|GENERIC NAME :|
|BRAND NAMES :|
|(1) Buprenex (Buprenorphine hydrochloride injection); (2) Subutex (buprenorphine sublingual tablets); (3) Suboxone (buprenorphine & naloxone sublingual tablets)
|STREET NAMES :|
|BRIEF DESCRIPTION :|
|(1) Buprenorphine injection is a parenteral opioid (narcotic) analgesic (pain killer) with 0.3 mg buprenorphine being approximately equivalent to 10 mg morphine sulfate in analgesic and respiratory depressant effects in adults. Buprenorphine exerts its analgesic effect via high affinity binding to mu (?) opioid receptors in the central nervous system. Although buprenorphine may be classified as a partial agonist, under the conditions of recommended use it behaves very much like classical mu (?) agonists such as morphine. One unusual property of buprenorphine observed in studies is its very slow rate of dissociation from its receptor. This could account for its longer duration of action than morphine, the unpredictability of its reversal by opioid antagonists. Buprenorphine demonstrates narcotic antagonist activity and has been shown to be equipotent with naloxone (Narcan) as an antagonist of morphine. (2), (3) Subutex and Suboxone are used for treatment of opiate dependence (*see Addictive and Abuse Potential below).
|INDICATIONS FOR USE :|
|(1) Buprenex Buprenorphine injection is indicated for the relief of moderate to severe pain. (2) Subutex This form of buprenorphine is approved for treatment of opiate dependence. It should be used as part of a complete narcotic dependence treatment plan. Tablets, sublingual 2 mg (as base) Tablets, sublingual 8 mg (as base) (3) Suboxone This form of buprenorphine is approved for treatment of opiate dependence. It should be used as part of a complete narcotic dependence treatment plan. Tablets, sublingual 2 mg buprenorphine base per 0.5 mg naloxone Tablets, sublingual 8 mg buprenorphine base per 2 mg naloxone
|ABUSE AND ADDICTIVE POTENTIAL :|
Buprenorphine is a partial agonist of the morphine type; i.e., it has certain opioid properties which may lead to psychic dependence due to an opiate-like euphoric (“high”) component of the drug. It is susceptible to abuse in both of the forms approved for treating opiate addiction. Subutex, the form that does not contain naloxone, is more vulnerable to abuse because it can be crushed and injected or snorted without causing withdrawal symptoms in the abuser. The FDA recommends that physicians limit the use of Subutex to supervised administration sessions; however, physicians are not required to do so, creating opportunities for Subutex diversion. Subutex has been prescribed legally for years in some foreign countries, where its diversion for illicit use is common. There are lucrative black markets for diverted Subutex in Germany, New Zealand, and the United Kingdom. In France, India, and Scotland, where buprenorphine is far more common in opiate addiction therapy than methadone, many individuals are addicted to Subutex. Suboxone is not available in these countries. Suboxone also can be diverted and abused; however, it is more likely to be abused by individuals who are addicted to low doses of opiates since it can precipitatewithdrawal symptoms in high doses. The naloxone in Suboxone guards against abuse by causing withdrawal symptoms in abusers who crush and either inject or snort the drug; however, law enforcement and pharmacist reporting indicates that Suboxone is being abused successfully when snorted and there are increasing reports of IV use. Using buprenorphine and heroin in combination does not produce increased effects, but if buprenorphine and methadone are abused together, the effects of both drugs are enhanced. Consequently, diverted buprenorphine may be attractive to patients currently using methadone for opiate addiction therapy. Despite controls designed to make buprenorphine diversion-proof, buprenorphine abuse is on the rise in the United States. Buprenorphine withdrawal is generally milder than that of a full agonist, but lasts longer because of its long half-life. Total duration can be up to two weeks, with symptoms lingering for a few months thereafter. Possible symptoms are listed below:
• Depression/dysphoric (negative) mood
• Nausea and vomiting
• Muscle aches and cramps
• Mild fever
• Lacrimation (tearing)
• Rhinorrhea (runny nose)
• Piloerection (goose bumps)
Caution should be used in prescribing to individuals who are known to be drug abusers or ex-narcotic addicts. The drug may not substitute in acutely dependent narcotic addicts due to its antagonist component and may induce withdrawal symptoms. If used to treat opiate dependence or detoxify an opiate addict, the patient must be allowed to withdraw sufficiently from the opiate he/she is dependent on (including signs and symptoms of opiate withdrawal) before beginning buprenorphine. If buprenorphine is started too early in the detoxification process, its opiate antagonistic properties will usually precipitate an acute and very unpleasant opiate withdrawal syndrome. The way this drug is prescribed for opiate dependence varies with patient’s physical condition, patient’s history, and the physician’s treatment plan and goals:
a. It can be used for short detoxification only over several days, and then tapered off over several days (less than 30 days).
b. It can be used for detoxification, then transitional maintenance at a steady state for several weeks or months, followed by tapering off.
c. It can be used for detoxification, followed by long term maintenance at a steady state for long term opiate replacement therapy.The use of Subutex and Suboxone in opiate addiction therapy is likely to become more common because of several advantages. Buprenorphine can be prescribed by a local doctor and obtained from a local pharmacy, providing patients with convenient access to treatment. Further, if DATA 2003 is passed, the number of patients that can be treated by group practices will increase. Because patients can visit their local doctors, buprenorphine therapy is far more discreet, making it preferable for many patients who must deal with the stigma attached to making daily trips to a methadone clinic. This treatment option also is more convenient than methadone therapy for many abusers who would otherwise have to drive long distances each day to obtain methadone. Further, buprenorphine therapy can provide treatment in rural areas with inadequate access to treatment and in areas where methadone clinics have reached full capacity.
|While it is possible to overdose on buprenorphine, it is safer than methadone because of its ceiling effect and decreased degree of respiratory depression. Also, because of the various safeguards in place, buprenorphine is more difficult to divert than methadone. The abuse of methadone poses a growing threat as evidenced by increasing mortality rates associated with it, whether diverted or legally prescribed. Overdosage with buprenorphine should be taken seriously. Symptoms may include sedation, hypotension (drop in blood pressure), respiratory depression and death. When buprenorphine overdose is suspected, immediate medical attention is advised.
|As with other potent opioids, clinically significant respiratory depression may occur. Patients receiving buprenorphine in the presence of other narcotic analgesics, general anesthetics, antihistamines, benzodiazepines, phenothiazines, other tranquilizers, sedative/hypnotics or other CNS depressants (including alcohol) may exhibit increased CNS depression. When such combined therapy is contemplated, it is particularly important that the dose of one or both agents be reduced. There may be serious problems also with use of this medication an individual with a closed head injury. It can elevate cerebrospinal fluid pressure and mask symptoms of closed head injury that could require immediate medical measures. The administration of buprenorphine, like all opioid analgesics, may obscure the diagnosis or clinical course in patients with acute abdominal conditions. Individuals with kidney (renal) or liver (hepatic) impairment must be monitored closely. Because of the narcotic antagonist activity of buprenorphine, use in the physically dependent individual may result in immediate withdrawal effects. CYP3A4 Inhibitors: Since the metabolism of buprenorphine is mediated by the CYP3A4 isozyme, coadministration of drugs that inhibit CYP3A4 activity may cause decreased clearance of Buprenorphine. Thus, patients coadministered with inhibitors of CYP3A4 such as macrolide antibiotics (e.g., erythromycin), azole antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritanovir) while receiving buprenorphine should be carefully monitored and dosage adjustment made if warranted. CYP3A4 Inducers: Cytochrome P450 inducers, such as rifampin, carbamazepine, and phenytoin, induce metabolism and as such may cause increased clearance of buprenorphine. Caution is advised when administering buprenorphine to patients receiving these medications and, if necessary, dose adjustments should be considered.
|SIDE EFFECTS :|
|The most frequent side effect in clinical studies involving 1,133 patients was sedation which occurred in approximately two-thirds of the patients. Although sedated, these patients could easily be aroused to an alert state. Other less frequent adverse reactions occurring in 5 to 10% of the patients were nausea and dizziness/vertigo. Occurring in 1 to 5% of the patients: Sweating Headache Hypotension (abnormally low blood pressure) Nausea/Vomiting Vomiting Hypoventilation (abnormally slow breathing and low oxygen levels) Miosis (pinpoint pupils) Other reported side effects include confusion, blurred vision, euphoria, fatigue, dry mouth, nervousness, depression, slurred speech, elevated blood pressure, tachycardia (abnormally rapid heart rate), bradycardia (abnormally slow heart rate), constipation, pruritus (itching), urinary retention, vivid dreams, appetite changes, and rash.
|FOR MORE INFORMATION :|
*This is a condensed description of this medication. For more details check with your physician, pharmacist, or resources such as The Physicians' Desk Reference (PDR)