Managing long-term high-dose prescription opioids in patients with non-cancer pain: The potential role of sublingual buprenorphine.

BACKGROUND: Opioids are frequently used to manage chronic non-cancer pain despite the lack of evidence of benefit and clear evidence of opioid-related harms. Patients undergoing high-dose opioid therapy are at risk of multiple complications, such as opioid toxicity, including fatal overdose and opioid dependence. OBJECTIVE: This article provides an overview of the pharmacology of buprenorphine and reviews current evidence for the use of high-dose sublingual buprenorphine-naloxone in the pharmacological management of patients at high risk of complications from chronic opioid use. DISCUSSION: Buprenorphine-naloxone is well tolerated by patients with chronic pain, and has the potential to improve pain scores and affective symptoms. This is exemplified in a case study based on these authors' experience in an addiction medicine setting. As the rates of pharmaceutical opioid prescribing and related harms continue to increase in Australia, buprenorphine-naloxone is a viable option to manage high-risk chronic pain patients who are unable to reduce or cease their opioid use.

Buprenorphine compared with methadone in opioid-dependent pregnant women: How does it affect neonatal abstinence syndrome?

BACKGROUND: The growing opioid epidemic in the United States has led to increasingly high rates of neonatal abstinence syndrome (NAS). Preliminary studies have shown that buprenorphine maintenance treatment (BMT) may lead to better outcomes for infants than methadone maintenance treatment (MMT). OBJECTIVES: The authors gathered recent evidence to answer the following PICO (population, intervention, comparison, and outcome) question: In opioid-dependent pregnant women, how does buprenorphine compared with methadone administration affect NAS? DATA SOURCES: A literature search was completed in PubMed, Scopus, Embase, and Web of Science databases and limited to the past 5 years. The following parameters were analyzed in the articles: NAS occurrence, length of hospital stay in days, NAS treatment length, and amount of pharmacotherapy administered to treat NAS. CONCLUSIONS: In comparison to methadone, buprenorphine exposure in utero is associated with significantly shorter hospital stays for the infant after delivery, shorter length of NAS treatment, and decreased frequency/duration of pharmacotherapy for NAS symptoms in the infant. IMPLICATIONS FOR PRACTICE: Based on the findings, a weak recommendation can be made for the use of BMT over MMT in opioid-dependent pregnant women. However, further research is necessary to definitively recommend buprenorphine over methadone use in this population, especially regarding the effect of maternal severity of addiction on adherence to BMT, and long-term effects of in utero buprenorphine exposure.

Availability of buprenorphine on the Internet for purchase without a prescription.

BACKGROUND: Use of illicit buprenorphine is increasingly recognized, but it is unknown if the Internet currently represents an accessible source. METHODS: A series of Internet searches were conducted. Twenty searches were performed on two different search engines. The first 100 results of each search were classified into categories based on content. All Internet pharmacies were searched for buprenorphine preparations and if available, sites were examined to determine if a prescription was required for purchase, for the cost of buprenorphine, the geographical origin of the pharmacy, and evidence of validation by an online pharmacy verification service. RESULTS: Of the 2000 links examined, 1422 were unique. Six percent of links were to illicit commercial sites, 2% were to legitimate commercial sites, and 2% were to illicit portal sites, which contained links to many illicit commercial sites. Twenty pharmacies offering buprenorphine for purchase without a prescription were identified. The monthly cost of a typical starting dose of 2 mg buprenorphine daily ranged between $232 and $1163 USD. No pharmacies were listed by online pharmacy verification services. CONCLUSION: Twenty online pharmacies advertising buprenorphine formulations for sale without a prescription were identified. Prices varied widely between illicit pharmacies but were uniformly more expensive than legitimate pharmacies. Illicitly obtained buprenorphine formulations appear to be relatively inaccessible and at high cost on the Internet.

Lack of analgesic efficacy in female rats of the commonly recommended oral dose of buprenorphine.

Previous work in our laboratory showed that the recommended oral dose of buprenorphine (0.5 mg/kg) was not as effective as the standard therapeutic subcutaneous dose for postoperative analgesia in male Long-Evans (hooded) and Sprague-Dawley (albino) rats. The aim of the current study was to extend this analysis to female rats. We measured the pain threshold in adult female rats in diestrus or proestrus before and 30 and 60 min after oral buprenorphine (0.5 mg/kg,), the standard subcutaneous dose of buprenorphine (0.05 mg/kg), or vehicle only (1 ml/kg each orally and subcutaneously). Female rats showed an increased pain threshold (analgesia) after subcutaneous buprenorphine but no change in pain threshold after either oral buprenorphine or vehicle only. Estrous cycle stage (proestrus versus diestrus) did not affect the analgesic effects of buprenorphine, but rats in proestrus showed significantly lower pain thresholds (less tolerance to pain) than did those in diestrus. These results show that the oral dose of buprenorphine recommended for postoperative analgesic care does not induce significant analgesia in female rats and therefore is not as effective as the standard subcutaneous dose.

Refractometry for quality control of anesthetic drug mixtures.

Injectable anesthetic drugs used in rodents are often mixed and further diluted to increase the convenience and accuracy of dosing. We evaluated clinical refractometry as a simple and rapid method of quality control and mixing error detection of rodent anesthetic or analgesic mixtures. Dilutions of ketamine, xylazine, acepromazine, and buprenorphine were prepared with reagent-grade water to produce at least 4 concentration levels. The refraction of each concentration then was measured with a clinical refractometer and plotted against the percentage of stock concentration. The resulting graphs were linear and could be used to determine the concentration of single-drug dilutions or to predict the refraction of drug mixtures. We conclude that refractometry can be used to assess the concentration of dilutions of single drugs and can verify the mixing accuracy of drug combinations when the components of the mixture are known and fall within the detection range of the instrument.

Treating opioid dependence. Growing implications for primary care.

Almost 3 million Americans have abused heroin. The most effective treatment for this concerning epidemic is opioid replacement therapy. Although, from a historical perspective, acceptance of this therapy has been slow, growing evidence supports its efficacy. There are 3 approved medications for opioid maintenance therapy: methadone hydrochloride, levomethadyl acetate, and buprenorphine hydrochloride. Each has unique characteristics that determine its suitability for an individual patient. Cardiac arrhythmias have been reported with methadone and levomethadyl, but not with buprenorphine. Due to concerns about cardiac risk, levomethadyl use has declined and the product may ultimately be discontinued. These recent safety concerns, specifics about opioid detoxification and maintenance, and new federal initiatives were studied. Opioid detoxification has a role in both preventing acute withdrawal and maintaining long-term abstinence. Although only a minority of eligible patients are engaged in treatment, opioid maintenance therapy appears to offer the greatest public health benefits. There is growing interest in expanding treatment into primary care, allowing opioid addiction to be managed like other chronic illnesses. This model has gained wide acceptance in Europe and is now being implemented in the United States. The recent Drug Addiction Treatment Act enables qualified physicians to treat opioid-dependent patients with buprenorphine in an office-based setting. Mainstreaming opioid addiction treatment has many advantages; its success will depend on resolution of ethical and delivery system issues as well as improved and expanded training of physicians in addiction medicine.