Pharmacotherapy for Nicotine
Dependence
David McFadden, MD, MPH Timothy J. Milbrandt, MS, TTS
Disclosures
• Dr. McFadden has participated in Pfizer-sponsored tobacco treatment seminars in Mexico, Brazil, and Chile
• Tim Milbrandt has no disclosures
• Will be discussing off label usage of medications
Outline
• Introduction of seven FDA approved medications
• Combination protocols
Question
• Which of these Nicotine Replacement medications both require prescriptions?
• A. Nicotine lozenges and Nicotine Inhaler
• B. Nicotine patch and Nicotine Nasal spray
• C. Nicotine inhaler and Nicotine nasal spray
FDA approved medications
• Five NRT (Nicotine based medications)
• Nicotine gum (OTC)
• Nicotine patch(OTC)
• Nicotine lozenges (OTC)
• Nicotine inhaler
• Nicotine nasal spray
• Bupropion
NRT
• Nicotine Gum
• 2 mg and 4 mg.
• Select dose based on estimated addiction level or cpd (cigarettes per day)
• 4 mg.
• Smoked first AM cigarette < 30 min. upon arising
• Or smokes > 20 cpd
Question
• Which form of NRT has the fastest absorption?
• A. Nicotine inhaler
• B. Nicotine lozenge
• C. Nicotine nasal spray
NRT-nasal spray
• Has fastest absorption rate of any NRT
• Unpopular due to nasal mucosal irritation
• Initial intolerance, but eventual acceptance
NRT --lozenges
• 2mg and 4 mg --dosage similar to gum
• Mini lozenges preferred by most
• Faster and more complete absorption than gum
• Technique important
• Educate patient --lozenge parked against buccal mucosa
• Do NOT swallow
NRT --patch
• Dosage calculated on cpd (1 mg./1 cpd)
• Example –
• smokes 40 cpd
• Rx. Nicotine patch 42 mg. (two 21 mg. patches)
• Often underdosed and then patient believes “not effective”
• Often discontinued prematurely (should be used for minimum of 12 weeks)
NRT inhaler
• Popular among smokers (hand to mouth action)
• Only available by prescription
• Technique is important
• take frequent shallow puffs; not deep inhalations as with respiratory inhalers.
• Absorption is through buccal mucosa; not lungs
Bupropion
• Antidepressant
• Interacts with many medications including MAO inhibitors and SSRIs
Contraindicated in patients with seizure disorder or prior head injury resulting in loss of
Varenicline
• Newest medication –2006
• Effective in patients with CVD and COPD
• Side effects
• Nausea
• Unusual dreams (sometimes pleasant)
• Possible psychiatric issues
Combinations
• NRT short acting (NG, NL, NNS, NI) with maintenance (Nicotine patch)
NRT with Bupropion (start Bupropion 1 week before quit date; NRT on quit date
NRT with Varenicline (start Var 1 week before quit date; NRT on quit date)
Bupropion with Varenicline (start both 1 week before quit date)
Varenicline/Buproprion combination
• Pilot study at Mayo• “Chanban” study (phase 2 study)
• Results: 58% quit rate at 6 months (cf 44% quit rate 3 months with Varenicline alone)
Reference: Ebbert, J.; Nicotine and
Tobacco Research 2009 11(3):234-239; Feb. 25, 2009
NRT Label changes
• FDA has determined the safety of NRT and proposed the following label changes:
• 1. Omit the “do not use” statement if you continue to smoke
• 2. begin using NRT on your quit date even if you are still smoking
• 3. If you feel the need to use NRT longer than the “specified period” (12 weeks), discuss with your health care provider
• Ref: FDA consumer Health information (April, 2013)
Case Study #1
• 48 year old female
• Hospitalized w/Opioid & Benzodiazepine abuse
• Has quit smoking successfully using Bupropion twice and would like to use it again
• Has suffered a seizure in the interim
• Reasons to quit - smoking is not, nor has it ever been a good fit for her
Case Study #1
• Reports smoking 20 cigarettes per day
• Currently using a 14 mg patch which is providing some relief
Case Study #1
• What would you advise?
• A - Stop the nicotine patch and start her on Varenicline
• B - Continue on 14 mg patch and advise her that the cravings should eventually subside
• C - Increase her patch dose to 21 mg and offer intermittent NRT such as the nicotine inhaler, for breakthrough cravings
Case Study #2
• 32 year old male who chews two tins of smokeless tobacco daily
• Quit chewing for 11 months using Bupropion, 42 mg patch, and 2 mg gum
• Stopped using patch because he felt like he was getting too much nicotine
• Stopped Bupropion because he didn’t think it was helping
Case Study #2
• Used 20 pieces of gum daily for 11 months
• Stopped using gum with concerns about his length of use
• Shortly thereafter he relapsed to using chewing tobacco due to nicotine withdrawal
• He returns and expresses a desire to be tobacco free
Case Study #2
• What do you do first?
• A - Provide him with prescriptions for
Bupropion, 42 mg patch, and gum again
• B - Suggest that he try Varenicline since the other pharmacotherapy plan did not work
• C - Offer him 4 mg nicotine gum since that is what worked best for him. (Lozenges are an option as well)
Case Study #3
• 61 year old male in St. Mary’s Hospital following myocardial infarction
• Smokes 50 cigarettes per day
• He is pleasantly surprised at how comfortable he is using 35 mg patch
• After discussing 42 mg patch plus ad lib NRT as a common dose for a 40 cigarette per day
smoker patient states a preference to remain on 35 mg patch and add 2 mg mini-lozenge
Case Study #3
• As the TTS what do you suggest?
• A – Try to convince him to use a higher patch dose
• B – Try to convince him to use Varenicline or
Bupropion to supplement his patch and lozenge
• C – Congratulate him on his decision to use 35 mg patch and mini-lozenges, and encourage him to call if he develops strong cravings or withdrawals
Case Study #4
• 32 year old male who was smoking 15-20 cigarettes per day
• He tried using 21 mg nicotine patch but it fell off so stopped after 3 days and started smoking
• Uses nicotine inhaler intermittently
• In the past month has reduced to 5 cpd
Case Study #4
• A – Assess patient’s interest in trying patches again and suggest medical tape to secure them and use in combination with inhaler as needed
• B – Congratulate him on decreasing to 5 cpd and revisit and strengthen patient’s motivation to quit smoking
• C – Explore potential obstacles to the
medication plan and problem-solve them in collaboration with the patient
Case Study #5 – 8 day Residential Patient
• 50 year old male in alcohol recovery for severalyears with chronic pain
• Smoked 10-20 cpd
• Day 1 – 21 mg patch, Varenicline 0.5 mg once daily, 2 mg gum
• Day 3 – Serum cotinine 438 (from day 1 prior to medications), many withdrawals and cravings to smoke
Case Study #5 - 8 day Residential Patient
• NEXT STEPS?• A – Add Bupropion
• B – Increase Varenicline to 1.0 BID
• C – Continue 21 mg patch
Case Study #5 - 8 day Residential Patient
• Increased to 42 mg patch, Varenicline 0.5 mgBID, and add nicotine gum.
• Day 6 – Serum cotinine 494 using 42 mg patch, gum, Varenicline 0.5 mg am, 1.0 mg pm. Urges and cravings minimal
• Day 8 Varenicline 1.0 BID, 42 mg patch, gum
• At 21 days smoke-free – patient was dizzy and reduced to 21 mg patch and felt better.
Case Study #5 - Residential Patient--
phone follow up
• At 25 days smoke-free – Patient felt nauseated so reduced Varenicline to 0.5 BID and
increased to 42 mg patch
• 35 days smoke-free – Patient nauseated and ill, stopped Varenicline, continues on 42 mg patch, gum
• 3.5 months after quit date patient reports that
he relapsed after six weeks and is now smoking 10-15 cigarettes per day. He set a new quit date and plans to use Varenicline 0.5 mg BID, 21 mg patch, and 2 mg lozenge