A New Option for Smoking Cessation in Australia

Cytisine has recently been approved for use in Australia, making it the first new chemical entity registered specifically for smoking cessation in almost 20 years. Cytisine is a plant-derived alkaloid belonging to the same drug class as varenicline. It is a partial agonist at nicotinic acetylcholine receptors and works to reduce the symptoms of nicotine withdrawal and the satisfaction associated with tobacco use.

While new to Australia, cytisine has been used for smoking cessation in parts of Europe for many decades. International interest in cytisine has increased in recent years, and in 2025 it was added to the World Health Organization (WHO) Essential Medicines List. Its growing use is supported by an expanding body of clinical evidence demonstrating effectiveness, coupled with a favourable safety profile.

Cytisine is available without a prescription as a Schedule 3 (Pharmacist Only) medicine for smoking cessation in adults.

Safety and efficacy

A systematic review and meta-analysis found moderate-certainty evidence that cytisine significantly improves smoking cessation rates compared with placebo or no treatment. People taking cytisine were more than twice as likely to quit smoking by the end of the study period (RR 2.65, 95% CI: 1.50-4.67). Its effectiveness appears comparable to varenicline, with no significant difference in smoking cessation outcomes between the two treatments.

Cytisine is generally well tolerated. In clinical trials, rates of adverse events were similar to those seen with placebo and varenicline. Reported adverse effects include:

• Nausea
• Gastrointestinal upset
• Dry mouth
• Dizziness
• Irritability
• Increased appetite
• Weight gain
• Sleep disorders (e.g. insomnia, abnormal dreams)
• Tachycardia
• Hypertension.

However, it is worth noting that adverse events may be difficult to distinguish from the symptoms of nicotine withdrawal.

Administration

A standard course of cytisine treatment involves a progressively reduced dosing frequency over a 25-day period, as shown in Table 1.

Table 1. Recommended dosing schedule for cytisine 1.5mg tablets

Patients may continue smoking during the start of treatment but should stop no later than day 5. Continuing to smoke during therapy increases the incidence and severity of adverse reactions. The manufacturer recommends that cytisine not be used in combination with NRT.

Place in Therapy

Smoking cessation guidelines recommend pharmacotherapy be individualised based on patient preference, previous quit attempts, contraindications, adverse effect profiles, and cost. The WHO recommends varenicline, NRT, bupropion, and cytisine as effective treatment options for tobacco cessation. While the Therapeutic Guidelines advise that most people will require pharmacotherapy, cytisine is not yet included in their recommendations.

First-line medications recommended by the Therapeutic Guidelines are:

• Combination NRT, i.e. a slow acting form of nicotine (e.g. patch) plus a medium-acting form (e.g. gum or lozenge) and/or a fast-acting form (e.g. mist spray);
• Varenicline; and
• Bupropion.

The Therapeutic Guidelines advise that varenicline is the most effective of the above options, with combination NRT a close second. Bupropion and NRT monotherapy are not as effective.

Nicotine replacement therapy

The Therapeutic Guidelines describe NRT as the most widely available and best tolerated form of drug therapy for smoking cessation. It is the least likely of the three first-line options to cause adverse effects and drug interactions.

Most people who smoke tobacco are likely to benefit from the use of slow-acting NRT in the form of a patch. The exception may be individuals who only smoke in highly specific situations.

Combining a patch with a faster-acting form of nicotine increases effectiveness. These faster-acting forms can also be combined with varenicline or bupropion if required to reduce cravings. Where NRT is not effective, the most common explanation is inadequate dose or incorrect use.

The dose of NRT is highly variable and based on the severity of nicotine dependence. It is recommended that NRT be continued for at least 12 weeks, although longer treatment durations are more effective.

While NRT is generally well tolerated, excess doses can cause mild symptoms of nicotine toxicity. This may include nausea, dizziness, and palpitations.

Varenicline

Varenicline is a partial agonist at neuronal nicotinic acetylcholine receptors. It binds with high affinity and selectivity to reduce the symptoms of craving and withdrawal, while also blocking the rewarding effects of smoking.

A typical dosing regimen is 0.5 mg once daily for the first 3 days, then 0.5 mg twice daily for 4 days, then 1 mg twice daily for 11 weeks. For patients who have successfully stopped smoking at this point, an additional 12-week course is recommended to increase the chance of long-term abstinence.

Nausea is a common adverse effect and may be minimised by taking doses with food. Alternatively, the dose may be halved if nausea is intolerable.

There are no known clinically significant drug interactions. Elimination is primarily via renal excretion, and dose adjustment is recommended in severe renal impairment.

Bupropion

Bupropion selectively inhibits the neuronal reuptake of noradrenaline and dopamine which is thought to contribute to its effectiveness in reducing the urge to smoke.

The typical dose is 150 mg once daily in the morning for the first 3 days, then 150 mg twice daily. The recommended treatment duration is at least seven weeks.

Insomnia is a very common adverse effect, although this tends to diminish with ongoing therapy. Dosing at bedtime should be avoided, taking care to ensure there is an interval of at least eight hours between doses.

As bupropion has a similar mechanism of action to many antidepressants, other neuropsychiatric adverse effects may occur including mood and behavioural changes. Hypertension has also been reported and may be severe in some cases. Discontinuation of bupropion may be required if a clinically significant rise in blood pressure is observed, and caution is required in patients with pre-existing cardiovascular disease. The concomitant use of monoamine oxidase (MAO) inhibitors is contraindicated, and at least 14 days should elapse between discontinuation of an MAO inhibitor and initiation of bupropion.

Bupropion is associated with a risk of seizures. The manufacturer contraindicates its use in patients with a history of seizures, tumour of the central nervous system (CNS), bulimia or anorexia nervosa, and during abrupt withdrawal from alcohol or benzodiazepines. Patients with other predisposing risk factors should only take bupropion if the potential benefit of smoking cessation outweighs the risk of a seizure. Other risk factors for seizures include medications (e.g. antipsychotics, antidepressants, tramadol, systemic steroids), alcohol misuse, and a history of head trauma.

A summary of medications for smoking cessation is shown in Table 2.

Table 2. Comparison of medications indicated for smoking cessation

Conclusion

Cytisine is newly available in Australia and provides an additional evidence-based pharmacological option for smoking cessation. It may be particularly useful for people who are unable to tolerate other treatments, have previously been unsuccessful with NRT, or prefer a non-nicotine medicine. Current evidence suggests efficacy and tolerability are broadly comparable to varenicline, although further direct comparative studies are warranted. As with all smoking cessation treatments, success rates are improved when pharmacotherapy is combined with behavioural support and regular follow-up.