CLINICAL GUIDE TO SMOKING CESSATION: CHOOSING THE RIGHT TREATMENT PATH

Faculty:

L. Austin Fredrickson, MD, FACP 

L. Austin Fredrickson is an Associate Professor of Internal Medicine at Northeast Ohio Medical University, where he serves as core faculty and teaches diagnostics, therapeutics, clinical skills, and health humanities. He is board-certified in general internal medicine and practices rural primary care. 

Liz Fredrickson, PharmD, BCPS

Liz Fredrickson, PharmD, BCPS, is an Associate Professor of Pharmacy Practice and Pharmaceutical Sciences at the Northeast Ohio Medical University (NEOMED) College of Pharmacy, where she is course director of the Parenteral Products and Basic Pharmaceutics Lab courses.

Kristina (Tia) Neu, RN

Kristina (Tia) Neu is a licensed Registered Nurse and author currently developing in-service training for healthcare professionals. She is a National Board-Certified Health & Wellness and Lifestyle Medicine Coach. Her work experience includes work in several areas of the healthcare profession, including psychiatric nursing, medical nursing, motivational health coaching, chronic case management, dental hygiene, cardiac technician, surgical technician, and clinical director of a Clinically Integrated Network (CIN).

Pamela Sardo, PharmD, BS

Pamela Sardo, PharmD, BS, is a freelance medical writer and licensed pharmacist. She is the founder and principal at Sardo Solutions in Texas. Pam received her BS from the University of Connecticut and her PharmD from the University of Rhode Island. Pam’s career spans many years in retail, clinics, hospitals, long-term care, Veterans Affairs, and managed health care responsibilities across a broad range of therapeutic classes and disease states.

Abstract

Tobacco use is the most common cause of preventable death in the United States. Smoking-related diseases include cardiovascular disease, chronic obstructive pulmonary disease (COPD), cancer, and poor reproductive health outcomes. Smoking cessation is essential for overall public health and quality of life. Withdrawal symptoms from smoking cessation make quitting smoking difficult for many patients. Several over-the-counter (OTC) and prescription products are available to help patients quit smoking, each with potential advantages and disadvantages.

Accreditation Statements

In support of improving patient care, RxCe.com LLC is jointly accredited by the Accreditation CouncilTM for Continuing Medical Education (ACCME®), the Accreditation Council for Pharmacy Education (ACPE®), and the American Nurses Credentialing Center (ANCC®), to provide continuing education for the healthcare team.

This activity was planned by and for the healthcare team, and learners will receive __ Interprofessional Continuing Education (IPCE) credits for learning and change.

Joint Universal Activity Number: The Joint Accreditation Universal Activity Numbers assigned to this activity are as follows:

Pharmacists: JA4008424-0000-26-058-H01-P

Pharmacy Technicians: JA4008424-0000-26-058-H01-T

Credits: 2 contact hour(s) (0.2 CEU(s)) of continuing education credit.

Credit Types:

IPCE Credits - 2 Credits

AAPA Category 1 Credit™️ - 2 Credits

AMA PRA Category 1 Credit™️ - 2 Credits

Pharmacy - 2 Credits

Type of Activity: Application

Media: Computer-Based Training (i.e., online courses)

Estimated time to complete activity: 2 contact hour(s) (0.2 CEU(s)), including Course Test and course evaluation.

Release Date: April 29, 2026 Expiration Date: April 29, 2029

Target Audience: This educational activity is for Physicians, Physician Assistants, Pharmacists, and Pharmacy Technicians

How to Earn Credit: From April 29, 2026, through April 29, 2029, participants must:

Read the “learning objectives” and “author and planning team disclosures;”

Take the “Educational Activity Pre-Test;”

Study the section entitled “Educational Activity;” and

Complete the Educational Activity Post-Test and Activity Evaluation. The Educational Activity Post-Test will be graded automatically. Following successful completion of the Educational Activity Post-Test with a score of 70% or higher, a statement of participation will be made available immediately. (No partial credit will be given.)

CME Credit: Credit for this course will be uploaded to CPE Monitor® for pharmacists. Physicians may receive AMA PRA Category 1 Credit™️ and use these credits toward Maintenance of Certification (MOC) requirements. Physician Assistants may earn AAPA Category 1 CME credit, reportable through PA Portfolio. All learners shall verify their individual licensing board’s specific requirements and eligibility criteria.

Statement of Need

Despite the availability of effective pharmacologic and behavioral interventions, smoking cessation rates remain suboptimal. Many healthcare professionals lack confidence in selecting and optimizing pharmacotherapy based on patient-specific factors. This activity is designed to improve clinicians' knowledge of smoking cessation therapies and enhance their ability to implement individualized, evidence-based treatment strategies.

Learning Objectives for Physicians and Physician Assistants: Upon completion of this educational activity, participants should be able to:

Describe the health risks of tobacco use and the clinical features of nicotine withdrawal

Differentiate smoking cessation pharmacotherapy options based on mechanism of action, dosing, and safety considerations

Recognize patient-specific factors and common barriers that impact smoking cessation success

Learning Objectives for Pharmacists: Upon completion of this educational activity, participants should be able to:

Identify the harms and effects of smoking and the signs of nicotine withdrawal

Compare the advantages of different over-the-counter nicotine replacement therapy options

Discuss the different mechanisms of action of prescription smoking cessation options

Identify barriers a patient may face with smoking cessation

Learning Objectives for Pharmacy Technicians: Upon completion of this educational activity, participants should be able to:

Identify available smoking cessation products, including over-the-counter and prescription options

Recognize common nicotine withdrawal symptoms and barriers to quitting

Assist patients by facilitating access to smoking cessation products and reinforcing basic use instructions under pharmacist supervision

Disclosures

The following individuals were involved in planning, developing, and/or authoring this activity: L. Austin Fredrickson, MD, FACP; Liz Fredrickson, PharmD, BCPS; Kristina (Tia) Neu, RN; and Pamela Sardo, PharmD, BS. None of the individuals involved in developing this activity has a conflict of interest or financial relationships related to the subject matter. There are no financial relationships or commercial or financial support relevant to this activity to report or disclose by RxCe.com or any of the individuals involved in the development of this activity. 

© RxCe.com LLC 2026: All rights reserved. No reproduction of all or part of any content herein is allowed without the prior, written permission of RxCe.com LLC.

Educational Activity Pre-Test

Which of the following is a common symptom of nicotine withdrawal?

Bradycardia

Decreased appetite

Irritability and cravings

Euphoria

Which of the following is a common barrier to successful smoking cessation?

Increased HDL cholesterol

Social and environmental triggers

Improved lung function

Decreased nicotine dependence

Which of the following nicotine replacement therapies provides a steady level of nicotine throughout the day?

Nicotine gum

Nicotine lozenge

Nicotine nasal spray

Nicotine transdermal patch

Educational Activity

Clinical Guide to Smoking Cessation: Choosing the Right Treatment Path

Introduction

Tobacco use remains the leading cause of preventable disease, disability, and death in the United States (US). For most patients, the path to smoking cessation is rarely a matter of willpower alone. While the clinical benefits of quitting are indisputable, the pathophysiology of nicotine dependence creates significant obstacles, and the resulting physical withdrawal and psychological triggers often undermine even the most motivated patients.

Research has consistently demonstrated that the gold standard for success is a multimodal approach integrating evidence-based pharmacotherapy with personalized behavioral support. As members of the interprofessional healthcare team, physicians, physician assistants, pharmacists, and pharmacy technicians are uniquely positioned to help bridge the gap between a patient's desire to quit and their long-term success. This continuing education activity explores the clinical efficacy of cessation agents and provides a framework for developing individualized, comprehensive protocols that address both the many facets of tobacco addiction.

Epidemiology and Public Health Impact

In the U.S., tobacco use is the number one cause of preventable disease, disability, and death.1 According to the Centers for Disease Control and Prevention (CDC), 12.5% of U.S. adults (approximately 30.8 million people) smoked cigarettes.2 Because of the prevalence of smoking, more than 16 million Americans live with a disease caused by smoking.3

Tobacco product use begins and is established primarily during adolescence.4 The CDC reported the following:4

In 2024, 1 of every 91 middle school students (1.1%) reported that they had smoked cigarettes in the past 30 days.

In 2024, nearly 1 of every 59 high school students (1.7%) reported that they had smoked cigarettes in the past 30 days.

In 2024, 1 in 29 middle school students (3.5%) reported using electronic cigarettes in the past 30 days.

In 2024, 1 in 13 high school students (7.8%) reported using electronic cigarettes in the past 30 days.

Each year, approximately 480,000 Americans will die prematurely due to smoking or exposure to secondhand smoke.5 The use of conventional cigarette smoking among youth and young adults has decreased over the past several decades; however, this population has dramatically increased e-cigarette use.6 Today, e-cigarettes are the most commonly used tobacco product among U.S. youth.6

In the 2020 Report of the Surgeon General on Smoking Cessation, more than two-thirds of smokers say they want to quit.1 Thousands of smokers try to quit each day, but due to the highly addictive nicotine component in cigarettes, it takes multiple attempts for most smokers to quit for good. The 2020 Report identified the cost associated with tobacco use: healthcare spending attributed to smoking exceeds $170 billion each year.1 There is also some positive news since the prevalence of current smoking declined from 52% in 1965 to 15.8% in 2017, with the decline being attributed to campaigns to keep people from starting the habit, promoting smoke-free environments, and progress made in pharmacological and behavioral smoking cessation treatments.1

Harm Caused by Smoking

Smoking significantly increases the risk of cardiovascular morbidity and mortality.7 Smoking can increase the risk of disease and death from cardiovascular disease. Smoking can also increase markers of inflammation and hypercoagulability and decrease high-density lipoprotein cholesterol levels. Smokers may see an increase in atherosclerosis as well as an increased risk of death from stroke.7 Types of cancers that can be increased due to smoking are acute myeloid leukemia (AML), bladder, lung, cervix, colon, rectum, esophagus, kidney, liver, mouth, throat, pancreas, stomach, and larynx (voice box).8 Quitting smoking is beneficial at any age, with better health benefits the earlier a person quits. Quitting smoking can also help protect family members, coworkers, friends, and others from the negative effects of secondhand smoke.1,9

Concerns for babies born to smoking mothers include the risk of small-for-gestational-age babies, delivering a low-birth-weight baby, decreased fetal growth, and the risk of preterm delivery.1 Fetal exposure to nicotine can result in sudden infant death syndrome, altered corpus callosum, auditory processing deficits, deficits in attention and cognition, effects on behaviors, and obesity.10,11

Drug Interactions Caused by Smoking

Tobacco smoke produces lung carcinogens, including polycyclic aromatic hydrocarbons (PAHs), which are potent inducers of the CYP-450 isoenzymes 1A1, 1A2, and possibly 2E1. Glucuronide conjugation may also be induced by PAHs. Pharmacokinetic drug interactions are caused by the PAHs in tobacco smoke.12 Nicotine exposure in the absence of PAHs caused by smoking, such as from nicotine replacement therapy (NRT), has limited pharmacokinetic drug interaction potential.12,13 Pharmacodynamic drug interactions associated with smoking are largely caused by nicotine activating the sympathetic nervous system, which can counter the actions of certain drugs. Other compounds in tobacco smoke have less significant effects on hepatic enzymes, including acetone, pyridine, heavy metals, benzene, and carbon monoxide. A clinically significant decrease in pharmacologic effect may be seen in drugs that are substrates of CYP1A2, as their metabolism can be induced in smokers. When a person quits smoking, dosages of medications may need to be reduced due to the quick dissipation of CYP1A2 induction. If an individual starts smoking while on medications that are CYP1A2 substrates, doses may need to be increased.12

The induction of CYP1A2 and CYP1A1 by PAHs causes decreased plasma concentrations of caffeine, chlorpromazine, clozapine, estradiol, flecainide, fluvoxamine, haloperidol, melatonin, mexiletine, mirtazapine, olanzapine, propranolol, ropinirole, tacrine, theophylline, and tizanidine.13 Clozapine concentrations have been found to be significantly lower in smokers than in non-smokers.12 Clozapine is an atypical antipsychotic, primarily metabolized by CYP1A2, with a narrow therapeutic window that requires monitoring as it may cause life-threatening neutropenia. Patients who are started on clozapine in an inpatient setting may need dosing adjusted in an outpatient setting if they begin or resume smoking.12 Another antipsychotic that is affected by smoking is olanzapine, which is primarily metabolized by direct N-glucuronidation. Olanzapine plasma concentrations have been found to be lower in smokers than in non-smokers due to increased drug clearance. Chlorpromazine, flecainide, fluvoxamine, and theophylline may also require an increased dosage in smokers, as smoking causes decreased serum concentrations that may affect the therapeutic efficacy. Heparin doses may need to be increased as smokers have an increased clearance of heparin and a decreased half-life, and smoking also has prothrombotic effects.12 Estrogen-containing hormonal contraceptives in combination with smoking increase the risk of adverse cardiovascular effects, including thromboembolism, ischemic stroke, and myocardial infarction. The risk of cardiovascular events combined with oral contraceptives is highest in women over 35 who are heavy smokers; however, the risk is present in all smokers using oral contraceptives. Progestin-only contraceptives are recommended if smoking cessation is not achievable or if other forms of birth control are not an option for the patient. Inhaled corticosteroids may have reduced efficacy in patients with asthma who smoke. Patients taking benzodiazepines who smoke may have decreased sedation and dizziness, possibly due to nicotine stimulating the central nervous system. Beta-blockers may be less effective as antihypertensives and at heart rate control, requiring a higher dose, due to nicotine-mediated sympathetic activation.12

Clinical Pearl: Smoking Drug Interactions

CYP1A2 induction → ↓ drug levels

Stopping smoking → ↑ drug levels (toxicity risk)

Monitor: clozapine, olanzapine, theophylline

Benefits of Quitting Smoking

Quitting smoking can reduce the risk of coronary heart disease, with risk sharply declining in the first 1 to 2 years after cessation. The risk continues to decrease, but more slowly, over the long term after that initial period.1,9 Women should quit smoking prior to trying to conceive; however, quitting at any time during the pregnancy can benefit the mother and baby’s health.10

Nicotine Withdrawal Symptoms

Long-term nicotine use can cause physical dependence that may induce withdrawal symptoms upon cessation. These withdrawal symptoms make it difficult for individuals to abstain from smoking, as they can be unpleasant.1 Symptoms of nicotine withdrawal may be seen within a few hours after the last dose of nicotine and peak on day two or three after going nicotine-free. These symptoms may last for a few days but can persist for several weeks, with severity decreasing after the third day. The most common symptom of nicotine withdrawal is urges or cravings for nicotine. Other common physical symptoms include headaches, nausea, dizziness, constipation, diarrhea, gas, cough, dry mouth, sore throat, nasal drip, chest tightness, and increased appetite/weight gain. Individuals may feel anxious, jumpy, irritable, grouchy, angry, frustrated, sad, or depressed. Some people may also experience trouble concentrating and trouble sleeping.14-17

Individuals may also struggle with the habits formed around tobacco use. For instance, if a person has a cigarette with breakfast each morning, this habit could make quitting more difficult, as they have associated having breakfast with also having a cigarette. If a person has a stressful situation at work and previously smoked each time that happened, they may also be tempted to smoke when put in a similar situation. Environmental cues, such as sights, sounds, or other sensations that an individual has associated with nicotine, can often induce cravings that tempt a person when trying to quit.1

Smoking Cessation Pharmacotherapy

Smoking cessation pharmacotherapy was not introduced until the 1980s. There are currently seven FDA-approved first-line medications for treating nicotine dependence, five being nicotine-based medications and two being non-nicotine oral medications. Less than one-third of smokers trying to quit use approved cessation medications or behavioral counseling to support the quit attempts. Evidence suggests that cessation medications plus behavioral counseling are very effective in combination, but are also effective in increasing smoking cessation individually. The use of smoking cessation medications helps to reduce physical symptoms that result from nicotine withdrawal, allowing smokers to focus on the behavioral and psychological aspects of quitting. Medication can also provide the benefit of reducing or eliminating the immediate reinforcing effects of nicotine by desensitizing the nicotinic receptors.1

Nicotine Replacement Options

Nicotine replacement products make up the majority of FDA-approved smoking cessation options.1 Prescription nicotine smoking cessation products were first introduced in 1984. In 1996, the FDA allowed over-the-counter (OTC) nicotine products for smoking cessation. Nicotine may be used independently to help patients quit smoking, but it is ideally combined with behavioral modification and support.18 Nicotine binds to nicotinic-cholinergic receptors at the autonomic ganglia, in the adrenal medulla, at neuromuscular junctions, and in the brain. It affects the central and peripheral nervous systems. Nicotine produces a stimulating effect mainly in the cortex and a rewarding effect in the limbic system. Low doses of nicotine predominantly give a stimulant effect, and high doses produce a predominant reward effect.19

An advantage to NRT is that the patches, gum, and lozenges are available over the counter. If a patient wants these OTC products covered by insurance, a prescription from a provider may be required; however, some insurers will deny coverage for OTC products even with a prescription. Nicotine nasal spray and oral inhaler both require a prescription. All five NRT options are similar in efficacy and deliver plasma nicotine concentrations that are lower than those of conventional cigarettes. The NRT options deliver the nicotine more slowly and at a lower level than cigarettes, which reduces the behavioral reinforcing effect of smoking.1 During the use of the gum, lozenge, or patches, it is okay if a patient is not fully successful at quitting immediately and smokes a cigarette. In this case, the patient should be encouraged to continue the quit attempt and discard the remaining cigarettes. Patients who use the nasal spray and inhaler should be instructed to stop smoking completely while using the product to avoid the risk of nicotine overdose.20 Using nicotine products can help to preserve lung function in patients who successfully quit smoking.21 Combinations of NRT may include using patches that are slower acting but provide a constant level of nicotine with any of the other forms of NRT, which all act faster and can be used to offset acute cravings. The combination of NRT with bupropion or varenicline can also achieve higher success rates than either option alone.1

Nicotine Gum

Nicotine gum is primarily absorbed in the oral mucosa and initially requires use every 1 to 2 hours to suppress withdrawal symptoms. Available flavors of nicotine gum include original, cinnamon, fruit, and mint. Dosing for nicotine gum typically starts with either 2 mg or 4 mg every 1 to 2 hours, then gradually decreases with the goal of 1 piece every 4 to 8 hours from weeks 10-12. Each piece of gum should be chewed slowly, and the gum should be “parked” between the cheek and tongue when a peppery or tingling sensation appears (with approximately 15 to 30 chews). When the tingling fades, the individual should resume chewing and repeat the chew-and-park method until most of the nicotine is gone (generally about 30 minutes; the tingling does not return when the gum is chewed). The gum should be parked in different areas of the mouth during each interval. Incorrect chewing techniques may cause lightheadedness, nausea/vomiting, and irritation of the throat and mouth. Individuals using nicotine gum may experience mouth/jaw soreness, hiccups, dyspepsia, and hypersalivation. The gum option may serve as an oral substitute for tobacco, may delay weight gain, and can be titrated by the individual to manage withdrawal symptoms. Nicotine gum can be used as needed, in combination with other products, to manage situational urges an individual may experience. Precautions for use with the gum are myocardial infarction within the last 2 weeks, serious underlying arrhythmias, serious or worsening angina pectoris, temporomandibular joint disease, pregnancy and breastfeeding, and adolescents.1 A 2019 review by Lindson, et al. (2019) found that using a 4-mg dose as opposed to a 2-mg dose increases the chances of successfully quitting smoking.22

Nicotine Lozenge

Nicotine lozenges are available OTC in 2 mg and 4 mg doses, in cherry and mint flavors. Dosing is similar to nicotine gum. Nicotine is absorbed through the oral mucosa, with initial dosages every 1 to 2 hours, tapering to completion over 12 weeks. A standard-size lozenge should dissolve in the mouth within 20 to 30 minutes, and a mini lozenge takes approximately 10 minutes. The release of nicotine from the lozenge may cause a warm, tingling sensation. Patients should be counseled not to chew or swallow the lozenge, to occasionally rotate it among different areas of the mouth, and to avoid food or beverages for 15 minutes before or during use of the lozenge. Adverse effects of the lozenge include nausea, hiccups, cough, heartburn, headache, flatulence, and insomnia. Like the gum, the lozenge can serve as an oral substitute for tobacco, may help delay weight gain, can be titrated to manage withdrawal symptoms, and can be used with other agents to manage situational urges. Precautions for the use of lozenges include a myocardial infarction within 2 weeks, serious underlying arrhythmias, serious or worsening angina pectoris, pregnancy and breastfeeding, and adolescents.1

Nicotine Patches

Nicotine patches are available in 7 mg, 14 mg, and 21 mg doses. Patches should be applied in the morning and deliver nicotine slowly and continuously over 16-24 hours. If a person complains of insomnia or bothersome dreams, they should be advised to remove the patches at bedtime. Dosing of the transdermal patch varies based on the number of cigarettes smoked daily. Patients who smoke more than 10 cigarettes per day should start at the 21 mg dose, and those who smoke less than 10 cigarettes per day should start at 14 mg. The dose is tapered over the course of treatment, lasting 8 to 10 weeks. The application site should be rotated daily to avoid using the same site for at least 1 week. Advantages of the patch include once-daily dosing to improve adherence, discreet use (it can be applied under clothing), the ability to combine with other agents, and consistent nicotine levels over 24 hours.1 Interestingly, the brand marketed as Nicotrol is instructed to be applied upon waking and removed at bedtime; whereas, the other brands, such as Nicoderm, Habitrol, and ProStep are designed to be worn for 24 hours. Adverse effects include local skin reactions (erythema, pruritus, burning), headaches, and sleep disturbances (insomnia, abnormal/vivid dreams). Disadvantages of the transdermal patch include the inability to titrate the dose to manage withdrawal symptoms acutely, and it is not recommended for patients with dermatologic conditions. Precautions for the use of transdermal patches include a myocardial infarction within 2 weeks, serious underlying arrhythmias, serious or worsening angina pectoris, pregnancy and breastfeeding, and adolescents.1 The same 2019 review by Lindson, et al., which suggested a 4-mg dose of gum leads to higher quit rates, also found that higher doses of nicotine patches appeared to have an advantage over lower doses of patches in helping people abstain from smoking.22 These findings were less certain than the success of nicotine gum but may be considered when helping patients choose OTC NRT.1,22

Nicotine Nasal Spray

Nicotine nasal spray is an aqueous solution available only with a prescription. Each nasal spray dose requires two sprays, one in each nostril, with each actuation delivering 0.5 mg of nicotine into the nasal mucosa. The nasal spray is typically dosed at 1 to 2 doses per hour, with the best results initially achieved with at least 8 doses per day (the minimum effective dose). A maximum of 5 doses can be used in one hour, and a maximum of 40 doses per day. Treatment with the nasal spray typically lasts 3 to 6 months.1 Patients should be counseled to prime the device prior to the first use by pumping the nasal spray into a tissue 6 to 8 times until a fine mist appears. If the nasal spray has been unused for 24 hours, the device should be primed again, using only 1 to 2 sprays until the mist appears. Patients should be counseled not to sniff, swallow, or inhale through the nose while the spray is being administered, and their heads should be slightly tilted back during administration. An advantage to the nasal spray is that it delivers nicotine more rapidly than all the NRT products; however, inhaling cigarette smoke still delivers nicotine faster than the nasal spray. When starting therapy with the nasal spray, nasal irritation can cause burning, sneezing, and watery eyes, which typically resolve within 1 to 2 days. Adverse effects when using the nasal spray may include nasal and/or throat irritation (hot, peppery, or burning sensation), rhinitis, tearing, sneezing, cough, and headache. The nasal spray can be titrated to rapidly manage withdrawal symptoms and can be used with other agents. The precautions for the nasal spray are the same as those for the gum, lozenge, and transdermal patch, including caution in patients with underlying chronic nasal disorders such as rhinitis, nasal polyps, and sinusitis.1

Nicotine Oral Inhaler

The nicotine oral inhaler is available as a prescription medication, with each cartridge delivering 4 mg of nicotine to the patient. Dosing of the oral inhaler ranges from 6 to 16 cartridges per day, with the initial dose of 1 cartridge every 1 to 2 hours. The best effects are seen with continuous puffing for 20 minutes, after which the nicotine in the cartridge is depleted. The cartridge should be inhaled into the back of the throat or puffed in short breaths. Patients should be counseled that, unlike a cigarette, the cartridge vapor should NOT be inhaled into the lungs, and no food or beverages should be consumed 15 minutes before or during medication use. Treatment should last 3 to 6 months. Adverse effects of the oral inhaler include mouth and/or throat irritation, cough, headache, rhinitis, dyspepsia, and hiccups. Advantages of the oral inhaler include the potential to serve as an oral alternative to tobacco, the ability to titrate the dose to manage withdrawal symptoms, the device mimicking the hand-to-mouth ritual of smoking, and its compatibility with other agents to manage situational urges. A disadvantage to this therapy is that cartridges may be less effective in cold environments. The precautions for the oral inhaler are the same as those for the gum, lozenge, and patch, and include individuals with bronchospastic disease.1

Bupropion

Bupropion sustained-release (SR) for smoking cessation gained FDA approval in 1997 and is only available with a prescription.1 An additional indication was added in 1999 that approved bupropion to be used in combination with nicotine transdermal patches for smoking cessation. Bupropion was originally marketed and still used as an antidepressant.1 The exact mechanism of action is unknown, but it is thought that bupropion blocks the reuptake of dopamine and norepinephrine, to a lesser extent, and it has some nicotine receptor-blocking activity.1 The increase in dopamine at neuronal sites may cause reduced nicotine cravings and a reduced urge to smoke. The increase in norepinephrine may reduce nicotine withdrawal symptoms. The typical dosing for bupropion SR for smoking cessation is 150 mg every morning for 3 days, then increasing to 150 mg twice daily, with a maximum dose of 300 mg/day. The patient should choose a “quit day” and start therapy 1 to 2 weeks prior to the quit day to allow the medication to reach steady state therapeutic levels.1 If a patient uses the nicotine transdermal patch in combination with bupropion, the patch should be initiated on the target “quit day,” and the patch can be continued for 8 to 20 weeks. The duration of therapy for bupropion therapy is 7 to 12 weeks, with maintenance dosing up to 6 months in some patients.1 A patient is generally considered non-responsive to bupropion treatment if they have not stopped smoking by the seventh week of treatment. The goal of therapy is complete abstinence from smoking. Patients should avoid taking bupropion right before bedtime as it may cause insomnia. Other adverse effects may include dry mouth, nausea, constipation, seizures, nervousness, difficulty concentrating, dizziness, rash, and, on rare occasions, neuropsychiatric symptoms.1 Patients using the nicotine transdermal patch in combination with bupropion should be monitored for treatment-induced hypertension. The advantages of bupropion therapy are the potential delay of weight gain from smoking cessation, it can be beneficial in patients who also have depression, and it may be combined with nicotine replacement agents. Precautions for using bupropion SR are concomitant therapy with medications or conditions known to lower the seizure threshold, hepatic impairment, adolescents, pregnancy, and breastfeeding, and treatment-emergent neuropsychiatric symptoms. Bupropion for smoking cessation is contraindicated in patients with a seizure disorder, patients taking concomitant bupropion therapy, current or prior diagnosis of bulimia or anorexia nervosa, simultaneous abrupt discontinuation of alcohol or sedatives/benzodiazepines, and the use of MAO inhibitors within 14 days of bupropion therapy.1

Varenicline

Varenicline was approved for smoking cessation by the FDA in 2006 and is available by prescription only. Oral varenicline is marketed specifically for smoking cessation and is a partial agonist of the α4β2 nicotinic acetylcholine receptor subtype. This receptor mediates dopamine release and is thought to be a major receptor involved in nicotine addiction. When varenicline activates this receptor, its maximal effect is about 50% that of nicotine. This action is thought to relieve the symptoms of nicotine withdrawal, including cravings, and blocks the effects of nicotine on the receptor if a patient smokes a cigarette, which diminishes the rewarding effects of cigarettes and reduces the desire and likelihood to continue smoking. Titration is used with varenicline: typically 0.5 mg every morning on days 1 to 3, 0.5 mg twice daily on days 4 to 7, then 1 mg twice daily for weeks 2 through 12. Varenicline should be started one week prior to the quit date; however, it may be initiated up to 35 days before the target quit day. After eating, varenicline should be taken with a full glass of water to reduce nausea. The duration of therapy is typically 12 weeks, with some patients requiring an additional 12-week course. Patients may reduce smoking frequency over the 12-week period prior to quitting and then continue the treatment for an additional 12 weeks. Dose adjustment is necessary for patients with renal impairment. The manufacturer recommends lowering the dosage if patients are not tolerating the medication due to adverse effects. Adverse effects of varenicline include nausea, insomnia, abnormal/vivid dreams, constipation, flatulence, vomiting, and neuropsychiatric symptoms. Precautions should be used in patients with severe renal impairment, pregnancy and breastfeeding, adolescents, and treatment-emergent neuropsychiatric symptoms.1

In 2009, the FDA mandated that bupropion and varenicline-containing products include a boxed warning highlighting the risk of serious neuropsychiatric symptoms. These symptoms included changes in behavior, agitation, hostility, suicidal thoughts and behavior, depressed mood, and attempted suicide. In 2016, this box warning was removed based on the results of a mandated clinical trial; however, pharmacists and providers should still counsel patients and monitor them for these symptoms. The clinical trial determined that the risk of serious neuropsychiatric side effects was lower than previously suspected.1

Off-label Therapies

Clonidine may be used off-label as an adjunct to psychosocial interventions in managing smoking cessation. Clonidine acts on the central nervous system to help reduce withdrawal symptoms.18 Clonidine should be started up to 3 days before or on the quit date. The initial dose is 0.1 mg by mouth once or twice daily for oral therapy, or 0.1 mg/24-hour patch applied once weekly for the transdermal patch. The dose may be increased by 0.1 mg/day weekly if needed, with oral doses divided throughout the day to improve tolerability. The duration of treatment generally ranges from 3 to 10 weeks. If the patient is on a higher dose, it is advisable to gradually reduce the dose over 2 to 4 weeks to reduce the likelihood of rebound effects, including increases in blood pressure, agitation, confusion, and/or tremor. Common side effects that may be experienced with clonidine therapy include dry mouth, sedation, dizziness, drowsiness, and constipation. Clonidine can be beneficial when a patient withdraws from multiple drugs, as it can also relieve the withdrawal symptoms of drugs other than nicotine.23

Nortriptyline is a tricyclic antidepressant that may also be used off-label as an adjunct to psychosocial interventions in the management of smoking cessation. The dose starts at 25 mg once daily and is gradually increased to a target of 75-100 mg once daily. Nortriptyline should be initiated 10 to 28 days before the quit date to attain steady-state concentrations. The duration of therapy in most trials has been approximately 12 weeks, with a maximum of 6 months. Nortriptyline may be considered in patients unable to use first-line medications due to contraindications, patients who have failed to quit with first-line therapy, or patients with a current or history of depression.

Naltrexone may be used off-label as an adjunct to psychosocial interventions for smoking cessation. Naltrexone has limited data for use, but has been used alone or in combination with nicotine patches to help patients attempting to quit smoking. In a study that evaluated the effects of naltrexone on smoking cessation outcomes and weight gain in nicotine-dependent men and women, naltrexone increased quit rates during treatment as well as reduced weight gain; however, the results were not sustained after discontinuing naltrexone.24

E-cigarettes and Vaping as an Alternative to Smoking

E-cigarettes are tobacco products that can deliver nicotine and are now the most commonly used tobacco product among youth in the United States. Most, but not all, e-cigarettes contain nicotine. Nicotine and vaping solutions contained in e-cigarettes are not regulated in the same way as FDA-approved dosage forms. These devices may also be referred to as “e-cigs,” “e-hookahs,” “mods,” “vape pens,” “vapes,” and “tank systems.” The use of e-cigarettes can further lead to the use of other tobacco products, including conventional cigarettes.

Vaping and e-cigarettes were originally seen as a tool for smoking cessation, but over time, they have not only attracted people who are trying to quit smoking but have also drawn the attention of non-smokers because of the efficient nicotine delivery as well as the large variety of available flavors.25-27 E-cigarettes are not FDA-approved smoking cessation therapies and should not be recommended as first-line treatment.

An advantage of e-cigarettes and vaping devices is the possibility of being used in smoke-free places. These devices are battery-powered and consist of an electric atomizer and replaceable cartridges containing water-based liquids called “e-liquids.” E-liquids are primarily composed of propylene glycol, glycerin, water, flavors, and variable amounts of nicotine. The atomizer heats the e-liquid, which is then vaporized and inhaled by the user.28

Electronic cigarette aerosols come into contact with pulmonary surfactants and impair critical surface tension, which reduces activity in the lungs and can contribute to lung dysfunction. Pulmonary surfactant reduces surface tension in the lungs, which is essential for breathing, allowing them to inflate and deflate with minimal pressure changes. The results of a study by Graham, et al., supported the hypothesis that exposure to e-cigarettes aerosols resulted in impaired surfactant function, and all exposed samples (regardless of device, additive, or vehicle composition) resulted in higher minimum surface tensions than just air-exposed samples.29 This study used bovine lipid extract surfactant (BLES) to assess the effects of the delivery vehicle on surfactant and the effects of aerosols from a variety of e-liquids containing flavorings and/or nicotine. When non-aerosolized, the e-liquid mixed with the BLES did not show significant differences in surface tension, showing the significance of aerosolization in inhibiting pulmonary surfactant. Most aerosol flavors produced similar inhibition, except for menthol and red wedding, which exhibited significantly higher minimum surface tensions than the other flavors. The study also notes that chemicals in e-liquids are not highly regulated, so effects can vary due to differences in e-liquid formulations and vehicle delivery. Aerosolization of different liquid formulations can also generate harmful chemicals, including formaldehyde, acetaldehyde, and acrolein. An interesting result from this study is that there were no significant differences in power levels (wattage) among the highest-power devices tested, suggesting two possibilities: the lowest wattage could have maximally affected surface tension, or reactive oxygen species production was not a major contributor to surfactant inhibition. Although the study was done in vitro, these effects should be extrapolated to the in vivo setting as a potential downfall of e-cigarettes and vaping. In the human setting, it should be noted that even if vaping does not induce surfactant alterations that are sufficient to cause lung dysfunction, settings in which surfactant is further challenged may cause more impairment, ultimately leading to decreased lung function.29

Smoking Cessation Treatment Approach

Assess readiness to quit

Identify contraindications

Select:

NRT (mild–moderate dependence)

Varenicline (highest efficacy)

Bupropion (if depression/weight concern)

Combine with behavioral support

Medication Selection Table

Patient ScenarioPreferred Option
Heavy smokerCombination NRT or varenicline
DepressionBupropion
Concern about weight gainBupropion
Rapid craving controlGum/lozenge/spray

Patient Case

Mr. J is a 52-year-old man with hypertension and mild depression who presents for a routine visit and states he is ready to quit smoking after 20 years of smoking.

What questions can be asked of the patient to plan a personalized approach to smoking cessation?

He reveals he smokes one pack a day. He wakes up at night craving a cigarette. He feels irritable and anxious when he goes too long without a cigarette. He tried unsuccessfully to quit in the past. His spouse still smokes.

What questions can be asked of the patient to finalize shared decision-making for a treatment plan?

He is concerned about gaining weight after he stops smoking. He asks for a medication that can help reduce his withdrawal symptoms. After discussion, he agrees to pick a quit date, start treatment, and use behavioral support along with medication to increase his chance of success. He was prescribed an upward titration of varenicline 0.5 mg every morning on days 1 to 3, then 0.5 mg twice daily on days 4 to 7, then 1 mg twice daily for weeks 2 through 12.

Barriers to Smoking Cessation

Quitting smoking can be difficult, and interventions used for smoking cessation should be individualized based on patient history and readiness for change.30 Behavioral counseling and cessation medications, especially when used in combination, increase the likelihood of successfully quitting.30 Ensuring that medication is covered under the patient’s insurance is helpful for compliance and aiding in smoking cessation.31 Some insurance plans do not cover over-the-counter products, such as nicotine gum and patches, which may cause a patient to have an unsuccessful quit attempt if they must pay a cash price.31 Counseling and quit-lines play an important role, as patients cannot control their surroundings. Quit-lines are available to individuals in every state and offer support through counseling, referrals to local programs, and free medications to people who want to quit tobacco. Pharmacies should have the 1-800-QUIT-NOW number readily available for patients. This phone number is a national portal that can help patients contact local state resources.32 Friends, family, and coworkers may still smoke around the patient, causing temptation. Patients going through a particularly stressful event may also relapse as a coping mechanism.33

Common Pitfalls:

Using NRT incorrectly (e.g., chewing gum too fast)

Not combining pharmacotherapy with counseling

Underdosing nicotine

Stopping therapy too early

What’s Next?

There are multiple investigations underway for smoking cessation. One study proposes using ChatGPT text messaging support.34 Another intervention under investigation uses a mobile application for pregnant patients who smoke.35 The FDA has accepted the New Drug Application (NDA) for cytisinicline, which is a plant-based nicotinic acetylcholine receptor partial agonist for smoking cessation in adults.36 The FDA also announced a Commissioner’s National Priority Voucher (CNPV) for this investigational product.37

Summary

Smoking cessation is vital to improving a patient’s overall health. Several medication options are available to help aid patients in smoking cessation. The availability of OTC products can be especially useful for these patients. Pharmacists and pharmacy technicians should be able to help patients find these products in the pharmacy and ensure they are kept fully stocked for easy access. Smoking cessation medications combined with behavioral modification and support can help patients succeed in their smoking cessation goals.

References

U.S. Department of Health and Human Services. Smoking Cessation. A Report of the Surgeon General. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2020. Accessed April 29, 2026. https://www.hhs.gov/sites/default/files/2020-cessation-sgr-full-report.pdf

Centers for Disease Control and Prevention. Tips from Former Smokers. Burden of Cigarette Use in the U.S. CDC. February 24, 2025. Accessed April 29, 2026. https://www.cdc.gov/tobacco/campaign/tips/resources/data/cigarette-smoking-in-united-states.html#:~:text=Cigarette%20smoking%20remains%20the%20leading,5

VanFrank B, Malarcher A, Cornelius ME, Schecter A, Jamal A, Tynan M. Adult Smoking Cessation - United States, 2022. MMWR Morb Mortal Wkly Rep. 2024;73(29):633-641. Published 2024 Jul 25. doi:10.15585/mmwr.mm7329a1

Centers for Disease Control and Prevention. Smoking and Tobacco Use. Youth and Tobacco Use. CDC. February 24, 2025. Accessed April 29, 2026. https://www.cdc.gov/tobacco/php/data-statistics/youth-data-tobacco/index.html

Centers for Disease Control and Prevention. Smoking and Tobacco Use. Cigarette Smoking. CDC. September 17, 2024. Accessed April 29, 2026. https://www.cdc.gov/tobacco/data_statistics/fact_sheets/fast_facts/index.htm?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Ftobacco%2Fdata_statistics%2Ffact_sheets%2Findex.htm

Centers for Disease Control and Prevention. Smoking and Tobacco Use. E-Cigarette Use Among Youth. CDC. October 17, 2024. Accessed April 29, 2026. https://www.cdc.gov/tobacco/e-cigarettes/youth.html

Klein LW. Pathophysiologic Mechanisms of Tobacco Smoke Producing Atherosclerosis. Curr Cardiol Rev. 2022;18(6):e110422203389. doi:10.2174/1573403X18666220411113112

Gallaway MS, Henley SJ, Steele CB, et al. Surveillance for Cancers Associated with Tobacco Use - United States, 2010-2014. MMWR Surveill Summ. 2018;67(12):1-42. Published 2018 Nov 2. doi:10.15585/mmwr.ss6712a1

Centers for Disease Control and Prevention. Smoking and Tobacco Use. Benefits of Quitting Smoking. CDC. May 15, 2024. Accessed April 29, 2026. https://www.cdc.gov/tobacco/about/benefits-of-quitting.html?CDC_AAref_Val=https://www.cdc.gov/tobacco/quit_smoking/how_to_quit/benefits/index.htm

Diamanti A, Papadakis S, Schoretsaniti S, et al. Smoking cessation in pregnancy: An update for maternity care practitioners. Tob Induc Dis. 2019;17:57. Published 2019 Aug 2. doi:10.18332/tid/109906

White O, Roeder N, Blum K, Eiden RD, Thanos PK. Prenatal Effects of Nicotine on Obesity Risks: A Narrative Review. Int J Environ Res Public Health. 2022;19(15):9477. Published 2022 Aug 2. doi:10.3390/ijerph19159477

Kroon LA. Drug interactions with smoking. Am J Health Syst Pharm. 2007;64(18):1917-1921. doi:10.2146/ajhp060414

Anderson GD, Chan LN. Pharmacokinetic Drug Interactions with Tobacco, Cannabinoids and Smoking Cessation Products. Clin Pharmacokinet. 2016;55(11):1353-1368. doi:10.1007/s40262-016-0400-9

McLaughlin I, Dani JA, De Biasi M. Nicotine withdrawal. Curr Top Behav Neurosci. 2015;24:99-123. doi:10.1007/978-3-319-13482-6_4

Cleveland Clinic. Noctine Withdrawal. Cleveland Clinic. Last updated on August 8, 2024. Accessed April 29, 2026. https://my.clevelandclinic.org/health/diseases/21587-nicotine-withdrawal

U.S. Department of Health and Human Services. National Institutes of Health. Managing Nicotine Withdrawal. Smokefree.gov. Undated. Accessed April 29, 2026. https://smokefree.gov/challenges-when-quitting/withdrawal/managing-nicotine-withdrawal

Centers for Disease Control and Prevention. Tips From Former Smokers®. How to Quit Smoking. 7 Common Withdrawal Symptoms. CDC. Last Reviewed: September 27, 2024. Accessed April 29, 2026. https://www.cdc.gov/tobacco/campaign/tips/quit-smoking/7-common-withdrawal-symptoms/

Gómez-Coronado N, Walker AJ, Berk M, Dodd S. Current and Emerging Pharmacotherapies for Cessation of Tobacco Smoking. Pharmacotherapy. 2018;38(2):235-258. doi:10.1002/phar.2073

NICOTROL- nicotine spray, metered. Prescribing Information. Pharmacia & Upjohn Company LLC. Updated May 29, 2025. Accessed April 29, 2026. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=acb7d02d-249b-4645-ac1b-8ff9a56dd244

Centers for Disease Control and Prevention. How to Use the Nicotine Nasal Spray. CDC. Last Reviewed: October 4, 2024. Accessed April 29, 2026. https://www.cdc.gov/tobacco/campaign/tips/quit-smoking/quit-smoking-medications/how-to-use-quit-smoking-medicines/how-to-use-nicotine-nasal-spray.html#:~:text=It%20is%20important%20not%20to%20smoke%20while%20using,away%20your%20cigarettes%20and%20get%20back%20on%20track

Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2022. Accessed April 29, 2026. https://goldcopd.org/wp-content/uploads/2021/11/GOLD-REPORT-2022-v1.1-22Nov2021_WMV.pdf

​​Lindson N, Chepkin SC, Ye W, Fanshawe TR, Bullen C, Hartmann-Boyce J. Different doses, durations and modes of delivery of nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev. 2019;4(4):CD013308. Published 2019 Apr 18. doi:10.1002/14651858.CD013308

Gourlay SG, Stead LF, Benowitz NL. Clonidine for smoking cessation. Cochrane Database Syst Rev. 2004;2004(3):CD000058. doi:10.1002/14651858.CD000058.pub2

King AC, Cao D, O'Malley SS, et al. Effects of naltrexone on smoking cessation outcomes and weight gain in nicotine-dependent men and women. J Clin Psychopharmacol. 2012;32(5):630-636. doi:10.1097/JCP.0b013e3182676956

Shafie-Khorassani F, Piper ME, Jorenby DE, et al. Associations of Demographics, Dependence, and Biomarkers With Transitions in Tobacco Product Use in a Cohort of Cigarette Users and Dual Users of Cigarettes and E-cigarettes. Nicotine Tob Res. 2023;25(3):462-469. doi:10.1093/ntr/ntac207

Bhatnagar A, Payne TJ, Robertson RM. Is There A Role for Electronic Cigarettes in Tobacco Cessation?. J Am Heart Assoc. 2019;8(12):e012742. doi:10.1161/JAHA.119.012742

Kosterman R, Epstein M, Bailey JA, Furlong M, Hawkins JD. The role of electronic cigarette use for quitting or reducing combustible cigarette use in the 30s: Longitudinal changes and moderated relationships. Drug Alcohol Depend. 2021;227:108940. doi:10.1016/j.drugalcdep.2021.108940

Marini S, Buonanno G, Stabile L, Ficco G. Short-term effects of electronic and tobacco cigarettes on exhaled nitric oxide. Toxicol Appl Pharmacol. 2014;278(1):9-15. doi:10.1016/j.taap.2014.04.004

Graham E, McCaig L, Shui-Kei Lau G, et al. E-cigarette aerosol exposure of pulmonary surfactant impairs its surface tension reducing function. PLoS One. 2022;17(11):e0272475. Published 2022 Nov 9. doi:10.1371/journal.pone.0272475

Centers for Disease Control and Prevention. Smoking and Tobacco Use. Clinical Interventions to Treat Tobacco Use and Dependence Among Adults. CDC. May 15, 2024. Accessed April 29, 2026. https://www.cdc.gov/tobacco/hcp/patient-care-settings/clinical.html

Masclans L, Davis JM. Access to effective smoking cessation medications in patients with medicare, medicaid and private insurance. Public Health Pract (Oxf). 2023;6:100427. Published 2023 Sep 10. doi:10.1016/j.puhip.2023.100427

Centers for Disease Control and Prevention. Smoking & Tobacco Use. 1-800-QUIT-NOW: 15 Years of Helping People Quit. CDC. October 7, 2019. Accessed April 29, 2026. https://www.cdc.gov/tobacco/tobacco-features/quitlines.html

Adams JM. Smoking Cessation-Progress, Barriers, and New Opportunities: The Surgeon General's Report on Smoking Cessation. JAMA. 2020;323(24):2470-2471. doi:10.1001/jama.2020.6647

Abroms LC, Wysota CN, Yousefi A, Wu TC, Broniatowski DA. ChatGPT-Based Chatbot for Help Quitting Smoking via Text Messaging: An Interventional Study. JMIR Form Res. 2025;9:e79402. Published 2025 Oct 10. doi:10.2196/79402

Blaga OM, Dascal MD, Onișor A, et al. Smartphone intervention for pregnancy smoking cessation with peer support: the study protocol of the SmokeFree Together 2.0 (SFT 2.0) randomised controlled trial. BMJ Open. 2025;15(3):e100259. Published 2025 Mar 24. doi:10.1136/bmjopen-2025-100259

Rigotti NA, Benowitz NL. An evaluation of cytisinicline for smoking cessation in adult smokers. Expert Opin Pharmacother. 2026;27(4):263-271. doi:10.1080/14656566.2026.2646283

US Food and Drug Adminstration. Commissioner's National Priority Voucher (CNPV) Pilot Program. FDA. Content current as ofApril 28, 2026. Accessed April 29, 2026. https://www.fda.gov/industry/commissioners-national-priority-voucher-cnpv-pilot-program#:~:text=Accelerated%20Drug%20Review%20for%20Companies,treatments%20inadequately%20address%20patient%20outcomes

DISCLAIMER

The information provided in this course is general in nature, and it is designed solely to provide participants with continuing education credit(s). This course and materials are not meant to substitute for the independent, professional judgment of any participant regarding that participant’s professional practice, including but not limited to patient assessment, diagnosis, treatment, and/or health management. Medical and pharmacy practices, rules, and laws vary from state to state, and this course does not cover the laws of each state; therefore, participants must consult the laws of their state as they relate to their professional practice.

Healthcare professionals must consult their employer, healthcare facility, hospital, or other organization for guidelines, protocols, and procedures to follow. The information provided in this course does not replace those guidelines, protocols, and procedures, but is for academic purposes only, and this course’s limited purpose is for the completion of continuing education credits.

Participants are advised and acknowledge that information related to medications, their administration, dosing, contraindications, adverse reactions, interactions, warnings, precautions, or accepted uses is constantly changing. Any person taking this course understands that such a person must make an independent review of medication information before any patient assessment, diagnosis, treatment and/or health management. Any discussion of off-label use of any medication, device, or procedure is informational only, and such uses are not endorsed hereby.

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