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Varenicline (Champix, Chantix)
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 quitting smoking.
3D Structure of Varenicline
Chemical Structure
of Varenicline
Indications
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.
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 (92-93%). A small proportion is glucuronidated, oxidated, N-formylated or conjugated to a hexose.[4] The
elimination half-life is about 24 hours.
Side Effects
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 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 behaviour, erratic behaviour, 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 the highly-publicized case of Carter Albrecht who was shot to death by his neighbour
after, in the apparent state of delirium, hitting his girlfriend and trying to force the entry in the neighbour’s house.[6]
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
behavioural and mood changes.[7] March 13, 2008 an article was published in Diabetes Medicine about an insulin-dependent diabetic
who had multiple episodes of hypoglycaemia which she had not had before taking varenicline and which stopped when varenicline
was stopped. [8]
History
Varenicline was discovered
at Pfizer through the research aimed at modifying the structure of cytisine,[9] a European smoking cessation aid and also
a partial α4β2-nicotinic antagonist.[10][11]
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.[12] 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.
References
1. 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.
2. a b
U.S. Food and Drug Administration. FDA
Approves Novel Medication for Smoking Cessation.
Press release,
11 May 2006.
3. Mihalak
KB, Carroll FI, Luetje CW (2006). "Varenicline is a partial agonist at alpha4beta2 and a full
agonist
at alpha7 neuronal nicotinic receptors". Mol. Pharmacol.
70 (3): 801–5. doi:10.1124/mol.106.025130.
PMID 16766716.
4. 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.
5. American
Cancer Society. Cancer Drug Guide: Varenicline. Retrieved on 2008-01-19.
6. ABC
News: Did Quit-Smoking Pill Lead to Man's Death?. Retrieved on 2007-12-15.
7. 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.
8. {{|Title=
Varenicline may trigger severe hypoglycaemia in Type 1 diabetes.|Author= Kristensen
PL,
Pedersen-Bjergaard
U, Thorsteinsson B.}}
9. Coe
JW, Brooks PR, Vetelino MG, et al (2005). "Varenicline: an alpha4beta2 nicotinic receptor partial
agonist
for smoking cessation". J. Med. Chem. 48 (10): 3474–7.
doi:10.1021/jm050069n. PMID 15887955.
10. Schwartz JL (1979). "Review and evaluation of methods of smoking
cessation, 1969-77. Summary of a
monograph".
Public Health Rep 94 (6): 558–63. PMID 515342. Full text at PMC: 1431736
11. Etter
JF (2006). "Cytisine for smoking cessation: a literature review and a meta-analysis". Arch. Intern.
Med. 166
(15): 1553–9. doi:10.1001/archinte.166.15.1553. PMID 16908787.
12. Kuehn
BM (2006). "FDA speeds smoking cessation drug review". JAMA 295 (6): 614.
doi:10.1001/jama.295.6.614.
PMID 16467225.
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