What is Buprenorphine?

BuprenorphineBuprenorphine is used in medication-assisted treatment (MAT) to help people reduce or quit their use of heroin or other opiates, such as pain relievers like morphine. Approved for clinical use in October 2002 by the Food and Drug Administration (FDA), buprenorphine represents the latest advance in medication-assisted treatment (MAT). Medications such as buprenorphine, in combination with counseling and behavioral therapies, provide a whole-patient approach to the treatment of opioid dependency. When taken as prescribed, buprenorphine is safe and effective.

The pharmacological and safety profile of Buprenorphine, the active ingredient in Suboxone, 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).

Unlike methadone treatment, which must be performed in a highly structured clinic, buprenorphine is the first medication to treat opioid dependency that is permitted to be prescribed or dispensed in physician offices, significantly increasing treatment access. Under the Drug Addiction Treatment Act of 2000 (DATA 2000), qualified U.S. physicians can offer buprenorphine for opioid dependency in various settings, including in an office, community hospital, health department, or correctional facility.

SAMHSA-certified opioid treatment programs (OTPs) also are allowed to offer buprenorphine, but only are permitted to dispense treatment.

As with all medications used in MAT, buprenorphine is prescribed as part of a comprehensive treatment plan that includes counseling and participation in social support programs.

Buprenorphine offers several benefits to those with opioid dependency and to others for whom treatment in a methadone clinic is not preferred or is less convenient.

The FDA has approved the following buprenorphine products:

  • Bunavail (buprenorphine and naloxone) buccal film
  • Suboxone (buprenorphine and naloxone) film
  • Zubsolv (buprenorphine and naloxone) sublingual tablets
  • Buprenorphine-containing transmucosal products for opioid dependency

How Buprenorphine Works

Buprenorphine has unique pharmacological properties that help:

  • Lower the potential for misuse
  • Diminish the effects of physical dependency to opioids, such as withdrawal symptoms and cravings
  • Increase safety in cases of overdose

Buprenorphine is an opioid partial agonist. This means that, like opioids, it produces effects such as euphoria or respiratory depression. With buprenorphine, however, these effects are weaker than those of full drugs such as heroin and methadone.

Buprenorphine’s opioid effects increase with each dose until at moderate doses they level off, even with further dose increases. This “ceiling effect” lowers the risk of misuse, dependency, and side effects. Also, because of buprenorphine’s long-acting agent, many patients may not have to take it every day.

Side Effects of Buprenorphine

Buprenorphine’s side effects are similar to those of opioids and can include:

  • Nausea, vomiting, and constipation
  • Muscle aches and cramps
  • Cravings
  • Inability to sleep
  • Distress and irritability
  • Fever

Buprenorphine Misuse Potential

Because of buprenorphine’s opioid effects, it can be misused, particularly by people who do not have an opioid dependency. Naloxone is added to buprenorphine to decrease the likelihood of diversion and misuse of the combination drug product. When these products are taken as sublingual tablets, buprenorphine’s opioid effects dominate and naloxone blocks opioid withdrawals. If the sublingual tablets are crushed and injected, however, the naloxone effect dominates and can bring on opioid withdrawals.

Buprenorphine Safety

People should use the following precautions when taking buprenorphine:

  • Do not take other medications without first consulting your doctor.
  • Do not use illegal drugs, drink alcohol, or take sedatives, tranquilizers, or other drugs that slow breathing. Mixing large amounts of other medications with buprenorphine can lead to overdose or death.
  • Do ensure that a physician monitors any liver-related health issues that you may have.

Pregnant or Breastfeeding Women and Buprenorphine

Limited information exists on the use of buprenorphine in women who are pregnant and have an opioid dependency. But the few case reports available have not demonstrated any significant problems resulting from use of buprenorphine during pregnancy. The FDA classifies buprenorphine products as Pregnancy Category C medications, indicating that the risk of adverse effects has not been ruled out.

Review SAMHSA’s Federal Guidelines for Opioid Treatment Programs – 2015 for more information about the use of buprenorphine in pregnancy. In the United States, methadone remains the current standard of care for the use of MAT with pregnant women who have opioid dependency.

Treatment with Buprenorphine

The ideal candidates for opioid dependency treatment with buprenorphine:

  • Have been objectively diagnosed with an opioid dependency
  • Are willing to follow safety precautions for the treatment
  • Have been cleared of any health conflicts with using buprenorphine
  • Have reviewed other treatment options before agreeing to buprenorphine treatment

Before buprenorphine treatment begins, policies and procedures should be in place to guarantee patient privacy and the confidentiality of personally identifiable health information. Under the Confidentiality Regulation, 42 Code of Federal Regulations (CFR) 2, information relating to substance use and alcohol treatment must be handled with a higher degree of confidentiality than other medical information.

Buprenorphine treatment happens in three phases:

  1. The Induction Phaseis the medically monitored startup of buprenorphine treatment performed in a qualified physician’s office or certified OTP using approved buprenorphine products. The medication is administered when a person with an opioid dependency has abstained from using opioids for 12 to 24 hours and is in the early stages of opioid withdrawal. It is important to note that buprenorphine can bring on acute withdrawal for patents who are not in the early stages of withdrawal and who have other opioids in their bloodstream.
  2. The Stabilization Phasebegins after a patient has discontinued or greatly reduced their misuse of the problem drug, no longer has cravings, and experiences few, if any, side effects. The buprenorphine dose may need to be adjusted during this phase. Because of the long-acting agent of buprenorphine, once patients have been stabilized, they can sometimes switch to alternate-day dosing instead of dosing every day.
  3. The Maintenance Phaseoccurs when a patient is doing well on a steady dose of buprenorphine. The length of time of the maintenance phase is tailored to each patient and could be indefinite. Once an individual is stabilized, an alternative approach would be to go into a medically supervised withdrawal, which makes the transition from a physically dependent state smoother. People then can engage in further rehabilitation—with or without MAT—to prevent a possible relapse.

Treatment of opioid dependency with buprenorphine is most effective in combination with counseling services, which can include different forms of behavioral therapy and self-help programs. Learn more about medication and counseling treatment.

Switch from Methadone to Buprenorphine

Patients can possibly switch from methadone to buprenorphine treatment, but because the two medications are so different, patients may not always be satisfied with the results. Studies indicate that buprenorphine is equally as effective as moderate doses of methadone. However, because buprenorphine is unlikely to be as effective as more optimal-dose methadone, it may not be the treatment of choice for patients with high levels of physical dependency.

A number of factors affect whether buprenorphine is a good choice for someone who is currently receiving methadone. Patients receiving buprenorphine can possibly be switched to methadone. Patients interested in learning more about switching their treatment should discuss this with their doctor.