Naloxone with buprenorphine

Reducing dosage and stopping treatment - Make the decision to discontinue therapy with buprenorphine or buprenorphine/naloxone after a period of maintenance or brief stabilization as part of a comprehensive treatment plan. Gradual and abrupt discontinuation have been used but there is not a best method of tapering the dose at the end of treatment. 

Administration (FDA) for the treatment of opioid addiction. Treatment is initiated with buprenorphine alone administered sublingually, followed by maintenance therapy with a combination of buprenorphine and naloxone (Suboxone) to minimize abuse potential. The partial agonist properties of buprenorphine limit its usefulness for the treatment of addicts who require high maintenance doses of opioids. However, conversion to maintenance treatment with higher doses of methadone, a full agonist, is possible. 

Preliminaiy evidence suggests that buprenorphine does not affect the antiretrovirai efficacy or pharmacokinetics of delavirdine and efavirenz. Deiavirdine may increase buprenorphine plasma levels and efavirenz may decrease buprenorphine levels, but the clinical significance has not been fully investigated. Delavirdine given with buprenorphine/naloxone has been shown to slightly prolong the QT interval. 

Combination studies The combination of buprenorphine + naloxone (Suboxone) has been compared with buprenorphine (Subu-tex) alone in 53 opioid-dependent subjects [199 ]. The combination was associated with a higher prevalence of adverse events (25 versus 18). Those who took the combination reported more nervous system disorders headache, somnolence, and vertigo), diarrhea, hyperhidrosis, fatigue, and general health deterioration. 

The approval of buprenorphine for the office-based treatment of opioid dependence represents a major departure from the earlier methadone clinic system. Physicians with addiction specialist credentials or those who have completed 8 hours of approved training can become qualified to treat up to 30 patients in their private offices. Stable patients may be given prescriptions for up to a month of medication. The combination buprenorphine/naloxone tablet is expected to have minimal risk for diversion. When taken subhnguaUy, as prescribed, naloxone has minimal biologic activity and does not interfere with the buprenorphine dose. However, if an attempt is made to inject the drug, the addict will experience the full antagonist effect of the naloxone. 

Sarton E, Teppema L, Dahan A (2008) Naloxone reversal of opioid-induced respiratory depression with special emphasis on the partial agonist/antagonist buprenorphine. Adv Exp Med Biol 605 486 91... 

There are two types of pharmaceutically important derivatives (a) Compounds with a hydroxyl substituent at position 14, such as in oxycodone and the antagonists naloxone and naltrexone, and (b) Diels-Alder adducts such as etorphine and buprenorphine, where the latter compounds are all derived from another opium alkaloid, (—)-thebaine (12) (Scheme 5.10). Because thebaine is a rather scarce alkaloid, several syntheses have been investigated. Quite recently, Australian scientists have been able to modify P. somniferum in such a way that thebaine is now a main alkaloid, so that it is becoming better available [28],... 

Q35 contains buprenorphine with naloxone Q36 contains caffeine... 

Suboxone contains buprenorphine, an opioid partial agonist used in opioid dependence in combination with naloxone. 

Endogenous opioids are peptides that are cleaved from the precursors proenkephalin, pro-opiomelanocortin, and prodynorphin. All contain the amino acid sequence of the pentapeptides [Met]- or [Leuj-enkephalin (A). The effects of the opioids can be abolished by antagonists (e.g., naloxone A), with the exception of buprenorphine. 

Acute abdominai conditions As with other p-opioid receptor agonists, the administration of buprenorphine or buprenorphine/naloxone may obscure the diagnosis or clinical course of patients with acute abdominal conditions. 

Buprenorphine is a semi-synthetic derivative of thebaine, one of the opium alkaloids. It is approximately 30 times as potent as morphine. A dose of 0.3 mg intramuscularly has a duration of analgesic action of 6-18 h. Buprenorphine is also effective sublingually. The average bio-availability by this route is about 55%, but absorption is slow and the time to achieve peak plasma concentrations is variable, with a range of 90-360 min. The onset of action is rather slow (5-15 min) after both intramuscular and intravenous administration, possibly due to slow receptor association. Buprenorphine binds to and dissociates from the p receptor very slowly, which may account for its low potential for physical abuse. It also means that buprenorphine-induced respiratory depression is difficult to reverse with naloxone, even with very high doses. Doxapram may in these circumstances be useful. Drowsiness and dizziness are the most common side effects, although they rarely... 

Buprenorphine Partial agonist at P-opioid receptors Attenuates acute effects of morphine Oral substitution therapy for opioid-addicts Long half-life (40 h) formulated together with naloxone to avoid illicit IV injections... 

Buprenorphine is derived from thebaine. It is a partial mu agonist with kappa antagonist activity. Buprenorphine has 25 to 50 times the potency of morphine. It is used to produce a longer-lasting analgesia than morphine. Effects of buprenorphine last longer because it is released more slowly from mu receptors than morphine. It is available as an injectable for intramuscular (IM) or intravenous administration in a 1-ml solution containing 0.3 mg buprenorphine (as buprenorphine HC1) for the relief of moderate to severe pain. It is also available to treat opioid dependence in the formulation of a tablet,51 alone or in combination with naloxone, in 2- or 8-mg... 

The bioavailability of the buprenorphine/naloxone tablet appears to be greater than the buprenor-phine-alone formulation, with the former similar to the drug in liquid form. Buprenorphine is approximately 96% plasma protein bound, primarily to a- and [3-globulin. The plasma half-life is... 

A number of narcotic antagonists based on the morphinan stmcture have been marketed—for example, Buprenorphine, Naloxone, Naltrexone, and Nalorfine. Nalmefene is being pursued for the treatment of alcohol abuse. Oxycodone, and its precursor Codeine, are marketed, with restrictions, as analgesics. noSee Chapter 9, Table 3. 

Sublingual buprenorphine is an alternative to methadone in treating opiate dependence, but its opioid agonist effects pose the risk of intravenous abuse and subsequent dependence. This abuse potential may be hmited by using a combination of buprenorphine with naloxone, which will precipitate opiate withdrawal when given... 

Naloxone is of limited use in reversing the effects of buprenorphine, because of its relative inability to displace it from opioid receptors. Naloxone Img had little effect on the respiratory depression caused by buprenorphine 300 J,g/70 kg, although both 5 and 10 pg produced consistent reversal, which was more complete with the larger dose (33). Insignificant effects on circulation and respiration have been reported at lower doses of buprenorphine (4.5-10 pg/kg) (34). 

---