NICOTINE REPLACEMENT THERAPY

NICOTINE REPLACEMENT THERAPY:

 

There are five forms of nicotine replacement therapy (NRT) available:  

Nicotine gum, 

Nicotine lozenge, 

Nicotine transdermal patch, 

Nicotine inhaler,

Nicotine nasal spray. 

The goal of nicotine replacement therapy is to deliver a sufficient dose of clean pharmaceutical-grade nicotine (free of carcinogens and manufactured under pharmaceutical conditions) to reduce nicotine withdrawal symptoms to a manageable level. 

All of the commercially available forms of NRT (gum, lozenge, transdermal patch, inhaler, and nasal spray) can increase the rate of quitting by 50% to 70%, regardless of setting.

Providing a more intense level of support can facilitate the likelihood that a patient will make a quit attempt. 


In controlled clinical trials, the experimental group received the active drug and a control group received a placebo. 

In evaluating the results, a relative risk with a value greater than 1 means that abstinence is more likely to occur in the experimental group than in the control group. 


Based on analysis of pooled data from multiple controlled clinical trials.

As with all medications, nicotine replacement products should be kept out of reach of children. 


General contraindications for use of nicotine replacement therapy include patients who have had a heart attack in the past 2 weeks, patients with serious arrhythmias, and patients with serious or worsening angina pectoris.

Nicotine replacement therapy has not been approved for use with populations for which there is insufficient evidence of effectiveness (i.e., pregnant women, smokeless tobacco users, light smokers, and adolescents).

A recent review of the literature suggests that the use of NRT can be effective with patients not ready to quit by encouraging and instructing unwilling smokers to substantially and persistently reduce their daily smoking as much as possible while they are receiving nicotine-replacement therapy.

Nicotine Gum:

Use and Dosage:

Nicotine gum needs to be used in a very specific manner to be effective and, like chewing gum, should not be swallowed. 

The gum is available over the counter in both brand-name and generic forms. 


The package insert describes appropriate use but clinicians should provide brief instructions on use and dosage. 

The gum is available in two strengths, 2 mg and 4 mg. 


For individuals who smoke more than 25 cigarettes per day, the 4-mg strength is recommended. 

In highly-dependent smokers there was a significant benefit of 4-mg gum compared with 2-mg gum.

The 2-mg strength is recommended for patients who smoke fewer than 25 cigarettes per day. 


It may be necessary to increase the dosage from 2 mg to 4 mg in patients whose withdrawal symptoms are not alleviated with the lower dose. 

When using the 2-mg dose, the total daily use should be limited to no more than 30 pieces a day. 


When using the 4-mg dose, individuals should limit use to no more than 24 pieces a day. 


Nicotine from the gum is absorbed through the buccal mucosa.

One advantage of the gum is that patients can use the gum as needed in combination with a steady-state nicotine delivery system such as the nicotine patch.

Contraindications:

The use of nicotine gum is contraindicated in patients with temporomandibular joint disease (TMJD) or chronic TMJ pain.

Side Effects:

Side effects of nicotine gum may include mouth ulcers, jaw muscle aches, dizziness, headaches, and nausea.

Patient Instructions:

Nicotine gum should be used regularly by chewing one piece of gum every 1-2 hours or chewing one piece of gum when the patient has the urge to smoke. 


It should be chewed slowly until there is a slight tingling in the mouth. 

The patient should stop chewing and place (park) the chewing gum between the cheek and gum. 


When the tingling subsides (after about one minute), the patient should resume chewing and the cycle repeated for about 30 minutes.

Tapering the use of nicotine gum can be accomplished by reducing the daily dose by one piece every 4-7 days or by decreasing the chewing time for each piece from 30 minutes to 10-15 minutes. 

Patients may substitute one or more pieces of sugarless gum for an equal number of pieces of nicotine gum. 

The nicotine gum should be discontinued when the craving for nicotine is satisfied by one or two pieces of gum per day. Prescribing information recommends use for a period of 12 weeks. 

However, patients may extend use to prevent relapse. According to the prescribing literature, the use of nicotine 
gum is discouraged for longer than 6 months due to the potential for dependence. 

Although use of nicotine gum is preferable to tobacco use because the gum contains no carcinogens, physiologic effects such as elevated blood pressure can occur with prolonged use of NRT. 

Nicotine gum should not be used within 15 minutes of eating or drinking, as the acidic pH of the mouth will interfere with the absorption of the nicotine through the buccal mucosa. 

Chewing the gum too rapidly might precipitate lightheadedness, nausea and vomiting,irritation of the throat and mouth, hiccups, and indigestion.

Nicotine Lozenge:

Use and Dosage:

The lozenge is available over the counter in both brand-name and generic forms. 


As with the nicotine gum, the package insert describes appropriate use, but clinicians should provide brief instructions on dosage and use. 

The dose equivalent of the lozenge delivers approximately 25% more nicotine than the gum.


If the patient smokes the first cigarette of the day within 30 minutes of waking up in the morning, the 4-mg lozenge is indicated.


If the patient smokes the first cigarette more than 30 minutes after waking, the 2-mg nicotine lozenge is recommended.

The recommended regimen for use of the lozenge is one lozenge every 1-2 hours for weeks 1-6 of treatment. 


Using at least nine lozenges per day will increase the chances of successful cessation. 

One lozenge every 2-4 hours is recommend for weeks 7-9 of treatment, then one lozenge every 4-8 hours for weeks 10-12. 

Patients should not use more than five lozenges in a 6-hour time period or more than 20 lozenges per day. 


If complete abstinence is not achieved at 12 weeks, lozenge use may be extended by increasing the time between dosing until the patient is comfortable.

However, the standard recommended duration of use is 3 to 6 months.

Precautions:

The nicotine lozenge should be used with caution in patients with active peptic ulcer disease or a severe sore throat.

Side Effects:

Possible side effects associated with the nicotine lozenge may include heartburn, nausea, mouth or throat irritation, headache, hiccups, and dizziness.

Patient Instructions:

The lozenge should be allowed to dissolve in the mouth over 20 to 30 minutes and should not be chewed or swallowed, as this will decrease nicotine delivery and increase the possibility of side effects. 


The lozenge should not be used within 15 minutes of eating or drinking as the acidic pH of the mouth will interfere with the absorption of the nicotine through the buccal mucosa.

Nicotine Transdermal Patch:

Use and Dosage:

The primary advantages of the patch include steady-state nicotine levels throughout the day and better compliance compared to other nicotine replacement medications that are used at specified intervals. 

The patch is available over the counter in both brand-name and generic forms. 


As with the other forms of nicotine replacements, the package insert describes appropriate use, but clinicians should provide brief instructions on dosage and use. 

Transdermal nicotine delivery systems consist of an impermeable surface layer, a nicotine reservoir, an adhesive layer, and a removable protective liner. 

Nicotine concentrations from the patch are lower and fluctuate less than those achieved with tobacco products: 

Plasma nicotine levels obtained via transdermal delivery are approximately 50% lower than those achieved with cigarette smoking.


Lower levels of nicotine still alleviate the symptoms of withdrawal but are far less likely to lead to dependence when compared to tobacco or other forms of NRT. 

Patches are available in three strengths: 21 mg, 14 mg, and 7 mg. 

The recommended dose is based on the number of cigarettes smoked per day as well as the nicotine dependence level. 

For those who smoke more than 15 cigarettes per day, use of a 21-mg patch is recommended for 4 weeks, followed by step-down dosing to 14 mg for 2 weeks, followed by a 7-mg patch for 2 weeks.

Contraindications:

Patients with dermatologic conditions (e.g., psoriasis, eczema, atopic dermatitis) are more likely to experience skin irritation and should not use the nicotine patch.

Side Effects:

The most common side effect of the patch is vivid dreams or sleep disturbances.


This reaction can be addressed by removing the patch before going to bed.


Other side effects include dizziness, headache, nausea, vomiting, diarrhea, and redness or swelling at the patch site.

Patient Instructions:

The patch should be applied to a clean, dry, hairless area of skin on the upper chest, upper arm, or hip. 


It should not be placed on areas of irritated, oily, scarred, or broken skin. 


Body hair at the application site will interfere with the effectiveness and adhesion of the patch, but the area should not be shaved as this may cause skin irritation and may alter the amount of drug absorbed. 

The patch should be applied to a different area each day to minimize the potential for local skin reactions. 


If mild redness occurs at the patch site, it may respond to treatment with an over-the-counter hydrocortisone cream (1%) or oral antihistamines. 


Hand washing is essential following patch application, as the nicotine on the hands may be transferred to the eyes or nose, causing stinging or redness. 

The patch may be worn while bathing, swimming, or exercising. 


If a skin rash develops after using a nicotine patch, or if the skin under the patch becomes swollen or very red, another patch should not be applied and the healthcare provider should be contacted.

Nicotine Inhaler:

Use and Dosage:

The nicotine inhaler is available only by prescription and at present only as a brand-name product. 


It consists of a two-piece plastic unit designed to deliver nicotine contained in individual cartridges. 

Each foil-sealed cartridge contains a porous plug impregnated with 10 mg of nicotine. 


Sharp spikes found on the interior of both mouthpiece components pierce the protective covering, allowing the release of nicotine vapor following inhalation. 

Given that the usual pack-a-day smoker repeats the hand-to-mouth motion up to 200 times per day, many smokers trying to quit find they miss the physical manipulation of the cigarette. 

The nicotine inhaler was designed to provide nicotine replacement in a manner similar to smoking while addressing the sensory and ritualistic factors that are important to many smokers. 


When a patient puffs on the inhaler mouthpiece, nicotine vapor is released and is absorbed through the buccal mucosa.


Contrary to what the term “inhaler” implies, very little of the nicotine reaches the lower respiratory tract (less than 5% of a dose). 

The absorption of nicotine takes place through the buccal mucosa. With an intensive inhalation regimen (80 puffs over 20 minutes), approximately 4 mg of nicotine are delivered, and of that, 2 mg are absorbed. 

Plasma nicotine levels are 50% to 70% lower than those achieved with cigarette smoking, and peak nicotine concentrations occur after 30 minutes compared to 5 minutes after cigarette smoking.


The initial dose for the inhaler should be individualized. 

The dose may be titrated to alleviate withdrawal symptoms. Generally 6 to 16 cartridges should be used throughout the day. 


The best effects are achieved by frequent, continual puffing (for 20 minutes).


Initial dosing should begin with at least 6 cartridges per day and can be increased as needed to a maximum of 16 cartridges per day for 3 to 12 weeks. 

The recommended duration of treatment is 3 months, after which use may be decreased by gradual reduction of the daily dose over the following 6 to 12 weeks. 


The safety and efficacy of the continued use of a nicotine inhaler for periods longer than 6 months have not been studied.

Contraindications:

Use of the nicotine inhaler is contraindicated in patients with known hypersensitivity or allergy to nicotine or to menthol. 

The inhaler has not been specifically studied in asthma or chronic pulmonary disease. 


Nicotine is an airway irritant that may precipitate bronchospasm, and therefore the nicotine inhaler should be used with caution in patients with bronchospastic disease. 

Patients should be informed that if they continue to smoke while using the product, they may experience adverse effects because peak nicotine levels will be higher than those experienced from smoking alone.

Side Effects:

The most common side effects are nausea, diarrhea, and hiccups. 

Local irritation in the mouth and throat was reported by 40% of patients. 

Coughing and rhinitis have also been reported, although these effects declined with continued use. 

Other side effects may include alterations in taste, pain in jaw and neck, and sinusitis.

Patient Instructions:

The patient should be instructed to align the marks on the mouthpiece and pull to separate the mouthpiece into two parts. 

The nicotine-containing cartridge should be inserted and pressed firmly into the bottom of the mouthpiece until the seal breaks. 


 Shallow puffing releases and vaporizes the nicotine, which then becomes absorbed through the buccal mucosa. 

The nicotine in the cartridge is delivered over approximately 20 minutes with vigorous puffing. 


Each cartridge can provide up to 300 to 400 puffs. 

If the inhaler is used for a shorter period of time, the same cartridge may be reused. 

However, once a cartridge is opened it is only good for one day. 

The inhaler should not be used within 15 minutes of eating or drinking as the acidic pH of the mouth will interfere with the absorption of the nicotine through the buccal mucosa. 

The nicotine inhaler is supplied with 42 cartridges and a plastic storage case.

Nicotine Nasal Spray

Use and Dosage:

Nicotine nasal spray is available only by prescription and is currently available only as a brand-name product. 


A metered-spray pump contains an aqueous solution of nicotine for administration to the nasal mucosa. 


When the pump is depressed, 50 µL of spray containing 0.5 mg of nicotine is dispensed. 

Nicotine is rapidly absorbed, and plasma nicotine concentrations attained via the nasal spray are comparable (but lower) to those achieved by smoking. 

The nasal spray has a faster onset of action (11-13 minutes) compared to the gum, lozenge, patch, or inhaler.The titrated dose of 1 mg of nicotine is delivered through two sprays, one 0.5-mg spray in each nostril. 

The recommended starting regimen is one or two doses per hour for 6-8 weeks, depending on the patient’s ability to manage withdrawal symptoms. 



This may be increased up to a maximum recommended dose of 40 mg (80 sprays, about half a bottle) per day. 

For best results, patients should be encouraged to use a minimum of eight doses per day during the first 6 to 8 weeks of therapy. 


The daily dose should be gradually decreased over an additional 4-6 weeks. If relapse is a concern, the duration of use can be extended to 6 months. 

Recommended strategies for discontinuing use include using only half a dose (one spray) at a time and using the spray less frequently. 

The nicotine nasal spray has the highest drug dependence profile of the nicotine replacement medications.


The extent of absorption is slightly reduced in patients with the common cold/rhinitis. 

In patients with rhinitis, the peak plasma concentration is reduced by approximately 20% and the time period to peak concentration prolonged. 

The use of a nasal vasoconstrictor will further prolong the time interval before peak plasma levels.

Contraindications:

Use of nicotine nasal spray is not recommended in patients with known chronic nasal disorders (e.g., allergy, rhinitis, nasal polyps, and sinusitis). 

Exacerbation of bronchospasm in patients with preexisting asthma has been reported. 

Use of the spray in patients with severe reactive airway disease is not recommended. 


Topical application of either nicotine or tobacco products irritates nasal mucosa. 

Tachycardia has been reported in association with nicotine nasal spray, although no serious cardiovascular events have been reported. 

Nicotine nasal spray therapy should be used with caution in patients with hyperthyroidism, pheochromocytoma, or insulin-dependent diabetes.

Concomitant use of acetaminophen, caffeine, imipramine, oxazepam, pentazocine, propranolol or other beta-blockers, theophylline, insulin, and adrenergic antagonists may require a decrease in dose. 


Use of adrenergic agonists such as dobutamine (Dobutrex, Inotrex), commonly employed in the treatment of heart failure, may require an increased dosage.

The amount of nicotine that is tolerated by an adult can produce symptoms of poisoning and could prove fatal if nicotine nasal spray is used or ingested by children or pets. 


A full bottle of nicotine nasal spray contains 100 mg of nicotine, some of which will still be in the bottle when it is discarded. 


Both used and unused containers should be kept out of the reach of children and pets.

Side Effects:

The most common side effects of the nasal spray are a hot, peppery feeling in the back of the nose or throat, a running nose, throat irritation, watering eyes, sneezing, and coughing.

Patient Instructions:

The thumb and index finger should be used to press the circles on the sides of the bottle to remove the child-resistant cap. 


Prior to use, the pump should be primed into a tissue by holding the bottle and pressing firmly on the glass bottom with the thumb until a fine spray is visible (about six to eight times). 

The tissue should be safely discarded after use. Before using the spray, ensure that the nose is clear.

The head should be tilted back slightly and the tip of the bottle inserted into the nostril as far as is comfortable. 


While breathing through the mouth, one metered dose should be dispensed in each nostril. 


Sniffing, swallowing, or inhaling through the nose while administering the medication increases the irritating effects of the spray. 

Allow 2-3 minutes before blowing the nose to allow the nicotine to be absorbed across the nasal mucosa. 


Contact with skin, eyes, and mouth should be avoided. 


If contact occurs, immediately rinse with water, as nicotine is readily absorbed across the skin and mucous membranes.

Bupropion SR (Zyban)

Use and Dosage:

Bupropion SR, a sustained-release antidepressant, is a non-nicotine aid to smoking cessation. 

Bupropion SR has been demonstrated to increase the likelihood of abstinence from smoking for as long as six months compared to treatment with a placebo.


In a 2005 study done by general practitioners in Italy, bupropion SR more than doubled the odds of continuous abstinence from smoking. 


Bupropion SR is available only by prescription and is dispensed in both generic and brand-name forms. 



The mechanism by which bupropion SR enhances the ability of patients to abstain from smoking is unknown. 



However, it is believed to be a weak inhibitor of the neuronal uptake of norepinephrine and dopamine. 


 Reductions of the following withdrawal symptoms are most pronounced: irritability, frustration, or anger; anxiety; difficulty concentrating; restlessness; and depressed mood or negative affect.

Bupropion SR is supplied in 150-mg tablets. 

Therapy should be initiated one week prior to the quit date to assure that therapeutic plasma levels of the drug are achieved. 



The titration dose is 150 mg by mouth in the morning for three days followed by 150 mg twice per day for the duration of therapy (7 to 12 weeks). 

The daily dose of bupropion SR for smoking cessation should not exceed 300 mg per day. 



For patients who remain abstinent after 7 to 12 weeks of treatment, ongoing therapy should be considered. 



Maintenance therapy at 300 mg bupropion SR per day can be continued for up to six months to prevent relapse. 



Dose tapering is not required when discontinuing treatment. 



If significant progress toward abstinence is not achieved by the seventh week of therapy, treatment should be discontinued.

Contraindications:

Use of bupropion SR is contraindicated in patients with a history of seizures, anorexia, or bulimia nervosa; patients being treated with Wellbutrin SR or MAO inhibitors; and patients undergoing abrupt discontinuation of alcohol or sedatives (including benzodiazepines). 

Three hundred fifty-one major drug interactions have been identified with concomitant use of bupropion SR  therefore, a thorough drug history should be completed prior to prescribing its use. 



Bupropion SR should be used with extreme caution in patients with severe hepatic cirrhosis.

Serious neuropsychiatric symptoms have been reported in patients taking bupropion SR for smoking cessation. 



These symptoms include changes in 

Mood (including depression and mania), 

Psychosis, 

Hallucinations, 

Paranoia, 

Delusions, 

Homicidal ideation, 

Hostility, 

Agitation, 

Aggression, 

Anxiety, 

Panic,  as well as Suicidal Ideation, Attempted Suicide, and Completed Suicide.

However, some of these symptoms have occurred in patients taking bupropion SR who continue to smoke. 


Most reported that symptoms occurred during treatment with bupropion SR, but some occurred after discontinuation of treatment with the drug. 


These events occurred in patients with and without mental disorders. 


Some patients experienced worsening of their psychiatric illnesses. 

All patients being treated with bupropion SR should be observed for neuropsychiatric symptoms or worsening of preexisting psychiatric illness.

The risks of bupropion SR should be weighed against the benefits of its use. The health benefits of quitting smoking are immediate and substantial. 

Bupropion SR should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus (pregnancy category C). 

Bupropion SR and its metabolites are secreted in human milk. 


Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug. 

The safety and effectiveness of bupropion SR in the adolescent population has not been established.

Side Effects:

Insomnia, dry mouth, dizziness, disturbed concentration, dream abnormality, rhinitis, rash, nervousness, nausea, diarrhea, anorexia, constipation, arthralgia, anxiety, and myalgia have been reported. 


The most common side effects reported are insomnia and dream abnormalities. 


Taking the second dose with dinner rather than at bedtime may reduce insomnia and dream abnormalities.

Patient Instructions:

Bupropion SR treatment should be initiated while the patient is still smoking, because approximately one week of treatment is required to achieve steady-state blood levels of bupropion. 


Patients should set a “target quit date” within the first two weeks of treatment, generally in the second week. 

The patient should begin taking 150 mg each day for the first three days. 



On the fourth day, the dose should be increased to one 150-mg tablet in the morning and one 150-mg tablet in the evening. 

This dosage should be continued through the end of treatment. 



There should be an interval of at least eight hours between doses. 



The tablet should be swallowed whole and not crushed, divided, or chewed. 

Treatment should be continued for 7 to 12 weeks. 



Drug therapy may be continued for an additional six months to help prevent relapse. 



Patients and support-givers should be advised to report any changes in neuro­psychiatric symptoms or worsening of preexisting psychiatric illness.

Varenicline (Chantix).

Mechanism of Action:

Varenicline acts as a partial agonist, targeting the nicotine receptors in the brain. 


By binding to and partially stimulating the α4β2 receptor, varenicline blocks nicotine while causing a reduced release of dopamine, decreasing the pleasurable effects of nicotine and reducing cravings. 


It has been demonstrated to increase the likelihood of abstinence from smoking for as long as one year compared to treatment with a placebo. 

In a 52-week trial comparing varenicline with a placebo, the continuous abstinence rate was significantly higher for the varenicline group than for the placebo group for weeks 13 to 24 (70.5% vs. 49.6%) as well as for weeks 13 to 52 (43.6% vs. 36.9%).

The abstinence rate of patients on varenicline therapy was superior to the patient group on bupropion SR in clinical trials. 


Continuous abstinence for varenicline at 52 weeks was 23% compared to 14.6% in the bupropion SR group.

Dosage:

The patient should set a date to stop smoking and begin varenicline one week before this date. 


Varenicline should be taken after eating and with a full glass of water.

Dosage schedule is 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

Patients should be treated for a minimum of 12 weeks. 

For patients who have successfully stopped smoking at the end of 12 weeks, an additional course of 12 weeks is recommended to further increase the likelihood of long-term abstinence. 

If smoking cessation is not achieved after 12 weeks of therapy or if relapse has occurred, treatment should be discontinued until factors contributing to the failed attempt have been identified and resolved. 

Clinicians should consider a temporary or permanent dose reduction in patients who cannot tolerate the side effects. 


The safety and efficacy of the use of varenicline in combination with other smoking cessation therapies has not been established.

Warnings and Precautions:

Caution should be exercised while driving or operating machinery until absence of side effects is established. Accidental injuries (e.g., traffic accidents) have been reported. 

Serious neuropsychiatric symptoms have been reported in patients being treated with varenicline, including changes in mood (e.g., depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, hostility, agitation, anxiety, and panic, as well as suicidal ideation, attempted suicide, and completed suicide.

 Depression has been reported in smokers undergoing a smoking cessation attempt without medication. 



 However, some of these symptoms have occurred in patients taking varenicline who continued to smoke. 



When symptoms were reported, most were during treatment, but some were following discontinuation of drug therapy. 

These events have occurred in patients with and without preexisting psychiatric disease. 



Some patients have experienced worsening of their psychiatric illnesses. 



All patients being treated with varenicline should be observed for neuropsychiatric symptoms or worsening of preexisting psychiatric illness.

The U.S. Food and Drug Administration (FDA) recently sponsored two observational studies of neuro­psychiatric adverse events with varenicline and determined that, based on post-marketing surveillance reports, the current warnings in the drug label remain appropriate.

On June 16, 2011, the FDA sent notification that varenicline may be associated with a small increased risk of certain adverse cardiovascular events in patients who have cardiovascular disease. 



This safety information was added to the medication’s warnings and precautions. 



Nevertheless, smoking is an independent and major risk factor for cardiovascular disease, and smoking cessation is of particular importance in this patient population. 

The clinician must weigh the known benefits of varenicline against its potential risks before recommending use of this drug by smokers with cardiovascular disease. 



Patients taking varenicline should contact their healthcare professional if they experience new or worsening symptoms of cardiovascular disease.

The FDA required the manufacturer to conduct a large, combined analysis (meta-analysis) of randomized, placebo-controlled trials. 



The FDA updated the public following completion of the meta-analysis with the information that there was indeed a small increased cardiovascular risk, though it was not statistically significant. 

The clinician should advise patients and caregivers that the patient should stop taking varenicline and contact a healthcare provider immediately if agitation, depressed mood, or changes in behavior or thinking that are not typical for the patient are observed, or if the patient develops suicidal ideation or suicidal behavior. 



The risks of varenicline should be weighed against the benefits of its use.

There have been infrequent reports of life-threatening angioedema requiring emergent medical attention due to respiratory compromise. 



Clinical signs included swelling of the face, mouth (tongue, lips, and gums), extremities, and neck (throat and larynx). 



In such cases, the patient should be instructed to discontinue the medication and seek immediate medical care.

For patients with severe renal impairment, the recommended starting dose is 0.5 mg once daily. 



The dose may then be titrated as needed to a maximum dose of 0.5 mg twice a day. 



For patients with end-stage renal disease undergoing hemodialysis, a maximum dose of 0.5 mg once daily may be administered if tolerated.



No dosage adjustment is necessary for patients with hepatic impairment. 



Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and renal function should be monitored.

Side Effects:

The most common adverse reactions are nausea, abnormal (e.g., vivid, unusual, or strange) dreams, constipation, flatulence, and vomiting. 


Nausea is the most common adverse reaction (up to 30% incidence rate). Dose reduction may be helpful.

Patient Instructions

Varenicline therapy should begin 1 week prior to the quit date. One 0.5-mg tablet should be taken daily for the first 3 days. 


For the next 4 days, one 0.5-mg tablet should be taken in the morning and one 0.5-mg tablet should be taken in the evening. 


After the first 7 days, the dose should be increased to one 1-mg tablet in the morning and one 1-mg tablet in the evening. 

This regimen should be continued through the end of treatment. 


It is important that varenicline be taken after eating and with a full glass of water to reduce nausea. 


Nausea and insomnia are common side effects and are usually transient. 

If the side effects are severe or persistent, patients should notify the dentist or physician so that a dose reduction can be considered.

Combination Pharmacotherapy:

Evidence indicates that using a combination of medications for smoking cessation significantly increases the likelihood of abstinence.


The decision to use medications in combination should be based on the clinician’s and patient’s perceptions of the adequacy of control of tobacco withdrawal symptoms. 

Consideration for the use of medications in combination should include the increased cost of medications and the possibility of increased side effects.

Approved combination medications include any of the following:

• Long-term (greater than 14 weeks) nicotine patch plus another form of nicotine replacement (nicotine gum and nicotine spray).
• Nicotine patch plus the nicotine inhaler.
• Nicotine patch plus bupropion SR9.