Utilizing buprenorphine–naloxone to treat illicit and prescription-opioid dependence

Figures & data

Figure 1 Clinical management: opioid substitution versus acute detoxification.

Abbreviations: Bup/nx, buprenorphine–naloxone; HIV, human immunodeficiency virus; HCV, hepatitis C virus.

Table 1 Induction onto bup/nx for short-, long-, and ultralong-acting opioids

	Short-acting (eg, heroin, oxycodone)	Long-acting (eg, morphine, OxyContin^®)	Ultralong-acting (eg, methadone)
Stage I: Early withdrawal –Fear of withdrawal, anxiety, craving	4–6 hours	8–12 hours	12–24 hours
Stage II: Mid-withdrawal –Insomnia, restlessness, anxiety, yawning, stomach cramps, lacrimation, rhinorrhea, diaphoresis, mydriasis	8–12 hours	12–24 hours	36–72 hours
Stage III: Late withdrawal –Diarrhea, vomiting, fever, chills, piloerection, muscle spasms, tremor, tachycardia, and hypertension	24–72 hours	48–72 hours	72–96 hours
Induction onto bup/nx	1. Switch to bup/nx 12–24 hours from last dose when in moderate withdrawal (COWS >12) 2. The goal is to reach a target dose of 12–16 mg buprenorphine during the first week	1. Switch to bup/nx 18–36 hours from last dose, when in moderate withdrawal (COWS >12) OR 1. Switch to equivalent dose of short-acting opiate 2. Maintain dose × 3 days, 3. Switch to bup/nx as per short-acting opiates	1. Taper methadone dose to 30 mg/day 2. Maintain 30 mg/day × 5–7 days 3. Switch to bup/nx >24 hours after last dose, when in moderate withdrawal (COWS >12)

Note: Sources of data: Kosten and O’Connor,⁵⁵ Dijkstra et al,⁵⁶ and Farrell.⁵⁷

Abbreviations: Bup/nx, buprenorphine–naloxone; COWS, Clinical Opioid Withdrawal Scale.

Table 2 Approximate opioid equivalencies compared with 10 mg of IV morphine

Generic name	Potency ratio (in IV morphine equivalent)	Equivalent doses (mg)a
Fentanyl	100–200	0.05–0.1
Hydromorphone IV	5	1.5
Heroin	1–2	5–10
Hydromorphone PO	1.3	7.5
Morphine IV	1	10
Methadone PO	0.5	20
Oxycodone PO	0.5	20
Morphine PO	0.5	20–30
Meperidine IM	0.13	75
Codeine PO	0.05	200
Meperidine PO	0.03	300

Notes:

a Equivalencies are approximate, and should be used with clinical judgment; clinicians must be particularly careful when the total equivalent opioid dose is more than 100 mg of methadone. Data source: Ducharme et al.⁶¹ Table originally published in Canadian Family Physician and reprinted with permission. Copyright © 2012.

Abbreviations: IM, intramuscular; IV, intravenous; PO, per os.

Figure 2 Bup/nx induction (day 1).

Notes: ^aUse higher dose (4 mg bup) in patients in severe withdrawal; ^bno improvement in withdrawal symptoms or persisting signs of mild-to-moderate withdrawal (COWS >4); ^cGunderson et al⁶⁰ suggests going up to 16 mg on the first day. Data sources: Center of Addiction and Mental Health,³³ Substance Abuse and Mental Health Services Administration,³⁴ Community Care Behavioral Health Organization,⁴⁵ Tompkins et al,⁵⁹ Gunderson et al,⁶⁰ and Kraus et al.⁷³
Abbreviations: Bup/nx, buprenorphine–naloxone; COWS, Clinical Opioid Withdrawal Scale; NSAIDs, nonsteroidal anti-inflammatory drugs; bup, buprenorphine.

Table 3 Symptomatic treatment of opioid withdrawal

Withdrawal symptoms		Somatic treatment	Dosing
Nausea and vomiting	→	Dimenhydrinate (Gravol^®)	50–100 mg PO/IM q4h prn
	→	Prochlorperazine (Stemetil^®)	5–10 mg PO q4h prn
Diarrhea	→	Loperamide (Imodium^®)	4 mg PO for diarrhea, then 2 mg PO prn (max: 16 mg/24 hr)
Myalgia	→	Acetaminophen (Tylenol^®)	325–650 mg PO q4h prn (max: 4,000 g/24 hr)
	→	Naproxen (Naprosyn^®)	500 mg PO bid × 4 days, then prn
Anxiety, dysphoria, lacrimation, rhinorrhea	→	Hydroxyzine (Atarax^®)	25–50 mg PO tid prn
Insomnia	→	Trazodone (Trazorel^®)	50–100 mg PO qhs × 4 days, then prn
↓ Sympathetic drive (tachycardia, hypertension) diaphoresis, restlessness	→	Clonidine (Nexiclon^®)a	0.1 mg PO qid × 4 days, thenb 0.05 mg PO qid × 2 days, then 0.025 mg PO qid, then stop

Notes:

a Monitor blood pressure prior to each dose, as clonidine may cause hypotension

b if <91 kg (200 lb) (doses need to be higher if >91 kg). Data source: Kosten and O’Connor⁵⁵ and Kleber et al.⁹²

Abbreviations: PO, per os; IM, intramuscular; q4h, quaque 4 hora (every 4 hours); prn, pro re nata (as needed); bid, bis in die (twice a day); tid, ter in die (three times a day); qhs, quaque hora somni (every night at bedtime); qid, quater in die (four times a day); max, maximum; hr, hours.

KostenTRO’ConnorPGManagement of drug and alcohol withdrawalN Engl J Med20033481786179512724485

 PubMed Web of Science ®Google Scholar

DijkstraBAKrabbePFDe JongCAvan der StaakCPPrediction of withdrawal symptoms during opioid detoxificationJ Opioid Manag2008431131919070269

 PubMedGoogle Scholar

FarrellMOpiate withdrawalAddiction199489147114757841858

 PubMed Web of Science ®Google Scholar

DucharmeSFraserRGillKUpdate on the clinical use of buprenorphine in opioid-related disordersCan Family Physician2012583741

 PubMed Web of Science ®Google Scholar

GundersonEWLevinFRRomboneMMVosburgSKKleberHDImproving temporal efficiency of outpatient buprenorphine inductionAm J Addict20112039740421838837

 PubMed Web of Science ®Google Scholar

Centre for Addiction and Mental HealthBuprenorphine/Naloxone for Opioid Dependence: Clinical Practice GuidelineTorontoCAMH2012 Available from: http://knowledgex.camh.net/primary_care/guidelines_materials/Documents/buprenorphine_naloxone_gdlns2012.pdfAccessed November 18, 2013

 Google Scholar

Substance Abuse and Mental Health Services AdministrationClinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction: A Treatment Improvement Protocol (TIP) 40Rockville, MDSAMHSA2004 Available from: http://buprenorphine.samhsa.gov/Bup_Guidelines.pdfAccessed November 18, 2013

 Google Scholar

Community Care Behavioral Health OrganizationSupporting recovery from opioid addiction: community care best practice guidelines for buprenorphine and Suboxone2013 Available from: http://www.ct.gov/dmhas/lib/dmhas/publications/Community_Care_BP_Guidelines_for_Buprenorphine_and_Suboxone.pdfAccessed November 18, 2013

 Google Scholar

TompkinsDABigelowGEHarrisonJAJohnsonREFudalaPJStrainECConcurrent validation of the Clinical Opiate Withdrawal Scale (COWS) and single-item indices against the Clinical Institute Narcotic Assessment (CINA) opioid withdrawal instrumentsDrug Alcohol Depend200910515415919647958

 PubMed Web of Science ®Google Scholar

KrausMLAlfordDPKotzMMStatement of the American Society of Addiction Medicine Consensus Panel on the use of buprenorphine in office-based treatment of opioid addictionJ Addict Med2011525426322042215

 PubMed Web of Science ®Google Scholar

KleberHDWeissRDAntonRFPractice guidelines for the treatment of patients with substance use disorderssecond editionArlington (VA)American Psychiatric Association (APA)82006 http://psychiatryonline.org/pdfaccess.ashx?ResourceID=243188&PDFSource=6Accessed November 18, 2013

 Google Scholar