Effective Management of Acute and Chronic Pain with Opioid Analgesics, 2nd Edition _ ________________
MEDICATIONS TO TREAT OUD The FDA has approved three medications for treating OUD: buprenorphine, methadone, and extended-release naltrexone (Table 5). Buprenorphine and methadone can reduce opioid cravings, and all three can prevent misuse. Each medication has a unique mechanism of action and involves different formulations, methods of induction and maintenance, patterns of administration, and regulatory requirements. METHADONE Methadone is a synthetic, long-acting opioid agonist that fully activates mu-opioid receptors in the brain. This activity reduces the unpleasant/dysphoric symptoms of opioid withdrawal, and, at therapeutic doses, it blunts the “highs” of shorter-acting opioids such as heroin, codeine, and oxycodone. Patients do not have to experience opioid withdrawal before starting methadone. It may, however, take days to weeks to achieve a therapeutic dose, which requires individualized monitoring in order to minimize cravings and reduce the risk of relapse. As a full agonist, methadone sustains opioid tolerance and physical dependence; thus missing doses may precipitate opioid withdrawal. Overdose risk is highest when beginning methadone treatment, after which risk is significantly lower compared to people who are not in treatment [67; 68]. Common side effects of methadone are constipation, vomiting, sweating, dizziness, and sedation. Although respiratory depression can be induced by methadone, the FDA advises that methadone not be withheld from patients taking benzodiazepines or other central nervous system depressants because the risk of overdose is even higher among patients not on methadone for OUD [68]. The other potential harms of methadone include hypogonadism, which is a potential side effect of chronic use of any opioid, and QTc segment prolongation.
BUPRENORPHINE Buprenorphine is a high-affinity partial opioid agonist at the mu-opioid receptor as well as an antagonist of the kappa opioid receptor. Like methadone, buprenorphine can relieve opioid withdrawal symptoms, and, because of its partial agonist effect, it can reduce the rewarding effect of other opioids used simultaneously with buprenorphine. Buprenorphine’s partial agonist status also translates into a lower risk of respiratory depression compared to methadone and other opioids. Buprenorphine is available as sublingual tablets, sublingual/ buccal films, subdermal implants, or extended-release subcutaneous injection. Some film and tablet formulations are combined with the opioid antagonist naloxone to discourage misuse by crushing and injecting the medication. (A buprenorphine-only patch [Butrans] is only FDA-approved as an analgesic.) Some forms of buprenorphine can be self- administered by patients after filling their prescription at regular pharmacies. As with methadone, buprenorphine sustains opioid tolerance and physical dependence in patients, so discontinuation can lead to withdrawal (although buprenorphine’s withdrawal syndrome may be less severe). The most common side effects are constipation, vomiting, headache, sweating, insomnia, and blurred vision. One risk of buprenorphine (as well as naltrexone) is the risk of precipitating opioid withdrawal at first dose if the patient has recently used either prescription or illicit drugs, due to buprenorphine’s partial-agonist properties high binding affinity for the opioid receptor. Thus, a patient must be in mild to moderate withdrawal prior to initiation to avoid precipitating withdrawal. Buprenorphine is not associated with QTc prolongation or cardiac arrhythmias. The various non-oral routes of buprenorphine avoid the significant hepatic metabolism inherent with oral administration and appear to be largely equivalent in their efficacy for maintaining abstinence and reducing risk of overdose.
FDA-APPROVED MEDICATIONS FOR OUD
Buprenorphine • Buprenorphine/naloxone buccal film (Bunavail)
• Buprenorphine/naloxone sublingual film (Suboxone, generics) • Buprenorphine/naloxone sublingual tablets (Zubsolv, generics) • Buprenorphine sublingual tablets (generics) • Buprenorphine subdermal implant (Probuphine) • Buprenorphine extended-release subcutaneous injection (Sublocade) Methadone
• Tablets (Dolophine, MethaDose, generics) • Oral concentrate (MethaDose, generics) Naltrexone extended-release injection (Vivitrol)
Table 5
18
MDUT1125
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