Nicotine Replacement Therapy

Nicotine replacement therapy gives nicotine without tobacco smoke to ease withdrawal and craving while a patient stops smoking. It roughly doubles quit rates compared with no pharmacological support. A combination of a patch (steady background nicotine) and a short-acting product (gum, lozenge, inhalator or spray for breakthrough cravings) is more effective than a single product. It is safe in most patients with stable cardiovascular disease, and is far safer than continued smoking.

Classification. Smoking cessation aid, nicotinic receptor agonist.

Mechanism. Delivers nicotine, which stimulates nicotinic acetylcholine receptors and relieves withdrawal and craving, at lower and slower-rising blood levels than cigarettes.

Pharmacokinetics. Absorbed through skin (patch, slow, peak 4 to 12 hours), mouth lining (gum, lozenge, mouth spray, peak 20 to 30 minutes), nose (spray, peak 5 to 10 minutes) and lungs (inhalator, via the mouth). Metabolised by CYP2A6 to cotinine. Half-life about 2 hours.

Choose the product and strength by the number of cigarettes smoked daily and the time to the first cigarette after waking.

Transdermal patch (24-hour).

• More than 10 cigarettes daily: 21 mg daily for 6 weeks, then 14 mg daily for 2 weeks, then 7 mg daily for 2 weeks.
• Up to 10 cigarettes daily: start 14 mg daily for 6 weeks, then 7 mg daily for 2 weeks.
• 16-hour patches (25 mg, 15 mg, 10 mg) are removed at night and used in a similar step-down.
• Apply to clean, dry, hairless skin each morning and rotate the site.

Gum or lozenge (short-acting).

• First cigarette within 30 minutes of waking: 4 mg.
• First cigarette later than 30 minutes after waking: 2 mg.
• Use 1 piece every 1 to 2 hours when cravings occur; usual maximum 15 pieces daily (up to 24 in some labels).
• Duration: up to 12 weeks, then reduce gradually.

Inhalator. 15 mg cartridge: draw on the mouthpiece as needed; 4 to 12 cartridges daily for up to 12 weeks, then reduce.

Nasal spray. One spray in each nostril when needed (1 to 2 doses an hour); maximum daily dose differs by label; use for up to 12 weeks, then reduce.

Mouth spray. 1 to 2 sprays (1 mg each) when cravings occur; limits differ by label.

Combination therapy. A 24-hour patch plus gum, lozenge, inhalator or spray for breakthrough cravings. Treat for 12 weeks and then taper.

Pregnancy. Offer behavioural support first; if that fails, short-acting products are preferred, and patches are removed at night.

Dose limits. Adolescents aged 12 to 17 years: use under specialist advice. Stop using nicotine products when nicotine toxicity symptoms occur.

Contraindications. Hypersensitivity to nicotine or the adhesive; non-smokers and children under 12 years should not use it. Use with caution within 2 weeks of a myocardial infarction, in unstable angina, severe arrhythmia, recent stroke, uncontrolled hypertension, hyperthyroidism, phaeochromocytoma, active peptic ulcer, diabetes, and severe liver or kidney disease.

Serious adverse effects. Nicotine toxicity (nausea, vomiting, sweating, pallor, tremor, tachycardia, confusion, convulsions), cardiac arrhythmias, severe skin reactions to patches, accidental ingestion by children (potentially fatal).

Common adverse effects. Patch: skin irritation, itching, sleep disturbance and vivid dreams. Gum or lozenge: mouth soreness, jaw ache, hiccups, nausea, indigestion. Inhalator: cough, throat irritation. Spray: nose or throat irritation. All: headache, dizziness, palpitations.

Interactions. Stopping smoking changes the levels of medicines metabolised by CYP1A2, because tobacco smoke (not nicotine) induces the enzyme: clozapine levels can rise by about 50% or more, olanzapine, theophylline, caffeine and some antidepressants also rise; insulin needs may fall. Adjust these medicines and monitor levels. Acidic drinks (coffee, fruit juice, soft drinks) reduce absorption of gum and lozenges, so avoid them for 15 minutes before use.

Common prescribing errors. Using a single product at too low a dose; not offering combination therapy; using the patch overnight in patients with sleep disturbance; not warning that clozapine, olanzapine or theophylline doses may need reduction when smoking stops; stopping at 4 weeks instead of 8 to 12 weeks; leaving products within reach of children.

Special groups.

• Pregnancy: use short-acting products with behavioural support when smoking cannot be stopped without them; remove patches at night.
• Breastfeeding: use short-acting products and time doses after feeding.
• Children: not for children under 12 years; keep out of reach.
• Older adults: no adjustment.
• Kidney impairment: use cautiously in severe impairment.
• Liver impairment: use cautiously in severe impairment.

Formulations. Patches 5 mg, 7 mg, 10 mg, 14 mg, 15 mg, 21 mg and 25 mg; gum 2 mg and 4 mg; lozenges 1 mg, 1.5 mg, 2 mg and 4 mg; inhalator 15 mg cartridge; nasal spray 10 mg/mL; mouth spray 1 mg a spray. For gum, chew slowly until the taste is strong, then park the gum between cheek and gum, repeating for 30 minutes. For lozenges, allow to dissolve slowly without chewing or swallowing. Do not eat or drink for 15 minutes before and during use.

Baseline. Smoking history and dependence, readiness to quit, cardiovascular and other disease, pregnancy status, medicines list (clozapine, olanzapine, theophylline, warfarin, insulin).

Monitoring. Review at 2 weeks, 4 weeks and 12 weeks. Ask about cravings, adverse effects and smoking lapses. Check levels or doses of clozapine, olanzapine and theophylline when smoking stops, and check glucose in diabetes.

Stopping. Step down the patch strength every 2 to 6 weeks and reduce short-acting products over several weeks. Treatment normally lasts 8 to 12 weeks; longer use is acceptable if it prevents relapse to smoking.

Referral and escalation. Refer to a smoking cessation service for behavioural support. Palpitations, chest pain or symptoms of nicotine toxicity need the product stopped and urgent review. Swallowing of products by a child needs emergency care.