not alter the pharmacokinetics of warfarin. Prothrombin time (INR) was not affected by varenicline. Smoking cessation itself may result in changes to warfarin pharmacokinetics (see section 4.4). Alcohol There are limited clinical data on any potential interaction between alcohol and varenicline. There have been post marketing reports of increased intoxicating effects of alcohol in patients treated with varenicline. A causal relationship between these events and varenicline use has not been established. Use with other therapies for smoking cessation Bupropion Varenicline did not alter the steady-state pharmacokinetics of bupropion. Nicotine replacement therapy (NRT) When varenicline and transdermal NRT were co-administered to smokers for 12 days, there was a statistically significant decrease i

Auszug; vollständigen Abschnitt im Original lesen.

HOS-094394 · has-interaction-information · PDF-Seite 27

Based on varenicline characteristics and clinical experience to date, CHAMPIX has no clinically meaningful drug interactions. No dosage adjustment of CHAMPIX or co-administered medicinal products listed below is recommended. In vitro studies indicate that varenicline is unlikely to alter the pharmacokinetics of compounds that are primarily metabolised by cytochrome P450 enzymes. Furthermore since metabolism of varenicline represents less than 10% of its clearance, active substances known to affect the cytochrome P450 system are unlikely to alter the pharmacokinetics of varenicline (see section 5.2) and therefore a dose adjustment of CHAMPIX would not be required. In vitro studies demonstrate that varenicline does not inhibit human renal transport proteins at therapeutic concentrations. Therefore, active substances that are cleared by renal secretion (e.g., metformin - see below) are unlikely to be affected by varenicline. Metformin Varenicline did not affect the pharmacokinetics of metformin. Metformin had no effect on varenicline pharmacokinetics. Cimetidine Co-administration of cimetidine, with varenicline increased the systemic exposure of varenicline by 29% due to a reduction in varenicline renal clearance. No dosage adjustment is recommended based on concomitant cimetidine administration in subjects with normal renal function or in patients with mild to moderate renal impairment. In patients with severe renal impairment, the concomitant use of cimetidine and varenicline should be avoided. Digoxin Varenicline did not alter the steady-state pharmacokinetics of digoxin. Warfarin Varenicline did not alter the pharmacokinetics of warfarin. Prothrombin time (INR) was not affected by varenicline. Smoking cessation itself may result in changes to warfarin pharmacokinetics (see section 4.4). 27 Alcohol There are limited clinical data on any potential interaction between alcohol and varenicline. There have been post marketing reports of increased intoxicating effects of alcohol in patients treated with varenicline. A causal relationship between these events and varenicline use has not been established. Use with other therapies for smoking cessation Bupropion Varenicline did not alter the steady-state pharmacokinetics of bupropion. Nicotine replacement therapy (NRT) When varenicline and transdermal NRT were co-administered to smokers for 12 days, there was a statistically significant decrease

Auszug; vollständigen Abschnitt im Original lesen.

HOS-094401 · has-pregnancy-information · PDF-Seite 50

Pregnancy A moderate amount of data on pregnant women indicated no malformative or foetal/neonatal toxicity of varenicline (see section 5.1). Animal studies have shown reproductive toxicity (see section 5.3). As a precautionary measure, it is preferable to avoid the use of varenicline during pregnancy (see section 5.1). Breast-feeding It is unknown whether varenicline is excreted in human breast milk. Animal studies suggest that varenicline is excreted in breast milk. A decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with CHAMPIX should be made taking into account the benefit of breast-feeding to the child and the benefit of CHAMPIX therapy to the woman. Fertility There are no clinical data on the effects of varenicline on fertility. Non-clinical data revealed no hazard for humans based on standard male and female fertility studies in the rat (see section 5.3). 50

HOS-094395 · has-pregnancy-information · PDF-Seite 28

Pregnancy A moderate amount of data on pregnant women indicated no malformative or foetal/neonatal toxicity of varenicline (see section 5.1). Animal studies have shown reproductive toxicity (see section 5.3). As a precautionary measure, it is preferable to avoid the use of varenicline during pregnancy (see section 5.1). Breast-feeding It is unknown whether varenicline is excreted in human breast milk. Animal studies suggest that varenicline is excreted in breast milk. A decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with CHAMPIX should be made taking into account the benefit of breast-feeding to the child and the benefit of CHAMPIX therapy to the woman. Fertility There are no clinical data on the effects of varenicline on fertility. Non-clinical data revealed no hazard for humans based on standard male and female fertility studies in the rat (see section 5.3).

HOS-094389 · has-pregnancy-information · PDF-Seite 6

Pregnancy A moderate amount of data on pregnant women indicated no malformative or foetal/neonatal toxicity of varenicline (see section 5.1). Animal studies have shown reproductive toxicity (see section 5.3). As a precautionary measure, it is preferable to avoid the use of varenicline during pregnancy (see section 5.1). Breast-feeding It is unknown whether varenicline is excreted in human breast milk. Animal studies suggest that varenicline is excreted in breast milk. A decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with CHAMPIX should be made taking into account the benefit of breast-feeding to the child and the benefit of CHAMPIX therapy to the woman. Fertility There are no clinical data on the effects of varenicline on fertility. Non-clinical data revealed no hazard for humans based on standard male and female fertility studies in the rat (see section 5.3).

HOS-094387 · has-warning-information · PDF-Seite 3

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 necessary (examples include theophylline, warfarin and insulin). As smoking induces CYP1A2, smoking cessation may result in an increase of plasma levels of CYP1A2 substrates. Neuropsychiatric symptoms Changes in behaviour or thinking, anxiety, psychosis, mood swings, aggressive behaviour, depression, suicidal ideation and behaviour and suicide attempts have been reported in patients attempting to quit smoking with CHAMPIX in the post-marketing experience. A large randomised, double-blind, active and placebo-controlled study was conducted to compare the risk of serious neuropsychiatric events in patients with and without a history of psychiatric 3 disorder treated for smoking cessation with varenicline, bupropion, nicotine replacement therapy patch (NRT) or placebo. The primary safety endpoint was a composite of neuropsychiatric adverse events that have been reported in post-marketing experience. The use of varenicline in patients with or without a history of psychiatric disorder was not associated with an increased risk of serious neuropsychiatric adverse events in the composite primary endpoint compared with placebo (see section 5.1 Pharmacodynamic properties - Study in Subjects with and without a History of Psychiatric Disorder). Depressed mood, rarely including suicidal ideation and suicide attempt, may be a symptom of nicotine withdrawal. Clinicians should be aware of the possible emergence of serious neuropsychiatric symptoms in patients attempting to quit smoking with or without treatment. If serious neuropsychiatric symptoms occur whilst on varenicline treatment, patients should discontinue varenicline immediately and contact a healthcare professional for re-evaluation of treatment. History of psychiatric disorders Smoking cessation, with or without pharmacotherapy, has been associated with exacerbation of underlying psychiatric illness (e.g. depression). CHAMPIX smoking cessation studies have provided data in patients with a history of psychiatric disorders (see section 5.1). In a smoking cessation clinical trial, neuropsychiatric adverse events were reported more frequently in patients with a history of psychiatric disorders compared to those withou

Auszug; vollständigen Abschnitt im Original lesen.

HOS-094399 · has-warning-information · PDF-Seite 47

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 necessary (examples include theophylline, warfarin and insulin). As smoking induces CYP1A2, smoking cessation may result in an increase of plasma levels of CYP1A2 substrates. 47 Neuropsychiatric symptoms Changes in behaviour or thinking, anxiety, psychosis, mood swings, aggressive behaviour, depression, suicidal ideation and behaviour and suicide attempts have been reported in patients attempting to quit smoking with CHAMPIX in the post-marketing experience. A large randomised, double-blind, active and placebo-controlled study was conducted to compare the risk of serious neuropsychiatric events in patients with and without a history of psychiatric disorder treated for smoking cessation with varenicline, bupropion, nicotine replacement therapy patch (NRT) or placebo. The primary safety endpoint was a composite of neuropsychiatric adverse events that have been reported in post-marketing experience. The use of varenicline in patients with or without a history of psychiatric disorder was not associated with an increased risk of serious neuropsychiatric adverse events in the composite primary endpoint compared with placebo (see section 5.1 Pharmacodynamic properties - Study in Subjects with and without a History of Psychiatric Disorder). Depressed mood, rarely including suicidal ideation and suicide attempt, may be a symptom of nicotine withdrawal. Clinicians should be aware of the possible emergence of serious neuropsychiatric symptoms in patients attempting to quit smoking with or without treatment. If serious neuropsychiatric symptoms occur whilst on varenicline treatment, patients should discontinue varenicline immediately and contact a healthcare professional for re-evaluation of treatment. History of psychiatric disorders Smoking cessation, with or without pharmacotherapy, has been associated with exacerbation of underlying psychiatric illness (e.g. depression). CHAMPIX smoking cessation studies have provided data in patients with a history of psychiatric disorders (see section 5.1). In a smoking cessation clinical trial, neuropsychiatric adverse events were reported more frequently in patients with a history of psychiatric disorders compared to those witho

Auszug; vollständigen Abschnitt im Original lesen.

HOS-094393 · has-warning-information · PDF-Seite 25

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 necessary (examples include theophylline, warfarin and insulin). As smoking induces CYP1A2, smoking cessation may result in an increase of plasma levels of CYP1A2 substrates. Neuropsychiatric symptoms Changes in behaviour or thinking, anxiety, psychosis, mood swings, aggressive behaviour, depression, suicidal ideation and behaviour and suicide attempts have been reported in patients attempting to quit smoking with CHAMPIX in the post-marketing experience. A large randomised, double-blind, active and placebo-controlled study was conducted to compare the risk of serious neuropsychiatric events in patients with and without a history of psychiatric disorder treated for smoking cessation with varenicline, bupropion, nicotine replacement therapy 25 patch (NRT) or placebo. The primary safety endpoint was a composite of neuropsychiatric adverse events that have been reported in post-marketing experience. The use of varenicline in patients with or without a history of psychiatric disorder was not associated with an increased risk of serious neuropsychiatric adverse events in the composite primary endpoint compared with placebo (see section 5.1 Pharmacodynamic properties - Study in Subjects with and without a History of Psychiatric Disorder). Depressed mood, rarely including suicidal ideation and suicide attempt, may be a symptom of nicotine withdrawal. Clinicians should be aware of the possible emergence of serious neuropsychiatric symptoms in patients attempting to quit smoking with or without treatment. If serious neuropsychiatric symptoms occur whilst on varenicline treatment, patients should discontinue varenicline immediately and contact a healthcare professional for re-evaluation of treatment. History of psychiatric disorders Smoking cessation, with or without pharmacotherapy, has been associated with exacerbation of underlying psychiatric illness (e.g. depression). CHAMPIX smoking cessation studies have provided data in patients with a history of psychiatric disorders (see section 5.1). In a smoking cessation clinical trial, neuropsychiatric adverse events were reported more frequently in patients with a history of psychiatric disorders compared to those withou

Auszug; vollständigen Abschnitt im Original lesen.