The correct answer is: C. Bupropion SR 150 mg - 1 tablet PO daily x 3 days, then 150 mg PO BID.

Bupropion is FDA approved for smoking cessation and is recommended as a second line agent by the ACC 2018 Expert Consensus Decision Pathway on Tobacco Cessation Treatment for patients with CVD. The guidelines recommend varenicline or combinations of nicotine replacement therapy as first line treatment options. However, this patient was not able to tolerate varenicline, so varenicline is not an option.¹ Additionally, the patient requested a daily pill that he can take with his other maintenance medications, so the combination nicotine replacement therapy (NRT) or a single NRT product should not be recommended. Some patients find daily administration of an oral dosage form much easier than having to chew gum every hour or remembering to put on a patch every morning. Furthermore, bupropion appears to be safe and effective in smokers with CVD history. The Study To Evaluate Cardiac Assessments Following Different Treatments Of Smoking Cessation Medications In Subjects With And Without Psychiatric Disorders (CATS) found no increased risk of hypertension or CV events in smokers treated with bupropion compared with NRT or placebo.¹ For smoking cessation, bupropion is started at 150 mg once daily for 3 days then increased to 150 mg twice daily based on response and tolerability.

One of bupropion's potential side effect includes altered appetite and weight, which is relevant to our patient who has a BMI of 31 kg/m². According to Wellbutrin's (bupropion) package insert, weight loss of greater than 5 lbs occurred in 28% of subjects.⁵ However, it is important to note that most of the initial studies of bupropion excluded smokers. Zyban (bupropion) studies which included smokers observed an increase in weight when individuals were treated with bupropion.⁶ Arterburn et al. found that non-smokers who were initiated on bupropion lost an average of 7.1 lbs. compared to fluoxetine users who were non-smokers (95% CI: -11.3, -2.8; p-value <0.01). Correspondingly, smokers who were started on bupropion treatment gained on average an estimated 2.2 lbs compared to fluoxetine users who were non-smokers (95% CI: -2.3, 6.8; p-value = 0.33).⁶ Even though this difference was not statistically significant it's important to note that weight changes may be highly dependent on the individual patient's baseline BMI. Additional side effects associated with bupropion include insomnia, headache, agitation, dizziness, diaphoresis, constipation, dry mouth and nausea/vomiting. Monitoring parameters include change in BMI, mental status for depression, suicidal ideation, anxiety, blood pressure, and renal and hepatic function.⁵

Option A is not correct. Varenicline therapy should be given for a total of 12 weeks, but KP was only able to tolerate three weeks of therapy. Although the ACC 2018 Expert Consensus Decision Pathway on Tobacco Cessation Treatment recommends varenicline as a first line treatment option for patients with stable CVD, the patient's concerns of recurrent and distressing dreams should not be ignored.1 The varenicline package insert states, "consider a temporary or permanent dose reduction in patents who cannot tolerate the adverse effects of Chantix (varenicline)."² It was evident that KP did not achieve the pharmacological benefit of varenicline at the specific duration, since he restarted his cigarettes after three weeks of varenicline therapy. Additionally, it appears that KP started having weird dreams within a couple of days after starting therapy, so a temporary dose reduction would not be advantageous. Abnormal dreams (e.g., vivid, unusual) were commonly reported (12.4%) at a greater frequency than placebo (4.5%) in a pooled analysis of clinical trials of varenicline. Sleep disorders, excluding insomnia and somnolence, were also commonly (4.8%) reported compared with a placebo rate of 2.8%.³ According to the varenicline package insert, "cases of somnambulism (i.e., sleepwalking) have [also] been reported which included harmful behavior to self, others or property. Instruct patients to not restart Chantix and notify their healthcare provider if they experience somnambulism."²

Option B is not correct. Nortriptyline is a third line agent for tobacco use disorder in patients with stable CVD according to the ACC 2018 Expert Consensus Decision Pathway on Tobacco Cessation Treatment Guidelines.¹ There is limited data on its use in patients with CVD. For eligible patients, nortriptyline is started at 25 mg once daily, 10 to 28 days prior to the selected quit date and should be titrated to 75 to 100 mg/day for 12 weeks or longer. This pharmacological option may be considered if the patient does not tolerate first and second line therapy. Potential side effects associated with nortriptyline therapy includes anxiety, nausea, vomiting, heart palpitations, hypertension, hyponatremia, dry mouth, blurred vision and constipation. Monitoring parameters include serum sodium with high-risk populations, blood pressure, heart rate, and suicidal ideations.⁴

Option D is not correct. Even though NRT combination is a first line treatment recommendation and single NRT is a second line treatment recommendation by the ACC 2018 Expert Consensus Decision Pathway on Tobacco Cessation Treatment Guidelines, this patient made it very clear that he wants to be on an oral tablet that he can take with his other maintenance medications. Nicotine gum is started at the 4 mg dose if the patient smokes within 30 minutes of waking or the 2 mg dose if the patient smokes more than 30 minutes after waking. Patients should be instructed to chew the nicotine gum until their mouth tingles and then "park" the gum inside the cheek until the tingling fades. Patients should repeat this "chew and park" method until about 30 minutes of use and then discard. It is recommended to use 1 piece per hour with a max dose of 24 pieces per day. Common side effects include mouth irritation, jaw soreness, heartburn, hiccups and nausea. It is important to educate patients that this product is not chewed in the same way as regular gum and requires careful instruction. It may also damage dental work and should not be administered within 15 minutes of food or drink.

References

1. Barua RS, Rigotti NA, Benowitz NL, et al. 2018 ACC expert consensus decision pathway on tobacco cessation treatment: a report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol 2018;72:3332-65.
2. Varenicline [package insert]. New York: Pfizer; 2016.
3. Savage RL, Zekarias A, Caduff-Janosa P. Varenicline and abnormal sleep related events. Sleep 2015;38:833-7.
4. Nortriptyline [package insert]. Missouri: Mallinckrodt Inc; 2007.
5. Bupropion [package insert]. North Carolina; GlaxoSmithKline; 2017.
6. Zyban [package insert]. North Carolina; GlaxoSmithKline; 2017.
7. Arterburn D, Sofer T, Boudreau DM, et al. Long-term weight change after initiating second-generation antidepressants. J Clin Med 2016;5.