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References ................................................................................................................................................................................. 54
4.2.4.5 Computer/web-based .................................................................................................................................................. 54
References ................................................................................................................................................................................. 55
4.3 Pharmacological treatment of tobacco dependence ..................................................................................................... 55
4.3.1. Treatment with NRT ........................................................................................................................................................ 57
4.3.1.1 Indications .......................................................................................................................................................................57
4.3.1.2 Mechanism of action ......................................................................................................................................................57
4.3.1.3 Clinical evidence for the efficacy of NRT .....................................................................................................................58
4.3.1.4 NRT Patch ........................................................................................................................................................................59
4.3.1.5 Oral nicotine replacement.............................................................................................................................................60
4.3.1.6 Prescribing instructions ................................................................................................................................................61
4.3.1.7 Contra-indications ..........................................................................................................................................................62
4.3.1.8 Adverse effects, precautions, warnings, drug interactions .....................................................................................63
4.3.2 Treatment with bupropion SR ........................................................................................................................................ 64
4.3.3 Treatment with varenicline ............................................................................................................................................. 67
4.3.3.1 Mechanism of action ......................................................................................................................................................67
4.3.3.2 Clinical evidence for efficacy of varenicline ................................................................................................................68
4.3.3.3 Varenicline in combination pharmacotherapy ..........................................................................................................70
4.3.3.4 Varenicline and counselling .........................................................................................................................................71
4.3.3.5 Indications .......................................................................................................................................................................71
4.3.3.6 Clinical use ......................................................................................................................................................................71
4.3.3.7 Contraindications............................................................................................................................................................72
4.3.3.8 Precautions imposed by varenicline therapy .............................................................................................................72
4.3.3.9 Tolerability and safety ....................................................................................................................................................72
4.3.4 Treatment with clonidine ................................................................................................................................................. 75
4.3.5 Treatment with nortriptyline ........................................................................................................................................... 76
4.3.6 Cytisine................................................................................................................................................................................77
References ................................................................................................................................................................................. 78
4.4 Individualized therapeutic schemes ................................................................................................................................. 81
4.4.1 Combination of pharmacological therapies ................................................................................................................. 81
4.4.1.1 General principles of combination pharmacotherapy ..............................................................................................81
4.4.1.2 Combination of nicotine replacement therapy (NRT) ................................................................................................82
References ................................................................................................................................................................................. 84
4.4.2 Recommendations for prolonging treatment duration .............................................................................................. 85
References ................................................................................................................................................................................. 87
4.5 Available evidence on other interventions to support tobacco cessation ................................................................... 87
References ................................................................................................................................................................................. 89
4.6 Recommendations for the smoking reduction approach ............................................................................................. 91
4.6.1 Smoking reduction with nicotine replacement ............................................................................................................ 92
4.6.2 Smoking reduction with varenicline.............................................................................................................................. 92

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