Indicators of Buprenorphine and Methadone Use and Abuse: What Do We Know?

Abstract

Abuse of prescription opioids is a growing problem. The number of methadone pain pills distributed now exceeds liquid methadone used in opioid treatment, and the increases in buprenorphine indicators provide evidence of the need to monitor and intervene to decrease the abuse of this drug. The need for additional and improved data to track trends is discussed, along with findings as to the characteristics of the users and combinations of drugs. Data on toxicities related to methadone or buprenorphine, particularly in combination with other prescribed drugs, are presented and clinical implications and considerations are offered. These findings underscore the need for physicians to be aware of potential toxicities and to educate their patients regarding these issues.

Management of opioid use disorders: a national clinical practice guideline

“…• Health Canada exemption is not required to prescribe buprenorphine-naloxone in most provinces and territories (Appendix 1) • Lower risk of overdose due to partial agonist properties and ceiling effect for respiratory depression (in the absence of benzodiazepines or alcohol) 19,24,25 • Lower risk of public safety harms if diverted 26,27 • Milder adverse effect profile 22,23 • Easier to transition from buprenorphine-naloxone to methadone if treatment is unsuccessful 22,23 • Shorter time to achieve therapeutic dose (1-3 d) [28][29][30] • Lower risk of toxicity and drug-drug interactions 31 • Milder withdrawal symptoms when discontinuing treatment; may be a better option for individuals with lower-intensity opioid dependence (e.g., oral opioid dependence, infrequent or no injection use, short history of opioid use disorder), and individuals planning to taper off opioid agonist treatment in a relatively short period 22,23 • Optimal for rural and remote locations where access to care is limited, methadone prescribers are lacking, or daily witnessed ingestion at a pharmacy is not feasible • More flexible dosing schedules (e.g., alternate-day dosing, earlier provision of 1-to 2-week take-home prescriptions, and unobserved home inductions) support patient autonomy and can reduce costs [32][33][34][35] • Easier to adjust and retitrate following missed doses, owing to its partial agonist properties…”

“…• Health Canada exemption is required to prescribe methadone in all provinces and territories • Higher risk of overdose 19,24,25,36 • More often prescribed as witnessed doses; prescription of take-home doses typically use slow graduated schedule (e.g., increase of 1 takehome dose per week about every 4 weeks), which can be inconvenient or not feasible for some patients • More severe adverse effect profile (e.g., somnolence, erectile dysfunction, cognitive blunting) 22,23 • Longer time to achieve therapeutic dose (several weeks) 36 • Can be more challenging to transition from methadone to buprenorphine-naloxone if treatment is unsuccessful 22,23 • Higher risk of public safety harms if diverted 26,27 • Higher potential for adverse drug-drug interactions (e.g., antibiotics, antidepressants, antiretrovirals) 31 • Associated with QTc prolongation and increased risk of cardiac arrhythmia in patients prescribed higher doses, with pre-existing risk factors or taking other medication(s) that prolong QTc interval 22,23 • Can be more expensive if prescribed as daily witnessed doses, mainly owing to fees associated with dispensing and witnessed ingestion 34,35 • Potentially lower treatment retention, particularly in higherintensity opioid use disorder with low-dose buprenorphinenaloxone 18 • May cause precipitated withdrawal if appropriate dose-induction protocols are not followed 30 • Suppression of withdrawal symptoms may be inadequate for individuals with high opioid tolerance 22,23 • Reversing effects of overdose can be challenging because of the pharmacology of buprenorphine (i.e., high affinity for opioid receptors and long half-life) 31 • Patients require education on how to take sublingual doses correctly (i.e., hold under tongue until dissolved -up to 10 minutes; do not drink or smoke, and minimize swallowing) • Nonadherence to treatment may require frequent reinductions Note: QTc = corrected QT.…”

Pharmacokinetics of Sublingual Buprenorphine and Naloxone in Subjects with Mild to Severe Hepatic Impairment (Child-Pugh Classes A, B, and C), in Hepatitis C Virus-Seropositive Subjects, and in Healthy Volunteers

“…However, when administered sublingually, naloxone is poorly absorbed and consequently has no or minimal pharmacological effects [8,9]. Buprenorphine/naloxone is also commonly used for treatment of chronic pain [10,11].…”

Methadone: Uses, Abuses, and Metabolism

“…Methadone can be abused and diverted just as any other opioid medication, and with the growing use of methadone for pain, growing numbers of overdoses have been observed with methadone [ 8 ]. For any chronic opioid therapy patient, but particularly one with red fl ags such as psychiatric illness or substance abuse history, it is essential to follow best practices in pain management.…”