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OPIOID MAINTENANCE TREATMENTTable 2Characteristics of Options for Maintenance TreatmentBuprenorphine andBuprenorphine/NaloxoneMethadonePharmacologic Action Buprenorphine: partial agonist Full agonistNaloxone: full antagonistRoute of Administration Sublingual OralDosing Buprenorphine: 2-32 mg; naloxone: 20-30 mg initially, then 60-120 mg0.5-8 mg; combination: 4:1 ratioAdministration Daily to 3 times/wk DailyCommon Side Effects Headache, nausea, sweating, rhinitis, Cardiac dysrhythmia, hypotension, diaphoresis,constipationconstipation, nausea, vomiting, dizziness,sedationContraindications Need for ongoing opioid agonists for Hypersensitivitypain relief, hypersensitivityPregnancy Concerns Category C; combination not Category C; current standard of care inrecommended in pregnancy—replace pregnancywith methadone or buprenorphineAccessibility Physician’s office or opioid Opioid treatment programtreatment programRegulatory Concerns Physician may prescribe only with Physician may prescribe only to opioid-DEA-issued registration certificate code; dependent patients for up to 72 h as bridge30-patient census/prescriber, then 100- to treatment entry; only licensed opioidpatient census after 1st y; pharmacy treatment programs may dispense; federalmay dispense up to 30-day supply regulations govern dispensing frequencybased on schedule III(e.g., daily, 3 times/wk, wkly)Insurance Coverage Specific to type of insurance Specific to type of insuranceDEA: Drug Enforcement Administration.Source: Reference 25.agonism allows buprenorphine to have a ceiling effect onthe opioid effects at higher doses, making it safer in theevent of overdose.Naloxone is a mu-opioid receptor antagonist withpoor oral bioavailability owing to limited absorption andextensive first-pass metabolism. It has a rapid onset ofaction when given intravenously. Because it has ahigher affinity for mu-opioid receptors than heroin, morphine,or methadone, naloxone displaces these drugs fromreceptors and blocks their effects. 17Buprenorphine/naloxone (Suboxone) is available asa 4:1 fixed combination. Subutex (buprenorphine), awhite tablet, is available in 2-mg and 8-mg strengths;Suboxone is an orange tablet and is available in 2/0.5-mg and 8/2-mg formulations. Buprenorphine israpidly absorbed sublingually, and peak effects are reached90 minutes after administration. Naloxone does notaffect the pharmacokinetics of buprenorphine. The meanhalf-life of buprenorphine is 37 hours; that of naloxoneis 1.1 hours. 18Dosing: Because buprenorphine displaces the other opioidfrom mu-receptor sites and induces withdrawal, itshould be initiated only when the patient already hasevident signs of withdrawal; otherwise, the patient mightassociate the buprenorphine with withdrawal, therebyreducing adherence. The buprenorphine/naloxone combinationis the drug of choice for initiating therapy inboth U.S. and European guidelines. Buprenorphine maybe started alone at doses of 4 mg to 8 mg or in combinationin a 4:1 ratio to naloxone. A second dose of 4mg may be given in 2 to 4 hours, and the patient maybe given an additional dose of 2 mg to 4 mg to takehome in case of withdrawal within the next 24 hours.The physician should monitor for buprenorphine-precipitatedwithdrawal while the patient is in the office.This is not to be confused with withdrawal from underdosingof buprenorphine, which usually occurs in thesecond half of the 24-hour dosing interval. 16The maintenance dose may be achieved by doublingthe dose each day, to a maximum of 24 mg to 32 mg.If withdrawal symptoms arise at any time during the24-hour dosing interval, the dose is too low and needsto be increased. If induction occurs too slowly, thepatient may prematurely terminate treatment. Therefore,it is important for the practitioner to be diligentin monitoring the patient. When converting to or fromthe naltrexone combination, a 1:1 ratio of the buprenorphinedose may be used. 16When the maintenance dose is achieved, buprenor-46U.S. Pharmacist • November 2009 • www.uspharmacist.com