Table 7. FDA-approved medications for OUD 147
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) Methadone Methadone is a synthetic, long-acting opioid agonist that fully activates mu-opioid receptors in the brain. 148 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 Buprenorphine Buprenorphine is a high-affinity partial opioid agonist at the mu-opioid receptor as well as an antagonist of the kappa opioid receptor. 153 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 simultaneous with buprenorphine. Buprenorphine’s partial agonist status also translates into a lower risk of respiratory depression compared to methadone and other opioids, 148 and a therapeutic dose may be achieved within a few days. 155 Buprenorphine is available as sublingual tablets, sublingual/buccal films, subdermal implants, or extended-release subcutaneous injection (Table 10). 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. “Buprenorphine treatment provides one of the rare opportunities in primary care to see dramatic clinical improvement: it’s hard to imagine a more satisfying clinical experience than helping a patient escape the cycle of active addiction.” --Wakeman et al. NEJM 2018;379(1):1-4
in the first two weeks of methadone treatment, 149 after which risk is significantly lower compared to people who are not in treatment. 150,151 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. 152 The other potential harms of methadone include hypogonadism, which is a potential side effect of chronic use of any opioid, and QTc segment prolongation. 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. 141 Thus, a patient must be in mild to moderate withdrawal prior to initiation to avoid precipitating withdrawal. The risk of opioid overdose declines immediately when patients with OUD initiate buprenorphine treatment. 145 The risk of hypogonadism is lower with buprenorphine compared to methadone, and buprenorphine is not associated with QTc prolongation or cardiac arrhythmias. 157 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. For example, a randomized trial comparing buprenorphine implant to sublingual buprenorphine found higher levels of negative urine screens and abstinence with the implant, but the differences did not reach statistical significance. 158
Page 26
Book Code: MDAZ1124
Powered by FlippingBook