1. NICOTINE REPLACEMENT THERAPY NRT Dr. Debbie Thompson; Dr. Jane Dumontet Clinical Pharmacy Specialists for Fraser Health Feb 2008

2. Objectives Understand the difference between cessation and withdrawal Understand the difference between cessation and withdrawal Review the various Nicotine Replacement Therapy options Review the various Nicotine Replacement Therapy options Contrast the symptoms of nicotine toxicity versus those of withdrawal, psychiatric symptoms, caffeine side effects Contrast the symptoms of nicotine toxicity versus those of withdrawal, psychiatric symptoms, caffeine side effects

3. Nicotine Withdrawal Patients without access to cigarettes abruptly due to non-smoking policies will experience withdrawal symptoms Initial Goal/Priority to make patients as comfortable as possible by preventing withdrawal symptoms to make patients as comfortable as possible by preventing withdrawal symptoms Thank-you for not smoking here! Thank-you for not smoking here! Secondary Goal  Cessation

4. Physiological Considerations Withdrawal Nonspecific symptoms Vary in intensity and duration Vary in intensity and duration Begin within hours Begin within hours Peak in 2 to 3 days Peak in 2 to 3 days Last weeks to months Last weeks to months Symptoms Irritability, frustration or anger Anxiety, restlessness Dysphoria or depressed mood Difficulty concentrating Increased appetite or weight gain Insomnia Decreased heart rate

5. Nicotine Withdrawal Immediate Immediate Nicotine Replacement Therapy Nicotine Replacement Therapy Gum, Lozenge, (Inhaler) Gum, Lozenge, (Inhaler) Patch Patch Delayed Delayed Bupropion Bupropion Varenicline Varenicline

6. Keep Nicotine Levels Close to Comfort Zone http://www.esr.cri.nz/competencies/populationhealth/NRT.htm

7. Nicotine Levels/24 Hours Continuous Smoking http://images2.clinicaltools.com/images/tobaccofree/nicotine_levels.gif

8. Nicotine Levels/120 Minutes Single Dose

9. Nicotine Cigarettes contain 6 to 11 mg of nicotine Cigarettes contain 6 to 11 mg of nicotine Smokers absorb between 1 to 3mg from each cigarette i.e. average 2mg Smokers absorb between 1 to 3mg from each cigarette i.e. average 2mg If a pack contains 20 cigarettes If a pack contains 20 cigarettes 20 cigarettes x average 2mg each = 40mg/day 20 cigarettes x average 2mg each = 40mg/day (1 PACK = 1 x 21 mg PATCH) (1 PACK = 1 x 21 mg PATCH) 1 Habitrol 21 patch is designed to provide 21 mg over 24 hours of which only about 76% reaches the bloodstream i.e. about 16mg

10. High Risk Smokers - Mentally Ill More likely to smoke longer, be heavy users, smoke high tar brands with high nicotine contents More likely to smoke longer, be heavy users, smoke high tar brands with high nicotine contents And smoke that cigarette to the bitter end And smoke that cigarette to the bitter end So likely getting more than 2mg out of each cigarette So likely getting more than 2mg out of each cigarette Psych Services 1999. 50:1346-50

11. NRT FH Protocol Nicotine patch Nicotine patch 7 mg patch - low nicotine dependence 7 mg patch - low nicotine dependence 14mg patch - moderate nicotine dependence 14mg patch - moderate nicotine dependence 21mg patch - high nicotine dependence 21mg patch - high nicotine dependence + for moderate or high nicotine dependence Nicotine 2 or 4 mg gum or lozenge prn to a maximum of 8/10 pieces respectively /24 hours + for moderate or high nicotine dependence Nicotine 2 or 4 mg gum or lozenge prn to a maximum of 8/10 pieces respectively /24 hours

12. DETAILED FAGERSTRŐM ASSESSMENT 1. How soon after waking do you have your first cigarette?  Within 5 minutes (3 points)  6- 30 mins (2 points)  31- 60 mins (1 point)  More than 1 hour (0 points) 2. Do you find it difficult to refrain from smoking in places where it is forbidden?  Yes (1 point)  No (0 points) 3. Which cigarette would you be most unwilling to give up?  First in morning (1 point)  Any others (0 points) 4. How many cigarettes, on average do you smoke per day?  31 or more (3 points)  21-30 (2 points)  11-20 (1 point)  10 or less (0 points) (1 point)  10 or less (0 points) 5. Do you smoke more frequently during the first hours after waking than during the rest of the day?  Yes (1 point)  No (0 points) 6. Do you smoke even if you are so ill that you are in bed most of the day?  Yes (1 point)  No (0 points) 7. Assign Score: SCORE = _________7-10 points = high nicotine dependence 4-6 points = moderate nicotine dependence 0-3 points = low nicotine dependence 0-3 points = low nicotine dependence 8. Ask the patient if they feel they need assistance with smoking abstinence in hospital (may not be needed if low nicotine dependence).  Yes  No

13. Ottawa Heart Protocol > 20 cigarettes/day = 21mg patch > 20 cigarettes/day = 21mg patch 10-20 cigarettes/day = 14mg patch 10-20 cigarettes/day = 14mg patch < 10 cigarettes/day = 7mg patch < 10 cigarettes/day = 7mg patch + prn gum or inhaler + prn gum or inhaler

14. Monitor for withdrawal symptoms Within first day to see how they are doing, particularly if very heavy smoker Within first day to see how they are doing, particularly if very heavy smoker May have to increase dose of patch – doctor’s order May have to increase dose of patch – doctor’s order Increase by 7mg at a time and reassess Increase by 7mg at a time and reassess Encourage use of prn gum, lozenge if not using and having cravings/withdrawal symptoms Encourage use of prn gum, lozenge if not using and having cravings/withdrawal symptoms If smoking while on NRT it is likely the dose is likely not high enough! If smoking while on NRT it is likely the dose is likely not high enough! (or if behaviourally they have absolutely no intention of quitting and are accessing cigarrettes every chance they get – the patch may not be the withdrawal method of choice) (or if behaviourally they have absolutely no intention of quitting and are accessing cigarrettes every chance they get – the patch may not be the withdrawal method of choice)

15. Nicotine Transdermal Patch Well absorbed through the skin Well absorbed through the skin Onset 1-2 hours Onset 1-2 hours Peak Peak Habitrol ® 5 to 6 hours Habitrol ® 5 to 6 hours Nicoderm ® 4 hours Nicoderm ® 4 hours Peak concentration: 6-12 hrs Peak concentration: 6-12 hrs Plateau: 8-10 hrs Plateau: 8-10 hrs http://www.quitsmoking.com/books/knowsmoking/chapter5.htm http://learn.genetics.utah.edu/units/addiction/drugs/delivery.cfm

16. Nicotine Transdermal Patch Plasma levels fall 1-2 hours after removing patch Plasma levels fall 1-2 hours after removing patch Duration of therapy Duration of therapy Habitrol – Taper dose by 7mg Q3-4 weeks Habitrol – Taper dose by 7mg Q3-4 weeks Nicoderm – 6,2,2 Nicoderm – 6,2,2 Arbitrary stop date NRT is much preferable and safer than continued smoking NRT is much preferable and safer than continued smoking

17. Nicotine Transdermal Patch (Nicoderm®, Nicotrol®, Habitrol®, Generics) Advantages Advantages Easy to use Easy to use Unobtrusive Unobtrusive Provides steady nicotine levels Provides steady nicotine levels Avoids gum side effects Avoids gum side effects Non-prescription Non-prescription Disadvantages Cannot adjust dose for cravings Nicotine released more slowly than other products Side effects Mild skin irritation or sensitivity Important to rotate sites Switch brands as needed Insomnia reported

18. Patch – choice of location Choose an area on skin on upper body or the upper outer part of arm. (UPPER & OUTER) Choose an area on skin on upper body or the upper outer part of arm. (UPPER & OUTER) To ensure that the patch will stick on well, make sure the skin is non-hairy, clean (not oily) dry and free of creams, lotions, oils or powder. To ensure that the patch will stick on well, make sure the skin is non-hairy, clean (not oily) dry and free of creams, lotions, oils or powder. Hair will interfere with the application of the patch and should be clipped away. Hair will interfere with the application of the patch and should be clipped away. Do not shave the area as this may irritate the skin. Do not shave the area as this may irritate the skin. Do not put a patch on skin that is inflamed, burned, has broken out, or is irritated in any way, because these conditions may alter the amount of drug absorbed. Do not put a patch on skin that is inflamed, burned, has broken out, or is irritated in any way, because these conditions may alter the amount of drug absorbed. Women should not apply the patch to their breasts. Women should not apply the patch to their breasts. Be sure to apply the patch to a different area each day. The same area should not be used again for at least one week Be sure to apply the patch to a different area each day. The same area should not be used again for at least one week

19. Patch application Using scissors, carefully cut open the pouch along the edge. Using scissors, carefully cut open the pouch along the edge. Remove any old patches from skin, fold in half with the sticky side inward and dispose of properly in the garbage. Remove any old patches from skin, fold in half with the sticky side inward and dispose of properly in the garbage. Remove the square shiny protective liner from the adhesive side of the patch. Remove the square shiny protective liner from the adhesive side of the patch. Immediately apply the sticky side of the patch to the skin and firmly press it on with the palm of your hand for 10 to 20 seconds. Immediately apply the sticky side of the patch to the skin and firmly press it on with the palm of your hand for 10 to 20 seconds. Make sure that it is sticking well, especially around the edges. Make sure that it is sticking well, especially around the edges. It helps to clean that area of skin with alcohol wipe before application. It helps to clean that area of skin with alcohol wipe before application. Medical adhesive tape may be used to help keep the patch on. Medical adhesive tape may be used to help keep the patch on. Wash hands with water only. Wash hands with water only. The patch should be worn for about 24 hours and be replaced everyday at about the same time. The patch should be worn for about 24 hours and be replaced everyday at about the same time.

20. Patch Tips If insomnia or bad dreams occur If insomnia or bad dreams occur Take patch off at night or if on multiple patches, consider taking off one Take patch off at night or if on multiple patches, consider taking off one Nicotine levels will drop overnight so encourage use first thing of gum or lozenge until patch kicks in Nicotine levels will drop overnight so encourage use first thing of gum or lozenge until patch kicks in Consider same procedure as with other patches i.e. extra line on MAR to indicate site and to document removal Consider same procedure as with other patches i.e. extra line on MAR to indicate site and to document removal More nicotine will be released if exercising heavily so suggest removal prior to exercise More nicotine will be released if exercising heavily so suggest removal prior to exercise If smoking – likely dose not high enough, if persistent in not choosing to quit (i.e. psychotic) and continuing to smoke perhaps patch not best choice If smoking – likely dose not high enough, if persistent in not choosing to quit (i.e. psychotic) and continuing to smoke perhaps patch not best choice

22. Nicotine Gum/Nicotine Lozenge http://www.quitsmoking.com/books/knowsmoking/chapter5.htm http://www.ennispharmacy.com/smokers.html Buccal absorption, slower Buccal absorption, slower 20 to 30 minutes of chewing releases 50 to 90% of nicotine 20 to 30 minutes of chewing releases 50 to 90% of nicotine Peak plasma concentrations Peak plasma concentrations 15 to 30 minutes after starting chewing 15 to 30 minutes after starting chewing Lozenges deliver 25 to 27% more nicotine than gum Lozenges deliver 25 to 27% more nicotine than gum

23. Nicotine Gum (Nicorette®) Advantages Advantages User controls dose User controls dose Oral substitute Oral substitute Non-prescription Non-prescription Sugar free Sugar free Delays weight gain Delays weight gain Side effects Side effects Gastrointestinal Gastrointestinal Oral disturbances Oral disturbances Jaw discomfort Jaw discomfort Hiccoughs Hiccoughs Disadvantages Proper chewing technique required Cannot eat or drink while chewing gum Can damage dental work Difficult for denture wearers to use

24. How to use the gum Place one piece of gum in mouth and chew very slowly once or twice. Place one piece of gum in mouth and chew very slowly once or twice. Stop chewing and "Park it" between your cheek and gums, and leave it there. Stop chewing and "Park it" between your cheek and gums, and leave it there. Wait a minute, and then repeat, "Parking" it again on the opposite side of your mouth. BITE, BITE, PARK. BITE, BITE, PARK. Wait a minute, and then repeat, "Parking" it again on the opposite side of your mouth. BITE, BITE, PARK. BITE, BITE, PARK. You may notice a peppery taste, or a slight tingling in your mouth – this is nicotine being released and absorbed. You may notice a peppery taste, or a slight tingling in your mouth – this is nicotine being released and absorbed. Do not chew continuously or too quickly like ordinary chewing gum. Doing so may result in light-headedness, nausea, hiccups or stomach upset because you are swallowing the nicotine Do not chew continuously or too quickly like ordinary chewing gum. Doing so may result in light-headedness, nausea, hiccups or stomach upset because you are swallowing the nicotine After about 30 minutes, all the nicotine will be released. After about 30 minutes, all the nicotine will be released. Discard the gum in the garbage. Discard the gum in the garbage.

25. Gum Tips Slow down if you start feeling uncomfortable Slow down if you start feeling uncomfortable Do not chew more than one piece of gum at a time Do not chew more than one piece of gum at a time Do not use more than 20 pieces per day. Do not use more than 20 pieces per day. Avoid drinking acidic beverages such as coffee, tea, pop, alcohol or citrus fruit juices before or during use of gum. Doing so may affect nicotine absorption. Avoid drinking acidic beverages such as coffee, tea, pop, alcohol or citrus fruit juices before or during use of gum. Doing so may affect nicotine absorption. Consult your dentist or doctor if injury or irritation to the mouth, teeth or dental work occurs. Consult your dentist or doctor if injury or irritation to the mouth, teeth or dental work occurs. Accidentally swallowing a piece of gum shouldn't harm an adult. Accidentally swallowing a piece of gum shouldn't harm an adult.

26. Nicotine lozenge Place one lozenge in mouth and allow it to dissolve slowly Place one lozenge in mouth and allow it to dissolve slowly Do not chew or swallow – the lozenge contains a controlled amount of nicotine, which needs to be absorbed slowly and gradually through the tissues in the mouth Do not chew or swallow – the lozenge contains a controlled amount of nicotine, which needs to be absorbed slowly and gradually through the tissues in the mouth A tingling, or warm sensation may occur A tingling, or warm sensation may occur Occasionally move the lozenge from one side of the mouth to the other Occasionally move the lozenge from one side of the mouth to the other It takes about 20-30 minutes for the lozenge to dissolve completely It takes about 20-30 minutes for the lozenge to dissolve completely

27. Lozenge Tips Do not eat or drink 15 minutes before using, or while the lozenge is in your mouth Do not eat or drink 15 minutes before using, or while the lozenge is in your mouth Do not use more than one lozenge at a time or continuously use one lozenge after another. Doing so may cause hiccups, heartburn, nausea or other side effects. Do not use more than one lozenge at a time or continuously use one lozenge after another. Doing so may cause hiccups, heartburn, nausea or other side effects. Do not use more than five lozenges in six hours, or more than 15 lozenges total per day. Do not use more than five lozenges in six hours, or more than 15 lozenges total per day.

28. NRT Side Effects Relatively few side effects Relatively few side effects Minor side effects mild headache, appetite stimulation, constipation, diarrhea, dizziness, dysmenorrhea, flushing, insomnia irritability Minor side effects mild headache, appetite stimulation, constipation, diarrhea, dizziness, dysmenorrhea, flushing, insomnia irritability Others include hiccups, jaw ache, sore throat Others include hiccups, jaw ache, sore throat

29. Of Note! Remember – there is a lot of nicotine left in a patch (a Habitrol patch that releases 21 mg actually contains 51 mg total) Remember – there is a lot of nicotine left in a patch (a Habitrol patch that releases 21 mg actually contains 51 mg total) A 21 mg patch of Nicoderm has 114mg total A 21 mg patch of Nicoderm has 114mg total 2 mg of a 4mg piece of gum 2 mg of a 4mg piece of gum 4mg of a 10mg inhaler cartridge 4mg of a 10mg inhaler cartridge DISPOSE OF SAFELY IN GARBAGE DISPOSE OF SAFELY IN GARBAGE Very toxic to nicotine naïve – children, animals Very toxic to nicotine naïve – children, animals WARN parents that this is not innocuous WARN parents that this is not innocuous

30. Supply and Charting Ensure ready access to gum and patch on ward Ensure ready access to gum and patch on ward Consider initial wardstock supply of both Consider initial wardstock supply of both If large anticipated # patients on a ward, consider wardstock for prn versus patient specific If large anticipated # patients on a ward, consider wardstock for prn versus patient specific Consider providing a few gum or lozenges at a time depending upon the compliance and understanding of the patient Consider providing a few gum or lozenges at a time depending upon the compliance and understanding of the patient How will this be charted? How will this be charted? Access to the inhaler? Access to the inhaler? Patients with patch allergy? Patients with patch allergy?

31. Considerations Withdrawal versus toxicity Withdrawal versus toxicity Depression Depression Drug interactions with smoking cessation and resumption Drug interactions with smoking cessation and resumption Cardiac risks Cardiac risks Discharge planning Discharge planning

32. Withdrawal vs. NRT Excess Nicotine Intoxication: Nicotine Intoxication: Pallor, diaphoresis Pallor, diaphoresis Tremor, headache, dizziness Tremor, headache, dizziness Confusion Confusion Tachycardia, Palpitations Tachycardia, Palpitations N/V/ D, abdominal pain N/V/ D, abdominal pain Hypersalivation Hypersalivation Treatment???? Treatment????

33. Withdrawal vs. Caffeine toxicity Sudden cessation of tobacco smoking may result in reduced caffeine clearance (~ 40%) Sudden cessation of tobacco smoking may result in reduced caffeine clearance (~ 40%) Caffeine-related side effects may occur if use remains the same or increase if drink more coffee for something to occupy them Caffeine-related side effects may occur if use remains the same or increase if drink more coffee for something to occupy them Nausea, nervousness, irritability, tremors, insomnia Nausea, nervousness, irritability, tremors, insomnia Differentiate between withdrawal symptoms of smoking cessation and excess caffeine!

34. Withdrawal vs. Psychiatry Symptoms Very important to differentiate as many symptoms overlap Very important to differentiate as many symptoms overlap Anxiety Anxiety Restlessness Restlessness Irritability Irritability Mood changes Mood changes

35. Depression Current and past depression more common in smokers Current and past depression more common in smokers Experience more depressive symptoms during withdrawal Experience more depressive symptoms during withdrawal Increased risk of recurrent depression after stopping Increased risk of recurrent depression after stopping JAMA 1990. 264:1546-9

36. Smoking Cessation and Drug Interactions Hydrocarbons in tobacco induce drug- metabolizing enzymes (not the nicotine) particularly CYP 1A2 Hydrocarbons in tobacco induce drug- metabolizing enzymes (not the nicotine) particularly CYP 1A2 Can take several weeks to get to maximum inhibition as well as to return to baseline following discontinuation Can take several weeks to get to maximum inhibition as well as to return to baseline following discontinuation Pharmacotherapy, 1998;18(1):84-112, Psychiatric times, 2005;22(6)

37. Psychiatric Medications Affected Extent of interaction highly variable Examples include; Caffeine Caffeine Antidepressants Antidepressants Imipramine, clomipramine, fluvoxamine, trazodone Imipramine, clomipramine, fluvoxamine, trazodone Variable effect on Amitriptyline and Nortriptyline Variable effect on Amitriptyline and Nortriptyline Antipsychotics Antipsychotics Fluphenazine, haloperidol, olanzapine, chlorpromazine, clozapine Fluphenazine, haloperidol, olanzapine, chlorpromazine, clozapine Benzodiazepines Benzodiazepines Alprazolam, lorazepam, oxazepam, diazepam Alprazolam, lorazepam, oxazepam, diazepam Desai HD et al. CNS Drugs 2001. 15(6):469-94

38. Clozapine and Olanzapine Individual cases of large increases in serum levels with smoking cessation Individual cases of large increases in serum levels with smoking cessation Consider baseline serum levels particularly of clozapine Consider baseline serum levels particularly of clozapine Monitor for increased adverse effects for the first few weeks after smoking cessation Monitor for increased adverse effects for the first few weeks after smoking cessation i.e.Sedation, increased drooling, dizziness

39. Nicotine, Smoking and Diabetes Tobacco smoking is known to aggravate insulin resistance; Insulin absorption is slowed from injection sites. Tobacco smoking is known to aggravate insulin resistance; Insulin absorption is slowed from injection sites. Cessation of NRT or tobacco smoking may decrease blood glucose Cessation of NRT or tobacco smoking may decrease blood glucose Stopping smoking will increase subcutaneous absorption of insulin Stopping smoking will increase subcutaneous absorption of insulin Recommend monitoring blood glucose concentrations when nicotine intake or smoking status changes Recommend monitoring blood glucose concentrations when nicotine intake or smoking status changes Dosage adjustments in antidiabetic agents may be required Dosage adjustments in antidiabetic agents may be required

40. Nicotine CV risk The use of NRT is not associated with any increase in the risk of MI, stroke or death The use of NRT is not associated with any increase in the risk of MI, stroke or death (N = 33,247 Hubbard 2005) Much more rapid absorption of nicotine when smoking Much more rapid absorption of nicotine when smoking Smoking produces higher nicotine peaks than NRT Smoking produces higher nicotine peaks than NRT Any patient who is at risk of smoking is safer on NRT than continuing to smoke Any patient who is at risk of smoking is safer on NRT than continuing to smoke http://www/quitsmoking.com/books/knowsmoking/chapter6.htm

41. At Discharge If an individual resumes smoking at discharge If an individual resumes smoking at discharge Levels of medication (particularly clozapine and olanzapine) are likely to fall potentially resulting in relapse Levels of medication (particularly clozapine and olanzapine) are likely to fall potentially resulting in relapse Plan Plan Baseline serum levels of clozapine, (olanzapine) Baseline serum levels of clozapine, (olanzapine) Provide information to discharge treatment team of smoking status Provide information to discharge treatment team of smoking status Provide education/information to patient of potential impact of changes in smoking habits and that they should inform their treatment team if they resume or quit smoking Provide education/information to patient of potential impact of changes in smoking habits and that they should inform their treatment team if they resume or quit smoking

42. Go Green Use Clean Nicotine GUM PATCH LOZENGES