Nicotine Patch Adverse Events Associated with NRT

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.

11.1.9.5 Nicotine Sublingual Tablet

The฀nicotine฀sublingual฀tablet฀may฀cause฀irritation฀or฀soreness฀in฀the฀mouth฀or฀throat,฀hic- cups,฀ nausea,฀ gastrointestinal฀ discomfort,฀ dry฀ mouth฀ or฀ cough฀ [66,฀ 67] .฀ Most฀ AEs฀ are฀ generally฀mild฀and฀occur฀soon฀after฀commencing฀treatment,฀and฀the฀incidence฀diminishes฀ as฀treatment฀continues.฀Use฀of฀nicotine฀sublingual฀tablets฀for฀6฀months฀has฀no฀adverse฀ effect฀on฀the฀oral฀mucosa฀or฀the฀loor฀of฀the฀mouth฀ [67] .

11.1.9.6 Nicotine Lozenge

The฀nicotine฀lozenge฀was฀tested฀in฀one฀study฀with฀1,818฀smokers฀ [11] .฀61.8฀of฀partici- pants฀reported฀one฀or฀more฀adverse฀effects฀during฀6฀months.฀Severe฀adverse฀effects฀were฀ experienced฀by฀17฀of฀the฀participants฀headache,฀diarrhoea,฀latulence,฀heartburn,฀hiccup,฀ nausea,฀coughing.฀However,฀detailed฀information฀about฀the฀frequency฀of฀adverse฀effects฀ will฀be฀available,฀if฀larger฀treatment฀numbers฀are฀reached.

11.1.10 Withdrawal Symptoms

Withdrawal฀symptoms฀vary฀in฀severity฀from฀person฀to฀person฀and฀may฀last฀for฀several฀ weeks฀to฀months.฀Like฀alcoholics,฀many฀ex-smokers฀are฀severely฀at฀risk฀because฀the฀least฀ cause฀going฀to฀a฀restaurant฀and฀having฀an฀alcoholic฀drink,฀meeting฀up฀with฀smokers,฀stress฀ situations฀may฀trigger฀a฀return฀to฀smoking.฀Many฀smokers,฀however,฀“merely”฀miss฀the฀ manual฀cues฀associated฀with฀the฀activity฀of฀smoking.฀Withdrawal฀symptoms฀are฀commonly฀ misinterpreted฀as฀AEs฀of฀nicotine฀products฀Table฀ 11.4 ,฀especially฀where฀the฀symptoms฀ are฀of฀a฀psychological฀nature. Very฀rarely฀a฀drug-induced฀dependence฀reaction฀may฀also฀develop฀during฀the฀course฀of฀ smoking฀cessation฀therapy฀with฀nicotine฀preparations.฀In฀these฀circumstances,฀ex-smokers฀ become฀dependent฀on฀the฀nicotine฀preparations฀themselves฀nasal฀spray฀฀chewing฀gum฀ and฀then฀frequently฀continue฀to฀use฀these฀products฀over฀a฀period฀of฀months.

11.1.11 Drug Interactions During Smoking Cessation

No฀systematic฀studies฀have฀been฀conducted฀on฀interactions฀between฀nicotine฀and฀other฀ concurrently฀administered฀medication.฀The฀metabolic฀processes฀in฀the฀liver฀are฀stimulated฀ principally฀by฀the฀combustion฀products฀of฀tobacco฀and฀not฀by฀nicotine.฀Tobacco฀smoke฀ induces฀the฀cytochrome฀P450฀enzymes฀CYP1A1,฀CYP1A2฀and฀possibly฀CYP2E1฀ [68] .฀ Smokers฀therefore฀metabolise฀various฀drugs฀more฀rapidly,฀and฀the฀converse฀of฀this฀situa- tion฀is฀that฀during฀smoking฀cessation฀the฀activity฀of฀the฀drugs฀in฀question฀may฀be฀increased฀