Substance Use Disorder: The Impact of the Clinical Pharmacy - - PowerPoint PPT Presentation

Substance Use Disorder: The Impact of the Clinical Pharmacy Specialist

Troy A. Moore, PharmD, MS, BCPP Clinical Pharmacy Specialist- Psychiatry Director, ASHP-Accredited PGY-2 Psychiatric Pharmacy Residency Program South Texas Veterans Health Care System Assistant Professor UT Health San Antonio Dept of Psychiatry- Division of Community Recovery, Research and Training

The American Pharmacist Association is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.

• Dr. Troy A. Moore, PharmD, MS, BCPP declare(s) no conflicts of interest, real or apparent, and no

financial interests in any company, product, or service mentioned in this program, including grants, employment, gifts, stock holdings, and honoraria.

CPE Information and Disclosures

 Target Audience: Pharmacists and Pharmacist Technicians  ACPE#: 0202-0000-18-213-L04-P/T  Activity Type: Knowledge-based

CPE Information

Learning Objectives

 Explain the role of the CPS in substance use disorder  Review the impact on access and quality  Highlight best practices related to substance abuse disorder

Self-Assessment Questions

 The gold standard medication for a pregnant women with OUD is?  The medication associated with reduced ED visits, lower inpatient admission, and

reduced healthcare costs for AUD is?

 The greatest benefit for smoking cessation is seen with medication, psychotherapy

• r combination treatment?

Cycles of Addiction

Dackis, C., & O'Brien, C. (2005). Neurobiology of Addiction: Treatment and Public Policy Ramifications. Nat Neurosci, Nov;8(11):1431-6.

Substance Use Disorder Terminology

Term Definition Misuse

Usage of a substance for a purpose that is inconsistent with legal or medical guidelines

Abuse

Maladaptive pattern of use despite knowledge of psychological or physical problems directly exacerbated by continued drug use

Aberrant Behavior

Type of behavior a drug misuser or abuser may engage in, such as recurrent requests for early prescription refills

Pseudo- Addiction**

Pattern of drug-seeking behavior in pain patients receiving inadequate pain management and mistaken for addiction, portraying an unfortunate interstice of warped emotional salience and undertreated pain in the setting of iatrogenic dependence to opioid analgesics. This may be considered an archaic term by some practitioners

Tolerance

Decrease in response to a drug dose that occurs with continued use, with both physiological and psychological factors contributing to its development

Withdrawal

Cluster of symptoms with varying degrees of severity that occur upon cessation or reduction of a psychoactive substance

Physical Dependence

Adaptation manifested by production of a withdrawal syndrome inducible upon abrupt cessation, rapid dose reduction, decreasing drug serum concentration, and/or administration of an antagonist

Psychological Dependence

Constellation of emotional reliance for a substance beyond its physical effects, often amplified in the drug’s absence

Substance Use Disorder Diagnostic Criteria

Hasin et al. Am J Psychiatry 2013; 170:834-851

Epidemiology of Opioid Misuse in Past Year: 2016

2016 NSDUH

Source: CDC WONDER; www.drugabuse.gov

Overdose Death Rates

Trends in rates of opioid-related of hospital stays and ED visits, 2008-2015

Center for Substance Abuse Treatment. (2005). Medication-Assisted Treatment for Opioid Addiction in Opioid Treatment Programs. Treatment Improvement Protocol (TIP) Series 43.

OUD Risk: Acute and Chronic

Diagnostic Criteria: Opioid Use Disorder

Medically Supervised Withdrawal (Detoxification): Scales

• Clinical Opiate Withdrawal Scale (COWS)
• Clinician scored; 11 questions
• Mild (5-12), moderate (13-24), moderately severe (25-36), severe (>36)
• Scales without clear categorization of totaled scores
• Subjective Opiate Withdrawal Scale (SOWS): patient scored; 16 questions
• Objective Opiate Withdrawal Scale (OOWS): clinician scored; 13 questions
• Clinical Institute Narcotic Assessment (CINA): clinician scored; 11 questions
• Narcotic Withdrawal Scale: clinician assessed physical findings as tool for

methadone initiation

• Scales for neonatal abstinence syndrome
• Modified Finnegan: table-based checklist for CNS,

metabolic/vasomotor/respiratory, and gastrointestinal disturbances

• Neonatal Abstinence Syndrome Scoring Chart: 10 questions; has

modification for premature neonates in sleeping score

Source: Wesson, D. R., & Ling, W. (2003). The Clinical Opiate Withdrawal Scale (COWS). J Psychoact ive Drugs, 35(2), 253–9.

Clinical Opiate Withdrawal Scale (COWS)

Medically Supervised Withdrawal (Detoxification): Goals of Treatment

• Not necessary to prevent death, in contrast to alcohol withdrawal syndrome
• Good opportunity to try and engage patients in treatment
• 2015 VA/SUD guidelines recommend detoxification with methadone or buprenorphine as first line
• Clonidine considered second line
• Detoxification without enrollment in treatment has little effect on relapse rate
• Adjuvant medications during taper
• Anxiety/dysphoria/lacrimation/rhinorrhea: hydroxyzine 25-50mg TID PRN
• Myalgia: APAP or NSAIDs
• Sleep disturbance: trazodone 50-100mg; gabapentin 300-1800mg
• Nausea: antiemetics (no specific preference)
• Diarrhea: bismuth subsalicylate or loperamide

Maintenance Treatment after Detoxification

• Pharmacotherapy with three FDA-approved medications
• Two available agonist medications with the full agonist methadone and

partial agonist buprenorphine

• Rationale for use include suppression of cravings and

withdrawal symptoms via stabilization of neuronal systems, in addition to blocking the acute effects of other opioids in the case of relapse

• Appropriate use allows patients to return to a productive

lifestyle and address the negative consequences that often arise due to OUD

• One available antagonist medication with naltrexone
• Intended for reinforcement of abstinence (via prevention of
• pioid intoxication)
• Does not directly affect the neuronal systems of OUD and

reduce craving

Center for Substance Abuse Treatment. (2005). Medication-Assisted Treatment for Opioid Addiction in Opioid Treatment Programs. Treatment Improvement Protocol (TIP) Series 43. Mattick, R., Breen, C., Kimber, J., & Davoli, M. (2009). Methadone maintenance therapy versus no opioid replacement therapy for opioid dependence. Cochrane Database Syst Rev, (3):CD002209

Pharmacotherapies for OUD

Methadone (MET) Buprenorphine and Buprenorphine/Naloxone (BUP) Naltrexone Oral (NTX) and Extended- Release Injection (XR-NTX) Route of Administration

Oral (liquid/powder/dispersible tablet) with consumption that is usually witnessed at an Opioid Treatment Program (OTP). Take-home doses allowed after meeting regulatory criteria Sublingual film or tablets that can be taken at home or in a physician’s office. 6-month implant and monthly IM injection available now Oral tablets to be taken at home or an intramuscular injection to be administered by a healthcare professional

Prescribing Restrictions

For treating OUD, can only be purchased and dispensed by certified OTPs or hospitals For treating OUD, prescribers must complete limited special training and qualify for a DEA prescribing waiver; does not have dispensary restrictions None; can be filled at any pharmacy

Evidence in OUD

MET has been the gold-standard treatment since FDA approval in 1960s; Cochrane reviews have demonstrated MET’s favorable treatment retention rate compared to placebo treatments and reduced rates of opioid positive urine drug screens Since passing of Drug Abuse Treatment Act in 2000, BUP has been used for office based management of OUD resulting in greater access and less stigmatized treatment; Cochrane reviews have noted BUP’s inferiority to MET for treatment retention, but BUP performs equally well in reduction

• f opioid positive urine drug screen rates

NTX is best reserved for highly motivated OUD patients (e.g. mandated treatment by a professional licensing board), as Cochrane reviews confirm the poor clinical utility of NTX due to poor adherence and low treatment retention; XR-NTX was approved in 2010 and has more encouraging data

Mechanism of Action

Full mu-opioid receptor agonist; also exhibits NMDA antagonism Partial mu opioid receptor agonist and kappa opioid receptor antagonist Full antagonist at mu, delta, and kappa opioid receptors

Center for Substance Abuse Treatment. (2005). Medication-Assisted Treatment for Opioid Addiction in Opioid Treatment Programs. Treatment Improvement Protocol (TIP) Series 43. Kampman, K., & Jarvis, M. (2015). American Society of Addiction Medicine (ASAM) National Practice Guideline for the Use of Medications in the Treatment of Addiction Involving Opioid Use. J Addict Med, 9(5):358-367. Center for Substance Abuse Treatment. (2006). Detoxification and Substance Abuse Treatment. Treatment Improvement Protocol (TIP) Series, No. 45; 2 Settings, Levels of Care, and Patient Placement.

Pharmacotherapies for OUD

Methadone (MET) Buprenorphine and Buprenorphine/Naloxone (BUP) Naltrexone Oral (NTX) and Extended- Release Injection (XR-NTX) Absorption

36% to 100% bioavailability Sublingual tablet has lower bioavailability (29%) than buccal film (46% to 65%) Variable bioavailability (5% to 40%)

Distribution

Lipophilic; 85% to 90% protein binding ~95% protein binding; CSF concentrations are ~15% to 25% of plasma concentrations 21% protein binding; large volume of distribution

Metabolism

Hepatic, primarily via CYP3A4 (consider HIV medications), 2B6, 2C19; half-life 9 to 87 hours Hepatic; primarily by CPY3A4 to active metabolite; half-life 37 hours for sublingual vs 27 hours for buccal Metabolized via non CYP-mediated dehydrogenase to an active metabolite

Excretion

Urine with <10% as unchanged drug; drug may sequester in tissues and prolong pharmacological effect despite low serum levels 70% Feces and 30% urine with ~33% total unchanged Primarily via urine with small amounts of unchanged drug

Interactions

Inhibits CYP2D6 moderately; major substrate

• f CYP3A4 and 2B6

Weak inhibitor for CYP1A2, 2A6, 2C19, and 2D6; major substrate of CYP3A4 None known enzymatic interactions, but will induce opioid withdrawal if administered in an opioid-using individual

Safety Concerns

Respiratory depression with overdose risk, especially with concomitant CNS depressants; increased risk of QTc prolongation Lower risk of respiratory depression with

• verdose relative to methadone is largely

negated in the presence of concomitant CNS depressants; risk of QTc prolongation is lower than methadone but not null XR-NTX has a REMS program focused on prevention of severe injection site reactions, but also for provider counseling against precipitated opioid withdrawal and hepatotoxicity

Center for Substance Abuse Treatment. (2005). Medication-Assisted Treatment for Opioid Addiction in Opioid Treatment Programs. Treatment Improvement Protocol (TIP) Series 43. Kampman, K., & Jarvis, M. (2015). American Society of Addiction Medicine (ASAM) National Practice Guideline for the Use of Medications in the Treatment of Addiction Involving Opioid Use. J Addict Med, 9(5):358-367. Center for Substance Abuse Treatment. (2006). Detoxification and Substance Abuse Treatment. Treatment Improvement Protocol (TIP) Series, No. 45; 2 Settings, Levels of Care, and Patient Placement.

Buprenorphine products

SAMHSA Treatment Improvement Protocol (TIP) 63, published February 2018: https://store.samhsa.gov/list/series?name=TIP-63-Medications-for-Opioid-Use-Disorders

Long-acting buprenorphine formulations: implant (Probuphine) and SC injection (Sublocade)

• Probuphine implant: 4 rods with 80mg buprenorphine per rod
• Inserted subdermally on inside of upper arm every 6 months
• Indication is for patients with sustained stability on <8mg daily buprenorphine
• Peak is 12 hours after insertion; steady state in ~4 weeks
• REMS program for prescribers and inserters
• Sublocade SC injection
• Two volumes available as refrigerated, prefilled syringes: 300mg/1.5ml &

100mg/0.5mL

• Injected into abdomen; requires initial 2-month load with 300mg and 100mg from

month 3 onward with option to return to 300mg dosing

• Indication is for moderate to severe OUD
• Peak is 24 hours after injection; steady state in 4-6 months
• REMS program for both pharmacy and healthcare setting (similar to Vivitrol)

Special populations

• Pregnancy
• Methadone is traditional gold star standard
• 2015 VA/DoD guidelines suggest buprenorphine (without naloxone) as

preferred over methadone if goal is to minimize neonatal abstinence syndrome

• 2015 guidelines give exception to methadone preference over buprenorphine if

treatment retention is a strong factor in planning

• Hepatic impairment
• Methadone has no limitations, although it is heavily hepatically metabolized –

lower dose and slower titration cautioned

• Buprenorphine cautioned in Child-Pugh moderate impairment – naloxone may

interfere with buprenorphine efficacy; mono-product ONLY in Child-Pugh severe impairment

• Naltrexone contraindicated with severe impairment and acute illness

Psychotherapy

 Mandatory for some modalities (methadone) while heavily recommended for

• thers

 Large Groups and Therapeutic Communities for OUD

Types Description Rating of Available Evidence in OUD

Network therapy

• Useful for frequent relapsers
• Identify and address relapse triggers
• Generate and maintain support of patient’s natural social

network Positive, limited Therapeutic communities

• Evolved out of Alcoholic Anonymous with heavy emphasis
• n personal willpower
• 12 to 18 month treatment duration in a long-term

residential setting Positive, limited Aversion therapies

• Counterconditions the body by developing an avoidant

response to substance use

• Uses nausea, faradic, and covert sensitization

Positive, limited; strongest evidence in daily drinkers

Herron, A., & Brennan, T. K. (2015). The ASAM Essentials of Addiction Medicine, Second Edition. Philadelphia: Wolters Kluwer. Ries, R. K., Fiellin, D. A., Miller, S. C., & Saitz, R. (2014). The ASAM Principles of Addiction Medicine. Philadelphia: Wolters Kluwer.

Psychotherapy

 Small groups for OUD

Types Description Milieu

• Common in residential programs
• Provide patients an opportunity to reflect on their experiences and insights from that day’s activities

Psychoeducational

• Provide specific information regarding a variety of topics related to addiction and recovery
• May include written assignments in addition to lectures or group discussions

Coping Skills

• Teach problem-solving methods, stress management, and relapse prevention strategies to improve

patients’ intrapersonal and interpersonal skills

Therapy groups

• Less structured and likely solicit patient discussion and sharing of problems, conflicts, and struggles
• Not intended to be didactic in contrast to psychoeducational groups

Evidence

• Controlled trials are limited, but those available show reductions in drug use, improved health, and

reduced social pathology

Barriers

• Early termination often involved time commitment problems, desire for individual treatment, or

general unwillingness to participate

• Within group barriers include low motivation to change, over-emphasis on external issues,

proselytizing and hiding behind AA/NA, and playing co-therapist

• Higher dropout rates reported in group therapy vs. individual therapy

Herron, A., & Brennan, T. K. (2015). The ASAM Essentials of Addiction Medicine, Second Edition. Philadelphia: Wolters Kluwer. Ries, R. K., Fiellin, D. A., Miller, S. C., & Saitz, R. (2014). The ASAM Principles of Addiction Medicine. Philadelphia: Wolters Kluwer.

Psychotherapy

 Individual Psychotherapy for OUD

Notable Types Elements of Focus Rating of Available Evidence in OUD

Motivational interviewing and motivational enhancement therapy Enhancing motivation; fostering treatment alliance Mixed; strongest for nicotine and alcohol use disorders Brief advice Enhancing motivation; fostering treatment alliance Unavailable Supportive-expressive therapy Development of coping skills Positive, limited Individual drug counseling Direct focus on substance abuse; enhancing motivation Unavailable; literature available for cocaine users Relapse prevention and coping skills Development of coping skills; managing contingencies Mixed 12-step facilitation Direct focus on substance abuse; enhancing motivation Mixed; strongest evidence for alcohol use disorder Contingency management and community reinforcement approach Managing contingencies; development of coping skills; direct focus on substance abuse Positive, robust (Cohen d > 0.6), (Dutra et al., 2008)

Herron, A., & Brennan, T. K. (2015). The ASAM Essentials of Addiction Medicine, Second Edition. Philadelphia: Wolters Kluwer. Ries, R. K., Fiellin, D. A., Miller, S. C., & Saitz, R. (2014). The ASAM Principles of Addiction Medicine. Philadelphia: Wolters Kluwer. Dutra, L., Stathopoulou, G., Basden, S. L., Leyro, T. M., Powers, M. B., & Otto, M. W. (2008). A Meta-Analytic Review of Psychosocial Interventions for Substance Use Disorders. Am J Psychiatry, 165:179-187.

Motivational Interviewing

 A form of collaborative conversation for strengthening a person's own motivation

and commitment to change

 Person-centered counseling style  Addresses ambivalence about change by paying particular attention to the

language of change

 Designed to strengthen an individual's motivation for and movement toward a

specific goal by eliciting and exploring the person's own reasons for change within an atmosphere of acceptance and compassion

 Can be used in multiple arenas  Mental Health  Substance Use Disorders  Chronic Medical conditions (diabetes, hypertension, asthma)

Motivational Interviewing

 Four Principles  Expressing empathy and avoiding arguing  Developing discrepancy  Rolling with resistance  Supporting self-efficacy (belief they can successfully make the change)

Goals of treatment: re-defining or refining “recovery”

• Consensus panels of policy, clinical, research, and recovery advocacy leaders identified

3 essential elements: sobriety, global health improvement, citizenship

• Sobriety can be defined as total abstinence or diagnostic remission
• Global health improvement encompasses physical, emotional, relational, and spiritual health
• Citizenship denotes positive community integration, such as social functioning and improved

quality of personal and family life

White, W. L. (2012). Medication‐Assisted Recovery from Opioid Addiction: Historical and Contemporary Perspectives. J Addict Dis, 31(3):199‐206.

Recovery

• SAMHSA TIP 63: “A process of change through which individuals improve their

health and wellness, live a self-directed life, and strive to reach their full potential…Although abstinence from all substance misuse is a cardinal feature of a recovery lifestyle, it is not the only healthy, prosocial feature”

• Traditional recovery oriented peer support organizations such Narcotics

Anonymous approach “recovery from addiction through abstinence” and have inconsistently embraced individuals who are on agonist/partial-agonist medications as “being in recovery,” often curtailing their presence at meetings but not shunning them entirely

• Ongoing debate persists between the divergence or convergence of “recovery”

and “remission”

• Remission typically refers to the subtraction of a pathology from a patient’s life
• r no longer meeting diagnostic criteria
• Recovery implies additions and further enrichment of the patient’s life

SAMHSA Treatment Improvement Protocol (TIP) 63, published February 2018: https://store.samhsa.gov/list/series?name=TIP-63-Medications-for-Opioid-Use-Disorders Bulletin #29. (1996). Retrieved from Narcotics Anonymous World Services: http://www.na.org/?ID=bulletins-bull29

Opioid Overdose Education and Naloxone Distribution (OEND)

 Everything you need and more for OEND!  https://vaww.portal2.va.gov/sites/mentalhealth/OEND/default.aspx  https://vaww.portal2.va.gov/sites/ad/SitePages/OEND.aspx  Stratification Tool for Opioid Risk Mitigation (STORM)  https://spsites.cdw.va.gov/sites/OMHO_PsychPharm/Pages/Real-Time-

STORM-Dashboard.aspx

 Opioid Therapy Risk Report  https://securereports2.vssc.med.va.gov/ReportServer/Pages/ReportViewer.as

px?/PC/Almanac/PAIN_ProviderWEB&rs:Command=Render

Opiate Overdose Education and Naloxone Distribution (OEND) Initiative

 Launched in May 2014  STVHCS launched in October 2014  Harm reduction and risk mitigation strategy  Aims to decrease opioid-related overdose deaths among Veterans Affairs

patients

 NOT meant to be treatment (naloxone is an antidote)  Naloxone kit distribution is paired with education about overdose prevention,

recognition, and rescue response

Legislative Mandate for OEND

 The spread of the opioid epidemic in the United States has led to passage of the

“Comprehensive Addiction and Recovery Act” on 7/22/16

 All VA Pharmacies are now equipped to dispense and educate Veterans on

naloxone kits

 No co-pay requirement for naloxone kits

Recommendations for Use

 Last updated in August 2016: Naloxone Rescue Kits  Updated older recommendations which used patient categories  Present patient considerations related to  Present or historical medical diagnoses  Present utilization of opioid medications  Specific patient care situations (e.g. low dose opioids if patient has alcohol

use disorder)

 Patients in hospice/palliative care are considered on a case by case basis and

not routinely used

Risk Factors for Overdose

 Four general categories  Unsafe combinations (opioid + benzodiazepine; opioid + stimulant)  Tolerance shifts (cross tolerance or break in therapy)  Physical health (pre-existing respiratory, renal, hepatic, or cardiac illness)  Lack of communication/solitary living situation (patients cannot self-inject the

antidote)

Naloxone HCl Nasal Spray

Instructions Image Step 1

Remove naloxone nasal spray from the box

Step 2

Peel back the tab with the circle to open the naloxone nasal spray

Step 3

Hold the naloxone nasal spray with your thumb on the bottom of the plunger and your first and middle fingers on either side of the nozzle

Step 4

DO NOT PRIME OR TEST THE SPRAY DEVICE. Tilt the person’s head back and provide support under the neck with your hand. Gently insert the tip of the nozzle into one nostril, until your fingers on either side of the nozzle are against the bottom of the person’s nose

Step 5

Press the plunger firmly to give the entire dose of naloxone nasal spray. Remove the nasal spray from the nostril after giving the dose

Step 6

If no reaction in 2-3 minutes or if the person stops breathing again, give the second dose of naloxone in the other nostril using a new naloxone nasal spray

Naloxone HCl Autoinjector

Instructions Image Step 1

Pull the auto-injector from the outer case

Step 2

Pull firmly to remove the red safety guard (do not touch the black base)

Step 3

Place the black end against the middle of the outer thigh, through clothing if necessary, then press firmly and hold in place for 5 seconds

Step 4

If no reaction in 2-3 minutes or if the person stops breathing again, give the second dose of naloxone using new auto-injector

Comparison of naloxone spray and autoinjector

Both products are FDA-approved for use in community settings, contain product labeling which includes instructions for layperson use, and are ready-to-use with no assembly required Nasal Spray Auto-injector Trade name

Narcan Evzio

Strength

4 mg/0.1 mL 0.4 mg/0.4 mL

Total volume of 2-unit package

8 mg/0.2 mL 0.8 mg/0.8 mL

Dosing

Spray 0.1 mL into one nostril; repeat with second device into the other nostril after 2-3 minutes if no or minimal response Inject into the outer thigh as directed by voice-prompt system. Place black side firmly on outer thing and depress and hold for 5 seconds. Repeat with 2nd device in 2-3 minutes if no or minimal response

Usability

90.5% successful use without training 90.5% successful use without training; 100% successful use with training

Storage requirements

Store at 59-77°F; excursions permitted from 39-104°F; store away from light Store at 59-77°F; excursions permitted from 39-104°F; store away from light

Disposal of used or expired product

No defined requirements Biohazard sharps container

Poll question

 Which class of opioids are responsible for the greatest number of opioid-related

deaths in 2016?

A.Heroin B.Natural and Semi-synthetic Opioids C.Methadone D.Synthetic Opioids other than Methadone

Poll question

 Which class of opioids are responsible for the greatest number of opioid-related

deaths in 2016?

A.Heroin B.Natural and Semi-synthetic Opioids C.Methadone D.Synthetic Opioids other than Methadone

Patient Case

 32 yo male comes in to emergency room reporting opiate withdrawal. Pt reports

utilizing $25 worth of IV heroin on a daily basis for 8 years. He reports last use was 14 hours ago. Pulse is currently 95. Reports nausea and diarrhea 20 mins

• ago. He is fidgety in his seat and appears flushed. He has a visible hand tremor

with outstretched arms. He appears anxious and slightly irritable. During interview he has yawned twice. His pupils maybe slightly larger than normal. He reports diffuse aches in his joints. He wipes his running a few times during the interview. Goosebump flesh noticed on his arms.

 Using the COWS, what is this patients withdrawal score and severity of his

current symptoms?

22

Patient Case: COWS Scoring

Patient Case

 Now that we have determined patient is in moderate opiate withdrawal, what

would you recommend for this patient and why?

Epidemiology of Alcohol Use Disorder

 Alcohol use is among the top three risk factors for global disease

burden, behind only high blood pressure and tobacco smoking

 Estimated 22.9% of population reported binge drinking; ~6.3%

classified as heavy drinkers

 ~17 million adults 18 and older had an AUD in 2014  65% of these patients were male  Only 1.5 million received treatment  majority were male  Alcohol related deaths  ~88,000 people (approximately 62,000 men and 26,000 women)

die from alcohol-related causes annually (4th leading cause of death)

 Veterans with AUD die on average 15 years earlier than veterans

without AUD

Substance Abuse and Mental Health Services Administration (SAMHSA). 2014 National Survey on Drug Use and Health (NSDUH). Tables 2.41B, 2.46B, 5.8A and 5.8B

Epidemiology of Alcohol Use Disorder

Source: Substance Abuse and Mental Health Services Administration (SAMHSA). 2014 National Survey on Drug Use and Health

Epidemiology of Alcohol Use Disorder

Alcohol Content/Limits

Standard drink is considered to be 0.6 fluid 0z or 14 g of “pure” alcohol Beer (12 oz); Wine (5 oz); Shot of 80-proof beverage (1.5 oz)

Single day limit* Weekly limit* Men

≤4 standard-size drinks ≤14 standard-size drinks

Women

≤3 standard-size drinks ≤7 standard-size drinks

Age >65

≤3 standard-size drinks ≤7 standard-size drinks

Source: NIAAA; https://pubs.niaaa.nih.gov/publications/AlcoholOverdoseFactsheet/images/drinks.png

Chronic Effects of Alcohol

Source: https://upload.wikimedia.org /Possible_long-term_effects_of_ethanol.svg

Laboratory Biomarkers

Biomarker Description Possible source of false positives Comments AST/ALT

Increases after heavy drinking lasting for several weeks Excessive coffee consumption, drugs  Ratio AST:ALT > 2:1 suggests liver damage from alcohol  AST more sensitive to EtoH use

Carbohydrate- deficient transferrin (CDT)

Increases after 2-3 weeks of daily, heavy drinking due to impairment of glycosylation of transferrin Rare genetic variant, biliary cirrhosis, end stage liver disease, smoking and obesity can alter values  Less sensitive for women and younger age  Good biomarker for relapse to heavy drinking

Ethyl glucoronide (EtG)

Ethanol metabolite found in urine; indicator that EtoH consumption occurred in last 3-4 days Alcohol in medications, hygiene products, etc.  Sensitive to as little as single drink  Highly sensitive to any Etoh consumption  Good indicator of relapse

Gamma glutamyl transferase (GGT)

Enzyme that increases after weeks – months of heavy Etoh use Liver and biliary disease; smoking;

• besity; diabetes, medications which

induce liver enzyme  Primarily reflects liver damage, often related to alcohol  Performs best in adults 30-60 years

Mean Corpuscular Volume (MCV)

Result of folate/vitamin B12 deficiency after long term EtoH use Hemolysis, bleeding disorders; anemia, folate deficiency; hypothyroidism; hyperglycemia  Poor biomarker of relapse  Higher sensitive in women than men

Phosphatidyl ethanol (PEth)

Direct serum based biomarker None likely but still need more data  Persistence in blood for as long as 3 weeks after a few days of drinking  Linear dose response relationship to EtoH

Standardized Rating Scales for AUD

Scale Name Description/Purpose/Use Values/Interpretation Clinical Institute for withdrawal Assessment-Alcohol Revised (CIWA-AR)

 10-item clinician rated scale  Gold standard for alcohol withdrawal assessment  Often used as part of symptom- triggered approach to treatment  9 items are rated from 0 (none) to 7(severe) and 1 item is rated from 0 (fully oriented) to 4 (disoriented)  <10 = Mild withdrawal: Medication likely not needed  10-18= Moderate withdrawal: May need medication  >18 = Severe withdrawal: Needs medication

Alcohol Use Disorders Identification Test (AUDIT)

 10 item clinician rated questionnaire that evaluates quantity/frequency of drinking, physiological dependence, and harmful use  AUDIT-C is abbreviated 3 item screening tool (see appendix)  Scores for each questionnaire rated on a scale of 0 (never) to 4 (often, daily) with higher scores indicating greater misuse  Scores >8 identify heavy drinkers and those with Etoh-use disorders  “Zones” of interventions based on AUDIT scores

CAGE: Cut down, Annoyed, Guilty, Eye

• pener

 4-item clinician or self-rated screening tool  Each item scored a 0 (no) or 1 (yes) with a higher score indicative of Etoh problems  A score of > 2 is a positive screen and suggests problem drinking  prompts the need for further assessment

Audit-C for AUD

Management- Brief Intervention

Alcohol Use Disorder. VA Academic Detailing provider piece. 2014

General Approach to Pharmacological Management in AUD

• AUDIT-C ≥6
• Patient presents with alcohol related

problems Consider diagnostic evaluation and/or pharmacotherapy

• Typically ≥3 months
• Continuing ≥1 year may be necessary to

prevent relapse

• Relapse risk is greatest during first 90 days

Length of pharmacotherapy treatment

• Little evidence to support using combination

pharmacotherapy for AUD

• Short-term combinations may be used if

patients experience a poor response to adequate trials of monotherapy combined with psychosocial interventions Combining different pharmacotherapies

Pharmacological Management in AUD

 FDA Approved Medications  Naltrexone oral  Naltrexone long-acting injection  Acamprosate  Disulfiram  Non-FDA Approved Medications  Topiramate  Gabapentin  Baclofen  Ondansetron  Varenicline

Pharmacological Management in AUD

 FDA Approved Medications  Naltrexone oral  Naltrexone long-acting injection  Acamprosate  Disulfiram  Non-FDA Approved Medications  Topiramate  Gabapentin  Baclofen  Ondansetron  Varenicline

Pharmacological Management in AUD

Lavinghousez C. Substance-Related Disorders. Chavez B, Ehret MJ, Haight RJ et al., eds. 2016-2017 BCPP Examination Review and Recertification Course. Lincoln, NE: CPNP; 2016:654-680

Efficacy Comparison

Efficacy Comparisons

NTX shown the most consistent efficacy in studies NTX associated with reduced ED visits, lower inpatient admission, and reduced healthcare costs Acamprosate prolongs time to first drink but has limited efficacy on reducing heavy drinking (see figure) Disulfiram evidence is somewhat limited but more effective with monitored administration

Source: Maisel NC, et al. Addiction. 2013

Poll Question

 Which agent has the best data for abstinence from alcohol?

• A. Naltrexone (Oral)
• B. Acamprosate
• C. Disulfiram
• D. Topiramate

Poll Question

 Which agent has the best data for abstinence from alcohol?

• A. Naltrexone (Oral)
• B. Acamprosate
• C. Disulfiram
• D. Topiramate

Epidemiology of Tobacco Use Disorder

 Smoking is the leading cause of preventable death  Cigarette smoking is responsible for more than 480,000 deaths

per year in the United States (US), including more than 41,000 deaths resulting from secondhand smoke exposure

 Total economic cost of smoking is more than $300 billion a

year in the US

 Worldwide, tobacco use causes nearly 6 million deaths per

year, and current trends show that tobacco use will cause more than 8 million deaths annually by 2030

National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2014 American Journal of Preventive Medicine 2014;48(3):326–333 Morbidity and Mortality Weekly Report 2018;67(2):53-9

2016 NSDUH: Number of Past Month Tobacco Users among People Aged 12 or Older

https://www.samhsa.gov/data/sites/default/files/NSDUH-FFR1-2016/images/nsduh-ffr1-fig01-2016.png

Risks of Smoking

https://www.cdc.gov/tobacco/infographics/health-effects/pdfs/he-infographic1.pdf?s_cid=bb-osh-effects-graphic-005

Smoking Cessation

 In 2015, nearly 7 in 10 (68.0%) adult cigarette smokers wanted to stop smoking  Since 2002, the number of former smokers has been greater than the number

• f current smokers

 Quitting smoking is hard and may require several attempts  People who stop smoking often start again because of withdrawal symptoms,

stress, and weight gain

 People who stop smoking greatly reduce their risk for disease and early death

Morbidity and Mortality Weekly Report 2018;67(2):53-9

CPS Role in Smoking Cessation

 Smokers who receive assistance from a clinician are 1.7-2.2x as likely to quit

successfully for ≥5 months

 Combined of behavioral counseling and pharmacotherapy is more effective than

either alone

 Treatment delivered by a variety of clinician types increases abstinence rates

U.S. Department of Health and Human Services, Public Health Service, June 2000 N Engl J Med 2002;346:506

The 5 A’s

 Ask (inquire smoking status regularly)  Advise (encourage smokers to quit)  Assess (evaluate readiness to quit)  Not ready to quit in the next month  Ready to quit in the next month  Recent quitter, quit within past 6 months  Former tobacco user, quit >6 months ago  Assist (provide smoking cessation efforts)  Arrange (arrange follow-up)

Agency for Healthcare Research and Quality, Rockville, MD. http://www.ahrq.gov/professionals/clinicians- providers/guidelines-recommendations/tobacco/5steps.html

Pharmacological Treatments

 Preferred  Nicotine Replacement Therapy (NRT)  Bupropion SR  Combination NRT  Varenicline  Nortriptyline  Clonidine

Counseling

 Cognitive-behavioral therapy (CBT)  Smokers who are ready to quit  Motivational interviewing  Smokers who are not ready to quit  Telephonic counseling  1-800-QUIT-NOW  I’m Ready to Quit!  https://www.cdc.gov/tobacco/campaign/tips/quit-

smoking/?s_cid=OSH_tips_D9170

Non-pharmacologic Treatments

 Hypnosis  Acupuncture  Exercise programs  May be effective to manage withdrawal symptoms acutely  Reduce craving and prolonged latency to smoking  Assist with smoking cessation

CPPO SUD SME WORKGROUP MEMBERS

 Sondra Adkinson  Abril Atherton  Christina Bonanno  Jeffrey Boyer  Jasmine Carpenter  Tim Chen  Cassandra Davis  Kamonica Craig  Erica Dimitropoulos  Elizabeth Dinges  Nicole Elharar  Nicole Fioravanti  Courtney Givens  Jessica Hawthorne  Terri Jorgenson  Allie Kaigle  Rashondra Bain Levarity  Julie McCutcheon  Shawn McFarland  Jeremy McKelvey  Taylor Modesitt  Shuang Ouyang  Stephanie Oh  Sadie Rostenburg  Kristyn Straw-Wilson  Rani Thamawatanakul  Andrea Winterswyk  Troy Moore– Co-Chair  Theresa Frey- Co-Chair  Cindy Gutierrez – CPAB Member  Tera Moore – CPPO Advisor  Ilene Robeck – Physician  Adam Gordon - Physician  Jason Hawkins - CPAB  Norm Hooten – PGY2 Resident  Virginia Torrise – PBM  Sarah Popish - AD

PROGRESS

 Meeting Monthly since February 2018

 Overview of SUD CPS encounters  Academic Detailing SUD Resources  Facility practice examples presented  Fact Sheet: Role of the CPS in Medication Assisted Treatment (MAT) for Opioid Use Disorder

(OUD) (released May 2018)

 Presented the role of the CPS in MAT for OUD on PACT Pain Champion Teleconference (June

2018)

 Presented Treating Substance Use Disorders in a Primary Care Setting on CPPO Monthly

PACT Teleconference Series (June 2018)

 Fact Sheet: Role of the CPS in Substance Use Disorders (in progress)

STATUS SUMMARY

In summary, the SUD SME was initiated in February 2018. Priority for FY18 is to develop and distribute the Fact Sheet: Role of the CPS in SUD and describe the

• ptimized model of care in SUD and integration of the CPS activities as part of the

team.

Encounters by CPS for SUD

FY16Q1 FY16Q2 FY16Q3 FY16Q4 FY17Q1 FY17Q2 FY17Q3 FY17Q4 FY18Q1 FY18Q2 FY18Q3

Opioid Tobacco Alcohol Other Illicit Marijuana Sedative Hypnotic

VHA PBM Clinical Pharmacy Program Office, 2018. Data on file.

High Priority Focus Areas

 Pending Deliverables for FY18  Fact Sheet: Role of the CPS in SUD (in progress)  Stepped Care for Opioid Use Disorder Train the Trainer (SCOUTT)

Conference

 Potential Barriers  Communication and collaboration with SUD initiatives  Collaboration with Program Offices involved in SUD

 Describe the optimized model of care in SUD and integration of the CPS activities as part of the team  Identify gaps in care and sites with hiring difficulties to improve the uptake and job opportunities for appropriately

trained CPS  Promoting practice to Pharmacy and Non-pharmacy Forums

 Fact Sheet

Stepped Care Model for MAT in OUD

 Opioid Crisis +/- Opioid Use Disorder threaten

 Lives of Veterans and  Access to PACT, Pain Clinic, …, while

 “Pain Management” through Choice is more risky

 Strategic resource re-allocation addresses

 Foundational Services needed for Pain & OUD  Improving function of other Core Services of

 Primary Care  Mental Health and  Rehabilitation

Additional Rationale Stepped Care Model for MAT in OUD: Interdisciplinary Model

 CARA required centralized, interdisciplinary review of patients on

• pioid therapy at high risk for an adverse event

 Substantial shortages of providers to deliver MAT for OUD  Opportunity to utilize MH and Pain CPS to bridge gaps on this

team (OUD, MH and Pain care needs)

 In addition to clinical care, CPS would have allocated time for

Academic Detailing with campaigns focused on Suicide Prevention, OSI and OUD identification and treatment

74

FLOW: Virtual High Risk Safety Clinic

High Risk: STORM Report

STORM: Strategic Tool for Opioid Risk Mitigation

CPS

Auto-Audit (Pop Health), Academic Detailing

RN Case Management

+/- Weekly Telehealth

Physician initial

Video Telehealth Appointment +/-Local Bridging

Acupuncture, Chiropractic

Veteran & PACT

+/-Local SA TP Opioid Use Disorder

CPS Medication Mgt, Tapers,

Risk Mitigation via Telehealth 75

VHA CPPO May 2018

Key Points

 Substance Use disorders have a significant impact on the health and well being of

many Americans

 Clinical Pharmacy Specialists can play a vital role in improving access of care and

treatment in veterans with OUD, AUD, and TUD

 CPS role in SUD treatment is expanding

 Optimizing a model of care  CPS integration into the treatment team

Answers To Self-Assessment Questions

 The gold standard medication for a pregnant women with OUD is?

 Methadone

 The medication associated with reduced ED visits, lower inpatient admission, and

reduced healthcare costs for AUD is?

 Naltrexone

 The greatest benefit for smoking cessation is seen with medication,

psychotherapy or combination treatment?

 Combination treatment

Questions

Closing Remarks

Troy A. Moore, PharmD, MS, BCPP Clinical Pharmacy Specialist- Psychiatry Director, ASHP-Accredited PGY-2 Psychiatric Pharmacy Residency Program South Texas Veterans Health Care System Assistant Professor UT Health San Antonio Dept of Psychiatry- Division of Community Recovery, Research and Training Troy.Moore3@va.gov

FDA Approved Medications for AUD

Naltrexone oral Naltrexone Injection Acamprosate Disulfiram

Mechanism of Action

Mu opioid receptor antagonist  blocks pleasurable effects of EtoH by decreasing DA release NMDA receptor antagonist  enhances GABA receptor activation and restores GABA/glutamate balance Alcohol desensitizing agent that irreversibly inhibits alcohol dehydrogenase  marked ↑aldehyde leading to undesirable effects

Use/Clinical pearls

• Effective at :

↓ drinking ↓ cravings ↑ abstinence

• Highest evidence shown with behavioral therapy
• Pts carry wallet card to alert medical personnel they are
• n naltrexone
• IM may benefit pts w/ non-adherence
• More effective for patients with a

goal of abstinence (>4 days of abstinence before therapy)

• May decrease cravings and alleviate

negative reinforcement

• More effective for patients with a goal of

abstinence and with monitored administration

• Reaction with alcohol can occur for up to 14

days after last dose

Onset and duration of action

• 15 to 60 minutes for onset;

24 hr duration

• 2 to 3 days for onset; up to

3-4 weeks duration

• onset appears to be rapid (within 3-

8 hrs); duration is variable

• Onset is rapid (up to 12 hrs for full effect);

duration of at least 1-2 wks

Dose initiation

• 25mg po on the first day

then increase to 50mg

• 380 mg IM (gluteal) monthly - 333 mg po TID x1 week
• 250 mg po daily

Maintenance

• 50mg daily po (or 100mg
• n M,W & 150mg on F)
• 380 mg IM monthly
• 666 mg po TID
• Average dose 250 mg po daily (range 150-

500mg/d)

Dosing in special populations

• Patients with hepatic or renal impairment may respond

to lower doses

• CrCl 30-50 mL/min: 333 mg po

three times daily

• CrCl ≤ 30 mL/min: Not

recommended

• Not applicable

Medications for AUD

FDA Approved Medications for AUD

Naltrexone oral Naltrexone Injection Acamprosate Disulfiram

Adverse effects

• Nausea/vomiting
• Headache
• Insomnia
• Dizziness
• Anxiety
• Same as oral
• Injection site reaction (pain,

pruritus, tenderness, bruising, induration, swelling)

• Diarrhea
• Insomnia
• Anxiety
• Depression
• Weakness
• Drowsiness
• Headache
• Psychosis
• Rash
• Metallic or garlic-like aftertaste
• Hepatitis

Monitoring

• LFTs at baseline at 6 months then yearly
• Suicidal thoughts and depression have been reported
• CrCl in higher risk patients (elderly,

renal impairment)

• Monitor for suicidal thoughts and

depression

• LFTs 10 – 14 days after start of treatment

then yearly

Drug interactions

• Opioid containing medications
• Naltrexone: ↑ Cmax of acamprosate

(no dosage adjustment required)

• Alcohol containing products
• CYP 2C9, 2E1 inhibitor

Contraindications

• Concomitant opioids
• Acute hepatitis or liver failure
• Opioid dependence or use within past 7 days
• CrCl ≤ 30 mL/min
• Severe myocardial disease
• Use of alcohol or alcohol containing products
• Concomitant or recent use of metronidazole
• Psychoses

Baseline evaluation

• Opioid free ≥ 7-10 days
• LFTs
• GGT
• Bilirubin
• Urine beta-HCG for

females

• same as oral
• adequate muscle mass for

injection

• CrCl
• Urine beta-HCG for females
• Abstinence x 4 days prior to

initiation may improve results

• Must be alcohol free

≥ 24 hrs and BAL = 0

• LFTs
• Medical and psychiatric assessment
• EKG
• Urine beta-HCG for females

Warnings

BBW for risk of dose related hepatocellular injury Does not diminish withdrawal symptoms BBW: never administer to pt at state of intoxication

Medications for AUD

Non-FDA Approved Medications for AUD

Topiramate Gabapentin Baclofen

Mechanism of Action

Unknown; may ↓DA in reward pathway through VTA-GABAA activity Unknown; may ↓DA in reward pathway Unknown; modulation of DA through GABA-B agonism

Use/Clinical pearls

• Effective at ↓drinking and ↑ abstinence
• Appears to be at least effective as NTX in ↓

heavy drinking and cravings

• Therapeutic effects seen as early as week 4
• Effective in abstinent patients and those still

drinking

• May be effective alone or in combination

with naltrexone at: ↓ drinking, ↓ cravings, ↓ insomnia, ↑ abstinence

• Gabapentin showed better response in

pts w/ hx of withdrawal compared to NTX

• Shown to be more effective for insomnia

than trazodone in AUD

• Can be used in patients with cirrhosis or liver

impairment

• May be effective at:

↓ drinking ↓ cravings ↑ abstinence

• Co-existing mental disorder may delay

effectiveness

Dose initiation

• 25 mg daily, increase dose by 25-50 mg/day

divided BID at weekly intervals

• 300 mg po at bedtime
• 5 mg po TID

Maintenance

• Doses studied range between 75 – 300 mg/day

divided BID (recommended max dose of 200mg by VA/DoD guidelines)

• Doses studied range between 600-1800

mg po at bedtime or divided BID

• Most commonly studied dose is 10-20 mg po TID but

growing evidence that higher doses may be needed (up to 270 mg/day)

Dosing in special populations

• CrCl < 70 mL/min: Give 50% of dose and use

slower titration

• Hepatic impairment: Clearance may be

reduced

• CrCl >15-29 mL/min: 200-700 mg po at

bedtime

• CrCl = 15 mL/min: 100-300 mg po at

bedtime

• Hemodialysis: reduce dose in proportion

to CrCl

• Renal dysfunction: dose adjustments may be

necessary (no specific recommendations)

Medications for AUD

Non-FDA Approved Medications for AUD (cont.)

Ondansetron Varenicline

Adverse effects

• Headache
• Fatigue
• Constipation
• Dizziness
• Fever
• Nausea/vomiting
• Constipation
• Headache
• Insomnia
• Abnormal dreams
• Irritability
• Suicidal ideation
• Depression

Monitoring

• BMP (electrolytes)
• Changes in behavior or thinking
• Suicidal ideation or behavior

Drug interactions

• Apomorphine (avoid)
• Drugs that prolong QT interval (use caution)
• May enhance the adverse/toxic effects of alcohol
• May enhance the adverse/toxic effects of nicotine
• H2-Antagonists, quinolone antibiotics and trimethoprim may increase the serum

concentration of varenicline

Contraindications

• Hypersensitivity to ondansetron or any other selective

5HT3 antagonist

• Hypersensitivity to varenicline

Baseline evaluation

• Magnesium and potassium level (↑ risk of QT

prolongation with low electrolyte levels)

• EKG if patient high risk for prolonged QT interval –

probably not needed due to low dose used in AUD

• CrCl
• Suicidal intent
• Neuropsychiatric symptoms

Medications for AUD

Comparison of naloxone spray and autoinjector

Both products are FDA-approved for use in community settings, contain product labeling which includes instructions for layperson use, and are ready-to-use with no assembly required Nasal Spray Auto-injector Trade name

Narcan Evzio

Strength

4 mg/0.1 mL 0.4 mg/0.4 mL

Total volume of 2-unit package

8 mg/0.2 mL 0.8 mg/0.8 mL

Dosing

Spray 0.1 mL into one nostril; repeat with second device into the other nostril after 2-3 minutes if no or minimal response Inject into the outer thigh as directed by voice- prompt system. Place black side firmly on

• uter thing and depress and hold for 5 seconds.

Repeat with 2nd device in 2-3 minutes if no or minimal response

Usability

90.5% successful use without training 90.5% successful use without training; 100% successful use with training

Storage requirements

Store at 59-77°F; excursions permitted from 39-104°F; store away from light Store at 59-77°F; excursions permitted from 39-104°F; store away from light

Disposal of used or expired product

No defined requirements Biohazard sharps container

Nicotine Replacement Therapy

Transdermal Nicotine Patch Nicotine Lozenge Nicotine Gum

7mg, 14mg, 21mg 2mg, 4mg 2mg, 4mg Longer-term Use Acute Use Acute Use >10 cigs/day: 21mg/day x 4-6 weeks, then 14mg/day x 2 weeks, then 7mg/day x 2 weeks ≤10 cigs/day: 14mg/day x 6 weeks, then 7mg/day x 2 weeks 1st cig >30 mins after waking: 2mg 1st cig ≤30 mins after waking: 4mg Weeks 1-6: 1 lozenge q1-2h Weeks 7-9: 1 lozenge q2-4h Weeks 10-12: 1 lozenge q4-8h 1st cig >30 mins after waking: 2mg 1st cig ≤30 mins after waking: 4mg Weeks 1-6: 1 piece q1-2h Weeks 7-9: 1 piece q2-4h Weeks 10-12: 1 piece q4-8h Replace patch daily, rotate sites Do NOT cut Allow to dissolve slowly Do NOT chew or swallow No food or beverages 15 mins before or during use Chew slowly and park as needed No food or beverages 15 mins before or during use Burning, itching, vivid dreams, headache Mouth irritation, nausea, hiccups, heartburn, sore throat, dizziness Mouth/jaw soreness, hiccups, dyspepsia, hypersalivation

Nicotine Replacement Therapy

Nicotine Nasal Spray Nicotine Inhaler

10mg/mL, Rx 10mg, Rx Acute Use Acute Use 1-2 doses/hour (1 dose = 1 spray in EACH nostril) MAX 40 doses/day up to 3-6 months Initially use 1 cartridge q1-2h Best effects with continuous puffing for 20 minutes Blow nose if not clear and tilt head back Do NOT sniff while spraying Inhale into back of throat or puff in short breaths Do NOT inhale into lungs No food or beverages 15 mins before or during use Nasal/throat irritation, sneezing, rhinitis, tearing Mouth/throat irritation, cough, headache, rhinitis, dyspepsia, hiccups

Adjunctive Smoking Cessation Pharmacology

Bupropion SR Varenicline Nortriptyline Clonidine

150mg 0.5mg, 1mg 25mg PO: 0.1mg; TD: 0.1-0.2mg/day patch q7Days Longer-term Use Longer-term Use Longer-term Use Longer-term Use 150mg PO QAM x3 days, then 150mg PO BID Begin 1-2 weeks prior to quit date Duration: 7-12 weeks, with maintenance up to 6 months Days 1-3: 0.5 mg PO QAM Days 4-7: 0.5 mg PO BID Weeks 2-12: 1 mg BID Begin therapy 1 week prior to quit date Severe renal impairment: max 0.5mg 25mg PO daily Begin 1-2 weeks before quit date Titrate to 75-100mg/day Duration of 12 weeks PO: 0.1mg daily; increase by 0.1 mg/day to 0.15- 0.75mg/day if required TD: 0.1-0.2mg/day patch q7Days Insomnia, dry mouth, nervousness, nausea, dizziness, constipation, rash, seizures Nausea, sleep disturbances, constipation, flatulence, vomiting Fast heart rate, blurred vision, urinary retention, dry mouth, constipation, weight gain/loss Constipation, dizziness, drowsiness, dry mouth, unusual tiredness/weakness