CHAMPIX (varenicline) Dosage And Administration

Dosing Considerations

Smoking-cessation therapies are more likely to succeed for patients who are motivated to stop smoking and who are provided additional counselling and /or support services. In the clinical trials on which approval was based, CHAMPIX was used with supportive counselling. Physicians should review the patient’s overall smoking-cessation plan that includes treatment with CHAMPIX.

The majority of clinical evidence in efficacy and safety was based on a 1.0 mg BID dose (see CLINICAL TRIALS). There is little clinical experience with doses above the maximum recommended dose of 1 mg BID.

There is limited data available for dose comparison. In the one randomized clinical trial that included both 1.0 mg BID and 0.5 mg BID arms and that was designed to compare each of the two doses to placebo, and not to each other, the quit rates for 1.0 mg BID (n=253), 0.5 mg BID (n=253) and placebo (n=121) were:

• for Weeks 9 to 12: 51%, 45%, and 12% respectively, and
• for Weeks 9 to 52: 23%, 19% and 4% respectively.

For further information on this study, see CLINICAL TRIAL, study 1.

Based on the limited data available, it cannot be concluded that there is a difference between the two doses in the rate of serious neuropsychiatric events (see ADVERSE REACTIONS, Neuropsychiatric Adverse Events in Randomized Double Blind, Placebo Controlled Clinical Studies of Varenicline).

CHAMPIX should be taken after eating and with a full glass of water.

Patients with Severe Renal Impairment

The maximum recommended dose for this population is 0.5 mg twice daily (see below : Special Populations, Patients with Impaired Renal Function).

Recommended Dose and Dosage Adjustment

Adults

Setting a Quit Date

There are three ways to set a quit date with CHAMPIX:

• Fixed quit approach: The patient sets a date to stop smoking. CHAMPIX dosing should start 1-2 Weeks before this date (see CLINICAL TRIALS).
  or
• Flexible quit approach: The patient begins CHAMPIX and then quits smoking between days 8 and 35 of treatment (ie between Weeks 2 and 5) (see ACTION AND CLINICAL PHARMACOLOGY, Special Populations, Flexibility in Setting a Quit Date).
  or
• Gradual quit approach: The patient starts taking CHAMPIX with a goal to quit smoking by end of 12 weeks of treatment. The patient should gradually reduce smoking during the first 12 weeks of treatment such as 50% reduction or more by 4 weeks of treatment, 75% or more by 8 weeks to reach 100% by 12 weeks (see ACTION AND CLINICAL PHARMACOLOGY, Special Populations).

Dosing Options

Following one week of titration, there is a choice of two doses for CHAMPIX: 0.5 mg BID or 1.0 mg BID.

As shown in the table below, the two titration schedules are identical from Day 1 to Day 7, separating at Day 8 when the patient either remains on 0.5 mg BID or moves up to 1.0 mg BID.

The choice of dosing regimen should be based on physician judgment and patient preference, following discussion with the patient (see also Dosing Considerations).

Once CHAMPIX treatment is initiated, the dose may be changed, temporarily or permanently, according to patient and physician judgments on tolerability and efficacy.

Patients who follow one of the first 2 approaches to setting a quit date (1-2 weeks after starting the treatment or between days 8 and 35 of treatment) 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 may be considered. No data are available on the efficacy of an additional 12 week course of treatment with CHAMPIX for patients who have not successfully stopped smoking at the end of 12 weeks.

Patients who follow the third approach to setting a quit date (Week 12) should be treated with CHAMPIX for 24 weeks.

Dose tapering may be considered. Regardless of whether the treatment course is 12 or 24 weeks, risk of smoking-cessation relapse is elevated in the period immediately following the end of drug treatment (see CLINICAL TRIALS). In addition, dose tapering may help minimize discontinuation symptoms (eg, increase in irritability, urge to smoke, depression, and/or insomnia), observed in up to 3% of patients at the end of treatment.

Special Populations

Psychiatric Patients
Patients with a history of psychiatric symptoms who are attempting to quit smoking should be monitored by their healthcare professional for new or worsened psychiatric events. Those with a current condition should be clinically stable. Patients should be instructed that if they develop worsened or new symptoms, to report these to their healthcare provider, so that dose adjustments of psychiatric medications and/or CHAMPIX may be considered (see also WARNINGS AND PRECAUTIONS, Special Populations, Psychiatric Patients).

Patients with Impaired Renal Function:
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 who experience intolerable adverse events, dosing may be reduced.

For patients with severe renal impairment, the recommended dose of CHAMPIX is 0.5 mg twice daily. Dosing should begin at 0.5 mg once daily for the first 3 days then increased to 0.5 mg twice daily. Based on insufficient clinical experience with CHAMPIX in patients with end-stage renal disease, treatment is not recommended in this patient population (see also WARNINGS AND PRECAUTIONS, Special Populations: Renal Impairment).

Patients with Hepatic Impairment:
No dosage adjustment is necessary for patients with hepatic impairment.

Patients with Epilepsy, Patients undergoing Chemotherapy, and Patients with GI disturbances such as irritable bowel: The use of CHAMPIX has not been studied in these patient populations (see WARNINGS AND PRECAUTIONS, Special Populations).

Dosing in Elderly Patients:
No dosage adjustment is necessary for elderly patients with normal renal function. However, varenicline is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function (see WARNINGS AND PRECAUTIONS, Special Populations: Geriatrics).