KAP Keys Based on TIP 43

Medication-Assisted Treatment for Opioid Addiction in Opioid Treatment
Programs

Knowledge Application Program

KAP Keys For Clinicians

Based on TIP 43

Medication-Assisted Treatment for Opioid Addiction in Opioid Treatment
Programs

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES

Substance Abuse and Mental Health Services Administration

Center for Substance Abuse Treatment

www.samhsa.gov

**Introduction**

KAP Keys were developed to accompany the Treatment Improvement Protocol
(TIP) Series published by the Center for Substance Abuse Treatment
(CSAT), Substance Abuse and Mental Health Services Administration
(SAMHSA). These KAP Keys are based entirely on TIP 43 and are designed
to meet the needs of the busy clinician for concise, easily accessed
"how to" information.

For more information on the topics in these KAP Keys, readers are
referred to TIP 43.

Other Treatment Improvement Protocols (TIPs) that are relevant to these
KAP Keys:

TIP 37: Substance Abuse Treatment for Persons With HIV/AIDS (2000)
BKD359

TIP 40: Clinical Guidelines for the Use of Buprenorphine in the
Treatment of Opioid Addiction (2004) BKD500

TIP 42: Substance Abuse Treatment for Persons With Co-Occurring
Disorders (2005) BKD515

**1. Information Obtained About and Provided to Patients During
Screening and Admission**

**Essential Information Obtained About Patients**

• Risk of suicide and other emergencies

• Age (patients younger than 18 must meet Federal and State eligibility
requirements for admission to an opioid treatment program \[OTP\])

• Method and level of opioid use and pattern of daily preoccupation with
opioids

• Other substances of abuse (e.g., alcohol, nicotine, illicit drugs) and
prescription and over-the-counter medicines used

• Treatment history, preferably from previous providers (requires
patient's informed written consent)

• Recovery environment (i.e., do living environment, social network,
co-residents, and housing status support or jeopardize treatment and
recovery?)

• Other recovery resources (e.g., family, friends, significant others,
neighbors, co-workers, insurance status, employment, education,
spirituality)

• Other compulsive behaviors (e.g., gambling, sexual disorders)

• Patient motivation and reasons for seeking treatment

**Essential Information Provided to Patients**

• Orientation to medication-assisted treatment (MAT): treatment methods,
optional programs, treatment requirements, roles and responsibilities of
all those involved

• Handbook (in patient's first language): information needed to comply
with treatment requirements

• OTP information requirements and methods: written consent to
treatment, program recordkeeping and confidentiality, patient rights,
grievance procedures, discharge policies

• Facility safety instructions and rules

• Information on family planning, gynecological health, menopause,
pregnancy testing (for women)

See TIP 43, pages 43--53.

**2. MAT Assessments**

**Medical Assessment**

• Physical examination

• Laboratory tests (possibly including TB, hepatitis, HIV, sexually
transmitted disease tests plus initial drug test and 8 random drug tests
per year)

• Determination of opioid addiction and treatment history, extent of
other substance use and treatment, medical history

**Induction Assessment**

• At least daily checks for signs of overmedication (intoxication or
sedation) or undermedication (withdrawal symptoms) during initial dosing

• Assurance that patients are not using benzodiazepines or alcohol
during induction

• Observed dosing to ensure medication ingestion

• Dosage adjustments until steady state is reached

**Comprehensive Assessment**

• Determination of patient motivation

• Continuing assessments of substance use

• Cultural background assessment

• Assessment of psychosocial factors (e.g., mental health,
sociodemographic status, family and social network, spiritual support,
physical or sexual abuse history, housing, legal status, employment and
military status, sexual orientation, insurance and financial status,
recreational activities)

See TIP 43, pages 49--60.

**3. Pharmacotherapeutic Medications for Opioid Addiction Treatment**

**Methadone**

Available Formulation: Oral solution, liquid concentrate,
tablet/diskette, and powder

Receptor Pharmacology: Full mu opioid agonist

FDA Approval: Never formally approved

DEA Schedule: II

Treatment Setting: Opioid treatment program

**LAAM**

Available Formulation: Oral solution

Receptor Pharmacology: Full mu opioid agonist

FDA Approval: 1993

DEA Schedule: II

Treatment Setting: Opioid treatment program

**Buprenorphine**

Available Formulation: Sublingual tablet

Receptor Pharmacology: Partial mu opioid agonist

FDA Approval: 2002

DEA Schedule: III

Treatment Setting: Physician\'s office, opioid treatment program, or
other health care setting

**Buprenorphine/Naloxone**

Available Formulation: Sublingual tablet

Receptor Pharmacology: Partial mu opioid agonist/mu antagonist

FDA Approval: 2002

DEA Schedule: III

Treatment Setting: Physician\'s office, opioid treatment program, or
other health care setting

**Naltrexone**

Available Formulation: Oral tablet

Receptor Pharmacology: Mu opioid antagonist

FDA Approval: 1984

DEA Schedule: Not scheduled

Treatment Setting: Physician\'s office, opioid treatment program, or any
substance abuse treatment program setting

See TIP 43, pages 26--32.

**4. Possible Side Effects of Opioid Agonist and Partial Agonist
Therapy**

**Whole Body Effects**

• Weakness, loss of energy (asthenia)

• Back pain, chills

• Fluid accumulation (edema)

• Hot flashes

• Flu syndrome and malaise

• Weight gain

**Gastrointestinal Effects**

• Constipation

• Dry mouth

• Nausea and vomiting

• Abdominal pain

**Musculoskeletal Effects**

• Joint pain (arthralgia)

• Muscle pain (myalgia)

**Nervous System Effects**

• Abnormal dreams

• Anxiety

• Decreased sex drive

• Depression

• Euphoria

• Headache

• Decreased sensitivity to tactile stimulation (hypesthesia)

• Insomnia

• Nervousness

• Somnolence

**Respiratory Effects**

• Cough

• Rhinitis

• Yawning

**Cardiac Effects**

• Electrocardiogram changes (possible QT prolongation with LAAM or high
doses of methadone)

• Postural hypotension

• Slowed heart rate (bradycardia)

**Hepatic Effects**

• Abnormal liver function tests

**Endocrine Effects**

• Hyperprolactinemia

• Absence of menstrual periods (amenorrhea)

**Skin and Appendage Effects**

• Sweating

• Rash

**Special Sensory Effects**

• Blurred vision

**Urogenital Effects**

• Difficult ejaculation

• Impotence

See TIP 43, pages 33--36.

**5. Reported Drug Interactions With Methadone**

Amitriptyline: Decreased clearance

Amprenavir: Decreased serum levels; possible decreased opioid effects

Amylobarbitone: Increased clearance

Ciprofloxacin: Increased opioid effects

Diazepam: Increased opioid effects

Efavirenz: Decreased plasma levels and opioid effects

Ethanol: Increased opioid effects and added sedation

Fluconazole: Decreased methadone clearance and increased SMLs\*

Fluoxetine: Increased SMLs

Fluvoxamine: Increased SMLs and increased opioid effects

Fusidic acid: Decreased opioid effects

Moclobemide: Increased opioid effects

Nelfinavir: Decreased SMLs

Nevirapine: Decreased SMLs and opioid effects

Paroxetine: Increased SMLs

Phenobarbital: Decreased SMLs and opioid effects

Phenytoin: Decreased SMLs and opioid effects

Rifampin: Decreased SMLs and opioid effects

Ritonavir: Decreased SMLs and opioid effects

Sertraline: Increased SMLs

Spironolactone: Increased clearance

\*Serum methadone levels

See TIP 43, pages 36--40.

**6. Strategies To Prevent or Minimize Harmful Drug Interactions in
MAT**

• Obtain a thorough drug and medication history, including results of
drug and other laboratory tests.

• When adding any drugs to a therapeutic regimen, start with low doses,
increase slowly, and monitor patient reactions closely.

• Educate patient about the risks of drug interactions, potentially
lethal drugs or medications during agonist-based pharmacotherapy,
possible cardiovascular risks, and possible effects of deviating from
dosage schedules and amounts.

• Substitute alternative medications that do not interact with opioid
treatment medications or have the least potential for interaction.

• Consider whether administering other medications with or without food
or altering dosing schedules might reduce the risk of drug interactions.

• Simplify the medication regimen to make it easier for patient to
adhere to it.

• Adjust opioid medication dosage based on patient response to avoid
drug interaction, but be vigilant for signs of withdrawal or sedation.

• Increase drug testing and monitoring of drug serum levels. Advise
patient of the physical signs of adverse interactions, and explain what
to do if these occur.

• Be aware of concomitant diseases (e.g., liver disease) that might
influence the potential for adverse drug interactions.

See TIP 43, pages 40--42.

**7. Medications/Substances That Alter Opioid Medication Levels in the
Body**

**Expected To Reduce Opioid Medication Level**

Carbamazepine

Dexamethasone

Ethosuximide

Primidone

Rifabutin

Troglitazone

**Expected To Increase Opioid Medication Levels\***

Amiodarone

Cannabinoids

Clarithromycin

Erythromycin

Grapefruit juice

Indinavir

Itraconazole

Ketoconazole

Metronidazole

Mibefradil

Miconazole

Nefazodone

Norfloxacin

Omeprazole (slight)

Quinine

Saquinavir

Troleandomycin

Zafirlukast

\*Although clarithromycin and erythromycin increase opioid medication
levels, azithromycin does not.

Adapted from Pharmacotherapy (Michalets 1998) with permission; with
additional information from Gourevitch and Friedland 2000 and
McCance-Katz et al. 2000.

See TIP 43, page 40.

**8. Criteria for Take-Home Medications and Maximum Take-Home Dose**

**SAMHSA Criteria To Allow Take-Home Medication Privileges**

• Absence of recent drug and alcohol abuse, behavioral problems,
criminal activity

• Regular OTP attendance

• Stable home environment and social relationships

• Acceptable time in comprehensive maintenance treatment

• Assurance of safe storage of medication

• Benefits of decreased OTP attendance clearly outweigh risks of
diversion

Source: 42 Code of Federal Regulations, Part 8 § 12(i).

First 90 days (months 1--3): 1 dose per week

Second 90 days (months 4--6): 2 doses per week

Third 90 days (months 7--9): 3 doses per week

Fourth 90 days (months 10--12): 6 days' supply per week

After 1 year of treatment: 2 weeks' supply

After 2 years of treatment: 1 month's supply (monthly OTP visits are
still required)

• Any patient may receive take-home medication for days when treatment
facilities are closed, including Sundays and holidays

• State requirements may vary

• No patient in short-term detoxification or interim maintenance may
receive take-home maintenance medication.

Source: 42 Code of Federal Regulations, Part 8 § 12(i).

See TIP 43, pages 81--85.

**9. Patient Counseling in MAT**

**Recommended Focuses**

• Providing support and guidance, especially to eliminate substance
abuse

• Monitoring other problem behaviors

• Helping patients comply with OTP rules

• Identifying problems needing referral and extended services

• Identifying and removing treatment barriers

• Providing motivational enhancement

**Standard Components**

• Identification of problems needing immediate attention (e.g.,
homelessness)

• Help locating and joining mutual-help groups (e.g., Narcotics
Anonymous, Methadone Anonymous)

• Education about addiction and effects of substance abuse

• Education about relapse prevention strategies

• Information about stress- and time-management techniques

• Assistance in developing a healthy lifestyle (e.g., exercise, good
nutrition, smoking cessation, avoidance of risky sexual behaviors)

• Assistance in joining socially constructive groups (e.g., community
and faith-based organizations)

• Continuing education on health issues (e.g., HIV/AIDS, hepatitis)

**Types of Group Counseling in MAT**

• Psychoeducational groups

• Skill development groups (e.g., relapse prevention, stress management,
substance use cessation)

• Cognitive--behavioral groups

• Interpersonal-process groups

• Support groups

**10. Common Topics for Patient Educational Sessions in MAT**

• Physical and psychological effects of opioid and other substance abuse

• Health information, including medical problems related to addiction,
smoking cessation, improving nutritional habits (including special needs
of persons with HIV), and exercise, including aerobic and meditative
exercises (e.g., yoga)

• Effects of drug use on family and other relationships

• Introduction to mutual-help groups such as Methadone Anonymous

• Effects and side effects of addiction treatment medications and
interactions with other drugs

• Symptoms of co-occurring disorders

• Compulsive behaviors besides substance abuse (e.g., gambling, sexual
behaviors)

• Skills to attain and sustain abstinence, such as anger management and
coping with cravings

• Developing non--drug-related leisure activities

• Stress management and relaxation

• Communication skills and assertiveness training

• Time management

• Parenting skills

• Avoidance of sexually transmitted diseases and promotion of
responsible sexual behavior

• Vocational planning and employment (sometimes linked with cognitive
testing and conducted with vocational agencies)

See TIP 43, pages 124--133.

**11. Characteristics of a Treatment Plan and a Multidisciplinary Team**

**Treatment Plan**

• Is based on a thorough patient history and assessment

• Is tailored to each patient's needs

• Has short- and long-term goals that reflect awareness of the patient's
abilities and limitations

• Describes actions needed to reach goals

• Indicates which goals require referral and followup

• Includes specific, measurable objectives

• Incorporates strategies for building therapeutic relationships with
patients

• Uses motivational enhancement to involve patients

• Is written in the patient's own words

• Describes the patient's strengths, abilities, and challenges

• Includes assessment of linguistic or cultural factors that affect
treatment

**Multidisciplinary Team**

• A physician trained in addiction psychiatry

• Nonphysician medical staff members (e.g., registered nurse, nurse
practitioner, physician's assistant)

• A pharmacist or pharmacy assistant

• Nonmedical professional staff members (e.g., case coordinator, social
worker, psychologist, vocational and educational specialist)

• A certified or licensed addiction specialist or drug counselor

• Nontreatment and administrative staff members (e.g., office manager,
clerical staff, receptionist, secretary)

• Security personnel who ensure the safety and well-being of patients
and staff on site

See TIP 43, pages 95--100.

**12. Associated Medical Problems**

**Acute Infections**

• Endocarditis

• Soft-tissue infections (e.g., cellulitis, abscesses)

• Necrotizing fasciitis

• Wound botulism

**Infectious Diseases**

• TB

• Syphilis

• Genital chlamydia

• Gonococcus infections

• Hepatitis A, B, and C

• HIV/AIDS

**Chronic Diseases**

• Diabetes

• Asthma

• Hypertension

• Chronic obstructive pulmonary disease

• Coronary artery disease

**Pain**

• Acute (e.g., associated with traumatic injury, labor and delivery)

• Chronic (e.g., associated with cancer, arthritis, disc disease)

See TIP 43, pages 163--173.

**13. Hepatitis C Evaluation Flowchart**

See TIP 43, pages 167--171.

**14. Cutoff Concentrations and Detection Times for Substances of
Abuse**

**Amphetamine**

Cutoff Concentrations (ng/mL): 1,000 (initial), 500 (confirmation)

Analytes Tested in Confirmation: Amphetamine

Urine Detection Time (days): 2--4

**Barbiturates**

Cutoff Concentrations (ng/mL): 200 (initial and confirmation)

Analytes Tested in Confirmation: Amobarbital, secobarbital, other
barbiturates

Urine Detection Time (days): 2--4 for short acting; up to 30 for long
acting

**Benzodiazepines**

Cutoff Concentrations (ng/mL): 200 (initial and confirmation)

Analytes Tested in Confirmation: Oxazepam, diazepam, others

Urine Detection Time (days): Up to 30 for long acting

**Cocaine**

Cutoff Concentrations (ng/mL): 300 (initial), 150 (confirmation)

Analytes Tested in Confirmation: Benzoylecgonine

Urine Detection Time (days): 1--3 for sporadic use; up to 12 for chronic
use

**Codeine**

Cutoff Concentrations (ng/mL): 300 (initial and confirmation)

Analytes Tested in Confirmation: Codeine, morphine

Urine Detection Time (days): 1--3

**Heroin**

Cutoff Concentrations (ng/mL): 300 (initial), 300, 10 (confirmation)

Analytes Tested in Confirmation: Morphine, 6-acetylmorphine

Urine Detection Time (days): 1--3

**Marijuana**

Cutoff Concentrations (ng/mL): 100, 50, 20 (initial), 15 (confirmation)

Analytes Tested in Confirmation: Tetra-hydrocannabinol (THC)

Urine Detection Time (days): 1--3 for casual use; up to 30 for chronic
use

**Methadone**

Cutoff Concentrations (ng/mL): 300 (intial and confirmation)

Analytes Tested in Confirmation: Methadone

Urine Detection Time (days): 2--4

**Methamphetamine**

Cutoff Concentrations (ng/mL): 1,000 (initial), 500, 200 (confirmation)

Analytes Tested in Confirmation: Methamphetamine, amphetamine

Urine Detection Time (days): 2--4

**Phencyclidine**

Cutoff Concentrations (ng/mL): 25 (initial and confirmation)

Analytes Tested in Confirmation: Phencyclidine

Urine Detection Time (days): 2--7 for casual use; up to 30 for chronic
use

ng/mL: nanograms per milliliter

Adapted from Cone 1997.

See TIP 43, pages 144--146.

**15. Urine Drug Testing Guidelines**

**General Preparation**

• Perform specimen collection in a therapeutic, humane environment.

• Clean bathrooms frequently, and supply with soap and toilet articles.

• Inform patients at admission of testing and collection procedures,
including whether and when observed dosing may be used, and their
responsibility.

• Use clinical judgment about need for direct observation of specimen
collection (vs. temperature strips, adulterant checks,
ambient-temperature guns, substitution of oral swabs) unless mandated by
State.

• Put testing policies and procedures in writing, and give each patient
a copy.

• Protect patients' dignity and privacy.

• Minimize opportunities for falsification (monitor bathrooms, have
patients leave parcels outside, allow only one patient in bathroom at a
time).

• Ensure confidentiality by storing specimens and records so only
authorized personnel can access them.

• Maintain universal safety precautions when handling specimens.

**Specific Procedures**

• Staff member greets patient and decides whether a specimen is required
(based on judgment or random list) before patient receives medication.

• Patient is sent to bathroom with a labeled container to provide
specimen.

• Staff member receives container and ensures a valid specimen (checks
warmth or uses temperature strips, adulterant checks,
ambient-temperature guns).

• Staff member packages specimen and sends it to the lab.

See TIP 43, pages 146--149.

**16. Common Immunoassays Used in Drug Testing**

EIA: EMIT, CEDIA (brand names). Syva, Boehringer Mannheim/Microgenics
(makers). Used widely; inexpensive; equipment available for automated,
high-volume rapid analysis; sensitive to some adulterants.

Fluorescence polarization: ADx, TDx (brand names). Abbott Diagnostics
(maker). Resistant to several adulterants; reasonably good quantitative
estimates of concentrations; slower and more expensive than EIA and
KIMS.

Kinetic interaction of microparticles (KIMS): OnTrak, TesTcup, OnLine
(brand names). Roche Diagnostics (maker). Equipment available for
automated, high-volume rapid analysis; used by some large laboratories.

Colloidal metal (CMI): Triage (brand name). Biosite Diagnostics (maker).
Used in onsite testing.

RIA: Abu-screen (brand name). Roche Diagnostics (maker). Labor
intensive; resistant to several adulterants; not used widely

Adapted from Swotinsky and Smith 1999, with permission of Medical Review
Officer Certification Council.

See TIP 43, pages 149--151.

**17. Frequently Used Substance Combinations and Common Reasons for
Use**

Heroin plus alcohol: Enhance a high; create euphoria or sedation

Heroin followed by alcohol: Medicate opioid withdrawal; medicate cocaine
overstimulation (e.g., anxiety, paranoia)

Heroin plus cocaine ("speedball\"): Enhance or alter cocaine euphoria

Heroin followed by cocaine: Medicate opioid withdrawal

Cocaine plus alcohol: Enhance high; reduce cocaine overstimulation
(e.g., anxiety, paranoia)

Cocaine followed by heroin: Reduce cocaine overstimulation (e.g.,
anxiety, paranoia); modulate the cocaine "crash"

Methadone plus alcohol: Create a high; sedate

Methadone plus cocaine: Reduce cocaine overstimulation (e.g., anxiety,
paranoia); moderate the cocaine "crash"

Methadone plus benzodiazepines: Create a high; sedate

Any opioid plus any nonbenzodiazepines sedative: Create a high; sedate

Any opioid followed by any nonbenzodiazepines: Medicate opioid
withdrawal

Any opioid plus amphetamine: Create a high

See TIP 43, pages 181--182.

**18. Common Medical and Obstetrical Complications Among Pregnant
Women**

**Medical Complications**

Anemia

Bacteremia/septicemia

Cardiac disease, especially endocarditis

Cellulitis

Depression and other mental disorders

Edema

Gestational diabetes

Hepatitis (acute and chronic)

Hypertension/tachycardia

Phlebitis

Pneumonia

Poor dental hygiene

STDs: Chlamydia, Condyloma acuminatum, Gonorrhea, Herpes, HIV/AIDS,
Syphilis

Tetanus

TB

Urinary tract infections: Cystitis, Pyelonephritis, Urethritis

Adapted from Finnegan 1979.

**Obstetrical Complications**

Abruptio placentae

Chorioamnionitis

Intrauterine death

Intrauterine growth retardation

Intrauterine passage of meconium

Low Apgar scores

Placental insufficiency

Postpartum hemorrhage

Preeclampsia

Premature labor/delivery

Premature rupture of membranes

Septic thrombophlebitis

Spontaneous abortion

Reprinted from Obstetrics and Gynecology Clinics of North America,
25(1), Kaltenbach et al., Opioid dependence during pregnancy. Effects
and man-agement, pp. 139--151, 1998, with permission from Elsevier.

See TIP 43, pages 212--215.

**19. Laboratory Tests for Pregnant Women Who Are Opioid Addicted**

• Complete blood count with differential and platelets

• SMA-12 chemistry screen

• Hepatic panel (liver function tests)

• Hepatitis B surface antigen (full panel if positive)

• Hepatitis C antibody

• Rubella titer

• Serology (Venereal Disease Research Laboratory or Rapid Plasma Reagin
tests)

• Sickle prep (if appropriate)

• Blood type; Rh and indirect Coombs Varicella (if unsure of history)

• HIV (with counseling)

• Urine tests

-- Urinalysis---routine and microscopic

-- Urine culture and sensitivity

-- Urine drug screen

• Tuberculin skin test (Mantoux)

• Alpha-fetoprotein between 15 and 21 weeks' gestation (optimal, 16 to
18 weeks)

• 1-hour, 50 milligrams (mg) glucose challenge test at 24 to 28 weeks'
gestation (at initial visit if risk factors)

• Repeat complete blood count and serology at 24 to 28 weeks' gestation

• Group B Strep vaginal-rectal culture at 35 to 37 weeks' gestation

Reprinted from Obstetrics and Gynecology Clinics of North America,
25(1), Kaltenbach et al., Opioid dependence during pregnancy. Effects
and management, pp. 139--151, 1998, with permission from Elsevier.

See TIP 43, pages 214--215.

**Ordering Information**

TIP 43

Medication-Assisted Treatment for Opioid Addiction in Opioid Treatment
Programs

Three Ways to Obtain Free Copies of All TIP Products

1\. Call SAMHSA's National Clearinghouse for Alcohol and

Drug Information (NCADI) at 800-729-6686,

TDD (hearing impaired) 800-487-4889.

2\. Visit NCADI's Web site at www.ncadi.samhsa.gov.

3\. Access TIPs online at www.kap.samhsa.gov.

Do not reproduce or distribute this publication for a fee without
specific, written authorization from the Office of Communications,
Substance Abuse and Mental Health Services Administration, U.S.
Department of Health and Human Services.

DHHS Publication No. (SMA) 07-4108

Printed 2005

Reprinted 2007