Safety profile of injectable hydromorphone and diacetylmorphine for long-term severe opioid use disorder.

AIMS: To review the safety profile of injectable hydromorphone and diacetylmorphine and explore if adverse events (AEs) or serious adverse events (SAEs) were associated with dose and patterns of attendance. METHODS: This was a non-inferiority randomized double-blind controlled trial (Vancouver, Canada) testing hydromorphone (n=100) and diacetylmorphine (n=102) for the treatment of severe opioid use disorder. Medications were delivered under the supervision of trained Registered Nurses up to three times daily. AEs were described using MedDRA codes. RESULTS: Most common related AEs included immediate post-injection reaction or injection site pruritus reactions, somnolence and opioid overdoses. Adjusted analysis indicated that participants in the hydromorphone group were less likely to have any related AE or SAE compared to the diacetylmorphine group. Related somnolence and opioid overdose events were distributed throughout the six months treatment period. In the diacetylmorphine group, five of the eleven related SAE opioid overdoses (requiring naloxone) occurred in the first 30days since most recent treatment initiation. Analysis of somnolence and opioid overdose (AEs and SAEs) event rates by received dose suggested a non-linear relationship. However, in the diacetylmorphine group higher event rates per person days were recorded at lower doses. CONCLUSIONS: When injectable hydromorphone and diacetylmorphine are individually dosed and monitored, their opioid-related side effects, including potential fatal overdoses, are safely mitigated and treated by health care providers. In the midst of an opioid overdose epidemic, injectable options are timely to reach a very important minority of people who inject street opioids and are not attracted to other treatments.

Directly observed therapy for the management of HIV-infected patients in a methadone program.

The objective of this prospective, observational clinical study was to evaluate the safety and efficacy of once-daily and twice-daily directly observed therapy (DOT) in human immunodeficiency virus (HIV)-infected patients undergoing methadone treatment. Methadone and highly active antiretroviral therapy (HAART) were dispensed daily as DOT, with patients in the twice-daily HAART group self-administering the second dose. Clinical and laboratory end points were monitored, along with the impact of ongoing cocaine use. We studied 54 patients coinfected with HIV and hepatitis C virus. At baseline, the median virus load was 111,000 copies/mL, and the median CD4+ cell count was 165 cells/mm3. After a median of 24 months, 17 of 29 patients in the once-daily HAART group and 18 of 25 in the twice-daily HAART group had virus loads of <400 copies/mL, regardless of ongoing cocaine use. Thirty-two patients required methadone dose adjustment, which was managed without modification of HAART. Treatment-limiting hepatic toxicity was rare. A DOT program of coadministered methadone and HAART can be implemented with good results, even for patients who continue to use cocaine.