P GUIDE FDA-APPROVED MEDICATIONS FOR SMOKING …

1 P HARMACOLOGIC P RODUCT G UIDE : FDA-A PPROVED M EDICATIONS FOR S MOKING C ESSATION. NICOTINE REPLACEMENT THERAPY (NRT) FORMULATIONS. BUPROPION SR VARENICLINE. GUM LOZENGE TRANSDERMAL PATCH NASAL SPRAY ORAL INHALER. Nicorette1, Generic Nicorette1, Generic NicoDerm CQ1, Generic Nicotrol NS2 Nicotrol Inhaler2 Zyban1, Generic Chantix2. PRODUCT. OTC Nicorette1 Mini OTC (NicoDerm CQ, generic) Rx Rx Rx Rx 2 mg, 4 mg OTC 7 mg, 14 mg, 21 mg (24-hr release) Metered spray 10 mg cartridge 150 mg sustained-release tablet mg, 1 mg tablet original, cinnamon, fruit, mint 2 mg, 4 mg; cherry, mint 10 mg/mL nicotine solution delivers 4 mg inhaled vapor Recent ( 2 weeks) myocardial Recent ( 2 weeks) myocardial Recent ( 2 weeks) myocardial Recent ( 2 weeks) Recent ( 2 weeks) Concomitant therapy with Severe renal impairment infarction infarction infarction myocardial infarction myocardial infarction MEDICATIONS /conditions known (dosage adjustment is Serious underlying arrhythmias Serious underlying arrhythmias Serious underlying arrhythmias Serious underlying Serious underlying to lower the seizure threshold necessary).

2 Serious or worsening angina pectoris Serious or worsening angina Serious or worsening angina arrhythmias arrhythmias Hepatic impairment Pregnancy3 and Temporomandibular joint disease pectoris pectoris Serious or worsening Serious or worsening Pregnancy3 and breastfeeding breastfeeding Pregnancy3 and breastfeeding Pregnancy3 and breastfeeding Pregnancy3 and breastfeeding angina pectoris angina pectoris Adolescents (<18 years) Adolescents (<18 years). Adolescents (<18 years) Adolescents (<18 years) Adolescents (<18 years) Underlying chronic nasal Bronchospastic disease Treatment-emergent Treatment-emergent disorders (rhinitis, nasal Pregnancy3 and neuropsychiatric symptoms4 neuropsychiatric polyps, sinusitis) breastfeeding BOXED WARNING REMOVED symptoms4. Severe reactive airway 12/2016 BOXED WARNING REMOVED.. PRECAUTIONS. Adolescents (<18 years). disease 12/2016. Contraindications: Pregnancy3 and Seizure disorder breastfeeding Adolescents (<18 years).

3 Concomitant bupropion ( , Wellbutrin) therapy Current or prior diagnosis of bulimia or anorexia nervosa Simultaneous abrupt discontinuation of alcohol or sedatives/benzodiazepines MAO inhibitors in preceding 14. days; concurrent use of reversible MAO inhibitors 1st cigarette 30 minutes after waking: 1st cigarette 30 minutes after >10 cigarettes/day: 1 2 doses/hour 6 16 cartridges/day 150 mg po q AM x 3 days, then Days 1 3: mg po q AM. 4 mg waking: 4 mg 21 mg/day x 4 6 weeks (8 40 doses/day) Individualize dosing; initially 150 mg po bid Days 4 7: mg po bid 1st cigarette >30 minutes after waking: 1st cigarette >30 minutes after 14 mg/day x 2 weeks One dose = 2 sprays (one in use 1 cartridge q 1 2 hours Weeks 2 12: 1 mg po bid 2 mg waking: 2 mg 7 mg/day x 2 weeks each nostril); each spray Do not exceed 300 mg/day delivers mg of nicotine to Best effects with continuous Begin therapy 1 2 weeks prior Begin therapy 1 week prior Weeks 1 6: Weeks 1 6: 10 cigarettes/day: the nasal mucosa puffing for 20 minutes to quit date to quit date 1 piece q 1 2 hours 1 lozenge q 1 2 hours 14 mg/day x 6 weeks Initially use at least 6 Allow at least 8 hours between Take dose after eating and Weeks 7 9: Weeks 7 9: 7 mg/day x 2 weeks Maximum cartridges/day doses with a full glass of water 1 piece q 2 4 hours 1 lozenge q 2 4 hours 5 doses/hour or Nicotine in cartridge is Dose tapering is not Weeks 10 12: Weeks 10 12: Rotate patch application site daily.

4 40 doses/day Avoid bedtime dosing to depleted after 20 minutes of minimize insomnia necessary 1 piece q 4 8 hours 1 lozenge q 4 8 hours do not apply a new patch to the For best results, initially active puffing Dosing adjustment is same skin site for at least one use at least 8 doses/day Dose tapering is not necessary Maximum, 24 pieces/day Maximum, 20 lozenges/day Inhale into back of throat or necessary for patients with DOSING. week Duration: 7 12 weeks, with Chew each piece slowly Allow to dissolve slowly (20 30 Do not sniff, swallow, or puff in short breaths severe renal impairment May wear patch for 16 hours if inhale through the nose maintenance up to 6 months in Park between cheek and gum when minutes for standard) patient experiences sleep Do NOT inhale into the selected patients Duration: 12 weeks; an as the spray is being lungs (like a cigarette) but additional 12-week course peppery or tingling sensation Nicotine release may cause a disturbances (remove at bedtime) administered appears (~15 30 chews) warm, tingling sensation puff as if lighting a pipe may be used in selected Duration: 8 10 weeks Duration: 3 months Resume chewing when tingle fades Do not chew or swallow Open cartridge retains patients Repeat chew/park steps until most of Occasionally rotate to different potency for 24 hours May initiate up to 35 days the nicotine is gone (tingle does not areas of the mouth No food or beverages 15 before target quit date OR.)

5 Minutes before or during may reduce SMOKING over a return; generally 30 min) No food or beverages 15 minutes use 12-week period of Park in different areas of mouth before or during use treatment prior to quitting No food or beverages 15 minutes Duration: up to 12 weeks Duration: 3 6 months and continue treatment for before or during use an additional 12 weeks Duration: up to 12 weeks NICOTINE REPLACEMENT THERAPY (NRT) FORMULATIONS. BUPROPION SR VARENICLINE. GUM LOZENGE TRANSDERMAL PATCH NASAL SPRAY ORAL INHALER. Mouth and throat irritation Mouth and throat irritation Local skin reactions (erythema, Nasal and/or throat Mouth and/or throat Insomnia Nausea Jaw muscle soreness Hiccups pruritus, burning) irritation (hot, peppery, irritation Dry mouth Sleep disturbances Hiccups GI complaints (dyspepsia, Sleep disturbances (abnormal or burning sensation) Cough Nausea (insomnia, abnormal/vivid GI complaints (dyspepsia, nausea) nausea) or vivid dreams, insomnia); Ocular irritation/tearing Hiccups Anxiety/difficulty dreams).

6 ADVERSE EFFECTS. May stick to dental work associated with nocturnal Sneezing GI complaints (dyspepsia, concentrating Headache nicotine absorption Cough . nausea) Constipation Flatulence Adverse effects more commonly experienced when chewing the lozenge Tremor Constipation or using incorrect gum chewing technique (due to rapid nicotine release): Rash Taste alteration Lightheadedness/dizziness Seizures (risk is ) Neuropsychiatric Nausea/vomiting Neuropsychiatric symptoms symptoms (rare; see Hiccups (rare; see PRECAUTIONS) PRECAUTIONS). Mouth and throat irritation Might serve as an oral substitute Might serve as an oral substitute Once-daily dosing associated Can be titrated to rapidly Might serve as an oral Twice-daily oral dosing is Twice-daily oral dosing is for tobacco for tobacco with fewer adherence problems manage withdrawal substitute for tobacco simple and associated with simple and associated Might delay weight gain Might delay weight gain Of all NRT products, its use is symptoms Can be titrated to manage fewer adherence problems with fewer adherence Can be titrated to manage Can be titrated to manage least obvious to others Can be used in withdrawal symptoms Might delay weight gain problems ADVANTAGES.

7 Withdrawal symptoms withdrawal symptoms Can be used in combination combination with other Mimics hand-to-mouth Might be beneficial in Offers a different Can be used in combination with Can be used in combination with with other agents; delivers agents to manage ritual of SMOKING patients with depression mechanism of action for other agents to manage situational other agents to manage consistent nicotine levels over situational urges Can be used in Can be used in combination patients who have failed urges situational urges 24 hours combination with other with NRT agents other agents Relatively inexpensive Relatively inexpensive Relatively inexpensive agents to manage Relatively inexpensive Most effective cessation situational urges (generic formulations) agent when used as monotherapy Need for frequent dosing can Need for frequent dosing can When used as monotherapy, Need for frequent Need for frequent dosing Seizure risk is increased Patients should be compromise adherence compromise adherence cannot be titrated to acutely dosing can compromise can compromise Several contraindications monitored for potential Might be problematic for patients Gastrointestinal side effects manage withdrawal symptoms adherence adherence and precautions preclude neuropsychiatric with significant dental work (nausea, hiccups, heartburn) Not recommended for use by Nasal administration Cartridges might be less use in some patients (see symptoms4 (see Proper chewing technique is might be bothersome patients with dermatologic might not be acceptable effective in cold PRECAUTIONS) PRECAUTIONS).

8 DISADVANTAGES. necessary for effectiveness and to conditions ( , psoriasis, or desirable for some environments ( 60 F) Patients should be monitored Cost of treatment minimize adverse effects eczema, atopic dermatitis) patients; nasal irritation Cost of treatment for potential neuropsychiatric Gum chewing might not be often problematic symptoms4 (see acceptable or desirable for some Not recommended for PRECAUTIONS). patients use by patients with chronic nasal disorders or severe reactive airway disease Cost of treatment COST/DAY5. 2 mg or 4 mg: $ $ 2 mg or 4 mg: $ $ $ $ $ $ $ $ $ (9 pieces) (9 pieces) (1 patch) (8 doses) (6 cartridges) (2 tablets) (2 tablets). 1. Marketed by GlaxoSmithKline. 2. Marketed by Pfizer. 3. The Clinical Practice Guideline states that pregnant smokers should be encouraged to quit without medication based on insufficient evidence of effectiveness and theoretical concerns with safety. Pregnant smokers should be offered behavioral counseling interventions that exceed minimal advice to quit.

9 4. In July 2009, the FDA mandated that the prescribing information for all bupropion- and varenicline-containing products include a black-boxed warning highlighting the risk of serious neuropsychiatric symptoms, including changes in behavior, hostility, agitation, depressed mood, suicidal thoughts and behavior, and attempted suicide. Clinicians should advise patients to stop taking varenicline or bupropion SR and contact a health care provider immediately if they experience agitation, depressed mood, or any changes in behavior that are not typical of nicotine withdrawal, or if they experience suicidal thoughts or behavior. If treatment is stopped due to neuropsychiatric symptoms, patients should be monitored until the symptoms resolve. Based on results of a mandated clinical trial, the FDA removed this boxed warning in December 2016. 5. Approximate cost based on the recommended initial dosing for each agent and the wholesale acquisition cost from Red Book Online.

10 Thomson Reuters, December 2018. Abbreviations: MAO, monoamine oxidase; NRT, nicotine replacement therapy; OTC, over-the-counter (nonprescription product); Rx, prescription product. For complete prescribing information and a comprehensive listing of warnings and precautions, please refer to the manufacturers' package inserts. Copyright 1999-2019 The Regents of the University of California. All rights reserved. Updated January 9, 2019.