Nicotine Chewing Gum Adverse Events Associated with NRT

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 erythema,฀edema฀and฀contact฀dermatitis฀ [23,฀56–58] .฀A฀meta-analysis฀of฀35฀trials฀reported฀ the฀overall฀incidence฀of฀localised฀skin฀reactions฀to฀be฀25฀in฀subjects฀in฀the฀active฀treat- ment฀group฀and฀13฀in฀the฀placebo฀group฀ [59] .฀Skin฀reactions฀are฀usually฀transient.฀The฀ incidence฀of฀systemic฀AEs,฀including฀nausea,฀vomiting,฀dizziness,฀headache,฀insomnia฀and฀ gastrointestinal฀ discomfort,฀ is฀ low฀ and฀ rarely฀ causes฀ discontinuation฀ from฀ treatment.฀ Several฀of฀these฀symptoms฀dizziness,฀headache,฀sleep฀disturbances฀may฀be฀attributable฀to฀ withdrawal฀symptoms.฀Sleep฀disturbance฀may฀also฀be฀attributable฀to฀therapy฀with฀the฀24-h฀ nicotine฀ patch,฀ as฀ it฀ is฀ more฀ common฀ than฀ during฀ placebo฀ therapy฀ 20฀ vs.฀ 7฀ [60] .฀ However,฀use฀of฀nicotine฀patch฀during฀waking฀hours฀only฀does฀not฀appear฀to฀cause฀this฀ problem฀ [60,฀61] . Some฀concerns฀were฀initially฀raised฀about฀the฀safety฀of฀NRT฀for฀smokers฀with฀heart฀ disease฀when,฀following฀the฀introduction฀of฀the฀nicotine฀patch฀in฀1992,฀a฀small฀number฀of฀ users฀ experienced฀ acute฀ myocardial฀ infarction.฀ However,฀ the฀ US฀ Food฀ and฀ Drug฀ Administration฀evaluated฀the฀issue฀using฀post-marketing฀surveillance฀data฀and฀concluded฀ that฀the฀nicotine฀patch฀did฀not฀contribute฀to฀an฀increase฀in฀the฀risk฀of฀myocardial฀infarction฀ [62] .฀Subsequent฀clinical฀studies฀have฀conirmed฀that฀patients฀with฀coronary฀heart฀disease฀ tolerate฀nicotine฀patches฀well,฀and฀no฀increase฀in฀either฀angina฀attacks฀or฀other฀cardiac฀ events฀has฀been฀noted฀in฀this฀population฀ [59,฀63,฀64] .

11.1.9.3 Nicotine Nasal Spray

The฀most฀common฀AEs฀with฀nicotine฀nasal฀spray฀are฀local฀irritant฀effects฀nasal฀irritation,฀ runny฀nose,฀sneezing,฀throat฀irritation,฀watering฀eyes,฀cough฀which฀occur฀most฀frequently฀ during฀the฀irst฀few฀days฀of฀treatment.฀Nasal฀irritation฀and฀runny฀nose฀have฀been฀reported฀ by฀approximately฀90฀of฀users฀ [9,฀45,฀47] ฀but฀local฀irritant฀effects฀were฀also฀common฀in฀ the฀placebo฀groups฀the฀placebo฀spray฀contained฀black฀pepper฀to฀maintain฀blinding.฀The฀ frequency฀of฀local฀AEs฀decreases฀within฀the฀irst฀week฀of฀use฀ [65] ฀and฀despite฀the฀high฀ initial฀incidence฀of฀local฀irritant฀effects฀few฀subjects฀discontinue฀treatment฀because฀of฀such฀ effects.฀The฀most฀common฀systemic฀events฀in฀clinical฀trials฀were฀headaches฀or฀dizziness,฀ which฀initially฀occurred฀among฀15–20฀of฀subjects฀after฀commencing฀treatment฀ [9,฀45,฀ 47] ฀but฀decreased฀with฀time฀to฀10฀after฀3฀weeks.฀Nausea,฀palpitations,฀sweating฀and฀ cold฀ hands฀ and฀ feet฀ occur฀ infrequently.฀ No฀ serious฀ cardiovascular฀ effects฀ have฀ been฀ reported฀with฀nicotine฀nasal฀spray.

11.1.9.4 Nicotine Inhaler

Local฀AEs฀are฀common฀during฀the฀irst฀few฀days฀of฀treatment,฀but฀these฀are฀generally฀mild฀ and฀diminish฀during฀repeated฀use.฀The฀most฀frequent฀are฀cough฀and฀irritation฀in฀the฀mouth฀ and฀throat฀ [9,฀48,฀52] .฀In฀clinical฀trials,฀the฀most฀common฀systemic฀AEs฀were฀headache฀ nicotine฀inhaler฀26,฀placebo฀20,฀gastrointestinal฀discomfort฀14฀vs.฀8฀and฀nausea฀ 10฀vs.฀7.