Varenicline tartrate for smoking cessation, side effects, how does it work, is it effective? Chantix
April 15, 2016 by
Ray Sahelian, M.D.


Varenicline is FDA-approved and marketed by Pfizer as Chantix in the US and Champix in Europe and Canada, manufactured by Pfizer.


Side effects, adverse reactions, danger of Chantix
Prescrire Int. 2015. Cardiac adverse effects of nicotine replacement therapy. Smoking markedly increases the risk of cardiovascular disease. Nicotine replacement therapy is available to assist in smoking cessation. To assess the cardiac adverse effects of nicotine replacement therapy, we conducted a review of the literature using the standard Prescrire methodology. A meta-analysis of 21 randomised, placebo-controlled trials published in early 2014 included a total of 11 647 patients, including 828 patients at high risk of cardiovascular events and 187 patients with acute coronary disorders. It showed that nicotine replacement therapy was associated with an increased risk of cardiac disorders, particularly palpitations, which are a known adverse effect of smoking. Among patients at high cardiovascular risk, 1.2% experienced a serious cardiovascular event, with no statistically significant difference versus placebo. Bupropion and varenicline both have serious adverse effects and have been less extensively evaluated in patients at high cardiovascular risk. In practice, when a drug is needed to assist in smoking cessation, nicotine appears to be a reasonable choice. Nicotine replacement therapy exposes patients to a risk of palpitations but rarely to serious cardiac disorders, even in individuals with a cardiovascular history. In addition, these adverse effects are better documented than those of bupropion and varenidine in such patients. Nonetheless, the cardiac effects of nicotine call for prudent use of nicotine replacement therapy: the minimum effective dose should be sought, and the goal should be total nicotine withdrawal.

Varenicline tartrate for smoking cessation
Varenicline may be effective in helping a smoker give up cigarettes according to a report in JAMA (Journal of the American Medical Association), 5 July, 2006. Varenicline tartrate may be more effective as Zyban (bupropion). The chances of having a relapse during the first six months after giving up are reduced when a smoker is on Varenicline. All the studies were funded by the makers of Varenicline, Pfizer. A JAMA editorial is skeptical of all the hype surrounding this new smoking cessation drug. Robert Klesges, University of Tennessee Health Science Center, Memphis, USA, says enthusiasm for a new smoking-cessation drug is always high when it first comes onto the market. Even though Varenicline has better results than either a placebo or Zyban, this does not necessarily mean it is the holy grail for smoking addicts.


Int J Clin Pract. Jan 29 2014. The long-term cost-effectiveness of varenicline (12-week standard course and 12 + 12-week extended course) vs. other smoking cessation strategies in Canada. The standard and extended courses of varenicline are decidedly cost-effective treatment regimes compared with alternative smoking cessation interventions and can provide significant cost savings to the healthcare system.


AIM Study - Only 14 percent effectiveness after one year of Vareniciline tartrate
Varenicline, a non-nicotine drug designed specifically for smoking cessation, appears to be safe and effective according to a study in the Archives of Internal Medicine. Varenicline binds to a nicotine receptor that's believed to trigger the rewarding effects felt with smoking. Because varenicline competes more strongly than nicotine to bind to the receptor, yet has less of a rewarding effect, the investigators figured that it would alleviate craving and withdrawal. In a study, Dr. Mitchell Nides, from Los Angeles Clinical Trials, and the Varenicline Study Group randomly assigned 626 people to varenicline tartrate at three different doses, or to sustained-release bupropion (better known as Zyban), or placebo. The participants used their assigned study drug for a week before quitting cigarettes completely. They took the pills for about seven weeks, then were followed for a year. At the end of 12 weeks, the confirmed continuous quit rates were 38 percent for the highest dose of varenicline, 19 percent for bupropion, and 10 percent for placebo. At 52 weeks, corresponding rates were 14 percent, 6 percent and 5 percent. Craving was significantly reduced at all weekly time points for highest-dose varenicline compared with placebo. Bupropion also reduced craving, but to a lesser extent. Archives of Internal Medicine, August 2006.


Varenicline tartrate is the new stop smoking pill on the block

Cigarette smoking remains an important risk factor for premature cardiovascular disease and its complications. There are clear benefits of cigarette smoking cessation on the rate of clinical outcomes, and in addition to behavioral therapies, various pharmacologic strategies have been developed to help achieve this goal. First-line therapies include nicotine replacement and/or bupropion. Second-line treatments include clonidine and nortriptyline. Additional treatment strategies, with less proven efficacy, include monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, opioid receptor antagonists, bromocriptine, anti-anxiety drugs, nicotinic receptor antagonists (eg, mecamylamine), and glucose tablets. Various approaches under investigation include the use of partial nicotine agonists (eg, varenicline), inhibitors of the hepatic P-450 enzyme (eg, methoxsalen), and cannaboid-1 receptor antagonists (eg, rimonabant), and nicotine vaccines.
     Dr. Sahelian says: I am quite cautious when new medicines are introduced because it is not uncommon that unforseen side effects could come up after a medicine is marketed to the public. At this point it is difficult to know whether Varenicline has side effects of any significant nature.

Vareniciline mechanism of action

Varenicline works in a different way from Zyban or nicotine-replacement therapies. Nicotine-replacement therapies give you a small dose of nicotine - the aim is to provide the smoker with his/her drug while he/she overcomes the enormous psychological problems that come with giving up. Zyban undermines the reuptake of addiction-linked brain chemicals by neurons - dopamanine and norepinephrine. Varenicline makes the patient produce more dopamine, which is supposed to help lower the cravings - at the same time brain cell receptors that help perpetuate addiction are blocked. However, another researcher adds a different twist to the mechanism of action of Varenicline. Perhaps Varenicline is also a partial agonist at the alpha4beta2 nicotinic acetylcholine receptor.


New smoking stopper?
FDA announced in May 2006 the approval of Varenicline (varenicline tartrate) tablets, to help cigarette smokers stop smoking. The active ingredient in Varenicline, varenicline tartrate, is a new molecular entity that received a priority FDA review because of its significant potential benefit to public health. Varenicline acts at sites in the brain affected by nicotine and may help those who wish to give up smoking in two ways: by providing some nicotine effects to ease the withdrawal symptoms and by blocking the effects of nicotine from cigarettes if they resume smoking.


Vareneciline for alcohol
Could vareneciline curb the urges to both smoke and drink? Varenicline is already available to help smokers kick the habit but some people say it help heavy drinkers quit, too. But, the track record thus far is not so good for vareneciline since in one study, after one year of use, only 14 percent of smokers were able to quit.
   Pfizer Inc. developed vareniciline drug specifically as a stop-smoking aid and has sold it in the United States since August 2006 under the brand name Chantix. Varenicline works by latching onto the same receptors in the brain that nicotine binds to when inhaled in cigarette smoke, an action that leads to the release of dopamine in the brain's pleasure centers. Taking the drug blocks any inhaled nicotine from reinforcing that effect. Alcohol may also act on the same locations in the brain. Varenicline, which makes smoking less rewarding, could do the same for drinking. A small study, done in rats suggests that is the case. In the new study, researchers trained rats to drink alcohol and measured the effect of varenicline once the animals became the laboratory equivalent of heavy drinkers. They found the drug curbed their drinking. Even when stopped, the animals resumed drinking but didn't binge. Just as varenicline doesn't work for all smokers, it's highly unlikely it would for all drinkers. "Is this going to be a cure-all? No, not for smoking or alcoholism because both diseases are more complicated than a single target or single genetic issue," said Allan Collins, a professor of pharmacology at the University of Colorado who was not connected to the study.


Vareniciline Review
Varenicline : A Review of its Use as an Aid to Smoking Cessation Therapy.
CNS Drugs. 2006. Keating GM, Siddiqui MA.Wolters Kluwer Health | Adis, Auckland, New Zealand, an editorial office of Wolters Kluwer Health, Conshohocken, Pennsylvania, USA.
Varenicline is an orally administered alpha4beta2 nicotinic acetylcholine (ACh) receptor partial agonist. It has been approved by the US FDA ( Chantix ) and the European Commission ( Champix ) for use as an aid to smoking cessation therapy. Varenicline is generally well tolerated treatment for use in smokers who want to quit. In two phase III trials, 12 weeks' treatment with varenicline was associated with higher continuous abstinence rates at weeks 9-12 than placebo or bupropion sustained-release (SR). In the longer term, continuous abstinence rates for weeks 9 through 52 demonstrated that the odds of remaining abstinent were 2.7 times higher with 12 weeks of varenicline treatment than with placebo; the significant difference between varenicline and bupropion SR was also maintained in the longer term in one trial. Moreover, varenicline appeared to attenuate the urge to smoke, negative affect withdrawal symptoms and the reinforcing effects of smoking. Among those achieving abstinence, an additional 12 weeks of varenicline therapy helped increase the likelihood of long-term abstinence. Thus, varenicline is a new agent for use as an aid to smoking cessation treatment.


Varenicline Research
Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial.
JAMA. 2006. Smoking Cessation Center, Department of Medicine, Oregon Health and Science University, Portland, OR, USA.
The alpha4beta2 nicotinic acetylcholine receptors (nAChRs) are linked to the reinforcing effects of nicotine and maintaining smoking behavior. Varenicline, a novel alpha4beta2 nAChR partial agonist, may be beneficial for smoking cessation. To assess efficacy and safety of Varenicline for smoking cessation compared with sustained-release bupropion (bupropion SR) and placebo. Varenicline was significantly more efficacious than placebo for smoking cessation at all time points and significantly more efficacious than bupropion SR at the end of 12 weeks of drug treatment and at 24 weeks.


Varenicline questions
I came across a study on the internet that you conducted on varenicline tartrate and I am wondering if you have come across/conducted any follow up studies. I am searching for some information to help my mother in law, who took it for about 6 weeks about 3 months ago and is having major physical and psychological varenicline side effects from it, which just seem to be getting worse. We've done hours of research on the internet in an attempt to find a doctor or course of treatment that will help her and haven't been able to find a single thing. Most of the information out there seems to relate to class action law suits, individual complaints and warnings, but nothing on what people are doing to try to counteract these effects. I was wondering if you could possibly direct me to someone or some course of treatment that can help her. Her GP is basically ignoring the situation. He told her that the drug has bound to the receptors in her brain and that hopefully it will go away, but she seems to be getting worse.
    I have not done studies with varenicline or side effects from the use of varenicline, I just reported the results of studies on his website and I have no further info on this topic at this time, July 2008. I wish your mother well and hopes the effects will dissipate or a good treatment is found.