Varenicline Chantix in Smoking Cessation

1. Varenicline (Chantix) in Smoking Cessation Kendra Bailey Advisor: Dr. Gurwell

2. Importance to Practice 1.3 billion smokers world wide 20.9% in the United States Obvious Health Risks Leading cause of preventable death Cardiovascular Disease 70% higher chance of dying from coronary artery disease Lung Disease Very difficult to quit Up to 60% relapse within first year Due to addictive nature of nicotine It is estimated that by 2015, 10% of deaths will be due to smoking. You can also increase your lifespan by 7-8 years by quitting. Nicotine has an affinity for many subtypes of neuronal nicotinic acetylcholine receptors located in the brain where is exhibits agonist effects and once these receptors are activated, dopamine is rapidly released and this elicits a pleasurable effect on the smoker which reinforces the addictive behavior (Rollema, 2007). This is the same modality used in other forms of substance abuse (Rollema, 2007) When the smoker attempts to quit, they experience withdrawal symptoms such as irritability, nausea, and headache, as well as the absence of the internal pleasure they received from smoking (Rollema, 2007). It is estimated that by 2015, 10% of deaths will be due to smoking. You can also increase your lifespan by 7-8 years by quitting. Nicotine has an affinity for many subtypes of neuronal nicotinic acetylcholine receptors located in the brain where is exhibits agonist effects and once these receptors are activated, dopamine is rapidly released and this elicits a pleasurable effect on the smoker which reinforces the addictive behavior (Rollema, 2007). This is the same modality used in other forms of substance abuse (Rollema, 2007) When the smoker attempts to quit, they experience withdrawal symptoms such as irritability, nausea, and headache, as well as the absence of the internal pleasure they received from smoking (Rollema, 2007).

3. Nicotine Replacement Therapy Nicotine Patches-FDA approved in 1991 Maintain nicotine levels lower than that achieved by smoking Quit rates 2.8 times higher than placebo Risk of nicotine toxicity if patient smokes while wearing the patch Nicotine Gum-FDA approved in 1984 Nicotine levels lower than with cigarettes and patches Poor compliance Patients need to be instructed on the proper way to chew the gum to avoid jaw soreness and GI effects caused by chewing too fast. Patients also don’t like that they have to avoid carbonated beverages for 15 minutes after chewing.Patients need to be instructed on the proper way to chew the gum to avoid jaw soreness and GI effects caused by chewing too fast. Patients also don’t like that they have to avoid carbonated beverages for 15 minutes after chewing.

4. Non-Nicotine Replacement Bupropion Atypical anti-depressant that agonizes dopamine and adrenergic receptors and antagonizes nicotine receptors Effective in those patients who are resistant to NRT and preferred in patients with some mental disorders Compared to placebo (quit rate 19.05%), quit rates were: 100 mg: 28.5% 150 mg: 28.6% 300 mg : 44.2% Total treatment time is 7-12 weeks, but can be extended up to one year Bupropion was discovered by coincidence when providers noticed that their smoking patients that they were treating for depression had decreased rates of smoking. Bupropion was shown to be more effective if it was paired w/ a NRT such as a patch. However, this can cause compliance issues in patients and could also cause a financial burden.Bupropion was discovered by coincidence when providers noticed that their smoking patients that they were treating for depression had decreased rates of smoking. Bupropion was shown to be more effective if it was paired w/ a NRT such as a patch. However, this can cause compliance issues in patients and could also cause a financial burden.

5. Varenicline Non-nicotine replacement therapy Received FDA approval in 2006 Discovered while attempting to develop a transdermal patch for Alzheimer's Disease Was shown to have smoking cessation properties, but was dismissed until Pfizer picked up on the research

6. Pharmacology of Varenicline MOA: partial nicotinic acetylcholine receptor agonist, binding specifically to the alpha 1 beta 2 receptor Stimulates dopamine release-pleasurable effects of nicotine, decrease in withdrawal Declined sense of satisfaction with smoking Oral administration, essentially total bioavailabilty Half life of 17-30 hours Only approximately 10% is metabolized by the liver.Only approximately 10% is metabolized by the liver.

7. Dosing Days 1-3: 0.5 mg once daily Days 4-7: 0.5 mg twice daily Week 2-12: 1 mg twice daily Patient can receive an additional 12 weeks of treatment if smoking cessation not obtained or danger of relapse Determined using Phase III trials Studies show that as dosage increased, quit rates increased 37.3% quit rate with 1 mg once daily, and 48.0% quit rate with 1 mg twice daily compared to placebo’s 17.1% If a patient relapses, studies show that it is best to talk to the patient and try to find a trigger for the relapse and address it to try to find a better coping mechanism or a way to avoid the trigger. Studies have shown that patients on varenicline have a later relapse date than those on placebo with days 198 for varenicline and 87 w/ placebo.If a patient relapses, studies show that it is best to talk to the patient and try to find a trigger for the relapse and address it to try to find a better coping mechanism or a way to avoid the trigger. Studies have shown that patients on varenicline have a later relapse date than those on placebo with days 198 for varenicline and 87 w/ placebo.

8. Tolerability Side effects very mild and include nausea, headache, vivid dreams, and weight gain Average weight gain 2.37-2.89 kg in 12 weeks Rare psychiatric side effects including mood swings, agitation, and aggression have been reported Varenicline not advised in patients with bipolar disorder or schizophrenia Use with caution in patients w/ renal impairment Cimetidine can cause increase in systemic exposure Does not effect digoxin, metformin, or warfarin. There was a case w/ a previously well controlled bipolar patient was given varenicline to replace their NRT and they experienced a manic episode one week later and the episode attributed to the dopamine release caused by the varenicline. In another incident, a well managed schizophrenic experienced psychosis after started varenicline and this was believed to be due to an increase in dopamine and norepinephrine caused by the drug. In these cases, a NRT or bupropion are more appropriate means of treatment. In the renally impared, serum concentrations can have a 2.7 fold increase. Patients that are diabetic and in HF would greatly benefit from this drug b/c they definitely do not need to smoke and this will not interfere w/ some common medications.There was a case w/ a previously well controlled bipolar patient was given varenicline to replace their NRT and they experienced a manic episode one week later and the episode attributed to the dopamine release caused by the varenicline. In another incident, a well managed schizophrenic experienced psychosis after started varenicline and this was believed to be due to an increase in dopamine and norepinephrine caused by the drug. In these cases, a NRT or bupropion are more appropriate means of treatment. In the renally impared, serum concentrations can have a 2.7 fold increase. Patients that are diabetic and in HF would greatly benefit from this drug b/c they definitely do not need to smoke and this will not interfere w/ some common medications.

9. Varenicline vs. other treatment options Varenicline vs. SR bupropion Quit rates at weeks 9-12 were 44.0% for varenicline, 29.5% bupropion, and 16.6% placebo Quit rates at weeks 24 and 52 continued to show varenicline more effective Varenicline vs bupropion, bupropion vs NRT Bupropion was found to be more effective than NRT at the 3 month and 1 year mark. Varenicline was found to be more effective than bupropion at the 3 month and 1 year mark. There haven’t been many direct studies comparing varenicline to other smoking cessation medications. This study consisted of patients w/ a mean age of 42-44.6 and they had smoked for 24.1-27.1 years. 80% had prior quit attempts. Another study using a similar patient population and methodology showed results w/ practically identical quit rates. Since bupropion was show more effective than NRT, and varenicline more effective than bupropion, it can be reasonably assumed that varenicline is more effective than NRTThere haven’t been many direct studies comparing varenicline to other smoking cessation medications. This study consisted of patients w/ a mean age of 42-44.6 and they had smoked for 24.1-27.1 years. 80% had prior quit attempts. Another study using a similar patient population and methodology showed results w/ practically identical quit rates. Since bupropion was show more effective than NRT, and varenicline more effective than bupropion, it can be reasonably assumed that varenicline is more effective than NRT

10. Limitations to Usage Cost!! On average $268.80 for 84 days of treatment With counseling and other maintenance, $638.80 Bupropion $227 for 60 tablets Although high initial cost, studies have shown varenicline to be more cost effective Cost benefit analysis show that varenicline gave employers $540.60 in savings compared to $269.80 by bupropion For bupropion to be more cost effective, cost for varenicline would have to exceed $616 and quit rates would have to be less than the reported 16.9% There isn’t a lot of insurance coverage for varenicline, leaving the patient to pay out of pocket for treatment. Studies are showing that there is an increasing rate of coverage for pharmacotherapy for smoking cessation, so maybe someday varenicline will be included in the coverage.There isn’t a lot of insurance coverage for varenicline, leaving the patient to pay out of pocket for treatment. Studies are showing that there is an increasing rate of coverage for pharmacotherapy for smoking cessation, so maybe someday varenicline will be included in the coverage.

11. Conclusions Would I use varenicline in my practice? Yes….when appropriate There needs to be more research! Direct studies vs. other treatments Remember: The patient needs to be willing to quit, otherwise the best drug in the world won’t work! I would use varenicline in patients that can afford it and do not have any pre-existing mental conditions such as bipolar disorder or schizophrenia. There aren’t a lot of direct studies that show varenicline’s success rates compared to other drugs. This, along w/ more cost benefit analyses, could result in more insurance coverage for varenicline. I would use varenicline in patients that can afford it and do not have any pre-existing mental conditions such as bipolar disorder or schizophrenia. There aren’t a lot of direct studies that show varenicline’s success rates compared to other drugs. This, along w/ more cost benefit analyses, could result in more insurance coverage for varenicline.

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