Drug Class Description

Generic Name

Drug Description

Presentation

Indications

Adult Dosage

Smoking cessation therapies are more likely to succeed for patients who are motivated to stop smoking and who are provided with additional advice and support.

CHAMPIX is for oral use. The recommended dose is 1 mg varenicline twice daily following a 1-week titration as follows:

The patient should set a date to stop smoking. CHAMPIX dosing should start 1-2 weeks before this date.

Patients who cannot tolerate adverse effects of CHAMPIX may have the dose lowered temporarily or permanently to 0.5 mg twice daily.

CHAMPIX tablets should be swallowed whole with water. CHAMPIX can be taken with or without food.

Patients should be treated with CHAMPIX for 12 weeks.

For patients who have successfully stopped smoking at the end of 12 weeks, an additional course of 12 weeks treatment with CHAMPIX at 1 mg twice daily may be considered

No data are available on the efficacy of an additional 12 weeks course of treatment for patients who do not succeed in stopping smoking during initial therapy or who relapse after treatment.

In smoking cessation therapy, risk for relapse to smoking is elevated in the period immediately following the end of treatment. In patients with a high risk of relapse, dose tapering may be considered.

Patients with renal insufficiency

No dosage adjustment is necessary for patients with mild (estimated creatinine clearance > 50 ml/min and 80 ml/min) to moderate (estimated creatinine clearance 30 ml/min and 50 ml/min) renal impairment.

For patients with moderate renal impairment who experience adverse events that are not tolerable, dosing may be reduced to 1 mg once daily.

For patients with severe renal impairment (estimated creatinine clearance < 30 ml/min), the recommended dose of CHAMPIX is 1 mg once daily. Dosing should begin at 0.5 mg once daily for the first 3 days then increased to 1 mg once daily. Based on insufficient clinical experience with CHAMPIX in patients with end stage renal disease, treatment is not recommended in this patient population.

Patients with hepatic impairment

No dosage adjustment is necessary for patients with hepatic impairment.

Dosing in elderly patients

No dosage adjustment is necessary for elderly patients. Because elderly patients are more likely to have decreased renal function, prescribers should consider the renal status of an elderly patient.

Paediatric patients

CHAMPIX is not recommended for use in children or adolescents below 18 years of age due to insufficient data on safety and efficacy.

Child Dosage

Elderly Dosage

Contra Indications

Special Precautions

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.

Depression, suicidal ideation and behaviour and suicide attempts have been reported in patients attempting to quit smoking with Champix in the post-marketing experience. Not all patients had stopped smoking at the time of onset of symptoms and not all patients had known pre-existing psychiatric illness. Clinicians should be aware of the possible emergence of significant depressive symptomatology in patients undergoing a smoking cessation attempt, and should advise patients accordingly. Champix should be discontinued immediately if agitation, depressed mood or changes in behaviour that are of concern for the doctor, the patient, family or caregivers are observed, or if the patient develops suicidal ideation or suicidal behaviour.

Depressed mood, rarely including suicidal ideation and suicide attempt, may be a symptom of nicotine withdrawal. In addition, smoking cessation, with or without pharmacotherapy, has been associated with exacerbation of underlying psychiatric illness (e.g. depression).

The safety and efficacy of Champix in patients with serious psychiatric illness such as schizophrenia, bipolar disorder and major depressive disorder has not been established. Care should be taken with patients with a history of psychiatric illness and patients should be advised accordingly.

There is no clinical experience with CHAMPIX in patients with epilepsy.

At the end of treatment, discontinuation of CHAMPIX was associated with an increase in irritability, urge to smoke, depression, and/or insomnia in up to 3% of patients. The prescriber should inform the patient accordingly and discuss or consider the need for dose tapering.

Interactions

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 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.

Alcohol: There is limited clinical data on any potential interaction between alcohol and varenicline

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 in average systolic blood pressure (mean 2.6 mmHg) measured on the final day of the study. In this study, the incidence of nausea, headache, vomiting, dizziness, dyspepsia, and fatigue was greater for the combination than for NRT alone.

Safety and efficacy of CHAMPIX in combination with other smoking cessation therapies have not been studied.

Adverse Reactions

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 events associated with study drug treatment or those possibly associated with nicotine withdrawal.

Clinical trials included approximately 4,000 patients treated with CHAMPIX for up to 1 year (average exposure 84 days). In general, when adverse reactions occurred, onset was in the first week of therapy; severity was generally mild to moderate and there were no differences by age, race or gender with regard to the incidence of adverse reactions.

In patients treated with the recommended dose of 1mg BID 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.

The treatment discontinuation rate due to adverse events was 11.4% for varenicline compared with 9.7% for placebo. In this group, the discontinuation rates for the most common adverse events in varenicline treated patients were as follows: nausea (2.7% vs. 0.6% for placebo), headache (0.6% vs. 1.0% for placebo), insomnia (1.3% vs. 1.2% for placebo), and abnormal dreams (0.2% vs. 0.2% for placebo).

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.

Post-marketing cases of myocardial infarction, depression and suicidal ideation have been reported in patients taking varenicline. There have also been reports of hypersensitivity reactions, such as angioedema and facial swelling.

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