Prescription Opioids: Risk Management and Strategies for Safe Use _ _________________________________ Methadone Therapy
the naloxone is activated to produce withdrawal symptoms. Buprenorphine occupies 85% to 92% of brain mu opioid receptors at 16 mg/day dosing and 94% to 98% at 32 mg/day. Daily doses of 4–16 mg are typically effective for most patients, with 16–24 mg the upper limit of recommended dosing [99; 188; 189]. Prior to January 2023, clinicians had to apply for a federally required Drug Addiction Treat- ment Act (DATA) Waiver (X-Waiver) in order to prescribe medications, like buprenorphine, for the treatment of opioid use disorder. Section 1262 of the Consolidated Appropriations Act of 2023 (also known as Omnibus bill) removed this requirement and allowed clinicians with schedule III authority on their DEA registration to prescribe buprenorphine if permitted by applicable state law [99; 190]. Several pharmacologic aspects of buprenorphine contribute to its safety and effectiveness as therapy for opioid addiction and make it highly suitable for use in primary care [191]. As a partial mu agonist, a ceiling effect exists for its maximal activity—beyond a certain dose, no additional benefit is experienced. In contrast to increases in the dose of pure opioid agonists such as methadone, a greater margin of safety exists from death by respiratory depression. Buprenorphine possesses a short plasma half-life (about four to six hours) and a long duration of action resulting from its high affinity for and slow dissociation from the mu opioid receptor [187]. This slow dissociation likely contributes to a reduction in the severity of withdrawal symptoms during detoxifi- cation, and the longer duration of action allows for the potential of alternate-day dosing [192]. Methadone and Buprenorphine Efficacy The efficacy literature indicates that higher-dose methadone (>50 mg daily, and 60–100 mg per day in particular) is more effective than lower doses in reducing illicit opioid and possibly cocaine use [193]. Higher-dose methadone is comparable to higher- dose buprenorphine (≥8 mg daily) on measures of treatment retention and reduction of illicit opioid use [193]. Although 30–60 mg per day of methadone may be effective in resolving opioid withdrawal symptoms, some patients require a maintenance dose ≥120 mg per day to eliminate illicit opioid use
Methadone has been in clinical use since 1965 as a treatment for opioid addiction. Its use is based on the principle that a long-acting mu opioid agonist at a sufficient dose prevents opioid withdrawal, blocks the desired effects if other opioid drugs are abused, and diminishes the craving for opioids [185]. A network of opioid treatment program regulatory and dispensing systems has been implemented to dispense methadone for opioid addiction, where the patient is administered methadone once a day under staff observation. Some stabilized patients are allowed up to a 30-day supply of take-home methadone, depending on their length of mainte- nance and compliance with other opioid treatment program rules. However, for some opioid-dependent persons, this system is not feasible due to lack of proximity to an opioid treatment program, a sched- ule that conflicts with that of an opioid treatment program, or concerns related to the social stigma associated with methadone [186]. Although the appropriate maintenance dose should be tailored to the individual on the basis of genetics and opioid use history, daily doses of 80–120 mg are common and are more likely to produce the desired opioid-blockade effect. Data indicate a greater reduc- tion in illicit opioid use from a daily dose of 80–100 mg than from a dose of 40–60 mg [183; 186]. A potential issue with methadone relates to its metabolism by the hepatic cytochrome P450 CYP3A4 enzyme and the numerous medications that may adversely interact with its metabolism to result in elevation of plasma methadone level or rapid elimination of the drug. This can lead to dan- gerous toxicity or lack of effectiveness, respectively [99; 183]. Buprenorphine Therapy Buprenorphine was the first drug approved for treat- ment of opioid addiction that can be prescribed in an office-based setting [187]. For use in opioid addiction therapy, buprenorphine is formulated into a product combined with the opioid antagonist nal- oxone and administered sublingually. When taken as prescribed, the naloxone component remains inert, but if the formulation is crushed and injected,
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