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Buprenorphine With Naloxone for Chronic Pain

Ask the Expert: June 2014

Question: Does adding naloxone to buprenorphine offer any benefit over using buprenorphine alone for the treatment of chronic pain?

Answer: Buprenorphine hydrochloride is available alone and in combination with naloxone in several formulations on the market. Buprenorphine injectable solution (Buprenex) and transdermal patch (Butrans) are approved by the FDA only for the treatment of moderate to severe chronic pain. Buprenorphine sublingual tablets and buprenorphine and naloxone sublingual tablets (Suboxone, Zubsolv) and sublingual film (Suboxone) are only FDA-approved for the treatment of opioid dependence.1

The prescribing of products approved for opioid dependence for that indication is limited to physicians with a unique identifier under the Drug Addiction Treatment Act;2 however, off-label prescribing of these products is allowed for uses deemed to be appropriate in a physician’s professional opinion. Any physician authorized to prescribe schedule III controlled medications can prescribe these agents for off-label indications.2,3

Buprenorphine is a schedule III opioid with partial μ-agonist and weak κ-antagonist activity. Although it is classified as a partial agonist, it acts like a full μ-opioid agonist at lower doses, with a ceiling analgesic effect at 32 mg/d due to its antagonistic properties. One characteristic that is unique to buprenorphine is its slower rate of dissociation from the μ-opioid receptor, giving it a longer half-life (6-9 h) than morphine. However, due to its increased affinity and decreased intrinsic activity at the μ-opioid receptor, buprenorphine can precipitate opioid withdrawal symptoms in opioid-dependent patients.3 Because of its low oral bioavailability, buprenorphine is prepared in sublingual, injectable, and transdermal formulations.

Naloxone is an opioid antagonist that competes with opioids at the opioid receptor sites. The sublingual bioavailability of naloxone is very poor. Its main role in the combination products with buprenorphine is to prevent drug diversion via intravenous injection.4

Clinical studies have evaluated the use of buprenorphine plus naloxone for the treatment of both acute and chronic pain, but few were well-designed studies investigating the combination in the treatment of chronic pain. The study design and results of 2 studies that investigated buprenorphine plus naloxone in the treatment of chronic pain are summarized in the Table.4,5 These studies were short-term studies incorporating various patient populations, and their overall methodologies were poor. None of the studies showed any significant differences in pain control or side effects between buprenorphine plus naloxone and buprenorphine alone.

Although few studies have been conducted in humans comparing buprenorphine plus naloxone to buprenorphine alone for the treatment of chronic pain and none have demonstrated greater benefit of buprenorphine plus naloxone in pain control, an advantage of the combination is that it may prevent misuse of the drug. Buprenorphine plus naloxone may be considered in patients with chronic pain who also are undergoing treatment for opioid dependence.3 Additional well-designed, long-term studies evaluating the effect of buprenorphine plus naloxone compared with buprenorphine alone in the treatment of chronic pain are necessary to fully determine any significant differences between these treatments. 

Last updated on: June 12, 2014
First published on: June 1, 2014