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Varenicline
From Wikipedia, the free encyclopedia
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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 | search in , |
| Pharmacokinetic data | |
| Bioavailability | ? |
| Protein binding | <20% |
| Metabolism | Limited (<10%) |
| Half life | 24 hours |
| Excretion | Renal (81–92%) |
| Therapeutic considerations | |
| Licence data |
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| Pregnancy cat. |
C(US) |
| Legal status |
℞ Prescription only |
| Routes | Oral |
Varenicline (trade name Chantix in the USA and Champix in Europe, Mexico and Canada, 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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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.
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 (81%). A small proportion is glucuronidated, oxidated, N-formylated or conjugated to a hexose.[4]
Side-effects, none common, include:[2]
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]
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]
- ^ Jorenby D E, Hays J T, Rigotti N A, Azoulay S, Watsky E J, Williams K E, Billing C B, Gong J, Reeves K R (2006). "Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial". JAMA 296 (1): 56–63. PMID 16820547.
- ^ a b c U.S. Food and Drug Administration. FDA Approves Novel Medication for Smoking Cessation. Press release, 11 May 2006.
- ^ Mihalak KB, Carroll FI, Luetje CW. Varenicline is a partial agonist at α4β2 and a full agonist at α7 neuronal nicotinic receptors. Mol Pharmacol 2006;70(3):801-5. PMID 16766716.
- ^ Obach RS, Reed-Hagen AE, Krueger SS, Obach BJ, O'Connell TN, Zandi KS, Miller S, Coe JW. Metabolism and disposition of varenicline, a selective alpha4beta2 acetylcholine receptor partial agonist, in vivo and in vitro. Drug Metab Dispos 2006;34:121-30. PMID 16221753.
- ^ ABC News: Did Quit-Smoking Pill Lead to Man's Death?. Retrieved on 2007-12-15.
- ^ Early Communication About an Ongoing Safety Review: Varenicline (marketed as Chantix). United States Food and Drug Administration (November 20 2007). Retrieved on 2007-11-21.
- ^ Coe JW, Brooks PR, Vetelino MG, Wirtz MC, Arnold EP, Huang J, Sands SB, Davis TI, Lebel LA, Fox CB, Shrikhande A, Heym JH, Schaeffer E, Rollema H, Lu Y, Mansbach RS, Chambers LK, Rovetti CC, Schulz DW, Tingley FD 3rd, O'Neill BT. Varenicline: an alpha4beta2 nicotinic receptor partial agonist for smoking cessation. J Med Chem 2005;48:3474-7. PMID 15887955.
- ^ Kuehn BM. FDA speeds smoking cessation drug review. JAMA 2006;295:614. PMID 16467225.
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|---|---|
| Nicotine dependence | Nicotine - Bupropion - Varenicline - Mecamylamine |
| Alcohol dependence | Disulfiram - Calcium carbimide - Acamprosate - Naltrexone - Nalmefene - Topiramate |
| Opioid dependence | Buprenorphine - Methadone - Levacetylmethadol - Heroin - Fentanyl - Dihydrocodeine - Dihydroetorphine - Clonidine - Lofexidine - Naltrexone - Ibogaine - 18-Methoxycoronaridine |
| Stimulant dependence | Dexamphetamine - Bupropion - Vanoxerine - Nocaine |