Table 2.

First-line agents recommended for smoking cessation

Drug	Posology	Method of administration	Possible adverse reactions	Advantages	Disadvantages	Precautions
NRT transdermal patch	If patient smokes at least 10 cigarettes per day: start with  21 mg/24 h for 4 weeks, then  14 mg/24 h for 2 weeks, then  7 mg/24 h for 2 weeks If patient smokes less than 10 cigarettes per day: start with  14 mg/24 h for 6 weeks, then  7 mg/24 h for 2 weeks	Apply a new patch every morning for 8–12 weeks on clean and dry skin Evidence of an efficacy increases if used for 3–6 months Change application site to prevent skin reactions Start using the day before or the same day the patient stops smoking	Skin reactions at the application site Insomnia or vivid dreams (in this case, patch could be removed before bedtime)	Easy to use Provide steady nicotine levels Maintenance therapy during combination NRT due to slow release (“controller”)	If craving appears, combine with a rapid-release NRT form (“reliever”)	Recent myocardial infarction (≤ 2 weeks) Serious arrhythmias Serious or worsening angina pectoris Pregnancy (category D) and breast-feedinga Adolescents (age < 18 years)
NRT gum	If patient smokes at least 25 cigarettes per day: 4 mg If patient smokes less than 25 cigarettes per day: 2 mg Recommended dose usually is 8–12 gums/24 h for at least 3 months	Chew until a slight oral tingling appears, then place the gum on the side of the mouth until the tingling vanishes, then start chewing again This procedure (chewing and placing aside) should be repeated for about 30 min, then the gum should be thrown away. Use a maximum of 1 gum per hour	Mouth irritation Jaw pain Heartburn Hiccup Nausea	Patient is aware of using the medication The method of administration “steals” the mouth to traditional cigarette It could be used in combination with patch as a “reliever” if craving occurs	Patient should be adherent to chewing technique It could be difficult to use with dentures and could damage teeth or dental works Eating and drinking should be avoided for 15 min before and during chewing of nicotine gum	Recent myocardial infarction (≤ 2 weeks) Serious arrhythmias Serious or worsening angina pectoris Temporo-mandibular joint disease Pregnancy and Breast-feedinga Adolescents (age < 18 years)
NRT lozenge	If patient smokes the first cigarette within 30 min of waking up: 4 mg If patient smokes the first cigarette 30 min after waking up: 2 mg Use for 3–6 months	Place the tablet in the mouth between the internal cheek and gum, leave there until it slowly dissolves Take 1 tablet every 1–2 h (maximum 20 per day)	Mouth irritation Jaw pain Heartburn Hiccup Nausea	Patient is aware of using the medication The method of administration “steals” the mouth to traditional cigarette It could be used in combination with patch as a “reliever” if craving occurs Easier to use in patients with denture, compared to chewing gum	Eating and drinking should be avoided for 15 min before and during tablet administration	Recent myocardial infarction (≤ 2 weeks) Serious arrhythmias Serious or worsening angina pectoris Pregnancy and breast-feedinga Adolescents (age < 18 years)
NRT oral inhaler	6–16 cartridges per day Every cartridge releases 4 mg of nicotine through 80 inhalations Use up to 6 months	Puff through the mouthpiece in short breaths (do not inhale deeply) until craving decreases Change the cartridge when the flavour disappears Use 1 cartridge every 1–2 h (maximum 16 per day)	Mouth irritation Cough if deeply inhaled	Patient is aware of using the medication It mimics the ritual hand-to-mouth action of smoking It could be used in combination with patch as a “reliever” if craving occurs	Many inhalations are needed to have an adequate efficacy	Recent myocardial infarction (≤ 2 weeks) Serious arrhythmias Serious or worsening angina pectoris Bronchospastic disorders Pregnancy (category D) and breast-feedinga Adolescents (age < 18 years)
NRT nasal spray	0.5 mg in each nostril, start with 1–2 sprays per hour to a maximum of 8–40 sprays per day Use for 3–6 months	Spray once in each nostril, every 1–2 h (maximum dose: 40 sprays in each nostril per day)	Irritation of nose or back in the throat Rhinitis Sneezing Coughing Watery eyes	Patient is aware of using the medication Route of administration with the fastest absorption among NRTs Excellent “reliever” in combination with patch	Route of administration with the greatest prevalence of adverse reactions among NRTs (especially the nasal irritation makes it often unusable)	Recent myocardial infarction (≤ 2 weeks) Serious arrhythmias Serious or worsening angina pectoris Chronic nasal disorders (rhinitis, nasal polyps, sinusitis) Severe reactive airway disease Pregnancy (category D) and breast-feedinga Adolescents (age < 18 years)
Varenicline	Day 1–3: 0.5 mg once daily, in the morning Day 4–7: 0.5 mg twice daily, in the morning and in the evening Day 8 to end of treatment: 1 mg twice daily, in the morning and in the evening Start 1 week before the day of smoking cessation Use for 3–6 months	Swallow with a full glass of water and take with food to minimize the risk of nausea	Nausea Insomnia Vivid dreams Headache	Easy to use The first day of smoking cessation can be flexible (from 1 week to 3 months after the first dose) Double effect: reduces both nicotine withdrawal symptoms and the pleasure associated with smoking	Possible psychiatric adverse reactions (as reported in a previous FDA warning, then withdrawn), that are actually not so frequent	Severe renal impairment (dosage adjustment is necessary) Pregnancy (category C) and breast-feedinga Adolescents (age < 18 years) Treatment-emergent neuropsychiatric symptoms: FDA boxed warning removed (December 2016)
Bupropion SR	Day 1–3: 150 mg once daily, in the morning from day 4: 150 mg twice daily for 3–6 months	Start therapy 1–2 weeks before target quit date	Insomnia Agitation Dry mouth Headache	Easy to use Could reduce weight increase typically associated with smoking cessation	Increased risk of seizures (do not use in patients with history of epilepsy or alcohol abuse)	Concomitant medications/conditions known to lower the seizure threshold Hepatic impairment Pregnancy (category C) and breast-feedinga Adolescents (age < 18 years) Treatment-emergent neuropsychiatric symptoms: FDA boxed warning removed (December 2016)

FDA Food and Drug Administration, NRT nicotine replacement therapy, SR sustained-release

^aGiven the insufficient evidence of effectiveness and theoretical safety concerns during pregnancy, pregnant smokers should be encouraged to quit without medication. Therefore, behavioral counselling interventions should be the first choice for pregnant smokers