Nicotine Replacement Therapy

Indications

• FDA-approved to reduce withdrawal symptoms and aid smoking cessation in adults, with patch, gum and lozenge available over the counter.
• Nasal spray and oral inhaler remain prescription-only and suit highly dependent smokers who need rapid craving relief.
• Combination therapy pairing a long-acting patch with a short-acting form is more effective than any single product and is now standard practice.
• Recommended by USPSTF and VA/DoD as first-line pharmacotherapy, and the preferred option in pregnancy when medication is judged necessary.
• Preloading before the quit date and reduce-to-quit schedules both increase abstinence and are supported by randomized evidence.
• Off-label uses include craving control for hospitalized inpatients who cannot smoke and short-term relief in smokeless tobacco users.

Mechanism of action

• Agonist at nicotinic acetylcholine receptors, chiefly alpha4beta2, occupying the same receptors that maintain tobacco dependence.
• Delivers nicotine more slowly and at lower peaks than inhaled smoke, which relieves withdrawal without reinforcing the addiction.
• The patch supplies steady baseline receptor occupancy while gum, lozenge, spray or inhaler cover cue-triggered craving surges.
• Buccal absorption is pH-dependent, so acidic beverages and coffee lower the pH of the mouth and sharply reduce nicotine uptake.
• Nicotine itself does not cause the malignancy and lung disease of smoking; combustion products such as tar and carbon monoxide do.

Pharmacokinetics

• The transdermal patch reaches plateau concentrations in 2-4 h and is supplied in 16 h and 24 h formats at 7, 14 and 21 mg strengths.
• Plasma nicotine half-life is about 2 h while the metabolite cotinine persists roughly 16 h, which is why cotinine is used for verification.
• Metabolized mainly by CYP2A6 to cotinine, with clearance faster in pregnancy, in menthol users and in rapid-metabolizer genotypes.
• Swallowed nicotine is largely destroyed by first-pass metabolism, so gum and lozenge must be absorbed across the buccal mucosa.
• The nasal spray gives the fastest rise, peaking near 10 min, while the inhaler is actually absorbed buccally rather than in the lung.

Dosing

• Patch for more than 10 cigarettes daily: 21 mg/24 h for 6 weeks, then 14 mg for 2 weeks, then 7 mg for 2 weeks; start at 14 mg if lighter.
• Gum: 2 mg if the first cigarette comes more than 30 min after waking, 4 mg if sooner; one piece every 1-2 h, up to 24 pieces daily.
• Use the chew-and-park technique with gum and let lozenges dissolve without chewing; avoid acidic drinks for 15 min before and during use.
• Lozenge dosing mirrors gum at 2 mg or 4 mg with a maximum of 20 units daily; the mini-lozenge dissolves faster with the same strengths.
• Nasal spray is 1-2 doses per hour to a maximum of 5 per hour or 40 daily; the inhaler is 6-16 cartridges daily.
• Treat for at least 8-12 weeks and extend when craving persists; long-term use is far safer than returning to cigarettes.

Adverse effects

• Local skin irritation or erythema affects up to half of patch users; rotate sites daily and treat with topical hydrocortisone if needed.
• Vivid dreams and insomnia are common with the 24 h patch and usually resolve if the patch is removed at bedtime.
• Gum causes jaw ache, hiccups, dyspepsia and mouth soreness, most of which trace back to chewing too fast rather than parking.
• Nasal spray produces nasal and throat irritation, sneezing, coughing and watery eyes in the majority of users during the first week.
• Symptoms of excess nicotine include nausea, dizziness, palpitations and headache, and are relieved by reducing the dose or frequency.
• Ingestion of gum, lozenges or a discarded patch by a young child or pet can be serious, so storage and disposal must be discussed.

Monitoring

• Track cigarettes per day, withdrawal symptoms and craving at weeks 1, 2 and 4, and raise the dose if craving persists rather than stopping.
• Inspect patch sites and review chewing or dissolving technique, since poor technique is the commonest cause of apparent failure.
• Recheck clozapine, olanzapine and theophylline levels one to two weeks after the patient stops smoking, regardless of NRT use.
• Exhaled carbon monoxide or urinary anabasine can verify abstinence, since cotinine will remain positive during NRT itself.
• Reassess mood in psychiatric patients, because nicotine withdrawal can transiently worsen depression and anxiety.

Interactions

• Stopping the smoke, not the nicotine, removes CYP1A2 induction and can nearly double clozapine, olanzapine, fluvoxamine and theophylline levels.
• Caffeine clearance also falls after quitting, so the same coffee intake produces more jitteriness, insomnia and anxiety.
• Acidic beverages including coffee, juice and soft drinks block buccal absorption of gum and lozenges for about 15 min.
• Combining NRT with varenicline or bupropion improves abstinence and is safe, though nausea and headache become more common.
• Nicotine itself has no significant CYP-mediated interactions, so no psychotropic dose change is required for the NRT product.

Special populations

• Pregnancy: behavioral treatment comes first; if NRT is used, intermittent forms are preferred and clearance is faster, so under-dosing is common.
• Lactation: far preferable to continued smoking; use short-acting forms and dose immediately after a feed to minimize milk levels.
• Pediatric labeling is for age 18 and older, and trial evidence for efficacy in adolescents is weak, so counseling remains the mainstay.
• Geriatric patients tolerate NRT well; the main issues are skin integrity with patches and dentures interfering with gum.
• Cardiovascular disease: NRT is safe in stable disease, but label caution applies within 2 weeks of myocardial infarction or with unstable angina.

Clinical pearls

• Patch plus PRN gum or lozenge beats any single form; most failures are simply under-dosed.
• No coffee, juice or soda for 15 min around gum or lozenge, or the nicotine will not absorb.
• Nicotine does not cause the cancer, the smoke does; say so plainly to justify long-term NRT.