Varenicline

Varenicline (trade name Chantix in the USA and Champix in Europe, Mexico, Canada and Australia, manufactured by Pfizer, usually in the form of varenicline tartrate) is a prescription medication used to treat smoking addiction. This medication is the first approved nicotinic receptor partial agonist. In this respect, it is pharmacokinetically different from other smoking cessation aids, such as the nicotinic antagonist, bupropion (trade name Zyban), 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 quitting smoking. In May 2006, it was approved for sale in the United States. On August 1, 2006, Pfizer announced that Chantix was 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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Use and dosing

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]

Varenicline is sold as 0.5 mg and 1 mg tablets. Titrating the dose from 0.5 mg every day for 3 days to 0.5 mg twice daily for 4 days to 1 mg twice daily is recommended. In the United States the standard maintenance dose is 1 mg twice daily, with variations as permitted by the Food and Drug Administration. 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 yet, 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.

Mechanism of action

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]

Pharmacokinetics

Most of the active compound is excreted renally (81%). A small proportion is glucuronidated, oxidated, N-formylated or conjugated to a hexose.^[4]

Side-effects

Side-effects, none common, include:^[2]

• Nausea
• Headache
• Vomiting
• Flatulence
• Insomnia
• Abnormal dreams
• Dysgeusia (alteration in taste)

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. It is unknown whether the psychiatric symptoms are related to the drug or to nicotine withdrawal symptoms, although not all patients had stopped smoking. FDA is aware of a highly-publicized case of Carter Albrecht who was shot to death by his neighbor after, in the apparent state of delirium, hitting his girlfriend and trying to force the entry in the neighbor's house.^[5] Although in this case the delirium appeared to be caused by taking varenicline with a high dose of alcohol, FDA asked Pfizer for additional cases that might be similar. The FDA also recommended that health care professionals and patients watch for behavioral and mood changes.^[6]

History

Varenicline was selected by Pfizer from a large number of compounds evaluated that showed affinity to the α ₄β₂ nicotinic receptor.^[7] It derives chemically from cytisine.

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.^[8] The agency's approval of the drug came on May 11, 2006.^[2]