Champix

What is Champix?

Champix (varenicline) is an oral medication prescribed for smoking cessation in adults and is produced in two forms:

• 0.5 mg film-coated tablets: White, capsular-shaped, biconvex tablets debossed with "Pfizer" on one side and "CHX 0.5" on the other side.
• 1 mg film-coated tablets: Light blue, capsular-shaped, biconvex tablets debossed with "Pfizer on one side and "CHX 1.0" on the other side.

In common with all Smoking Cessation therapies it is more likely to succeed for patients who are motivated to stop smoking and who are provided with additional advice and support.

How do I take Champix?

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

The recommended dose is 1 mg varenicline twice daily as follows:

Days 1 - 3:	0.5 mg once daily
Days 4 - 7:	0.5 mg twice daily
Day 8 - End of treatment:	1 mg twice daily

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 and 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 Kidney problems

No dosage adjustment is necessary for patients with mild (estimated creatinine clearance> 50 ml/min and LESS-THAN OR EQUAL TO (8804) 80 ml/min) to moderate (estimated creatinine clearance GREATER-THAN OR EQUAL TO (8805) 30 ml/min and LESS-THAN OR EQUAL TO (8804) 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 Liver problems

No dosage adjustment is necessary for patients with hepatic impairment.

Usage by 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.

Usage by Children and Teenagers

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

Contra-indications

Allergy to the active ingredient or any of the tablet ingredients.

Special warnings and 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 necessary (examples include theophylline, warfarin and insulin). As smoking induces CYP1A2, smoking cessation may result in an increase of plasma levels of CYP1A2 substrates.

Smoking cessation, with or without pharmacotherapy, has been associated with the exacerbation of underlying psychiatric illness (e.g. depression). 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.

Interaction with other medicinal products and other forms of interaction

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).

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.

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

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

Pregnancy and Breastfeeding

There are no adequate data from the use of Champix in pregnant women. Studies in animals have shown reproductive toxicity. The potential risk for humans is unknown. Champix should not be used during pregnancy.

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 patient.

Effects on ability to drive and use machines

Champix may have minor or moderate influence on the ability to drive and use machines. Champix may cause dizziness and drowsiness and therefore may influence the ability to drive and use machines. Patients are advised not to drive, operate complex machinery or engage in other potentially hazardous activities until it is known whether this medicinal product affects their ability to perform these activities.

Undesirable effects

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).