Introduction to Buprenorphine

Opioid addiction is a significant health problem in the US, with an estimated 2.5 million prescription drug-addicted patients and 800,000 heroin abusers (Loxterkamp, 2006). Opioid addiction negatively impacts the health of users, disrupts their families, and is detrimental to the public in terms of costs and crime. Until recently, the only treatment for opioid-addicted patients was methadone maintenance therapy provided solely in federally regulated programs.

The passage of the Drug Addiction Treatment Act of 2000 (DATA) enables physicians to prescribe or dispense Schedule III, IV, and V narcotic drugs [4] if they are waivered. Becoming waivered requires that specific criteria [5] be met. As a consequence, physicians are playing an increasingly influential role in substance abuse treatment. Since buprenorphine is a Schedule III drug, physicians can now prescribe, dispense, or administer it to patients in their office, greatly expanding the availability and accesibility of opioid addiction treatment. Other characterisics and advantages of buprenorphine include:

• Sold under the brand name Suboxone (buprenorphine/naloxone tablet or film) and the generic buprenorphine tablet
• Administered sublingually
• Can be prescribed to both patients abusing prescription opioids and patients abusing heroin
• Milder withdrawal symptoms due to its partial-agonist property (methadone is a full-agonist) (Krantz and Mehler, 2004)
• Minimal oral bioavailibility, leading to less potential for diversion
• As effective as methadone treatment for reducing opioid use in addicts (Greenwald et al., 2002; Mattrick et al, 2002)

Over 10,000 physicians have received buprenorphine certification since the passage of DATA in 2000. Another recent step forward was the Office of National Drug Control Policy Reauthorization Act of 2006 (ONDCPRA), which increased the number of patients a qualified physician can treat with buprenorphine from 30 to 100.

Mechanism of Drug Action

Buprenorphine is a partial opioid agonist. It binds to the receptors in the brain that are responsible for opioid intoxication (mu receptors). Buprenorphine has high affinity for these receptors and therefore is not displaced by other opioids. Because it is only a partial agonist, it does not produce as much euphoria but it does suppress withdrawal and cravings. In high doses it can precipitate withdrawal.

Drug Interactions

Buprenorphine metabolizes to norbuprenorphine via cytochrome CYP 3A4. Therefore, you should consider lower doses of buprenorphine for patients who are already taking cytochrome inhibitors (eg: azole antifungals, macrolide antibiotics, HIV antivirals, and protease inhibitors). Failure to do so may cause an increase in the plasma concentration of buprenorphine. Central nervous system depressants taken at the same time as buprenorphine might cause serious overdose or death.
These include:

• Benzodiazepines
• Alcohol
• Sedatives
• Tranquilizers
• Antidepressants

Precautions

Buprenorphine should be used with caution in the following populations:

• Elderly patients
• Weak patients
• Patients with severe hepatic, pulmonary, or renal impairment
• Patients with myxedema or hypothyroidism
• Patients with CNS depression
• Patients with acute alcoholism

For the complete list of precautions, please refer to the resource provided below.

Contraindications

Buprenorphine has an excellent safety profile but there are some important contraindications.
Buprenorphine is not indicated for:

• Patients under age 16
• Pregnant women

Side Effects

Side effects of buprenorphine are few and well tolerated by most patients; they are usually most troublesome during the buprenorphine induction period. According to Reckitt Benckiser, the developers of Suboxone®, the most commonly reported side effects in order of prevalence include:

• Headaches
• Withdrawal syndrome
• Pain
• Nausea
• Insomnia
• Sweating

(Reckitt Benckiser Healthcare, 2005)

Independent clinical trials of buprenorphine have reported many of these same side effects. Other possible side effects include the following:

• Constipation
• Drowsiness
• Mood disturbances

(Lintzeris et al., 2001)

Side effects that cause discomfort to the patient should be treated symptomatically or, in the long-term, treated by the following:

• Lowering the dose of buprenorphine
• Giving the patient time to become slightly tolerant to the medication
• Making lifestyle changes (such as increased dietary fiber for constipation)

(Lintzeris et al., 2001)

Comparison to Other Opioid Treatments

Methadone is the only other approved opioid maintenance treatment. While methadone is inexpensive and well-studied treatment and may be the appropriate treatment for certain patients, there are several advantages of buprenorphine over methadone. Buprenorphine:

• Is a Schedule III narcotic drug, while methadone is Schedule II - more tightly controlled - and is not approved for office-based treatment.
• Produces milder withdrawal symptoms than methadone and has a lower risk of overdose due to ceiling effect
• Is less likely to be diverted due to its combination with naloxone (Krantz and Mehler, 2004).

In a recent meta-analysis of research, Connock et al. (2007) found:

• For flexible doses, methadone (20-120 mg daily) had superior retention in treatment to buprenorphine (4-16 mg daily)
• no significant difference in opioid use
• level of mortality may be lower with buprenorphine
• no significant difference in rate of serious adverse events

Summary