What happens when you take smoking with varenicline?
Varenicline, sold under the brand name Chantix, is a partial agonist at the alpha4-beta2 nicotinic acetylcholine receptor — the receptor subtype most responsible for nicotine's rewarding effects in the brain. It does two things at once: it binds the receptor and stimulates it weakly, providing partial satisfaction of nicotine craving and reducing withdrawal symptoms, and it occupies the receptor so that nicotine from cigarettes cannot bind and produce its usual rewarding spike. Continued smoking while taking varenicline therefore produces less of a buzz than smoking alone, which is part of how the drug helps people quit.
The interaction with smoking is not dangerous in the same sense as a drug-drug toxicity, but it has clinical consequences worth understanding. First, varenicline does not stop you from smoking — it makes smoking less rewarding so quitting becomes easier. Patients typically start varenicline 1 to 2 weeks before their target quit date and continue smoking during this lead-in. Some people find they have already lost interest in cigarettes before their quit date arrives.
Second, combining varenicline with nicotine replacement therapy (gum, patches, lozenges) is sometimes done to improve quit rates, but it increases the rate of common side effects. The Chantix prescribing information specifically notes that co-administration with transdermal nicotine for up to 12 days did not change nicotine pharmacokinetics, but the incidence of nausea, headache, vomiting, dizziness, dyspepsia, and fatigue was greater with the combination than with nicotine replacement therapy alone. In one cited study, 36% of patients on the combination discontinued treatment due to side effects compared with 6% on nicotine replacement alone.
Why is this important?
Varenicline is one of the most effective smoking cessation medications available. Meta-analyses consistently show it outperforms placebo, nicotine replacement therapy alone, and bupropion as a single agent for achieving sustained abstinence. Understanding how to use it well, including how it interacts with continued smoking and with nicotine replacement, can mean the difference between a successful quit attempt and an early discontinuation.
Nausea is the most common side effect, affecting roughly 30% of patients taking the full maintenance dose. For most it is mild to moderate and tolerable, but for some it leads to discontinuation. Continued heavy smoking during the early weeks of treatment may worsen nausea because smoking itself can cause nausea independent of the drug. Slowly titrating the dose, taking varenicline with food and a full glass of water, and avoiding empty-stomach dosing can mitigate this.
The Chantix label historically carried a black box warning for neuropsychiatric effects including depressed mood, suicidal ideation, and changes in behavior. The boxed warning was removed in 2016 after the large EAGLES trial found no significant increase in serious neuropsychiatric events compared with placebo, nicotine patch, or bupropion. However, the prescribing information still notes that some patients experience changes in mood, agitation, or unusual dreams, and that vivid dreams are common. Patients should report serious mood changes or thoughts of self-harm to their prescriber immediately.
Other warnings include the potential for seizures (especially in patients with a seizure history or who lower seizure threshold with other drugs), cardiovascular events in patients with established cardiovascular disease, somnambulism and other sleep-related behaviors, and accidental injury — including a documented risk that varenicline can impair driving in some users.
What should you do?
Start varenicline 1 to 2 weeks before your target quit date as directed: 0.5 mg once daily for 3 days, then 0.5 mg twice daily for 4 days, then 1 mg twice daily through week 12. You can also start an alternative schedule where the quit date is set in week 5. Take each dose with food and a full glass of water to minimize nausea.
Do not be discouraged if you continue to smoke during the first week or two of treatment. Many patients find their interest in cigarettes fades before they consciously decide to quit. By the target quit date, the rewarding effect of nicotine from cigarettes should be substantially blunted, making cessation easier.
If your prescriber suggests combining varenicline with a nicotine patch — sometimes done to improve quit rates in heavy smokers — expect more side effects, particularly nausea and headache. Some patients tolerate the combination well; others find it intolerable and discontinue. There is no danger in stopping if needed, but talk to your prescriber rather than just stopping silently.
Watch for and report serious neuropsychiatric symptoms: severe depression, suicidal thoughts, agitation, hostility, or psychosis. Seek immediate care for seizures, allergic reactions including angioedema, or severe skin reactions. Use caution operating heavy machinery or driving until you know how varenicline affects you, given the rare reports of impaired driving and somnambulism.
Which specific products are affected?
This interaction is specific to varenicline, sold under the brand name Chantix in the United States (Champix in many other countries). Generic varenicline tartrate became available after the brand patent expired. Varenicline is taken orally as 0.5 mg and 1 mg tablets, typically in a 12-week course that can be extended to 24 weeks for patients who have quit successfully and want to consolidate their abstinence.
Smoking includes all combustible tobacco products: cigarettes, cigars, pipes, and roll-your-own. The interaction also applies in concept to electronic cigarettes and vaping products that deliver nicotine, and to nicotine replacement therapies including patches (NicoDerm CQ), gum (Nicorette), lozenges, inhaler, and nasal spray. The decision to combine varenicline with nicotine replacement should be individualized.
Bupropion (Zyban, Wellbutrin) is the other major smoking cessation medication and is sometimes combined with varenicline in research settings, with modestly improved quit rates but more side effects. Combination cessation therapy should be guided by an experienced clinician.
The bottom line
Varenicline works by partially activating the same brain receptors that nicotine targets, dulling cigarette satisfaction and easing withdrawal. Continued smoking during the start-up phase is expected and not dangerous. Combining varenicline with nicotine replacement can improve quit rates but increases nausea and other side effects. Take varenicline with food and water, follow the dose titration schedule, and report mood changes or thoughts of self-harm to your prescriber promptly.