Nicotine Sublingual Tablet Nicotine Nasal Spray

11.1.6 Nicotine Inhaler

The฀inhaler฀consists฀of฀a฀plastic฀housing฀with฀mouthpiece฀designed฀to฀hold฀a฀disposable฀ porous฀cartridge฀impregnated฀with฀10฀mg฀nicotine.฀When฀the฀patient฀draws฀air฀into฀the฀ mouth฀through฀the฀inhaler,฀nicotine฀from฀the฀cartridge฀is฀vaporised.฀At฀room฀temperature,฀ 13฀µg฀nicotine฀is฀released฀by฀one฀draw฀on฀the฀10-mg฀inhaler฀ [48] .฀In฀total,฀approximately฀ 4฀mg฀is฀absorbed฀from฀a฀10-mg฀inhaler;฀a฀maximum฀of฀50฀is฀available฀to฀the฀systemic฀ circulation฀and฀the฀inhalation฀technique฀buccal฀or฀pulmonary฀is฀of฀marginal฀importance฀ in฀ terms฀ of฀ the฀ dose฀ and฀ steady-state฀ plasma฀ concentrations฀ achieved฀ see฀ Fig.฀ 11.5 .฀ Following฀the฀use฀of฀the฀inhaler฀for฀20฀min,฀bioavailability฀is฀not฀higher฀with฀pulmonary฀ inhalation฀deep฀drawing฀than฀with฀buccal฀inhalation฀shallow฀pufing.฀Thus,฀the฀blood฀ nicotine฀levels฀produced฀with฀the฀inhaler฀are฀approximately฀30฀of฀those฀seen฀in฀chronic฀ cigarette฀smokers฀see฀Fig.฀ 11.5 ฀ [49,฀50] .฀Details฀of฀the฀effectiveness฀of฀the฀inhaler฀in฀ smoking฀cessation฀are฀presented฀in฀Table฀ 11.2 .

11.1.7 Nicotine Lozenge

Two฀new฀oral฀forms฀of฀nicotine฀formulations฀have฀recently฀been฀introduced:฀the฀1-mg฀ lozenge฀ UK฀ and฀ Sweden฀ without฀ published฀ pharmacokinetic฀ or฀ eficacy฀ data,฀ and฀ a฀฀ a 50 40 30 20 Nicotine Plasma level [ngml] 10 5 10 15 20 Time [min] 25 30 90 Nicotine Plasma level [ngml] Time [min] 50 40 30 20 10 5 10 15 20 25 30 b Fig. 11.5 ฀฀฀a฀Mean฀arterial฀ open฀circle฀and฀jugular฀ venous฀closed฀circle฀ plasma฀nicotine฀level฀after฀ using฀one฀inhaler฀for฀5฀min฀ n฀=฀7.฀b฀Mean฀arterial฀ open฀circle฀and฀jugular฀ venous฀closed฀circle฀ plasma฀nicotine฀level฀after฀ smoking฀one฀cigarette฀over฀5฀ min฀n฀=฀7.฀Note฀that฀the฀ AV฀difference฀is฀reversed฀for฀ the฀inhaler฀relative฀to฀the฀ cigarette฀ [49] 2-฀and฀4-mg฀lozenge.฀Compared฀with฀the฀analogous฀gum฀formulations,฀the฀lozenges฀deliver฀ small฀amounts฀more฀nicotine฀than฀the฀gum฀formulations฀if฀the฀area฀under฀curves฀were฀ measured฀ [54] .฀The฀eficacy฀of฀the฀2-฀and฀4-mg฀lozenge฀was฀tested฀in฀one฀multicentre฀and฀ placebo-controlled฀trial฀for฀smoking฀cessation฀over฀52฀weeks฀with฀lozenge฀use฀up฀to฀12฀ and฀ad฀libitum฀24฀weeks฀ [11] .฀The฀two฀lozenge฀strengths฀were฀distributed฀according฀to฀ the฀grade฀of฀dependency฀FTND.฀The฀28฀day฀abstinence฀at฀6฀weeks฀dose-dependent฀29฀ vs.฀46.0฀and฀48.7฀abstinence;฀OR฀=฀2.10,฀CI:฀1.59–2.79฀and฀3.69,฀CI:฀2.74–4.96;฀p฀฀ 0.001;฀placebo฀vs.฀2-฀and฀4-mg฀lozenge฀ [11] .

11.1.8 Treatment and Dosage

Treatment฀with฀nicotine฀products฀may฀be฀given฀over฀a฀period฀of฀2–3฀months.฀Nicotine฀ patches฀provide฀mean฀transdermal฀delivery฀over฀16฀or฀24฀h฀of฀0.9฀mg฀nicotineh.฀Lower฀ strength฀patches฀0.6฀or฀0.3฀mgh฀may฀also฀be฀used฀optionally฀at฀a฀later฀stage฀in฀the฀treat- ment฀course.฀Up฀to฀16฀pieces฀of฀nicotine฀chewing฀gum฀4฀mg฀strength฀may฀be฀used฀over฀a฀ 24-h฀period.฀If฀it฀is฀to฀be฀used฀successfully฀and฀without฀producing฀unpleasant฀symptoms,฀ nicotine฀gum฀should฀be฀chewed฀slowly฀over฀a฀period฀of฀30฀min;฀the฀patient฀chews฀the฀gum฀ once฀or฀twice฀using฀the฀molars฀on฀one฀side,฀waits฀for฀30฀s฀and฀then฀repeats฀the฀process฀ using฀the฀molars฀on฀the฀other฀side.฀If฀the฀gum฀is฀chewed฀too฀rapidly,฀suficient฀nicotine฀may฀ be฀released฀within฀a฀few฀minutes฀to฀cause฀nausea,฀salivation,฀retching฀and฀indigestion.฀In฀ future,฀instead฀of฀chewing฀gum,฀sublingual฀tablets฀may฀also฀be฀used,฀and฀this฀formulation฀ may฀ be฀ especially฀ advantageous฀ for฀ people฀ who฀ wear฀ dentures.฀ Nicotine฀ nasal฀ spray฀ releases฀0.5฀mg฀per฀spray.฀One฀spray฀is฀recommended฀into฀each฀nostril฀corresponding฀to฀ 1฀mg฀nicotine฀in฀total.฀Two฀or฀a฀maximum฀of฀three฀doses฀are฀recommended฀per฀hour.฀For฀ details฀of฀the฀inhaler,฀see฀Sect.฀ 11.1.5 .฀The฀medical฀management฀of฀the฀ex-smoker฀involves฀ estimating฀the฀extent฀to฀which฀the฀cravings฀diminish฀with฀time฀after฀smoking฀cessation฀in฀ order฀to฀ensure฀that฀NRT฀is฀not฀halted฀too฀early฀and฀that฀the฀nicotine฀dose฀is฀not฀reduced฀ too฀rapidly.฀As฀is฀evident฀from฀the฀data฀summarised฀in฀Fig.฀ 11.3 ,฀no฀nicotine฀product฀gener- ates฀the฀plasma฀nicotine฀concentrations฀achieved฀by฀cigarette฀smoking฀because฀the฀release฀ of฀nicotine฀from฀these฀products฀while฀most฀rapid฀from฀the฀nasal฀spray฀is฀slower฀than฀from฀ a฀cigarette฀ [6] .฀It฀is฀therefore฀understandable฀that฀the฀daily฀nicotine฀doses฀administered฀ must฀be฀tailored฀to฀the฀individual฀patient’s฀level฀of฀dependence฀and฀the฀number฀of฀฀cigarettes฀ Inhaler n Parameter Effectiveness฀active฀ treatment฀vs.฀placebo References 3฀months฀ad฀libitum 222 CO,฀cotinine 21฀vs.฀6฀6฀months [48] 6฀months 286 CO 15฀vs.฀5฀1฀year [51] 6฀months 223 CO,฀cotinine 13฀vs.฀8฀1฀year [9] 6฀months฀ad฀libitum 247 CO,฀cotinine 35฀vs.฀22฀1฀year [52] 4฀months 400 CO 9.5฀vs.฀3฀2฀years [53] 12฀weeks฀combined฀with฀ nicotine฀patch 30 Cotinine 30฀12฀weeks a [25] Table 11.2 ฀฀฀Study฀results฀of฀smoking฀cessation฀with฀the฀nicotine฀inhaler a No฀placebo฀group