Introduction
Varenicline is a prescription medication used to treat smoking addiction. This medication is the first approved nicotinic receptor partial agonist. Specifically, varenicline is a partial agonist of the alpha4/beta2 subtype of the nicotinic acetylcholine receptor. In addition it acts on alpha3/beta4 and weakly on alpha3beta2 and alpha6-containing receptors. A full agonism was displayed on alpha7-receptors.
On March 9, 2015, the U.S. Food and Drug Administration warned that Varenicline, in the form of Pfizer Inc's quit-smoking drug, Chantix, has been associated with seizures and that some patients who drink while taking the drug may become aggressive or black out. Pfizer is conducting an additional safety study of the drug, results of which are expected in late 2015. The FDA said it is keeping the black box in place at least until the results of the trial are announced.
Uses
Varenicline is a partial agonist at nicotinic acetylcholine receptors used as an aid in smoking cessation.
For use as an aid in smoking cessation.
Associated Conditions
Pharmacodynamics
Varenicline is a partial nicotinic acetylcholine receptor agonist, designed to partially activate this system while displacing nicotine at its sites of action in the brain.
Mechanism of Action
Varenicline is an alpha-4 beta-2 neuronal nicotinic acetylcholine receptor partial agonist. The drug shows high selectivity for this receptor subclass, relative to other nicotinic receptors (>500-fold alpha-3 beta-4, >3500-fold alpha-7, >20,000-fold alpha-1 beta gamma delta) or non-nicotinic receptors and transporters (>2000-fold). The drug competitively inhibits the ability of nicotine to bind to and activate the alpha-4 beta-2 receptor. The drug exerts mild agonistic activity at this site, though at a level much lower than nicotine; it is presumed that this activation eases withdrawal symptoms.
Protein Binding
Less than 20%.
Route of Elimination
Varenicline undergoes minimal metabolism, with 92% excreted unchanged in the urine. Renal elimination of varenicline is primarily through glomerular filtration along with active tubular secretion possibly via the organic cation transporter, OCT2.
Half Life
The elimination half-life of varenicline is approximately 24 hours
Food Interactions
- Avoid excessive or chronic alcohol consumption. Varenicline may increase the effects of alcohol; therefore, reduce consumption of alcohol when starting varenicline.
Dosage
The patient should set a date to stop smoking. Begin Varenicline dosing one week before this date. Alternatively, the patient can begin Varenicline dosing and then quit smoking between days 8 and 35 of treatment.
The recommended dose of Varenicline is 1 mg twice daily following a 1-week titration as follows:
- Days 1-3: 0.5 mg once daily
- Days 4-7: 0.5 mg twice daily
- Day 8-end of treatment: 1 mg twice daily
For patients who are sure that they are not able or willing to quit abruptly, consider a gradual approach to quitting smoking with Varenicline. Patients should begin Varenicline dosing and reduce smoking by 50% from baseline within the first four weeks, by an additional 50% in the next four weeks, and continue reducing with the goal of reaching complete abstinence by 12 weeks. Continue Varenicline treatment for an additional 12 weeks, for a total of 24 weeks of treatment. Encourage patients to attempt quitting sooner if they feel ready
Patients who are motivated to quit, and who did not succeed in stopping smoking during prior Varenicline therapy for reasons other than intolerability due to adverse events or who relapsed after treatment, should be encouraged to make another attempt with Varenicline once factors contributing to the failed attempt have been identified and addressed.
Consider a temporary or permanent dose reduction in patients who cannot tolerate the adverse effects of Varenicline.