All varenicline PBS listings will be streamlined
Varenicline (0.5 mg and 1 mg tablets) is listed on the PBS General Schedule for the treatment of adults with nicotine dependence, as an aid to achieving abstinence from smoking.1,2
From 1 May 2017 all varenicline PBS listings were amended from Authority required to Authority required (streamlined).3,4
The positive recommendation was made by the Pharmaceutical Benefits Advisory Committee (PBAC) at its November 2016 meeting.3
The PBAC advised that varenicline remains suitable for prescribing by nurse practitioners, in addition to medical practitioners.4
See the PBS website for varenicline PBS listings and restrictions.
The PBAC previously considered varenicline’s restriction level
Varenicline’s restriction level was previously reviewed by the PBAC in March 2015, as part of the Post-market Review of Authority Required PBS Listings.4
At that time, the PBAC recommended that varenicline remain as Authority required.4
The PBAC considered that the National Medicines Policy objective of medicines meeting appropriate standards of safety would be enhanced by keeping the non-streamlined listing.4
The PBAC was also concerned that a streamlined listing may have led to inappropriate continuous use of varenicline and that the market for smoking cessation aids had not yet stabilised.4
This latest PBAC decision – to recommend the streamlined listing of varenicline – followed its advice to the sponsor to make a formal submission to address safety concerns regarding psychiatric events with varenicline.4
A quick overview of varenicline’s history with the PBAC is summarised in Table 1 below.
Table 1: Varenicline's history with the PBAC4
|Year||PBAC action on varenicline|
|2007||TGA registered as an aid for smoking-cessation in adults.|
|2008||First listed on the PBS.|
|2009||PBAC recommended change to PBS listing to allow a further 12 weeks of treatment in responders.|
|2012||PBAC rejected request to permit a further course of treatment for people who did not stop smoking or relapsed after completing treatment.|
|2014||PBAC recommended request (resubmission) for an additional course of treatment within 12 months, on the basis of cost effectiveness compared with bupropion, NRT and placebo.|
|2015||PBAC recommended varenicline remain Authority Required, following the Post-market Review of Authority Required PBS Listings.|
TGA Safety Update to the PI to include potential for psychiatric symptoms and alcohol to increase the risk of neuropsychiatric events during treatment with varenicline.a
|2016||Varenicline PBAC submission, following DUSC findings that changes to the restriction level of NRT therapies did not substantially impact the utilisation of RPBS subsidised NRT treatment.|
a Further changes to the PI have since been made in 2017 to make information about psychiatric symptoms more prominent.5
DUSC: Drug Utilisation Sub Committee; NRT: nicotine replacement therapy; PBAC: Pharmaceutical Benefits Advisory Committee; PI: Product Information; R/PBS, Repatriation Pharmaceutical Benefits Scheme / Pharmaceutical Benefits Scheme; TGA: Therapeutic Goods Administration.
PBAC consideration of the EAGLES study
Results from a single study, the Phase IV EAGLES study (NCT01456936), were submitted to the PBAC to support the streamlined listing of varenicline.4
An overview of the EAGLES study is provided in Table 2 below.
The PBAC considered that results of the EAGLES study supported the comparative safety of varenicline, bupropion, nicotine replacement therapy (NRT) and placebo.4
The PBAC considered that varenicline was non-inferior to bupropion with regard to safety, and likely to be non-inferior to NRT and placebo.4
Table 2: Key characteristics of the EAGLES study6
|Category||EAGLES study characteristics|
|Neuropsychiatric adverse eventsb|
|Most frequent adverse events|
b The primary endpoint was a composite measure based on postmarketing reports of neuropsychiatric adverse events in smokers taking varenicline and bupropion. The primary endpoint was met when participants reported at least one event coding to any of 261 MedDRA-derived preferred terms across 16 symptom categories during treatment or within 30 days of treatment discontinuation that met pre-established severity criteria.
c For the significant associations, odds ratios ranged from 4.00 (3.20 to 5.00, p < 0.0001) with varenicline versus placebo at weeks 9–12 in the non-psychiatric cohort to 1.41 (1.11 to 1.79, p = 0.0047) with varenicline versus bupropion at weeks 9–24 in the psychiatric cohort.
PBAC consideration of 2016 DUSC data
The February 2016 DUSC review showed that the utilisation of smoking-cessation medicines subsidised by the Pharmaceutical Benefits Scheme and Repatriation Pharmaceutical Benefits Scheme did not substantially change when NRT products had their listings changed from 'Authority required' to 'Authority required (streamlined)' on 1 December 2013.7
Therefore, the PBAC considered that changing the authority level of varenicline was also unlikely to substantially impact utilisation trends.4
Other PBAC considerations
The PBAC noted that no new or increased safety signals with varenicline were identified in the latest TGA Periodic Safety Update Report and Risk Management Plans.4
The PBAC considered whether it was appropriate to include a caution for patients with a history of psychiatric disorders or alcohol/drug misuse to be monitored while taking varenicline.4
A caution was not recommended because risks of neuropsychiatric adverse events were well documented in the approved PI.4
In addition, other mechanisms, including practice software, already correlate medical records and prescribing history.
The PBAC noted that attempting to quit smoking may be associated with an increase in neuropsychiatric events in people with a history of neuropsychiatric disorders.4
Gaps in the evidence
The EAGLES study had several limitations, which potentially limit the study’s generalisability. These factors were acknowledged by the study authors.6
Due to eligibility criteria of the EAGLES study (see Table 2), the results may not be generalisable to:6
- lighter, less dependent smokers (fewer than 10 cigarettes per day)
- people with alcohol- or drug-use disorders
- people with psychiatric conditions who are untreated
- people with symptomatically unstable psychiatric conditions
- people at high-risk of self-injury or suicidal behaviour.
In addition, the EAGLES study was not powered to detect differences in rare events (such as completed suicide), and the 24-week duration and monitoring requirements may not reflect real-life attempts to quit smoking.6
Practice Points for managing side effects with varenicline
People who take varenicline may experience side effects, either due to the medicine or due to nicotine withdrawal.2,8
People who stop smoking, with or without varenicline, may experience dysphoric or depressed mood, insomnia, irritability, frustration, anger, anxiety, confusion, restlessness, decreased heart rate, and increased appetite or weight gain.2
People with pre-existing psychiatric illness are more likely to experience adverse events6 with post-marketing reports of neuropsychiatric symptoms, some serious, as well as worsening of pre-existing psychiatric illness.2
- Assess the patient and family for any history of psychiatric illness prior to initiating treatment.2
- Continue to monitor patients with pre-existing psychiatric illness for the development of neuropsychiatric symptoms, including suicidal ideation.2
- Counselling should include the patient’s family, carers or friends depending on who the patient’s closest contacts are.
- Counsel the patient about the increased risk of psychiatric symptoms.5
- Advise patients and their families to stop varenicline immediately and seek urgent medical advice if the patient:2,8
- experiences changes in mood, behaviour or thinking that are not usually typical for the patient
- experiences suicidal ideation or behaviour
- develops a rash or skin reaction
- has existing heart or blood vessel problems and notices any changes in symptoms.
- experiences changes in mood, behaviour or thinking that are not usually typical for the patient
- Inform patients that drinking alcohol while taking varenicline can increase their risk of experiencing changes in mood, behaviour or thinking.2,8
- Inform patients that they may experience irritability, urge to smoke, depression, and/or insomnia when they finish taking varenicline:2
- patients can be reassured that symptoms are likely to be temporary; they may want to have fast-acting NRT at hand in case they have an overwhelming urge to smoke.9
- Remember that varenicline may lower the seizure threshold in people with a history of seizures.2,8
- Be aware that physiological changes resulting from smoking cessation may alter pharmacokinetics or pharmacodynamics of some medicines (eg, theophylline, warfarin and insulin).2
- Encourage smokers to stay motivated to quit, and advise them that varenicline should be used alongside a counselling program, such as the one offered by Quitline (137 848).
- Australian Government Department of Health. The Pharmaceutical Benefits Scheme. PBS Schedule: Varenicline (accessed 3 February 2017).
- Pfizer Australia Pty Ltd. Varenicline (Champix) product information (accessed 3 February 2017).
- Australian Government Department of Health. The Pharmaceutical Benefits Scheme. Recommendations made by the PBAC - November 2016 (accessed 3 February 2017).
- Australian Government Department of Health. The Pharmaceutical Benefits Scheme. Public Summary Document (PSD) November 2016 PBAC Meeting (accessed 28 March 2017)
- Therapeutic Goods Administration. Medicines Safety Update Volume 7 Number 1, February 2016. 2016 (accessed 12 October 2017).
- Anthenelli RM, Benowitz NL, West R, et al. Neuropsychiatric safety and efficacy of varenicline, bupropion, and nicotine patch in smokers with and without psychiatric disorders (EAGLES): a double-blind, randomised, placebo-controlled clinical trial. Lancet 2016;387:2507-20.
- Australian Government Department of Health. The Pharmaceutical Benefits Scheme. Drug Utilisation Sub Committee: Smoking cessation therapy, February 2016 (accessed 3 February 2017).
- Pfizer Australia Pty Ltd. Varenicline (Champix) consumer medicine information (accessed 3 February 2017).
- Australian Medicines Handbook. Drugs for nicotine dependence: Varenicline. Adelaide: AMH Pty Ltd (accessed 22 February 2017).