Buprenorphine and naloxone co-administration in opiate-dependent patients stabilized on sublingual buprenorphine

Harris, Debra; Jones, Reese T.; Welm, Susette; Upton, Robert A.; Lin, Emil T.; Mendelson, John

doi:10.1016/s0376-8716(00)00126-5

Cited by 122 publications

(91 citation statements)

References 31 publications

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“…However, a study by Strain et al (1997) demonstrated that when higher doses of intramuscular buprenorphine (4, 8, and 16 mg) were administered to individuals maintained on 8 mg of sublingual buprenorphine, opioid-like effects were produced, suggesting that buprenorphine alone may have abuse liability in buprenorphine-maintained individuals. Furthermore, Harris et al (2000) showed that intravenous administration of the buprenorphine/naloxone combination (4 mg of each drug) did not precipitate withdrawal in individuals maintained on 8 mg of sublingual buprenorphine (but see Eissenberg et al, 1996). Whether high doses of the buprenorphine/naloxone combination would have abuse liability in buprenorphine-maintained individuals is currently unknown.…”

Section: Discussionmentioning

confidence: 99%

Self-Administration of Intravenous Buprenorphine and the Buprenorphine/Naloxone Combination by Recently Detoxified Heroin Abusers

Comer¹,

Collins²

2002

J Pharmacol Exp Ther

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Buprenorphine is a partial -opioid agonist and -opioid antagonist currently under development as a maintenance medication for heroin dependence. Because of concerns about illicit diversion of buprenorphine, a combination tablet containing buprenorphine and naloxone has been developed. The present study evaluated the reinforcing effects of intravenously administered placebo, buprenorphine alone (BUP; 2 and 8 mg), and the buprenorphine/naloxone combination (BUP/NX; 2 mg of buprenorphine plus 0.5 mg of naloxone, and 8 mg of buprenorphine plus 2 mg of naloxone) in recently detoxified heroin abusers during a 6-week inpatient study. Participants (n ϭ 6) were detoxified from heroin over approximately 1 week immediately after admission. During the next 5 weeks, the reinforcing effects of placebo, BUP, and BUP/NX were evaluated. Participants first received a dose of drug and $20 and then were given the opportunity to self-administer either the dose or $20 during choice sessions. Progressive ratio break point values were significantly higher after active drug, compared with placebo, but they did not significantly differ as a function of dose or drug. In contrast, positive subjective ratings were higher after administration of BUP compared with BUP/NX, and these ratings increased in a dose-dependent manner. BUP and the combination had few effects on performance. Relative to placebo, both BUP and BUP/NX decreased pupil diameter, but there were no significant differences in pupil diameter as a function of drug or dose. These results demonstrate that both BUP and BUP/NX served as reinforcers under these conditions and that they may have similar abuse liability in recently detoxified individuals who abuse heroin.Both phase I and II clinical trials have demonstrated that buprenorphine is effective in treating opioid dependence (Bickel and Amass, 1995;Johnson et al., 2000). Despite its clear clinical utility, several lines of evidence suggest that buprenorphine has some abuse liability. Studies using nonhuman primates showed that buprenorphine serves as a reinforcer (Negus and Woods, 1995). For example, Winger and Woods (2001) showed that rates of responding maintained by buprenorphine were higher than placebo but lower than rates of responding for the full -agonists heroin and alfentanil (Winger and Woods, 2001). Another study demonstrated that buprenorphine was less reinforcing than heroin but equivalent to methadone (Mello et al., 1988). Thus, buprenorphine is self-administered by laboratory animals, and under some conditions, is self-administered at rates comparable with full -agonists.In humans, two studies examined the reinforcing effects of buprenorphine in heroin users maintained on sublingual buprenorphine in outpatient treatment settings (Petry and Bickel, 1999;Amass et al., 2000). Petry and Bickel (1999) examined the reinforcing effects of sublingual buprenorphine. Participants who were given the opportunity to choose between sublingual buprenorphine and money almost exclusively self-administered buprenorphine...

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Section: Discussionmentioning

confidence: 99%

Self-Administration of Intravenous Buprenorphine and the Buprenorphine/Naloxone Combination by Recently Detoxified Heroin Abusers

Comer¹,

Collins²

2002

J Pharmacol Exp Ther

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“…While some data showed that parenterally administered combination of naloxone with buprenorphine only partially attenuates the effects of buprenorphine in opiate agonist-dependent subjects, this effect was not significant in non-dependent individuals [16]. With respect to naloxone's potential for inducing a severe withdrawal when the co-formulation is injected, there are reports indicating that, in individuals whose symptoms are stable on buprenorphine maintenance, the injected combination including naloxone seems to lack the capacity to significantly displace buprenorphine from well saturated receptors [16,40].…”

Section: Can Buprenorphine With Naloxone Be Actually Safer Than Buprementioning

confidence: 99%

“…The scientific community continues to be engaged in a valid discussion regarding the effectiveness of adding naloxone to the coformulation as a deterrent of intravenous use and, by extension, also of diversion [11,40,41]. However, the risks of intravenous drug use cannot be underestimated, especially in pregnancy (discussed further in this article).…”

Section: Pharmaco-economical Reasoningmentioning

confidence: 99%

“…Our understanding of current evidence leads us to believe that naloxone does not play an important role, particularly when administered concurrently with buprenorphine in patients on long-term buprenorphine maintenance [16,40]. The aversive effect with parenteral, but much less so with sublingual buprenorphine/naloxone combination for individuals dependent on full opiate receptor agonists, has been reported to decrease the desirability of the combination for parenteral use but the extent of the deterrent effect in practice remains controversial [11,41,43].…”

Section: Associated Health and Socio-economic Risksmentioning

confidence: 99%

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Buprenorphine with, or without, Naloxone for Pregnant Women?–Review of Current Evidence and Practice in Massachusetts

Kršák¹,

Trowbridge²,

Regan³

et al. 2017

J Alcohol Drug Depend

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Opioid use disorder has reached the level of an epidemic. Potential complications of unsafe injections, lifestyle, overdose and withdrawal are particularly concerning in pregnant women as the risk therein extends also to the foetus. The main medications in treatment of opioid use disorder are methadone, naltrexone and buprenorphine products. Naloxone (pregnancy class: B) was carefully selected to be a part of Suboxone ® in 4:1 ratio to buprenorphine (pregnancy class: C) as a deterrent for intravenous use. Naloxone's bioavailability, delivered sublingually, is minimal (<10%) yet there is a theoretical concern that a potential precipitated withdrawal could incite premature labor and fetal demise. For this reason, it is recommended that buprenorphine be used alone in this setting. However, a limited amount of data exists, showing relative safety of this combination in pregnant women when compared to other alternatives. Furthermore, current evidence in non-pregnant individuals shows that the risk of withdrawal due to naloxone is in most instances insignificant. The merit of adding naloxone as a disincentive for injecting opioids has been debated, yet the significance of preventing maternal and fetal exposures to the risk of blood stream infections, sepsis, blood-borne pathogens, bleeding and other complications is clear and warrants focused consideration. In Massachusetts, the state health insurer requires prior authorization for all forms of buprenorphine other than buprenorphine/naloxone combination films, which further complicates access to care specifically in pregnancy. Waiting periods and treatment interruptions rather than naloxone are thus much more likely to cause adverse outcomes in this population.

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“…Publications investigating the extraction and analysis of BUP, NBUP and NALOX are not as populous as those involving buprenorphine (and its metabolite) and naloxone as singly entities. The nature of these studies tends to be of a clinical nature and not forensic toxicological one [27][28][29][30][31][32][33]. In this study, the authors have taken a forensic approach to apply the method to medico-judicial cases.…”

Section: Introductionmentioning

confidence: 99%

Urine analysis of buprenorphine/norbuprenorphine/ naloxone in drugs and driving cases

Elian¹,

Hackett²

2015

J Appl Bioanal

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Buprenorphine is now being detected as a drug of abuse in drugs/driving cases alongside side naloxone. Being a semi synthetic opiate, it has the potential to impair motorists in a similar fashion to morphine. Many laboratories have observed that buprenorphine does not produce a positive response with typical opiate immunoassays or routine basic GC-MS drug screens. In this study, samples of urine were enzymatically hydrolyzed after which they were extracted on mixed mode solid phase (SPE) columns, after which the extracted samples were analyzed by LC-MS/MS analysis in positive multiple reaction monitoring mode. The LOD/LOQ were determined to be 0.5 and 1.0 ng/mL, respectively for the analytes; linearity (10 to 1000 ng/mL) and (r 2 >0.999). The recovery of the analytes was found to be greater than 90%. Interday/intraday analysis was found to <8% and <10%, respectively. Matrix effects were determined to be <6%.

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Buprenorphine and naloxone co-administration in opiate-dependent patients stabilized on sublingual buprenorphine

Cited by 122 publications

References 31 publications

Self-Administration of Intravenous Buprenorphine and the Buprenorphine/Naloxone Combination by Recently Detoxified Heroin Abusers

Self-Administration of Intravenous Buprenorphine and the Buprenorphine/Naloxone Combination by Recently Detoxified Heroin Abusers

Buprenorphine with, or without, Naloxone for Pregnant Women?–Review of Current Evidence and Practice in Massachusetts

Urine analysis of buprenorphine/norbuprenorphine/ naloxone in drugs and driving cases

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