1 Treatment of Spit Tobacco Use Lowell C. Dale, MD Jon O. Ebbert, MD, MSc Assistant Professors of Medicine, Mayo Medical School Community Internal Medicine & Nicotine Dependence Center Lowell C. Dale, MD Jon O. Ebbert, MD, MSc Assistant Professors of Medicine, Mayo Medical School Community Internal Medicine & Nicotine Dependence Center

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use. 2 Goal of Workshop Explore & share collective knowledge of spit tobacco dependence & treatment

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use. 3 Spit Tobacco - Definitions “Smokeless” - industry term“Smokeless” - industry term –Implies safety –Should be replaced with “spit” SnuffSnuff –Dry –Moist (i.e., Copenhagen, Skoal) Chewing tobaccoChewing tobacco –Loose leaf (i.e., Redman) –Plugs –Twists

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use. 4 Top Selling ST Brands, Thousands of Pounds MOIST SNUFF AND FINE CUT TOBACCO BRANDS Brand Company 1997 SKOAL US Tobacco 22,213.0 COPENHEGAN US Tobacco 20,550.0 KODIAK Conwood 6,428.0 LOOSE LEAF CHEWING TOBACCO BRANDS Brand Company 1997 RED MAN Swedish Match 11,001.0 LEVI GARRETT Conwood BEECH NUT National Tobacco 7,118.0 Maxwell Consumer Report

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use. 5 Background - Marketing & Sales In 1999, newspaper, magazine, and point of sale advertising approached $170 million. Annual revenues from ST sales peaked at $1,940 million. [Federal Trade Commission, 2001] In 1999, newspaper, magazine, and point of sale advertising approached $170 million. Annual revenues from ST sales peaked at $1,940 million. [Federal Trade Commission, 2001]

6 Who Uses ST?

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use. 7 Background - Prevalence In the U.S., 1991: 5.3 million people regularly used ST By the year 2000, among individuals > 12 years of age: 7.6 million regular ST users [USDHSS, 2000; U.S. Census, 2000] In the U.S., 1991: 5.3 million people regularly used ST By the year 2000, among individuals > 12 years of age: 7.6 million regular ST users [USDHSS, 2000; U.S. Census, 2000]

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use. 8 Background - Prevalence Among individuals > 12 years of age: 6.5% males 0.5% females Highest rates of current ST use are found in American Indians and Alaska Natives. Northern Plains Native Americans: 25% prevalence of adult men [USDHHS, 1998] Among individuals > 12 years of age: 6.5% males 0.5% females Highest rates of current ST use are found in American Indians and Alaska Natives. Northern Plains Native Americans: 25% prevalence of adult men [USDHHS, 1998]

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use. 9 Background - Prevalence ST use is higher in rural areas than in urban areas [Centers for Disease Control and Prevention, 1993 #1820] Use is reported to be higher in small towns than in large cities [Marcus, 1989 #909] The highest prevalence of ST use is found among: White males between the ages of 18 and 25 White males between the ages of 25 and 35 [Smith, 1999 #3] ST use is higher in rural areas than in urban areas [Centers for Disease Control and Prevention, 1993 #1820] Use is reported to be higher in small towns than in large cities [Marcus, 1989 #909] The highest prevalence of ST use is found among: White males between the ages of 18 and 25 White males between the ages of 25 and 35 [Smith, 1999 #3]

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use. 10 Background - Prevalence Among the population 12 years of age or older who had used ST in the last month: 0.8% of the Hispanic population 1.3% among Hispanic males 2.0% of the African-Americans 2% among African-American males, and 0.2% among all women [NHSDA, 1998 #2173]. The prevalence of ST use within the past year among college-age women was 1.3% [Rigotti, 2000 #2031]. Among the population 12 years of age or older who had used ST in the last month: 0.8% of the Hispanic population 1.3% among Hispanic males 2.0% of the African-Americans 2% among African-American males, and 0.2% among all women [NHSDA, 1998 #2173]. The prevalence of ST use within the past year among college-age women was 1.3% [Rigotti, 2000 #2031].

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use. 11 Background - Health Implications Use of ST products can lead to: Nicotine addiction ST use is a risk factor for: Periodontal disease Tooth decay Oral cancer [National Institute of Health, 1986] Use of ST products can lead to: Nicotine addiction ST use is a risk factor for: Periodontal disease Tooth decay Oral cancer [National Institute of Health, 1986]

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use. 12 Spit Tobacco: Health Effects Bad Breath Stained Teeth Poor Wound Healing Periodontal Disease gingival recession tooth (bone attachment) loss erosion of enamel dental caries Bad Breath Stained Teeth Poor Wound Healing Periodontal Disease gingival recession tooth (bone attachment) loss erosion of enamel dental caries

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use. 13

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use. 14 Leukoplakia Silverman et al., 1984 Followed 257 patients w/ leukoplakia 7.2 years on average 45 (17.5%) developed SCC Conservative estimates: 3-6% Silverman et al., 1984 Followed 257 patients w/ leukoplakia 7.2 years on average 45 (17.5%) developed SCC Conservative estimates: 3-6%

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use. 15

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use. 16 Spit Tobacco: Health Effects Oral Cancer 4 fold increase in moderate ST Users 7 fold increase in heavy ST Users Oral Cancer 4 fold increase in moderate ST Users 7 fold increase in heavy ST Users

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use. 17 Background - Health Implications May increase the risk for cancer of the: Esophagus Larynx Stomach Pancreas [Connolly, 1986; Mattson, 1989] May increase the risk for cancer of the: Esophagus Larynx Stomach Pancreas [Connolly, 1986; Mattson, 1989]

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use. 18 Background - Health Implications ST use associated with risk factors for cardiovascular disease Elevated blood pressure and cholesterol levels. [Bolinder, 1992; Bolinder, 1994; Tucker, 1989; National Institute of Health, 1986] Laboratory rat models - ST extracts exhibit adverse effects on fetal viability and development. [Paulson, 1988] ST use associated with risk factors for cardiovascular disease Elevated blood pressure and cholesterol levels. [Bolinder, 1992; Bolinder, 1994; Tucker, 1989; National Institute of Health, 1986] Laboratory rat models - ST extracts exhibit adverse effects on fetal viability and development. [Paulson, 1988]

19 ST Pharmacology

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use. 20 Biomarkers: Nicotine vs. Cotinine Nicotine Direct measurement of the addictive drug Extensive first pass hepatic metabolism Half-life 120 minutes Cotinine Major metabolite of nicotine Pharmacologically inactive Quantitative marker of nicotine intake Pre-abstinence levels correlate with withdrawal and treatment outcome in smokers Half-life hours Clinically more practical to measure Nicotine Direct measurement of the addictive drug Extensive first pass hepatic metabolism Half-life 120 minutes Cotinine Major metabolite of nicotine Pharmacologically inactive Quantitative marker of nicotine intake Pre-abstinence levels correlate with withdrawal and treatment outcome in smokers Half-life hours Clinically more practical to measure

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use. 21 Cotinine Serum cotinine concentrations have been shown to be associated with relapse to smoking and level of dependence in smokers. ST users swallow a large amount of nicotine First-pass hepatic metabolism Cotinine levels may not accurately reflect levels of CNS exposure to nicotine Serum cotinine concentrations have been shown to be associated with relapse to smoking and level of dependence in smokers. ST users swallow a large amount of nicotine First-pass hepatic metabolism Cotinine levels may not accurately reflect levels of CNS exposure to nicotine

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use. 22 Spit Tobacco Pharmacology Absorbed dose (bioavailability) of nicotine is twice that obtained from smoking a cigarette: chewing tobacco4.5 mg moist snuff3.6 mg 4 mg nicotine gum1.9 mg cigarette 1.8 mg Absorbed dose (bioavailability) of nicotine is twice that obtained from smoking a cigarette: chewing tobacco4.5 mg moist snuff3.6 mg 4 mg nicotine gum1.9 mg cigarette 1.8 mg

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use. 23 Spit Tobacco Pharmacology Slower absorption than with smoking Peak concentration at 30 minutes Persistent absorption for up to 60 minutes after tobacco removed slow release from mucus membranes absorption of swallowed nicotine Slower absorption than with smoking Peak concentration at 30 minutes Persistent absorption for up to 60 minutes after tobacco removed slow release from mucus membranes absorption of swallowed nicotine

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use. 24 Spit Tobacco Pharmacology Blood nicotine concentration (ng/ml) Benowitz, NL et al. Nicotine absorption and cardiovascular effects with smokeless tobacco use: comparison with cigarettes and nicotine gum. Clin Pharmacol Ther 1988; 44: Benowitz et al, 1988.

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use. 25

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use. 26 Benowitz et al, 1989.

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use. 27 ST Characteristics Affecting Nicotine Blood Levels Concentration of nicotine in ST product Size of the tobacco cuttings Long cut Fine cut (higher) Lower acid level of product - higher free nicotine Concentration of nicotine in ST product Size of the tobacco cuttings Long cut Fine cut (higher) Lower acid level of product - higher free nicotine

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use. 28 Nicotine Content of Tobacco Products

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use. 29 CDC, Free Nicotine as a Function of pH

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use. 30 Fant, RV et al. Pharmacokinetics and pharmacodynamics of moist snuff in humans. Tobacco Control 1999; 8: Nicotine Pharmacology Different ST Products

31 ST Dependence & Withdrawal

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use. 32 Measuring Dependence in ST Users Predictors of nicotine dependence (modified FTQ) Using ST within 30 minutes of waking up Using ST when sick/mouth sores ST in mouth > 30 minutes Intentionally swallowing tobacco juice ST in mouth all day Strong cravings when abstinent Greater than 15 dips/day Predictors of nicotine dependence (modified FTQ) Using ST within 30 minutes of waking up Using ST when sick/mouth sores ST in mouth > 30 minutes Intentionally swallowing tobacco juice ST in mouth all day Strong cravings when abstinent Greater than 15 dips/day Boyle, 1995

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use. 33 Frequency of Withdrawal Symptoms in ST Users 85% Strong need/urge 63% Irritability 55% Restless 41% Concentration difficulties 39% Hunger 9% Sadness/depressed 85% Strong need/urge 63% Irritability 55% Restless 41% Concentration difficulties 39% Hunger 9% Sadness/depressed

34 What are Challenges to Treating or Addressing the Needs of ST Users? What are Potential Solutions?

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use. 35 Literature Review Question: “What interventions are effective for ST users?” Searched for and identified all randomized controlled trials treating ST users only. Question: “What interventions are effective for ST users?” Searched for and identified all randomized controlled trials treating ST users only.

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use. 36 Literature Review: Conclusions Meta-analyses: Bupropion SR may be an effective intervention for ST users. NRT may be an effective intervention for ST users. Behavioral interventions are effective. Among the behavioral interventions, the use of an oral examination appears to be associated with the greatest treatment effect. Meta-analyses: Bupropion SR may be an effective intervention for ST users. NRT may be an effective intervention for ST users. Behavioral interventions are effective. Among the behavioral interventions, the use of an oral examination appears to be associated with the greatest treatment effect. Ebbert et al., Addiction.

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use. 37 Literature Review: Conclusions Behavioral Interventions with largest effect: Severson, 1998: Usual dental care and office intervention (advice to quit, quit date setting), self-help materials (pamphlets and oral replacement), self-help video & telephone support compared with usual care. Walsh, 1999: Oral examination with feedback, photos of ST effects, advice to quit, self-help manual, optional brief counseling (e.g., set quit date, triggers, withdrawal discussion), optional nicotine gum, & telephone support. Behavioral Interventions with largest effect: Severson, 1998: Usual dental care and office intervention (advice to quit, quit date setting), self-help materials (pamphlets and oral replacement), self-help video & telephone support compared with usual care. Walsh, 1999: Oral examination with feedback, photos of ST effects, advice to quit, self-help manual, optional brief counseling (e.g., set quit date, triggers, withdrawal discussion), optional nicotine gum, & telephone support. Ebbert et al., Addiction.

38 Nicotine Patch Percentage Replacement

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use. 39 Evidence for Inadequate Replacement Dale et al., 1995.

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use. 40 High Dose NRT Initial Nicotine Patch Dosing Schedule

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use. 41 Percentage Replacement Percentage replacement: steady state nicotine x 100 baseline nicotine Monitor for therapeutic/side effects. Percentage replacement: steady state nicotine x 100 baseline nicotine Monitor for therapeutic/side effects.

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use. 42 Percentage Replacement Therapeutic drug monitoring with goal of 100% replacement ST: serum nicotine test of choice Serum nicotine at baseline Ad libitum ST use Choose dose and recheck serum nicotine after 3 days Steady state Therapeutic drug monitoring with goal of 100% replacement ST: serum nicotine test of choice Serum nicotine at baseline Ad libitum ST use Choose dose and recheck serum nicotine after 3 days Steady state

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use. 43 Snuff Substitutes Young’s Chew Smokey Mountain Golden Eagle Oregon Mint Winner’s Edge Bac-Off Jerky Sunflower Seeds Young’s Chew Smokey Mountain Golden Eagle Oregon Mint Winner’s Edge Bac-Off Jerky Sunflower Seeds

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use. 44 Recommended ST Treatment Approach 1) Behavioral treatment Oral examination +/- oral replacement products 2) Bupropion 150 mg po qd x 3 days then bid Quit 1 week later Continue for 3-6 months 3) Tailored nicotine patch therapy +/- gum for self-titration 1) Behavioral treatment Oral examination +/- oral replacement products 2) Bupropion 150 mg po qd x 3 days then bid Quit 1 week later Continue for 3-6 months 3) Tailored nicotine patch therapy +/- gum for self-titration

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use. 45 “Paul” 34 years old Spit tobacco for 28 years Now: Copenhagen 1 tin/day Quit attempts: 4-5, longest 2 days Exam: plaque, supragingival calculus, erythema and inflamed tissue, areas of leukoplakia on the labial vestibule opposite lower incisors 34 years old Spit tobacco for 28 years Now: Copenhagen 1 tin/day Quit attempts: 4-5, longest 2 days Exam: plaque, supragingival calculus, erythema and inflamed tissue, areas of leukoplakia on the labial vestibule opposite lower incisors

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use. 46 “Paul” Nicotine Level: 40 ng/ml Cotinine Level: 402 ng/ml Treatment: Bupropion SR 150 bid Residential Program 42 mg nicotine patch Nicotine gum as needed Snuff substitute as needed Nicotine Level: 40 ng/ml Cotinine Level: 402 ng/ml Treatment: Bupropion SR 150 bid Residential Program 42 mg nicotine patch Nicotine gum as needed Snuff substitute as needed

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use. 47 “Paul” Day 2: Difficulty sleeping, strong cravings, constantly thinking about Copenhagen. Using mint snuff oral substitute. Plan: Increase to 56 mg nicotine patch/day Day 2: Difficulty sleeping, strong cravings, constantly thinking about Copenhagen. Using mint snuff oral substitute. Plan: Increase to 56 mg nicotine patch/day

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use. 48 “Paul” Day 4: Slept much better. Significant decrease in cravings. Continues with snuff substitute. Nicotine level: 37 ng/ml Cotinine level: 318 ng/ml Day 4: Slept much better. Significant decrease in cravings. Continues with snuff substitute. Nicotine level: 37 ng/ml Cotinine level: 318 ng/ml

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use. 49 “Paul” Day 8: Dismiss on 56mg/day nicotine patch for 4 weeks and then taper as tolerated; bupropion SR 150 bid for at least 3 months. Follow-up with counselor regularly by telephone. Month 4: Continuous abstinence. Day 8: Dismiss on 56mg/day nicotine patch for 4 weeks and then taper as tolerated; bupropion SR 150 bid for at least 3 months. Follow-up with counselor regularly by telephone. Month 4: Continuous abstinence.

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use. 50 Pilot project 8-day inpatient program Didactics, group therapy/individual therapy Tailored pharmacotherapy Combination (bupropion & NRT) Percentage replacement Dental hygienist visit and a dental examination with photographs of suspicious lesions. Pilot project 8-day inpatient program Didactics, group therapy/individual therapy Tailored pharmacotherapy Combination (bupropion & NRT) Percentage replacement Dental hygienist visit and a dental examination with photographs of suspicious lesions. Residential Treatment Program

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use. 51 Oral photographs - individualized feedback Residential Treatment Program

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use programs - January, February, June 24 male ST users Median age (IQR): 39 (33-69) Median ST use (IQR): 3.5 (2-7) cans/pouches per wk 3 programs - January, February, June 24 male ST users Median age (IQR): 39 (33-69) Median ST use (IQR): 3.5 (2-7) cans/pouches per wk Results

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use. 53 Results

54 Case Studies

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use. 55 Case 1: 16 year-old male One pouch Redman Leaf chewing tobacco and/or one tin of Copenhagen per three days x 3 years Reason for visit: Second violation for spit tobacco use on school grounds. Off baseball team till addresses tobacco through a program. Mom concerned about use History: Hx of asthma, depression, ADHD; sees Psychiatrist, medications - Ritalin One pouch Redman Leaf chewing tobacco and/or one tin of Copenhagen per three days x 3 years Reason for visit: Second violation for spit tobacco use on school grounds. Off baseball team till addresses tobacco through a program. Mom concerned about use History: Hx of asthma, depression, ADHD; sees Psychiatrist, medications - Ritalin

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use. 56 Case 1: 16 year-old male Attempts: Few recalled. Longest abstinence: 3 days Withdrawal: more irritable and depressed Mood: Likes to see what he can get away with. Most friends use chew; likes to use with them. Thinks he is being treated unfairly. Barriers: boredom, peers, perception of enhanced performance Attempts: Few recalled. Longest abstinence: 3 days Withdrawal: more irritable and depressed Mood: Likes to see what he can get away with. Most friends use chew; likes to use with them. Thinks he is being treated unfairly. Barriers: boredom, peers, perception of enhanced performance

57 How Should We Treat this ST User?

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use. 58 High Dose NRT Initial Nicotine Patch Dosing Schedule

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use. 59 Case 2: 49 year-old male Seven cans of Copenhagen per week for 15 years Reason for visit: wishes to quit because he is concerned about cancer. History: Hx of alcoholism associated with withdrawal. Seven cans of Copenhagen per week for 15 years Reason for visit: wishes to quit because he is concerned about cancer. History: Hx of alcoholism associated with withdrawal.

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use. 60 Case 2: 16 year-old male Attempts: none Withdrawal: intense cravings Barriers: fells it helps keep him motivated at work; outdoor activities (hunting, fishing) are associated with use as well. Attempts: none Withdrawal: intense cravings Barriers: fells it helps keep him motivated at work; outdoor activities (hunting, fishing) are associated with use as well.

61 How Should We Treat this ST User?

Dale, Ebbert. Workshop. Treatment of Spit Tobacco Use. 62 High Dose NRT Initial Nicotine Patch Dosing Schedule

63 Has this workshop changed your practice or approach to ST users?