Treatment and Dosage Nicotine

smoked฀daily฀see฀Table฀ 11.3 .฀ Figure฀11.1 ฀summarises฀the฀eficacy฀of฀the฀various฀nicotine฀ products,฀based฀on฀published฀reports฀from฀the฀literature,฀with฀a฀6-month฀period฀of฀absti- nence฀from฀smoking฀being฀the฀criterion฀for฀success. NRT฀is฀the฀appropriate฀instrument฀for฀helping฀the฀dependent฀smoker฀to฀achieve฀smok- ing฀cessation.฀Its฀effectiveness฀is฀increased฀2–3-fold฀if฀the฀smoker฀wants฀to฀stop.฀While฀ Table 11.3 ฀฀฀Stepwise฀schedule฀for฀smoking฀cessation฀with฀nicotine฀products฀patch฀with฀transdermal฀ release฀of฀0.9฀mgh,฀4฀mg฀chewing฀gum,฀nasal฀spray฀containing฀0.5฀mgspray฀and฀sublingual฀tablets฀ containing฀2฀mg Level Diagnostic฀criteria Therapeutic฀schedule฀daily฀doses 1฀Mild FTND฀1–2,฀5–10฀cigarettes day,฀CO:฀10–15฀ppm Medical฀consultation฀to฀educate฀the฀smoker฀ about฀the฀harmful฀effects฀of฀smoking฀on฀ health฀and฀about฀hisher฀personal฀situation฀ based฀on฀individual฀indings, a ฀one฀piece฀of฀ chewing฀gum,฀as฀required,฀when฀the฀urge฀to฀ smoke฀a฀cigarette฀is฀strong 2฀Moderate FTND฀³3;฀15฀cigarettes day;฀CO:฀10–20฀ppm Initially,฀up฀to฀12฀pieces฀of฀nicotine฀chewing฀ gum฀or฀one฀nicotine฀patch,฀plus฀a฀few฀pieces฀ of฀nicotine฀gum฀only฀in฀the฀initial฀days฀of฀ treatment;฀depending฀how฀the฀ex-smoker฀ feels,฀continue฀the฀treatment฀for฀2–3฀weeks,฀ then฀reduce฀the฀dose฀as฀appropriate 3฀Severe FTND฀³5;฀15–25฀ciga- rettes฀day;฀CO:฀15–35฀ ppm One฀nicotine฀patch฀plus฀6–12฀pieces฀of฀nicotine฀ gum,฀depending฀on฀urge฀to฀smoke,฀or฀ nicotine฀nasal฀spray฀one฀spray฀into฀each฀ nostril฀every฀time฀there฀is฀an฀urge฀to฀smoke;฀ not฀more฀than฀two฀applicationsh;฀continue฀ the฀treatment฀for฀3–6฀weeks,฀then฀reduce฀the฀ dose฀as฀appropriate;฀supply฀the฀ex-smoker฀ with฀a฀product฀nicotine฀chewing฀gum฀or฀ nasal฀spray฀as฀relief฀for฀craving฀or฀strong฀ urge฀to฀smoke฀during฀the฀ensuing฀months 4฀Very฀severe FTND b ฀³7;฀25–40฀ cigarettesday;฀CO c :฀ 30–45฀ppm One฀nicotine฀patch฀plus฀10–12฀pieces฀of฀ nicotine฀chewing฀gum d ฀plus฀nicotine฀nasal฀ spray฀one฀spray฀into฀each฀nostril฀as฀ required,฀until฀craving฀or฀the฀urge฀to฀smoke฀ is฀relieved;฀continue฀treatment฀for฀2–4฀ weeks฀and฀then฀discontinue฀one฀nicotine฀ product฀chewing฀gum;฀later฀halve฀the฀dose฀ administered฀by฀patch,฀retain฀the฀nasal฀spray฀ to฀relieve฀craving฀for฀up฀to฀6฀months฀this฀ will฀not฀be฀required฀at฀all฀on฀various฀days FTND฀Fagerström฀Test฀for฀Nicotine฀Dependence;฀CO฀carbon฀monoxide฀concentration฀ [1] .฀The฀ level฀of฀dependence฀is฀classiied฀in฀four฀grades a These฀consultations฀are฀also฀compulsory฀at฀higher฀dependence฀levels b An฀internal฀correlation฀between฀the฀FTND฀and฀CO฀values฀has฀not฀been฀conirmed.฀The฀two฀values฀ are฀only฀approximately฀linked฀with฀each฀other c The฀CO฀levels฀measured฀are฀inluenced฀by฀the฀time฀when฀smoking฀took฀place.฀An฀interval฀of฀30฀ min฀should฀be฀observed฀between฀the฀last฀cigarette฀and฀the฀measurement฀of฀CO d Instead฀of฀the฀4฀mg฀chewing฀gum,฀the฀2฀mg฀sublingual฀tablet฀may฀also฀be฀used patches฀are฀more฀convenient฀to฀use฀than฀chewing฀gum฀or฀nasal฀spray,฀they฀are฀less฀effective฀ for฀the฀relief฀of฀cravings฀when฀compared฀with฀nasal฀spray,฀in฀particular.฀Although฀only฀a฀ few฀studies฀have฀been฀published฀on฀the฀combined฀use฀of฀two฀different฀nicotine฀formula- tions฀patch฀+฀chewing฀gum฀or฀nasal฀spray,฀and฀chewing฀gum฀+฀nasal฀spray฀or฀patch฀+฀ inhaler,฀the฀suppression฀of฀cravings฀is฀the฀crucial฀issue฀with฀regard฀to฀failure฀in฀many฀dis- sonant฀ex-smokers฀once฀smoking฀cessation฀therapy฀has฀begun.฀Medical฀management฀has฀a฀ pivotal฀role฀to฀play฀during฀smoking฀cessation฀therapy฀ [5] . Our฀own฀experiences฀with฀the฀treatment฀of฀several฀hundred฀smokers฀are฀set฀out฀sche- matically฀in฀Table฀ 11.3 .฀The฀schedule฀cannot฀be฀deined฀rigidly฀because฀while฀the฀level฀of฀ dependence฀can฀be฀identiied฀–฀it฀is฀so฀shaped฀by฀the฀patient’s฀personality฀structure,฀includ- ing฀hisher฀own฀willpower฀–฀the฀therapist฀must฀repeatedly฀expect฀the฀unexpected. Where฀the฀goal฀of฀therapy฀is฀total฀smoking฀cessation,฀it฀is฀important฀to฀warn฀patients฀ emphatically฀to฀stop฀smoking฀completely฀while฀taking฀nicotine฀products.฀If฀the฀objective฀ is฀ reduced฀ smoking฀ “harm฀ reduction”,฀ the฀ number฀ of฀ cigarettes฀ smoked฀ should฀ not฀ exceed฀10day.฀In฀this฀case,฀nicotine฀therapy฀should฀be฀tailored฀accordingly. Gender฀differences฀may฀play฀a฀role฀in฀the฀eficacy฀of฀NRTs.฀This฀was฀analysed฀in฀a฀ meta-analytical฀review฀of฀90฀effect฀sizes฀obtained฀from฀a฀sample฀of฀21฀double-blind,฀pla- cebo-controlled฀randomized฀studies฀ [55] .฀It฀was฀shown฀that฀although฀NRT฀was฀more฀effec- tive฀ for฀ men฀ than฀ placebo฀ at฀ 3-,฀ 6-฀ and฀ 12-month฀ follow-ups,฀ the฀ beneits฀ of฀ NRT฀ for฀ women฀were฀clearly฀evident฀only฀at฀the฀3-฀and฀6-month฀follow-ups.฀Also,฀giving฀NRT฀in฀ conjunction฀ with฀ high-intensity฀ nonpharmacological฀ support฀ was฀ more฀ important฀ for฀ women฀than฀men.฀It฀was฀concluded฀that฀long-term฀maintenance฀of฀NRT฀treatment฀gains฀ decrease฀more฀rapidly฀for฀women฀than฀men฀ [55] .

11.1.9 Adverse Events Associated with NRT

The฀symptoms฀of฀nicotine฀toxicity฀range฀from฀nausea,฀abdominal฀pain฀and฀vomiting,฀diz- ziness฀and฀headache฀to฀dyspnoea,฀convulsions฀and฀respiratory฀failure.฀Regular฀cigarette฀ smokers฀develop฀tolerance฀to฀many฀of฀the฀effects฀of฀nicotine,฀and฀stopping฀smoking฀is฀ associated฀with฀various฀nicotine฀withdrawal฀symptoms฀including฀dysphoria,฀irritability,฀ anxiety,฀dificulty฀concentrating,฀restlessness,฀insomnia,฀decreased฀heart฀rate฀and฀increased฀ appetite.฀Withdrawal฀symptoms฀are฀often฀mistaken฀for฀adverse฀events฀AEs฀associated฀ with฀NRT฀products.

11.1.9.1 Nicotine Chewing Gum

The฀most฀frequently฀reported฀systemic฀AEs฀with฀nicotine฀2-฀and฀4-mg฀gum฀are฀headache,฀ dizziness,฀gastrointestinal฀discomfort,฀nausea฀and฀vomiting,฀while฀local฀AEs฀include฀sore฀ mouth฀or฀throat.฀Less฀frequent฀adverse฀reactions฀include฀palpitations,฀erythema฀and฀urti- caria.฀ Atrial฀ ibrillation฀ and฀ allergic฀ reactions฀ have฀ been฀ reported,฀ but฀ these฀ are฀ rare฀ Table฀ 11.4 .฀A฀slight฀throat฀irritation฀and฀increase฀in฀salivation฀may฀occur฀on฀commencing฀ treatment,฀and฀excessive฀swallowing฀of฀dissolved฀nicotine฀may฀cause฀hiccups.฀The฀unusual฀ taste฀of฀nicotine฀gum฀may฀initially฀be฀considered฀unpleasant.฀Some฀local฀effects฀are฀related฀ to฀chewing฀technique,฀and฀their฀incidence฀can฀be฀reduced฀with฀proper฀instruction.

11.1.9.2 Nicotine Patch

The฀ most฀ common฀ adverse฀ effects฀ associated฀ with฀ the฀ use฀ of฀ the฀ nicotine฀ transdermal฀ patch฀applied฀for฀16฀or฀24฀h฀are฀local฀skin฀reactions฀at฀the฀site฀of฀application,฀such฀as฀฀itching,฀ Formulation Adverse฀effects Frequency฀ Patch CNS:฀headache,฀dizziness,฀sleep฀disturbance a 1 Gastrointestinal:฀nausea,฀vomiting Local:฀erythema,฀itching Circulation:฀palpitations 0.1–1.0 Skin:฀urticaria Cardiovascular:฀atrial฀ibrillation 0.1 Chewing฀gum CNS:฀headache,฀dizziness 1 Gastrointestinal:฀hiccups,฀eructation,฀nausea,฀vomiting Local:฀sore฀mouth฀or฀throat,฀aching฀jaw฀muscles Circulation:฀palpitations 0.1–1.0 Skin:฀erythema,฀urticaria Cardiovascular:฀atrial฀ibrillation 0.1 Hypersensitivity:฀such฀as฀angiooedema Nasal฀spray CNS:฀headache,฀dizziness 1 Gastrointestinal:฀nausea,฀vomiting Local:฀nasal฀and฀throat฀irritation,฀cough,฀nose฀bleed,฀ rhinitis,฀sneezing,฀watering฀eyes Circulation:฀palpitations 0.1–1.0 Cardiovascular:฀atrial฀ibrillation 0.1 Inhaler CNS:฀Headache,฀dizziness 1 Gastrointestinal:฀hiccups,฀dyspepsia,฀nausea,฀vomiting Local:฀mouth฀or฀throat฀irritation,฀cough,฀pharyngitis,฀ rhinitis Circulation:฀palpitations 0.1–1.0 Cardiovascular:฀atrial฀ibrillation 0.1 Sublingual฀tablet CNS:฀headache,฀dizziness 1 Gastrointestinal:฀hiccups,฀nausea Local:฀sore฀mouth฀or฀throat,฀dry฀mouth,฀cough,฀burning sensation฀in฀mouth Circulation:฀palpitations 0.1–1.0 Cardiovascular:฀atrial฀ibrillation 0.1 Lozenge Cf.฀Sect.฀ 11.1.7 b Table 11.4 ฀฀฀Adverse฀effects฀reported฀during฀treatment฀with฀nicotine฀replacement฀therapy฀NRT฀cf.฀ Sect.฀ 11.1.9 a With฀the฀24-h฀patch,฀worn฀day฀and฀night b Data฀not฀yet฀available