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Pronunciation | /vəˈrɛnɪkliːn/ və-REN-i-kleen |
Trade names | Champix, Chantix, Tyrvaya, others |
Other names | OC-01 |
AHFS/Drugs.com | Monograph |
MedlinePlus | a606024 |
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Routes of administration | By mouth, nasal spray |
Drug class | Nicotinic agonist |
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Protein binding | <20% |
Metabolism | Limited (<10%) |
Elimination half-life | 24 hours |
Excretion | Kidney (81–92%) |
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Chemical and physical data | |
Formula | C13H13N3 |
Molar mass | 211.268 g·mol−1 |
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Varenicline, sold under the brand names Chantix and Champix among others, is a medication used for smoking cessation [5] [7] and for the treatment of dry eye disease. [6] [8] It is a nicotinic receptor partial agonist [5] and a cholinergic agonist. [6] When activated, this receptor releases dopamine in the nucleus accumbens, the brain's reward center, thereby reducing cravings and withdrawal symptoms associated with smoking cessation. [9]
Common side effects of varenicline include nausea, insomnia, abnormal dreams, headache, and nasopharyngitis (inflammation of the nose and throat). [7] Despite these potential adverse effects, varenicline has proven efficacy in helping individuals quit smoking. It is estimated that approximately one in eleven smokers who use varenicline successfully remain abstinent from tobacco at six months. [10]
It is on the World Health Organization's List of Essential Medicines. [11] The medication is available as a generic medication. [12] In the United States, varenicline was prescribed over 1 million times in 2020, ranking as the 275th most commonly prescribed medication. [13] [14]
Varenicline is indicated for use as an aid to smoking cessation treatment [5] and for the treatment of the signs and symptoms of dry eye disease. [6]
Varenicline is used to help people stop smoking tobacco (smoking cessation). A meta-analysis found that 20% of people treated with varenicline remain abstinent from smoking at one year. [15] In a 2009 meta-analysis, varenicline was found to be more effective than bupropion (odds ratio 1.40) and nicotine replacement therapies (NRT) (odds ratio 1.56). [16]
A 2013 Cochrane overview and network meta-analysis concluded that varenicline is the most effective medication for tobacco cessation and that smokers were nearly three times more likely to quit tobacco use while on varenicline than with placebo treatment. Varenicline was more efficacious than bupropion or NRT and as effective as combination NRT for cessation of tobacco smoking. [17] [18]
Mild nausea is the most common side effect and is seen in approximately 30% of people taking varenicline, though this rarely (<3%) results in discontinuation of the medication. [18] Other less common side effects include headache, difficulty sleeping, and vivid dreams. Rare side effects reported by people taking varenicline compared to placebo include change in taste, vomiting, abdominal pain, flatulence, and constipation. It has been estimated that for every five subjects taking varenicline at maintenance doses, there will be one event of nausea; and for every 24 of 35 treated subjects, there will be an event of constipation or flatulence. Gastrointestinal side-effects lead to discontinuation of the drug in 2% to 8% of people using varenicline. [19] [20] Incidence of nausea is dose-dependent: incidence of nausea was higher in people taking a larger dose (30%) versus placebo (10%) as compared to people taking a smaller dose (16%) versus placebo (11%). [5]
In 2007, the US Food and Drug Administration (FDA) announced it had received post-marketing reports of thoughts of suicide and occasional suicidal behavior, erratic behavior, and drowsiness among people using varenicline for smoking cessation. In 2009, the FDA required varenicline to carry a boxed warning that the medication should be stopped if any of these symptoms are experienced. [21]
A 2014 systematic review (literature research) did not find evidence of an increased suicide risk. [22] Other analyses have reached the same conclusion and found no increased risk of neuropsychiatric side effects with varenicline. [17] [18] No evidence for increased risks of cardiovascular events, depression, or self-harm with varenicline versus nicotine replacement therapy was found in one post-marketing surveillance study. [23]
In 2016, the FDA removed the black box warning. [24] People are still advised to stop the medication if they "notice any side effects on mood, behavior, or thinking." [24] [25] [26]
In June 2011, the US FDA issued a safety announcement that varenicline may be associated with "a small, increased risk of certain cardiovascular adverse events in people who have cardiovascular disease." [27]
A prior 2011 review had found increased risk of cardiovascular events compared with placebo. [28] Expert commentary in the same journal raised doubts about the methodology of the review, [29] [30] concerns which were echoed by the European Medicines Agency and subsequent reviews. [31] [32] Of specific concern were "the low number of events seen, the types of events counted, the higher drop-out rate in people receiving placebo, the lack of information on the timing of events, and the exclusion of studies in which no-one had an event."
In contrast, multiple recent systematic reviews and meta-analyses have found no increase in overall or serious adverse cardiovascular events (including for individuals at risk of developing cardiovascular disease) associated with varenicline use. [32] [33] [34] [35]
Varenicline displays full agonism on α7 nicotinic acetylcholine receptors and is a partial agonist on the α4β2, α3β4, and α6β2 subtypes. [36] [37] [38]
Varenicline's partial agonism on the α4β2 receptors rather than nicotine's full agonism produces less effect of dopamine release than nicotine's. This α4β2 competitive binding reduces the ability of nicotine to bind and stimulate the mesolimbic dopamine system—similar to the method of action of buprenorphine in the treatment of opioid addiction. [18]
Most of the active compound is excreted by the kidneys (92–93%). A small proportion is glucuronidated, oxidised, N-formylated or conjugated to a hexose. [39]
Use of Cytisus plants as a smoking substitutes during World War II [40] led to use as a cessation aid in eastern Europe and extraction of cytisine. [41] Cytisine analogs led to varenicline at Pfizer. [42] [43] [44]
Varenicline received a priority review by the US FDA in February 2006, shortening the usual ten-month review period to six months because of its demonstrated effectiveness in clinical trials and perceived lack of safety issues. [45] The agency's approval of the drug came in May 2006. [46] [47] In September 2006, it was approved for sale in the European Union. [7]
In September 2021, Pfizer announced a recall of "all lots of its anti-smoking treatment, Chantix [Varenicline], due to high levels of cancer-causing agents called nitrosamines in the pills". [48] This followed a July 2021 announcement by the FDA that it was "alerting patients and health care professionals to Pfizer's voluntary recall of nine lots of the smoking cessation drug" and further recalls by Pfizer on 19 July and 8 August. [49] In June 2021, Pfizer paused distribution of Chantix worldwide; [50] "the distribution halt was out of an abundance of caution, pending further testing", the company said in an email. [51] According to the Pfizer Inc. 2020 Form 10-K Annual Report, high-revenue products by the company include[d] Chantix/Champix (varenicline) to treat nicotine addiction, which recorded direct product revenues of more than $1 billion in 2019, $919 million in 2020, and $398 million in 2021 (the lower 2021 revenue was due, in part, to the basic product patent expiration for Chantix in the US in November 2020 and in Europe in September 2021, and the aforementioned Pfizer voluntary recall across multiple markets and a global pause in shipments of Chantix). [52] [53]
In October 2021, the US FDA approved Oyster Point Pharma to market Tyrvaya as a new route of varenicline administration through nasal spray for the treatment of dry eye disease. [54]
Nicotine is a naturally produced alkaloid in the nightshade family of plants and is widely used recreationally as a stimulant and anxiolytic. As a pharmaceutical drug, it is used for smoking cessation to relieve withdrawal symptoms. Nicotine acts as a receptor agonist at most nicotinic acetylcholine receptors (nAChRs), except at two nicotinic receptor subunits where it acts as a receptor antagonist.
Drugs used in diabetes treat diabetes mellitus by decreasing the glucose level in the blood. With the exception of insulin, most GLP receptor agonists, and pramlintide, all are administered orally and are thus also called oral hypoglycemic agents or oral antihyperglycemic agents. There are different classes of hypoglycemic drugs, and their selection depends on the nature of diabetes, age, and situation of the person, as well as other factors.
Smoking cessation, usually called quitting smoking or stopping smoking, is the process of discontinuing tobacco smoking. Tobacco smoke contains nicotine, which is addictive and can cause dependence. As a result, nicotine withdrawal often makes the process of quitting difficult.
Bupropion, sold under the brand name Wellbutrin among others, is an atypical antidepressant primarily used to treat major depressive disorder and to support smoking cessation. It is also popular as an add-on medication in the cases of "incomplete response" to the first-line selective serotonin reuptake inhibitor (SSRI) antidepressant. Bupropion has several features that distinguish it from other antidepressants: it does not usually cause sexual dysfunction, it is not associated with weight gain and sleepiness, and it is more effective than SSRIs at improving symptoms of hypersomnia and fatigue. Bupropion, particularly the immediate release formulation, carries a higher risk of seizure than many other antidepressants, hence caution is recommended in patients with a history of seizure disorder.
Rosiglitazone is an antidiabetic drug in the thiazolidinedione class. It works as an insulin sensitizer, by binding to the PPAR in fat cells and making the cells more responsive to insulin. It is marketed by the pharmaceutical company GlaxoSmithKline (GSK) as a stand-alone drug or for use in combination with metformin or with glimepiride. First released in 1999, annual sales peaked at approximately $2.5-billion in 2006; however, following a meta-analysis in 2007 that linked the drug's use to an increased risk of heart attack, sales plummeted to just $9.5-million in 2012. The drug's patent expired in 2012.
Nicotine replacement therapy (NRT) is a medically approved way to treat people with tobacco use disorder by taking nicotine through means other than tobacco. It is used to help with quitting smoking or stopping chewing tobacco. It increases the chance of quitting tobacco smoking by about 55%. Often it is used along with other behavioral techniques. NRT has also been used to treat ulcerative colitis. Types of NRT include the adhesive patch, chewing gum, lozenges, nose spray, and inhaler. The use of multiple types of NRT at a time may increase effectiveness.
Nicotine gum is a chewing gum containing the active ingredient nicotine polacrilex. It is a type of nicotine replacement therapy (NRT) used alone or in combination with other pharmacotherapy for smoking cessation and for quitting smokeless tobacco.
Beta2-adrenergic agonists, also known as adrenergic β2 receptor agonists, are a class of drugs that act on the β2 adrenergic receptor. Like other β adrenergic agonists, they cause smooth muscle relaxation. β2 adrenergic agonists' effects on smooth muscle cause dilation of bronchial passages, vasodilation in muscle and liver, relaxation of uterine muscle, and release of insulin. They are primarily used to treat asthma and other pulmonary disorders. Bronchodilators are considered an important treatment regime for Chronic obstructive pulmonary disease (COPD) and are usually used in combination with short acting medications and long acting medications in a combined inhaler.
Long-acting β adrenoceptor agonists are usually prescribed for moderate-to-severe persistent asthma patients or patients with chronic obstructive pulmonary disease (COPD). They are designed to reduce the need for shorter-acting β2 agonists such as salbutamol (albuterol), as they have a duration of action of approximately 12 hours in comparison with the 4-to-6-hour duration of salbutamol, making them candidates for sparing high doses of corticosteroids or treating nocturnal asthma and providing symptomatic improvement in patients with COPD. With the exception of formoterol, long-acting β2 agonists are not recommended for the treatment of acute asthma exacerbations because of their slower onset of action compared to salbutamol. Their long duration of action is due to the addition of a long, lipophilic side-chain that binds to an exosite on adrenergic receptors. This allows the active portion of the molecule to continuously bind and unbind at β2 receptors in the smooth muscle in the lungs.
Guanfacine, sold under the brand name Tenex (immediate-release) and Intuniv (extended-release) among others, is an oral alpha-2a agonist medication used to treat attention deficit hyperactivity disorder (ADHD) and high blood pressure. Guanfacine is FDA-approved for monotherapy treatment of ADHD, as well as being used for augmentation of other treatments, such as stimulants. Guanfacine is also used off-label to treat tic disorders, anxiety disorders and PTSD.
Cytisine, also known as baptitoxine, cytisinicline, or sophorine, is an alkaloid that occurs naturally in several plant genera, such as Laburnum and Cytisus of the family Fabaceae. It has been used medically to help with smoking cessation. Although widely used for smoking cessation in Eastern Europe, cytisine remains relatively unknown beyond it. However, it has been found effective in several randomized clinical trials, including some in the United States and a large one in New Zealand, and is being investigated in additional trials in the United States and a non-inferiority trial in Australia in which it is being compared head-to-head with the smoking cessation aid varenicline. It has also been used entheogenically via mescalbeans by some Native American groups, historically in the Rio Grande Valley predating even peyote.
An electronic cigarette (e-cigarette) or vape is a device that simulates tobacco smoking. It consists of an atomizer, a power source such as a battery, and a container such as a cartridge or tank filled with liquid. Instead of smoke, the user inhales vapor. As such, using an e-cigarette is often called "vaping". The atomizer is a heating element that vaporizes a liquid solution called e-liquid, which quickly cools into an aerosol of tiny droplets, vapor and air. E-cigarettes are activated by taking a puff or pressing a button. Some look like traditional cigarettes, and most kinds are reusable. The vapor mainly comprises propylene glycol and/or glycerin, usually with nicotine and flavoring. Its exact composition varies, and depends on several things including user behavior.
Nicotine dependence is a state of dependence upon nicotine. Nicotine dependence is a chronic, relapsing disease defined as a compulsive craving to use the drug, despite social consequences, loss of control over drug intake, and emergence of withdrawal symptoms. Tolerance is another component of drug dependence. Nicotine dependence develops over time as a person continues to use nicotine. The most commonly used tobacco product is cigarettes, but all forms of tobacco use and e-cigarette use can cause dependence. Nicotine dependence is a serious public health problem because it leads to continued tobacco use, which is one of the leading preventable causes of death worldwide, causing more than 8 million deaths per year.
Dianicline (SSR-591,813) is a drug developed by Sanofi-Aventis which acts as a partial agonist at neural nicotinic acetylcholine receptors. It is subtype-selective, binding primarily to the α4β2 subtype. It is being developed as a medication for the treatment of nicotine dependence to assist in smoking cessation. Dianicline is very similar to the already marketed drug varenicline and it is unclear what advantages it will have over the older drug, although it may have an improved side effect profile. It has been through human trials up to Phase II, although results have not yet been reported. Drug development has been discontinued after reporting of unfavourable results during Phase III trials.
Glucagon-like peptide-1 (GLP-1) receptor agonists, also known as GLP-1 analogs, are a class of drugs that reduce blood sugar and energy intake by activating the GLP-1 receptor. They mimic the actions of the endogenous incretin hormone GLP-1 that is released by the gut after eating.
Schizophrenia and tobacco smoking have been historically associated. Smoking is known to harm the health of people with schizophrenia, and to negatively affect their cognition.
Dulaglutide, sold under the brand name Trulicity among others, is a medication used for the treatment of type 2 diabetes in combination with diet and exercise. It is also approved in the United States for the reduction of major adverse cardiovascular events in adults with type 2 diabetes who have established cardiovascular disease or multiple cardiovascular risk factors. It is a once-weekly injection.
SGLT2 inhibitors, also called gliflozins or flozins, are a class of medications that inhibit sodium-glucose transport proteins in the nephron, unlike SGLT1 inhibitors that perform a similar function in the intestinal mucosa. The foremost metabolic effect of this is to inhibit reabsorption of glucose in the kidney and therefore lower blood sugar. They act by inhibiting sodium-glucose transport protein 2 (SGLT2). SGLT2 inhibitors are used in the treatment of type 2 diabetes. Apart from blood sugar control, gliflozins have been shown to provide significant cardiovascular benefit in people with type 2 diabetes. As of 2014, several medications of this class had been approved or were under development. In studies on canagliflozin, a member of this class, the medication was found to enhance blood sugar control as well as reduce body weight and systolic and diastolic blood pressure.
Jed Eugene Rose is an American academic professor, inventor and researcher in the field of nicotine and smoking cessation. Rose is presently the President and CEO of the Rose Research Center, LLC in Raleigh, North Carolina. Additionally, he is the Director of the Duke Center for Smoking Cessation at Duke University Medical Center.
Nicotine vaccine is a novel immunological strategy for treating nicotine addiction. Nicotine vaccine uses active immunization as the methodology to create polyclonal antibodies to the antigens, which is then used to treat drug abuse. The immune system is then able to identify nicotine as a foreign substance and initiate an immune reaction targeting the drug. As a result, the quantity of nicotine that enters the brain would decrease after receiving the vaccine. In preclinical studies, nicotine vaccines have demonstrated the ability to combat the negative effects of nicotine abuse, but none of the developed vaccines has been authorized for use in clinical trials as a smoking cessation strategy. Theoretically, the decrease of nicotine's rewarding effects should result in smoking cessation. Some companies have tested candidate vaccines in clinical trials, but evidence failed to show the adequate antibody responses or exhibit superior efficacy to factors concerning placebo.