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Varenicline |
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Varenicline
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| Systematic (IUPAC) name | |
| 7,8,9,10-tetrahydro-6,10-methano- 6H-pyrazino(2,3-h)(3)benzazepine |
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| Identifiers | |
| CAS number | 375815-87-5 |
| ATC code | N07 |
| PubChem | |
| Chemical data | |
| Formula | C13H13N3 |
| Mol. mass | 211.267 g/mol |
| SMILES | & |
| Pharmacokinetic data | |
| Bioavailability | ? |
| Protein binding | <20% |
| Metabolism | Limited (<10%) |
| Half life | 24 hours |
| Excretion | Renal (81–92%) |
| Therapeutic considerations | |
| Licence data |
, |
| Pregnancy cat. |
C(US) |
| Legal status |
℞ Prescription only |
| Routes | Oral |
Varenicline (trade name Chantix in the USA and Champix in Europe and other countries, marketed by Pfizer, usually in the form of varenicline tartrate) is a prescription medication used to treat smoking addiction. Varenicline is a nicotinic receptor partial agonist. In this respect, it is similar to cytisine and different from nicotinic antagonist, bupropion, and nicotine replacement therapies (NRTs) like nicotine patches (commonly, "the patch") and nicotine gum. As a partial agonist, it both reduces cravings for and decreases the pleasurable effects of cigarettes and other tobacco products, and through these mechanisms it can assist some patients in stopping smoking.
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Varenicline is indicated for (suggested for use in) smoking cessation. It is an alternative to NRTs and agonist medication and has demonstrated greater efficacy than them in comparable studies.1
The FDA has approved its use for twelve weeks. If smoking cessation has been achieved it may be continued for another twelve weeks.2
Varenicline has not been tested in children, those under 18 years old, or pregnant women, and therefore is not recommended for use by these groups. Women currently breastfeeding should also avoid this product, since varenicline may pass into the breast milk, leading to unknown effects on the child.
Varenicline is a partial agonist of the α4β2 subtype of the nicotinic acetylcholine receptor. In addition it acts on α3β4 and weakly on α3β2 and α6-containing receptors. A full agonism was displayed on α7-receptors.3
Most of the active compound is excreted renally (92-93%). A small proportion is glucuronidated, oxidated, N-formylated or conjugated to a hexose.4 The elimination half-life is about 24 hours.
Nausea occurs commonly in people taking varenicline. Other less common side effects include headache, difficulty sleeping, and abnormal dreams. Rare side effects reported by people taking varenicline compared to placebo include change in taste, vomiting, abdominal pain, flatulence, and constipation.5 In May 2008, Pfizer updated the safety information associated with Chantix, noting that "some patients have reported changes in behavior, agitation, depressed mood, suicidal thoughts or actions." 6
In November 2007, the FDA announced it had received post-marketing reports that patients using Chantix for smoking cessation had experienced several serious symptoms, including suicidal ideation and occasional suicidal behavior, erratic behavior, and drowsiness. On February 1, 2008 the FDA issued an Alert to further clarify its findings, noting that "it appears increasingly likely that there is an association between Chantix and serious neuropsychiatric symptoms." It is unknown whether the psychiatric symptoms are related to the drug or to nicotine withdrawal symptoms, although not all patients had stopped smoking. The FDA is aware of the highly-publicized case of Carter Albrecht who, in an apparent state of delirium, was shot to death by his neighbour after hitting his girlfriend and then trying to forcibly enter the neighbor's house.7 Although in this case the delirium appeared to be caused by taking varenicline with a high dose of alcohol, the FDA asked Pfizer for additional cases that might be similar. It also recommended that health care professionals and patients watch for behavioral and mood changes.8
Institute for Safe Medication Practices (ISMP) conducted an analysis of post-marketing adverse effects reports received by the FDA. According to this analysis, in the fourth quarter of 2007 varenicline accounted for more reports of serious side effects than any other drug. Suicidal acts and ideation, psychosis, and hostility or aggression, including homicidal ideation, were the most prominent psychiatric side effects. Multiple reports suggested that varenicline may be related to the loss of glycemic control and new onset of diabetes, heart rhythm disturbances, skin reactions, vision disturbances, seizures, abnormal muscle spasms and other movement disorders. ISMP noted that the reports do not establish causality and only identify potential causes, and concluded that further research and a priority review of the data by the FDA is necessary. 9
On Thursday, May 22, 2008, The New York Times reported that the U.S. Federal Aviation Administration (F.A.A.) had announced the day before a ban on the use of Chantix (varenicline tartrate) for both pilots and air traffic controllers, due to concerns with possible adverse neuropsychiatric effects which could be detrimental to public safety.10
On Sunday, May 25, 2008, The Los Angeles Times reported that over 2 dozen traffic accidents had been linked to Chantix and reported to the FDA. Warnings had previously been issued by Pfizer regarding the risks of Chantix while driving. However, these warnings have largely been ignored by doctors and patients.11
On Tuesday, June 17, 2008, The Washington Times reported on its Front Page that the United States Department of Veterans Affairs was testing Chantix on war veterans with Post Traumatic Stress Disorder without properly warning them of the side effects, and that in one case a veteran was almost killed when he had a psychotic episode and threatened police officers.12
On October 23, 2008, the Institute for Safe Medication Practices issued an analysis of prescription drug-related injuries reported to the FDA during the first quarter of 2008. According to the report, varenicline had more reported incidents than any other drug, with 1001 new cases of adverse effects and 50 more deaths reported (Heparin, the drug with the second highest number of injury reports, had 779 new cases, most of which were connected to a contaminate inadvertently introduced into the drug in early 2008). In comparison, the ISMP reported that in the first quarter of 2008 there were 17 serious injury reports for nicotine-replacement products, and 44 reports for bupropion (sold as Zyban as a smoking cessation medication). Varenicline did not rank in the ten drugs with the most related deaths, but did rank first in reports of suicide or self-injury, with 228 reports citing these effects. The ISMP noted that the high number of varenicline-related injury reports may be related to the publicity surrounding the medication's potential side effects. 13
Varenicline was discovered at Pfizer through the research aimed at modifying the structure of cytisine,14 a European smoking cessation aid and also a partial α4β2-nicotinic antagonist.1516
Varenicline received a "priority review" by the U.S. Food and Drug Administration in February 2006, shortening the usual 10-month review period to 6 months because of its demonstrated effectiveness in clinical trials and perceived lack of safety issues.17 The agency's approval of the drug came on May 11, 2006.2 Beginning August 1, 2006, varenicline has been available for sale in the United States, and on September 29, 2006, it was approved for sale in the European Union.
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Wikinews has related news: New drug for smoking cessation is under investigation |
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