Oxymorphone

Oxymorphone is contraindicated in patients with significant respiratory depression in unmonitored settings. MOR activation in brainstem respiratory centers reduces respiratory drive in a dose-dependent manner; patients with baseline respiratory compromise face amplified risk of fatal respiratory arrest.

Contraindicated in acute or severe bronchial asthma in unmonitored settings. Patients with compromised baseline respiratory function are at substantially increased risk of fatal respiratory depression when MOR agonist effects are superimposed.

Oxymorphone has high abuse liability confirmed by human laboratory data (abuse-related subjective ratings equivalent to oxycodone 40 mg at equi-dose) and epidemiological surveillance (RR 2.91 for abuse increase post-OxyContin reformulation). The Scott County HIV outbreak demonstrates extreme compulsive use patterns. Individuals with a history of substance use disorder are at substantially elevated risk.

Hepatic impairment may increase oxymorphone exposure due to reduced glucuronidation capacity. Dose adjustment is likely required, though no specific pharmacokinetic studies in hepatic impairment populations have been published.

Renal impairment reduces clearance of glucuronide metabolites. Dose adjustment is likely required, particularly given the additional risk of TMA/AKI documented with IV formulation abuse. No specific pharmacokinetic studies in renal impairment populations have been published.

Contraindicated in patients with known hypersensitivity to oxymorphone hydrochloride or any component of the formulation. Allergic reactions including anaphylaxis may occur.

Contraindicated in known or suspected GI obstruction including paralytic ileus. Oxymorphone reduces gastrointestinal motility via enteric MOR activation, which can precipitate or worsen bowel obstruction with potentially life-threatening consequences.

Ethanol co-ingestion increases peak plasma concentration of oxymorphone by 14–80% without proportional change in total exposure, accelerating onset and increasing respiratory depression risk. Independent pharmacodynamic CNS depression compounds this effect. All documented oxymorphone fatalities involved co-intoxicants including alcohol.

Concurrent use of benzodiazepines, other opioids, GHB/GBL, or sedative-hypnotics with oxymorphone produces additive to synergistic respiratory depression. Postmortem case data (Vorce 2010) document fatal oxymorphone-alprazolam combination at oxymorphone blood concentration of 0.13 mg/L.