Buprenorphine:  A New Treatment For Opiate Addiction

Buprenorphine's pharmacological and safety profile  makes it an attractive treatment for patients addicted to opioids as well as for the medical professionals treating them. Buprenorphine is a partial agonist at the mu opioid receptor and an antagonist at the kappa receptor. It has very high affinity and low intrinsic activity at the mu receptor and will displace morphine, methadone, and other opioid full agonists from the receptor. Its partial agonist effects imbue buprenorphine with several clinically desirable pharmacological properties: lower abuse potential, lower level of physical dependence (less withdrawal discomfort), a ceiling effect at higher doses, and greater safety in overdose compared with opioid full agonists.

At analgesic doses, buprenorphine is 20-50 times more potent than morphine. Because of its low intrinsic activity at the mu receptor, however, at increasing doses, unlike a full opioid agonist, the agonist effects of buprenorphine reach a maximum and do not continue to increase linearly with increasing doses of the drug-the ceiling effect. One consequence of the ceiling effect is that an overdose of buprenorphine is less likely to cause fatal respiratory depression than is an overdose of a full mu opioid agonist.

In the pharmacotherapy of opioid addiction, buprenorphine, as a partial opioid agonist, can be thought of as occupying a midpoint between opioid full agonists (e.g., methadone, LAAM) and opioid antagonists (e.g., naltrexone, nalmefene). It has sufficient agonist properties such that individuals addicted to opioids perceive a reinforcing subjective effect from the medication, often described in terms of "feeling normal."

 In higher doses, and under certain circumstances, its antagonist properties can cause the precipitation of acute withdrawal if administered to an individual who is physically dependent on opioids and maintained on a sufficient dose of a full agonist. In this scenario, buprenorphine can displace the full agonist from the mu receptors, yet not provide the equivalent degree of receptor activation, thereby leading to a net decrease in agonist effect and the onset of withdrawal. Furthermore, because of the high affinity of buprenorphine for the opioid receptor, this precipitated abstinence syndrome may be difficult to reverse. Buprenorphine produces a blockade to subsequently administered opioid agonists in a dose-responsive manner. This effect makes the drug particularly appealing to well-motivated patients, as it provides an additional disincentive to continued opioid use.

Buprenorphine can produce euphoria, especially if it is injected. Buprenorphine does produce physical dependence, although it appears to do so to a lesser degree than do full opioid agonists, and it appears to be easier to discontinue at the end of medication treatment.

Buprenorphine has several pharmaceutical uses. It is a potent analgesic, available in many countries as a 0.3-0.4mg sublingual tablet (Temgesic). Until 2002, the only form of buprenorphine approved and marketed in the United States was the parenteral form for treatment of pain (Buprenex).

Buprenex: 
Not To Be Used For Addiction Management

Buprenex is an injectable formulation of buprenorphine indicated for the relief of moderate to severe pain.  In the past, clinicians have occasionally prescribed Buprenex off-label for opioid detoxification.  However, Buprenex does not carry an indication for addiction management and should not be used for this purpose, especially given the approval of Suboxone and Subutex for this indication.  Also, due to its intravenous rather than sublingual administration, Buprenex is more likely to be diverted and abused. 

Pharmacists who receive Buprenex prescriptions for which the dosage (a tapering one, for example) suggests use for detoxification need to contact the prescriber and advise him or her of the need to use the form of buprenorphine that corresponds with the indication.  Conversely, Suboxone and Subutex prescriptions that appear to be for pain management should contact the prescriber and recommend use of an indicated medication.

Buprenorphine prescriptions written for the management of opioid addiction, but not pain management, require pharmacists to verify that the prescriber is a physician certified to prescribe buprenorphine for this indication.  

 In 2002, two sublingual tablet formulations of buprenorphine were approved by FDA as opioid addiction treatment medications: buprenorphine alone (Subutex) and a combination tablet containing buprenorphine plus naloxone in a 4:1 ratio (Suboxone). Both of these tablets are Schedule III opioids and therefore eligible for use in the treatment of opioid addiction under DATA 2000.  Note that, as of the date of this publication, Subutex and Suboxone are the only forms of buprenorphine that are indicated and can be legally used for the treatment of opioid addiction in the United States-neither Buprenex nor its generic equivalent can be used legally to treat opioid addiction.

Dosage Forms Of Buprenorphine Available in the United States (as of July 2004)

Buprenorphine = Subutex=2 or 8mg (sl) Tablets=Opioid Addiction

                                                                                                    Buprenorphine /Naloxone in 4:1 ratio = Suboxone=2 or 8mg (sl) Tablets= Opioid Addiction

Buprenorphine=Buprenex=Injectable Ampoules=Moderate to Severe Pain                                                                               

Buprenorphine=Buprenorphine Injectable Ampoules= Moderate to Severe
Pain (Generic)

All are manafactured by Reckitt Benckiser except the Injectable (Generic)and it is manafactured by Abbott Laboratories.

Many of the large clinical studies of buprenorphine in the treatment of opioid addiction in the United States have been conducted under the joint sponsorship of the National Institute on Drug Abuse (NIDA) and Reckitt Benckiser, the company holding the buprenorphine patent. The most extensive clinical experience with buprenorphine used for treatment of opioid addiction is in France, where the medication has been available for office-based treatment of opioid addiction since February 1996. In France, buprenorphine can be prescribed for maintenance treatment by both addiction specialists and general practitioners. It is estimated that close to 70,000 patients are currently receiving maintenance treatment with buprenorphine in France.

Buprenorphine doses studied for opioid addiction treatment have ranged from 12 mg to 16-32 mg, depending upon the formulation (solution versus tablet), with duration of treatment lasting from a few weeks to years. Using the outcome measures of illicit opioid use, retention in treatment, and assessment for adverse events, studies have shown that buprenorphine treatment reduces opioid use, retains patients in treatment, has few side effects, and is acceptable to most patients (Johnson et al. 1992, 2000; Ling et al. 1996, 1998; O'Connor and Fiellin 2000).

Although buprenorphine has been abused and injected by individuals addicted to opioids in countries where the sublingual tablet is available as an analgesic, its abuse potential appears substantially less than that of full opioid agonists. To reduce the potential for abuse even further, the sublingual tablet dosage form combining buprenorphine with naloxone was developed by NIDA and Reckitt Benckiser.

The buprenorphine/naloxone combination tablet appears to have reduced abuse potential compared with buprenorphine alone when studied in opioid-dependent populations. It works on the principle that naloxone is approximately 10-20 times more potent by injection than by the sublingual route. Therefore, if the combination is taken sublingually, as directed, the small amount of naloxone available should not interfere with the desired effects of buprenorphine. If the combination form is dissolved and injected by an individual physically dependent on opioids, however, the increased bioavailability of naloxone via the parenteral route should precipitate an opioid withdrawal syndrome.

Suboxone is approved for Opioid Addiction. It comes in two sizes and is a combination of buprenorphine and naloxone. I hope you will continue on with us for we have lots of information to share with you about buprenorphine.   

Suboxone (Buprenorphine 2mg and Naloxone 0.5mg) 

       Suboxone (Buprenorphine 8mg and Naloxone 2mg)

All Images displayed are for imformation and user's convenience only

References:(1) Clinical Guidelines For The Use of Buprenorphine in the Treatment of Opiate Addiction TIP 40(9/2004)  SAMHSA.GOV 

                (2) Pharmacy Today May 2004 (Buprenex:Not To Be Used  For Addiction Management)

Deborah Shrira,Editor                    Date: February 2007

Dee Black, Assistant Editor        Updated: January 2012