From 1 October 2014 the NOTE to the PBS listing for varenicline tartrate (0.5 mg [11 tablets] plus 1 mg [42 tablets], 53 tablets total; and 1 mg [56 tablets]) has changed to permit another course of varenicline (instead of bupropion) in patients who did not stop smoking after an initial 12- or 24-week treatment course, provided that 6 months have elapsed between starting the previous course of varenicline and the subsequent course.1

Previously, only one course (12 or 24 weeks) of varenicline was PBS subsidised in any 12-month period.

PBS listing

Varenicline is currently PBS listed for short-term (12 or 24 week), sole PBS-subsidised therapy as an aid to achieving abstinence in a patient who has indicated they are ready to stop smoking.

Initial treatment is for 12 weeks, and for those who have abstained from smoking, an additional 12 weeks of treatment may be undertaken.

Patients are required to enter a comprehensive support and counselling program.

Varenicline may be prescribed by nurse practitioners.

This change to the PBS listing NOTE to permit a further course of varenicline, in place of bupropion, within 6 months of starting a previous course of varenicline, was recommended by the Pharmaceutical Benefits Advisory Committee (PBAC) at its March 2014 meeting on the basis of acceptable cost effectiveness relative to placebo, bupropion and nicotine replacement therapy (NRT).1

Other than the change to the restriction to permit a further course of treatment within a 12-month period in patients who did not stop smoking after an initial 12- or 24-week treatment, the intent of the restriction and the Authority required listing criteria remain unchanged.

Place in therapy

Varenicline is an alternative treatment to placebo, bupropion and NRT in people who have failed to abstain or who have relapsed within 6–12 months of a previous 12-week course of varenicline.

Under the previous restriction patients were required to wait at least 12 months from the date of first approval of varenicline before starting a subsequent attempt to quit with varenicline re-treatment. Previously, the only available option for treatment in patients within 6 months of a failed course of varenicline was bupropion, another PBS listed oral smoking cessation treatment.

Acceptable safety with repeated courses, but data are limited

A recent meta-analysis considered safety of various smoking-cessation agents, including data from 14 varenicline trials with more than 6000 participants.2

The study found no significant difference between varenicline and placebo in their rates of serious adverse events, including no excess of neuropsychiatric or cardiac events (Table 1). However, the authors advised that the safety of varenicline is still under investigation.

Table 1 Serious adverse events associated with varenicline treatment in treatment-naïve patients compared with placebo


Risk ratio

95% CI

Serious adverse events


0.72 to 1.55

Neuropsychiatric events


0.17 to 1.67

Cardiovascular events


0.62 to 2.56

CI: confidence interval

Most of the existing safety data relate to varenicline-treatment-naïve patients, and there are limited data for repeated and extended exposure.

Studies included in the meta-analysis involved 12-week and 24-week courses of treatment.

The main adverse event reported was nausea, generally at mild to moderate levels, which subsided over time. Participants also experienced raised levels of insomnia, abnormal dreams and headache.2

To date only one trial (NCT01244061) has been conducted in varenicline-experienced patients, although treatment did not exceed a 12-week course.3 These results have not yet been published in peer-reviewed medical journals but were considered by the PBAC.

The PBAC considered that repeated courses of varenicline within a 12-month period were of acceptable safety, based on the currently known safety profile of varenicline, considering both worldwide usage and information provided in the sponsor's submission.1 This change will result in some patients using varenicline for extended periods and prescribers should consider the benefits and risks of repeated exposure at an individual patient level.

Concern regarding risk of cardiovascular and neuropsychiatric effects

Postmarketing surveillance of varenicline has raised concern about neuropsychological effects and risk of cardiovascular events.

The risk to cardiovascular safety was addressed in a recent meta-analysis reported by the U.S. Food and Drug Administration, which showed a small, statistically non-significant increase in cardiovascular events in people taking varenicline.4

The latest safety data do not support a risk of neuropsychological effects attributable to varenicline and it remains unclear to what extent nicotine withdrawal or other factors associated with smoking cessation contribute.2

However the U.S. Food and Drug Administration in 2009 required a boxed warning for varenicline in the US highlighting the risk of neuropsychiatric symptoms5 and, following a recent sponsor submission to FDA to have the warning removed, FDA has announced the warning will remain pending completion of a phase 4 trial due in August 2015.6 Some guidelines continue to recommend patients be monitored for unusual mood changes, depression, behaviour disturbance and suicidal thoughts.7

Read more about cardiovascular safety in people treated with varenicline.

Superior efficacy in continuous abstinence

A meta-analysis confirms that varenicline increases the chances of quitting (main outcome defined as continuous abstinence for 6 months or longer) compared with placebo, bupropion and NRT in treatment-naïve patients (Table 2).2

Table 2 Efficacy of varenicline compared with placebo or other smoking cessation therapies


Odds ratio*

95% CI*

Varenicline vs placebo


2.40 to 3.47

Varenicline vs bupropion


1.29 to 1.96

Varenicline vs NRT


1.29 to 1.91

* Based on a network analysis
NRT: nicotine replacement therapy

For more information

Read more about smoking cessation options.