About Suboxone

In October 2002, the Food and Drug Administration (FDA) approved buprenorphine monotherapy product, Subutex®, and a buprenorphine/naloxone combination product, Suboxone®, for use in opioid addiction treatment. The combination product is designed to decrease the potential for abuse by injection. Subutex® and Suboxone® are currently the only Schedule III, IV, or V medications to have received FDA approval for this indication. Note that aside from Subutex® and Suboxone®, other forms of buprenorphine (e.g., Buprenex®) are not approved for treatment of opioid addiction.

The FDA approval of these buprenorphine formulations does not affect the status of other medication-assisted opioid addiction treatments, such as methadone and LAAM (levo-alpha-acetyl-methadol). As indicated in Title 42 Code of Federal Regulations Part 8 (42 CFR Part 8), these treatments can only be dispensed, and only in the context of an Opioid Treatment Program. Also, neither the approval of Subutex® and Suboxone®, nor the provisions of DATA 2000, affect the use of other Schedule III, IV, or V medications, such as codeine, that are not approved for the treatment of addiction.

Formulations

Suboxone®, a sublingual tablet, comes in two dosage forms: 2 mg buprenorphine/0.5 mg naloxone and 8 mg buprenorphine/2 mg naloxone. Subutex®, also a sublingual tablet, is available in 2 mg and 8 mg strengths. The Subutex® and Suboxone® drug labels are available on the FDA Web site at: http://www.fda.gov/cder/drug/infopage/subutex_suboxone/default.htm

Applied Pharmacology

Buprenorphine is an opioid partial agonist. This means that, although buprenorphine is an opioid, and thus can produce typical opioid agonist effects and side effects such as euphoria and respiratory depression, its maximal effects are less than those of full agonists like heroin and methadone. At low doses buprenorphine produces sufficient agonist effect to enable opioid-addicted individuals to discontinue the misuse of opioids without experiencing withdrawal symptoms. The agonist effects of buprenorphine increase linearly with increasing doses of the drug until at moderate doses they reach a plateau and no longer continue to increase with further increases in dose—the “ceiling effect.” Thus, buprenorphine carries a lower risk of abuse, addiction, and side effects compared to full opioid agonists. In fact, in high doses and under certain circumstances, buprenorphine can actually block the effects of full opioid agonists and can precipitate withdrawal symptoms if administered to an opioid-addicted individual while a full agonist is in the bloodstream.

Buprenorphine has poor oral bioavailability and moderate sublingual bioavailability. Formulations for opioid addiction treatment are in the form of sublingual tablets.

Buprenorphine is highly bound to plasma proteins. It is metabolized by the liver via the cytochrome P4503A4 enzyme system into norbuprenorphine and other metabolites. The half-life of buprenorphine is 24–60 hours.

Safety

Because of its ceiling effect and poor bioavailability, buprenorphine is safer in overdose than opioid full agonists. The maximal effects of buprenorphine appear to occur in the 16–32 mg dose range for sublingual tablets. Higher doses are unlikely to produce greater effects.

Respiratory depression from buprenorphine (or buprenorphine/naloxone) overdose is less likely than from other opioids. There is no evidence of organ damage with chronic use of buprenorphine, although increases in liver enzymes are sometimes seen. Likewise, there is no evidence of significant disruption of cognitive or psychomotor performance with buprenorphine maintenance dosing.

Information about the use of buprenorphine in pregnant, opioid-addicted women is limited; the few available case reports have not demonstrated any significant problems due to buprenorphine use during pregnancy. Suboxone® and Subutex® are classified by the FDA as Pregnancy Category C medications.

Side Effects

Side effects of buprenorphine are similar to those of other opioids and include nausea, vomiting, and constipation. Buprenorphine and buprenorphine/naloxone can precipitate the opioid withdrawal syndrome. Additionally, the withdrawal syndrome can be precipitated in individuals maintained on buprenorphine. Signs and symptoms of opioid withdrawal include:

• Dysphoric mood
• Piloerection
• Nausea or vomiting
• Diarrhea
• Muscle aches/cramps
• Yawning
• Lacrimation
• Mild fever
• Rhinorrhea
• Insomnia
• Pupillary dilation
• Craving
• Sweating
• Distress/irritability

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