ALKERMES EXHIBIT 2018
`Amneal Pharmaceuticals LLC v. Alkermes Pharma Ireland Limited
`IPR2018-00943
`
`Page 1 of 39
`
`

`

`Medication for the Treatment of
`Alcohol Use Disorder:
`A Brief Guide
`
`U.S. Department of Health and Human Services
`Substance Abuse and Mental Health Services Administration
`Center for Substance Abuse Treatment
`Division of Pharmacologic Therapies
`
`1 Choke Cherry Road
`
`Rockville, MD 20857
`
`
`
`Page 2 of 39
`
`

`

` 
`
`Acknowledgments
`This publication was prepared for the Substance Abuse and Mental Health Services Administration
`(SAMHSA) by JBS International, Inc. under contract number HHSS283200700003I/HHSS28342007T,
`with SAMHSA, U.S. Department of Health and Human Services (HHS). CDR Alina Salvatore, R.Ph.,
`M.S., and LCDR Brandon T. Johnson, M.B.A., served as the Contracting Officer Representatives.
`Disclaimer
`The views, opinions, and content expressed herein are the views of the authors and do not necessarily
`reflect the official position of SAMHSA, the National Institute on Alcohol Abuse and Alcoholism (NIAAA)
`or HHS. Nothing in this document constitutes an indirect or direct endorsement by SAMHSA, NIAAA, or
`HHS of any non-federal entity’s products, services, or policies and any reference to a non-federal
`entity’s products, services, or policies should not be construed as such. No official support of or
`endorsement by SAMHSA, NIAAA, or HHS for the opinions, resources, and medications described is
`intended to be or should be inferred. The information presented in this document should not be
`considered medical advice and is not a substitute for individualized patient or client care and treatment
`decisions.
`Public Domain Notice
`All materials appearing in this volume except those taken directly from copyrighted sources are in the
`public domain and may be reproduced or copied without permission from SAMHSA or the authors.
`Citation of the source is appreciated. However, this publication may not be reproduced or distributed for
`a fee without the specific, written authorization of the Office of Communications, SAMHSA, HHS.
`
`Electronic Access and Printed Copies
`This publication may be downloaded or ordered at http://store.samhsa.gov. Or call SAMHSA at 1­
`
`877-SAMHSA-7 (1-877-726-4727) (English and Español).
`Recommended Citation
`Substance Abuse and Mental Health Services Administration and National Institute on Alcohol Abuse
`and Alcoholism, Medication for the Treatment of Alcohol Use Disorder: A Brief Guide. HHS Publication
`
`No. (SMA) 15-4907. Rockville, MD: Substance Abuse and Mental Health Services Administration,
`2015.
`Originating Office
`Division of Pharmacologic Therapies, Center for Substance Abuse Treatment, Substance Abuse and
`Mental Health Services Administration, 1 Choke Cherry Road, Rockville, MD 20857. HHS Publication
`No. (SMA) 15-4907. Printed 2015.
`
`
`i
`
`Page 3 of 39
`
`

`

`Medication for the Treatment of Alcohol Use Disorder: A Brief Guide
`
`CONTENTS
`Introduction ............................................................................................................................... 1
`
` 
`
`Considering Medications ......................................................................................................... 2
`
` 
`
`Screening and Assessing Patients .........................................................................................7
`
` 
`Screening for Risky Alcohol Use ......................................................................................7
`
` 
`Assessing the Need for Medication-Assisted Treatment ..................................................7
`
` 
`
`Developing a Treatment Plan and Selecting a Medication ....................................................9
`
` 
`Setting Goals for Medication-Assisted Treatment ............................................................9
`
` 
`Components of the Treatment Plan .................................................................................9
`
` 
`Educating the Patient and Obtaining Informed Consent ..................................................9
`
` 
`Evaluating the Need for Medically Managed Detoxification ...........................................10
`
` 
`Integrating Pharmacologic and Nonpharmacologic Therapies .......................................11
`
` 
`Addressing Co-Occurring Disorders ..............................................................................11
`
` 
`Treating Adolescents and Young Adults ........................................................................12
`
` 
`Treating Pregnant and Postpartum Women ...................................................................12
`
` 
`Treating Older Adults .....................................................................................................12
`
` 
`Selecting a Medication ...................................................................................................13
`
` 
`
`Medication-Assisted Treatment ............................................................................................18
`
` 
`Initiating Treatment with Disulfiram ................................................................................18
`
` 
`Initiating Treatment with Naltrexone...............................................................................18
`
` 
`Initiating Treatment with Acamprosate ...........................................................................20
`
` 
`Treating People with Co-Occurring Disorders ................................................................20
`
` 
`
`Monitoring Patient Progress ..................................................................................................20
`
` 
`Monitoring ...................................................................................................................... 20
`
` 
`Adjusting the Treatment Plan .........................................................................................21
`
` 
`
`Summary ................................................................................................................................. 23
`
` 
`
`
`Appendix A: Members of the Consensus Panel, Staff, and Consultants .....................24
`
` 
`
`Appendix B: Sources of Helpful Information .......................................................................26
`
` 
`
`Appendix C: Acknowledgments ............................................................................................29
`
` 
`
`References .............................................................................................................................. 30
`
` 
`
`ii
`
`Page 4 of 39
`
`

`

`Medication for the Treatment of Alcohol Use Disorder: A Brief Guide
`
`INTRODUCTION
`
`
`Current evidence shows that medications are
`underused in the treatment of alcohol use
`disorder, including alcohol abuse and
`dependence.*
`This is of concern because of the
`
`high prevalence of alcohol problems in the
`general population.1,2 For example, data show
`that an estimated 10 percent to 20 percent of
`patients seen in primary care or hospital
`settings have a diagnosable alcohol use
`disorder.3,4 People who engage in risky drinking
`often have physical and social problems related
`to their alcohol use. Problems with alcohol
`influence the incidence, course, and treatment
`of many other medical and psychiatric
`conditions.2
`
`Yet, of the 18.0 million people who met the
`criteria for alcohol dependence or abuse in
`2013, only a small subset (1.4 million) received
`any type of formal treatment (excluding mutual-
`help groups)—ranging from a single meeting
`with a counselor to participation in a specialized
`treatment program.3
`
`Although many experts in addiction believe that
`patients with moderate or severe alcohol-
`related problems should be offered medication-
`assisted treatment (MAT) on a routine basis,1
`considerable resistance to the use of MAT
`
`persists. A diagnosis of alcohol use disorder
`continues to carry significant social exclusion,
`which affects both the individual who receives
`the diagnosis and the health care professionals
`to whom that individual may turn for care. In
`part, the social exclusion continues because of
`a lack of understanding of alcohol use disorder
`as a treatable medical disorder2 even though,
`more than 50 years ago, the American Medical
`
`Association (AMA) affirmed that dependence on
`alcohol and other drugs is a medical disorder.5
`
`The AMA encouraged physicians and other
`clinicians, health care organizations, and
`policymakers to frame all their activities and
`decisions in ways that reflect that fact.
`
`                                                                 
` * Within this document “alcohol abuse” and “alcohol
`
` 
`dependence” are used when discussing medication indications
`or research that is based upon this terminology. For a summary
`
`of important differences between DSM-IV and DSM-5, please
` 
`see the box on this page.
`
`Alcohol Use Disorder: A Comparison
`Between DSM-IV and DSM-5
`“In May 2013, the American Psychiatric
`Association issued the 5th edition of the
`Diagnostic and Statistical Manual of Mental
`
`Disorders (DSM-5). Although there is
`considerable overlap between DSM-5 and
`DSM-IV, the prior edition, there are several
`important differences: DSM–IV described two
`distinct disorders, alcohol abuse and alcohol
`dependence, with specific criteria for each.
`DSM-5 integrates the two DSM-IV disorders,
`alcohol abuse and alcohol dependence, into a
`single disorder called alcohol use disorder
`(AUD) with mild, moderate, and severe
`subclassifications. Under DSM-5, anyone
`meeting any two of the 11 criteria during the
`same 12-month period would receive a
`diagnosis of AUD. The severity of an AUD—
`mild, moderate, or severe—is based on the
`
`number of criteria met:
` Mild: The presence of 2 to 3 symptoms
`
` Moderate: The presence of 4 to 5
`
`symptoms
` Severe: The presence of 6 or more
`
`symptoms
`The DSM-5 eliminates legal problems as a
`criterion, adds craving as a criterion for an AUD
`diagnosis and modifies some of the criteria
`descriptions with updated language.”
`
`––National Institute on Alcohol
`Abuse and Alcoholism6
`
`
`To clarify the situation, the National Institute on
`Alcohol Abuse and Alcoholism (NIAAA) and the
`Substance Abuse and Mental Health Services
`Administration (SAMHSA) jointly convened a
`Consensus Panel on New and Emerging
`Pharmacotherapies for Alcohol Use Disorders
`and Related Comorbidities (see Appendix A).
`The panel, which brought together experts in
`alcohol research, clinical care, medical
`education, and public policy, reviewed current
`evidence on the effectiveness of available
`medications for the treatment of alcohol use
`disorders and developed guidance for the use
`of medications in clinical practice.1 The panel’s
`guidance is summarized in this document.
`
`1
`
`Page 5 of 39
`
`

`

`Medication for the Treatment of Alcohol Use Disorder: A Brief Guide
`
`CONSIDERING MEDICATIONS
`
`
` Direct involvement of physicians and other health
`
`care professionals in identifying and treating
`alcohol use disorder is possible, practical, and
`necessary. The medications described here have
`been shown to be effective in, and are approved
`by the Food and Drug Administration (FDA) for,
`the management of alcohol dependence or the
`prevention of relapse to alcohol use.7,8,9,10,11
`
`Specifically:
` Acamprosate calcium is indicated for the
`maintenance of abstinence from alcohol in
`patients dependent on alcohol who are
`abstinent at treatment initiation.
`
` Disulfiram is an aid in the management of
`selected patients who want to remain in a
`state of enforced sobriety so that supportive
`and psychotherapeutic treatment may be
`applied to best advantage.
` Oral naltrexone (naltrexone hydrochloride
`tablet) is indicated for the treatment of alcohol
`dependence.
`
` Extended-release injectable naltrexone is
`indicated for the treatment of alcohol
`dependence in patients who have been able
`to abstain from alcohol in an outpatient
`setting.
`
`
`
`
`Clinicians should consider prescribing one of
`these medications when treating a patient who is
`dependent on alcohol or who has stopped
`drinking but is experiencing problems including
`cravings or relapses. Patients with moderate or
`severe alcohol use disorder, including those who
`have physiologic dependence or who are
`experiencing cravings and have not improved in
`response to psychosocial approaches alone, are
`particularly strong candidates for medication-
`assisted treatment.1,2
`
`Medications should be prescribed as part of a
`comprehensive treatment approach that includes
`counseling and other psychosocial therapies
`
`(through referral to a psychiatrist, psychologist, or
`
`professional counselor) and social supports
`(through participation in Alcoholics Anonymous
`and other mutual-help programs).1,2
`
`Table 1 summarizes information about each
`medication approved by the FDA for the
`treatment of alcohol use disorder and/or the
`prevention of relapse to alcohol use.
`
`
`
`
`2
`
`Page 6 of 39
`
`

`

`Medication for the Treatment of Alcohol Use Disorder: A Brief Guide
`
`TABLE 1: Medications Approved for Use in the Treatment of Alcohol Use Disorder†
`
`
`
`
`Frequency of
`Administration
`Principal Action
`
`Clinical
`Uses/Ideal
`
`Candidates
`
`
`
` Disulfiram
`
`
`Daily
`
`When taken in combination with alcohol,
`causes a significant physical reaction,
`involving nausea/vomiting, flushing, and
`heart palpitations. The knowledge that such
`
`reactions are likely if alcohol is consumed
`
`
`acts as a deterrent to drinking.
`Given sufficient amounts of alcohol in the
`patient’s system, more severe reactions
`may occur, such as respiratory depression,
`cardiovascular collapse, arrhythmias,
`myocardial infarction, acute congestive
`
`heart failure, unconsciousness,
`convulsions, and death.
`
` Candidates include patients dependent on
`
`alcohol who have completed alcohol
`withdrawal. Ideally, candidates are
`committed to abstinence and willing to take
`disulfiram under the supervision of a family
`
`member or treatment program.
`
`Naltrexone
`
`
`-
`oral and extended release injectable
`
`formulations
`Daily (oral) or monthly (extended-release
`
`injectable)
`Blocks opiate receptors that are involved in the
`rewarding effects of drinking and craving for
`
`alcohol.
`Extended-release injectable naltrexone is
`administered every 4 weeks, thereby minimizing
`opportunities for nonadherence, as compared with
`daily oral ingestion. The monthly injection also
`
`
`
`produces a more consistent and predictable blood
`level of the drug, because the depot injection
`
`bypasses first-pass metabolism.
`
`Oral naltrexone and extended-release injectable
`naltrexone are indicated for the treatment of
`alcohol dependence in patients who can abstain
`from alcohol in an outpatient setting before the
`initiation of treatment. Naltrexone has not been
`shown to be effective in patients who are drinking
`at treatment initiation.
`
`Both formulations may have the greatest benefit in
`patients who can discontinue drinking on their own
`for several days before treatment initiation.
`Extended-release injectable naltrexone is also
`indicated for the prevention of relapse to opioid
`
`dependence following detoxification.
`
`Acamprosate
`
`delayed-release tablets
`Three times per day
`
`Is thought to reduce symptoms of protracted
`abstinence by counteracting the imbalance
`
`between the glutamatergic and GABAergic
`systems associated with chronic alcohol
`exposure and alcohol withdrawal.
`
`
`Acamprosate is indicated for the
`
`maintenance of abstinence in patients who
`are dependent on alcohol and are abstinent
`at treatment initiation.
`
`The efficacy of acamprosate in promoting
`abstinence has not been demonstrated in
`
`subjects who have not completed
`
`detoxification or who have not achieved
`alcohol abstinence before beginning
`treatment.
`
`                                                                 
`† This table highlights some properties of each medication. It does not provide complete information and is not intended as a substitute for the package inserts or other drug reference sources
` 
`used by clinicians (see http://www.dailymed.nlm.nih.gov for current package inserts). For patient information about these and other drugs, visit the National Library of Medicine’s MedlinePlus
`(http://www.medlineplus.gov). Whether a medication should be prescribed and in what amount are matters to be discussed between an individual and his or her health care provider. The
`
`prescribing information provided here is not a substitute for the clinician’s judgment, and the National Institutes of Health and SAMHSA accept no liability or responsibility for use of the
` 
`information in the care of individual patients.
`
`3
`
`Page 7 of 39
`
`

`

`Acamprosate
`
`delayed-release tablets
`Contraindicated in patients with severe
`
`renal impairment and in those who have a
`
`known hypersensitivity to the drug or its
`components.
`
`
`Medication for the Treatment of Alcohol Use Disorder: A Brief Guide
`
`
`
`
`Disulfiram
`
`Contraindications Contraindicated in the presence of severe
`
`myocardial disease or coronary occlusion,
`psychoses, pregnancy, and in those with
`high levels of impulsivity, suicidality, and
`hypersensitivity to disulfiram or to other
`thiuram derivatives used in pesticides and
`
`rubber vulcanization.
`
`Patients who are taking or have recently
`
`
`taken metronidazole, paraldehyde, alcohol,
`or alcohol-containing preparations (e.g.,
`cough syrups, tonics) should not be given
`disulfiram.
`Disulfiram labeling also includes several
`important precautions regarding drug–drug
`interactions. See the package insert for
`specific contraindications.
`
`
`
`Naltrexone
`
`-
`oral and extended release injectable
`
`formulations
`Contraindicated in patients receiving opioid
`
`analgesics and those receiving long-term opioid
`therapy or anticipating a need for opioids (e.g.,
`surgery), because it could precipitate a severe
`
`opioid withdrawal or block opioid analgesia;
`patients currently dependent on opioids, including
`those being maintained on opioid agonists such as
`methadone or partial agonists such as
`buprenorphine; patients in acute opioid withdrawal;
`patients who have failed the naloxone challenge
`test or whose urine tests positive for opioids.
`Contraindicated in patients with a history of
`
`sensitivity to polylactide-co-glycolide,
`carboxymethyl cellulose, or any components of the
`diluent used for the injectable medication.
`
`It should not be given to patients whose body mass
`precludes intramuscular (IM) injection with the 2­
`inch needle provided. Inadvertent subcutaneous
`injection may cause a severe injection-site
`reaction.
`Although not in current labeling, the consensus of
`the panel is that use should be avoided in patients
`with serum aminotransferase levels greater than
`five times the upper limit of normal, except where
`the benefits outweigh the risks.
`
`4
`
`Page 8 of 39
`
`

`

`Medication for the Treatment of Alcohol Use Disorder: A Brief Guide
`
`
`
`
`Warnings
`
`
`Disulfiram
`
` Use with caution in patients with heart
`
`disease, diabetes, hypothyroidism,
`epilepsy, cerebral damage, chronic or
`acute nephritis, acute hepatitis or other
`hepatic diseases, and in patients older than
`
`60.
`
`Hepatic toxicity (including hepatic failure
`resulting in liver transplantation or death)
`has been infrequently reported. Severe and
`sometimes fatal hepatitis associated with
`
`disulfiram may develop after many months
`of therapy. Hepatic toxicity has occurred in
`patients with or without a history of
`
`abnormal liver function.
`
`Patients should be advised to immediately
`notify their physician of any early
`
`
`symptoms of hepatitis, including fatigue,
`weakness, malaise, anorexia, nausea,
`vomiting, jaundice, or dark urine.
`
`Liver function tests (taken at baseline and
`10–14 days later) are suggested to detect
`any hepatic dysfunction that may result
`from disulfiram therapy. In addition,
`complete blood counts and serum
`chemistries, including liver function tests,
`should be monitored.
`
`Psychotic reactions have been noted,
`attributable to the unmasking of underlying
`
`psychoses in patients.
`
`
`Acamprosate
`
`delayed-release tablets
`Before initiating treatment with
`
`acamprosate, evaluate the patient’s renal
`function through a standard panel for urea,
`electrolytes, and serum creatinine to rule
`out severe renal impairment.
`For patients with moderate renal
`impairment (creatinine clearance of 30–50
`mL/min), a reduced dose of acamprosate
`(one 333 mg tablet 3 times a day) is
`recommended.
`Because of elevated risk of diminished
`
`renal function in people ages 65 or older,
`baseline and frequent renal function tests
`are important in this population.
`
`
`Naltrexone
`
`-
`oral and extended release injectable
`
`formulations
`Cases of hepatitis and clinically significant liver
`dysfunction were observed in association with
`
`
`extended-release injectable naltrexone treatment.
`Discontinue use of naltrexone in the event of
`symptoms or signs of acute hepatitis.
`
`Use with caution in patients with moderate to
`
`severe renal impairment.
`Patients should take no opioids, including opioid-
`containing medications, for a minimum of 7 days
`before starting naltrexone to avoid precipitating
`
`opioid withdrawal.
`
`Patients needing opioid analgesia or patients with
`a history of opioid use disorder may respond to
`lower doses of opioids after treatment with
`extended-release injectable naltrexone. Failure to
`carefully titrate opioid dose could result in
`potentially life-threatening opioid intoxication and
`overdose.
`Patients should be told of the serious
`consequences of trying to overcome the opioid
`blockade.
`
`
`5
`
`Page 9 of 39
`
`

`

`
`
`Use in Pregnant
`and Postpartum
`
`Women
`
`Medication for the Treatment of Alcohol Use Disorder: A Brief Guide
`
`
`Disulfiram
`
`Pregnancy: The FDA has not assigned a
`pregnancy category. The safe use of this
`
` drug in pregnancy has not been
`established. Therefore, disulfiram should
`
` be used during pregnancy only when, in
`the judgment of the physician, the probable
`
`benefits outweigh the possible risks.
`Nursing: Do not give disulfiram to nursing
`mothers.
`
`
`Naltrexone
`
`-
`oral and extended release injectable
`
`formulations
` Pregnancy: FDA Pregnancy Category C‡
`
`
`Nursing: Transfer of naltrexone and 6ß-naltrexol
`into human milk has been reported with oral
`naltrexone. Because animal studies have shown
`that naltrexone has a potential for tumorigenicity
`
`and other serious adverse reactions in nursing
`infants, an individualized treatment decision should
`
` be made whether a nursing mother will need to
`discontinue breastfeeding or discontinue
`
`naltrexone.
`
`Acamprosate
`
`delayed-release tablets
` Pregnancy: FDA Pregnancy Category C‡
`
`Nursing: It is not known whether
`acamprosate is excreted in human milk.
`
`
`
`
`
`
` SOURCE: SAMHSA and NIAAA. (2012, September). Report of the SAMHSA-NIAAA Consensus Panel on New and Emerging Pharmacotherapies for Alcohol Use
`Disorders and Related Comorbidities. Rockville, MD: SAMHSA.
`
`
`
`                                                                 
` ‡ Animal studies have shown an adverse effect on the fetus and there are no adequate, well-controlled studies in humans, but potential benefits may warrant use of the drug in some pregnant
` 
` 
`women despite potential risks.
`
`6
`
`Page 10 of 39
`
`

`

`Medication for the Treatment of Alcohol Use Disorder: A Brief Guide
`
`SCREENING AND ASSESSING PATIENTS
`
`Clinicians should routinely screen their patients for
`at-risk drinking, provide brief interventions as
`needed, and assess for alcohol use disorder when
`indicated.2
`Screening for Risky Alcohol Use
`Universal screening for alcohol problems can be
`conducted concurrently with screening for other
`medical disorders as part of a routine examination.
`By systematically screening every patient with a
`validated screening tool, the clinician can effectively
`identify patients with risky or dependent levels of
`alcohol use. This approach has been shown to be
`superior to a case-finding approach.
`Screening also should be conducted before
`prescribing one of the many medications that may
`interact negatively with alcohol or if a patient reports
`using an over-the-counter product or herbal
`preparation that may precipitate an adverse reaction.
`Screening is especially important in patients who:
`• Are pregnant or trying to conceive.
`• Are at risk for binge drinking or heavy drinking.
`• Have health problems that may be induced or
`exacerbated by alcohol (e.g., cardiac arrhythmia,
`depression or anxiety, dyspepsia, insomnia, liver
`disease, a history of traumatic injury).
`• Have one or more chronic health problems (e.g.,
`diabetes, heart disease, hypertension,
`gastrointestinal [GI] disorders, chronic pain) that
`are not responding to treatment.7
`• Have social or legal problems that may be
`caused or worsened by alcohol use (e.g.,
`marital/family issues, driving-while-under-the-
`influence convictions).
`Screening can be conducted through use of a
`simple, validated self-report instrument such as the
`Alcohol Use Disorders Identification Test (AUDIT)
`(http://www.whqlibdoc.who.int/hq/2001
`/WHO_MSD_MSB_01.6a.pdf), which takes fewer
`than 5 minutes to complete, or a single interview
`question: “How many times in the past year have
`you had ___ or more drinks in a day?” (five drinks
`for men and four drinks for women). The single
`question can be used at any time, either in
`conjunction with AUDIT or alone.7 Study results
`have shown that, when used in a primary care
`setting, the single question was 82 percent sensitive
`in detecting individuals who had alcohol problems.12
`
`A useful overview of screening and intervention
`strategies can be found in a document called
`Alcohol Misuse: Screening and Behavioral
`Counseling Interventions in Primary Care
`(http://www.uspreventiveservicestaskforce
`.org/uspstf/uspsdrin.htm) (see Appendix B). Many
`U.S. primary care physicians rely on these United
`States Preventive Services Task Force
`recommendations to guide how they conduct
`preventive practice. Clinicians should also consider
`using Screening, Brief Intervention, and Referral to
`Treatment (SBIRT), an approach in which screening
`is followed up as appropriate with brief intervention,
`and with referral to treatment for those needing
`more extensive care (http://www.samhsa.gov/sbirt)
`(see Appendix B).
`Assessing the Need for Medication-
`Assisted Treatment
`A patient who reports one or more heavy drinking
`days in the past year (or who has an AUDIT score
`greater than 8) should receive further
`assessment.2,7,8,9,10,11 Consideration should be
`given to the factors motivating a patient toward
`treatment, the patient’s stage of change, the
`potential for relapse, the severity of any
`concomitant medical and psychiatric problems, the
`patient’s ability to tolerate medications, and
`whether the patient is pregnant (in which case,
`medications associated with adverse physical
`effects, such as disulfiram, should be avoided).
`Patient History. Although the evidence
`supporting inclusion of each element is not
`conclusive, consensus opinion is that an
`assessment should include a medical and
`psychiatric history, a substance use history, and an
`evaluation of family and psychosocial supports.13
`Information from family members and significant
`others can provide useful perspectives on the
`patient’s status, as can communication with or
`records from clinicians who treated the patient in
`the past.13
`It also is advisable to access the patient’s
`prescription drug use history through the state’s
`prescription drug monitoring program (PDMP),
`where available,13 to detect unreported use of
`other medications, such as opioid analgesics or
`sedative-hypnotics, that may interact negatively
`
`7
`
`Page 11 of 39
`
`

`

`Medication for the Treatment of Alcohol Use Disorder: A Brief Guide
`
`with alcohol or with alcohol treatment
`medications.
`Physical Examination. The physical
`examination should evaluate neurocognitive
`function, identify sequelae of alcohol use, and
`look for evidence of hepatic dysfunction.14
`
`Although many patients with alcohol use disorder
`
`have no specific abnormal findings on physical
`examination, when present, these abnormal
`findings provide evidence of the severity of a
`patient’s alcohol problem. For example,
`longstanding alcohol consumption may be
`marked by many classic features, such as
`physical manifestations of cirrhosis,
`
`encephalopathy, and vitamin deficiencies.
`Alcohol consumption may also provoke
`tachycardia (including supraventricular
`tachycardias), tremor of the hand or tongue,
`elevated blood pressure, hepatosplenomegaly, a
`
`tender liver edge, peripheral neuropathy, spider
`angiomata, conjunctival injection, and
`unexplained trauma.2,14,15,16
`
`
`Laboratory tests help confirm the presence of
`heavy drinking and identify alcohol-related
`damage.
`
`Laboratory Testing. Laboratory tests help
`confirm the presence of heavy drinking and
`identify alcohol-related damage. Initial and follow-
`up laboratory testing can help motivate patients
`and reinforce their progress in treatment.2
`
`Although no single laboratory test can definitively
`point to an alcohol use disorder diagnosis in the
`absence of other information,14 the following tests
`can be helpful in identifying heavy drinking and
`possible alcohol-related abnormalities:16,17
`
` Blood alcohol levels are useful measures of
`recent alcohol consumption and can indicate
`physical or legal incapacity to perform specific
`tasks, including driving.
` Carbohydrate-deficient transferrin (CDT),
`gamma-glutamyl transpeptidase (GGT), and
`aspartate aminotransferase (AST) levels can
`be useful biomarkers because they often are
`elevated in people who have chronically
`consumed significant amounts of alcohol.16
`
`Some studies suggest that biomarkers such
`as AST, GGT, and CDT are most useful when
`used in combination.16,17,18,19
`
`
`8
`
` Tests for ethyl glucuronide (EtG), an alcohol
`metabolite, are highly sensitive for alcohol;
`however, this sensitivity is a potential
`drawback as well as a strength, because
`exposure to even small amounts of alcohol
`(e.g., those found in some foods and
`cosmetics) can trigger a positive test
`result.16,17,20 However, use of appropriate
`laboratory cutoffs make it more likely that a
`positive test is an indication of recent alcohol
`use.20
`
` Phosphatidylethanol, another alcohol
`metabolite, is a promising new biomarker that
`is highly sensitive in detecting chronic drinking
`(three or more drinks a day for 1 or 2 weeks).
`It can be detected in the blood for 2 to 4
`weeks after drinking has stopped.16,20,21,22
`
`Several laboratory tests can help the clinician
`establish a patient’s overall health status and
`identify alcohol-related damage and
`contraindications to the use of specific
`medications.23,24 These include:
` Complete blood count: Alcohol overuse can
`
`cause anemia and have direct toxic effects on
`bone marrow. An assessment of hematologic
`laboratory indices is useful when considering
`pharmacologic treatment of alcohol use
`disorder. Many people who are alcohol
`dependent have elevated corpuscular volume
`(macrocytosis).
`
` Testing for vitamin deficiencies: Individuals
`with alcohol use disorder may not consume a
`healthful diet, resulting in vitamin deficiencies
`that lead to abnormal cellular function. For
`example, deficiencies in thiamine, folic acid,
`and pyridoxine are seen in people with
`
`physiological alcohol dependence, and those
`deficiencies contribute to abnormal cell
`function. Vitamin deficiencies may also lead to
`Wernicke-Korsakoff/amnesic syndrome in
`patients whose alcohol consumption is very
`excessive.
` Hepatic and renal testing: The use of
`
`medications to treat alcohol use disorder
`requires evaluation of organ systems that are
`involved in the metabolism and excretion of
`those medications. For example, naltrexone
`and disulfiram should be used with caution in
`patients who have liver disease, whereas
`naltrexone and acamprosate should be used
`with caution in patients with renal impairment.
`Therefore, hepatic and renal system testing
`
`Page 12 of 39
`
`

`

`Medication for the Treatment of Alcohol Use Disorder: A Brief Guide
`
`
`
` should be done as part of the patient
`
`assessment.
`
` Other tests: Initial laboratory work should
`include a urine toxicology screen to assess for
`
`
`other substances, and women of childbearing
`age should have a pregnancy test.
`
`
`
`DEVELOPING A TREATMENT PLAN AND
`
`SELECTING A MEDICATION
`
`Components of the Treatmen