oxymorphone and Thrombotic-Microangiopathies

We describe the case of a 35-year-old man presenting with thrombotic microangiopathy (TMA) and renal impairment following, as he later disclosed, intravenous injection of oral formulation tamper-resistant extended-release oxycodone hydrochloride (Oxycontin). Recurrent misuse of this agent was associated with relapsing TMA despite treatment with terminal complement inhibitor eculizumab. Cases of TMA have been reported in the USA in association with intravenous misuse of extended-release oxymorphone (Opana ER) after the introduction of a new non-crushable formulation in 2012. There are two reported accounts of TMA associated with tamper-resistant Oxycontin, which became available in Australia in 2014. This is the first documented case in which eculizumab was used. This case illustrates the practical diagnostic challenges in identifying TMA disorders, and the importance of a detailed drug history. It also highlights the need to clarify what role, if any, eculizumab therapy has in cases of drug-associated TMA.

Topics: Adult; Analgesics, Opioid; Antibodies, Monoclonal, Humanized; Complement Inactivating Agents; Delayed-Action Preparations; Humans; Injections, Intravenous; Male; Opioid-Related Disorders; Oxycodone; Oxymorphone; Renal Insufficiency; Substance Abuse, Intravenous; Thrombotic Microangiopathies

Since 2012, a number of case reports have described the occurrence of thrombotic microangiopathy (TMA) following IV abuse of extended-release oxymorphone hydrochloride (Opana ER), an oral opioid for long-term treatment of chronic pain. Here, we present unique clinical features of 3 patients and investigate IV exposure to the tablet's inert ingredients as a possible causal mechanism. Guinea pigs were used as an animal model to understand the hematopathologic and nephrotoxic potential of the inert ingredient mixture (termed here as PEO+) which primarily contains high-molecular-weight polyethylene oxide (HMW PEO). Microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury were found in a group of 3 patients following recent injection of adulterated extended-release oxymorphone tablets. Varying degrees of cardiac involvement and retinal ischemia occurred, with TMA evident on kidney biopsy. A TMA-like state also developed in guinea pigs IV administered PEO+. Acute tubular and glomerular renal injury was accompanied by nonheme iron deposition and hypoxia-inducible factor-1α upregulation in the renal cortex. Similar outcomes were observed following dosing with HMW PEO alone. IV exposure to the inert ingredients in reformulated extended-release oxymorphone can elicit TMA. Although prescription opioid abuse shows geographic variation, all physicians should be highly inquisitive of IV drug abuse when presented with cases of TMA.

Topics: Acute Kidney Injury; Analgesics, Opioid; Animals; Delayed-Action Preparations; Female; Guinea Pigs; Humans; Kidney; Male; Oxymorphone; Polyethylene Glycols; Thrombotic Microangiopathies

Topics: Analgesics, Opioid; Humans; Oxymorphone; Purpura, Thrombotic Thrombocytopenic; Thrombotic Microangiopathies

There have been recent reports and warnings of a thrombotic thrombocytopenic purpura-like illness associated with intravenous abuse of a prescription narcotic intended for oral use. Oral extended-release oxymorphone hydrochloride (Opana ER) is an opioid agonist that has undergone a tamper-resistant reformulation. However, instances of melting and dissolving tablets with subsequent injection continue to occur. We report 3 cases of hemolytic anemia and acute kidney injury associated with intravenous abuse of this reformulated drug. All 3 patients underwent native kidney biopsy that showed thrombotic microangiopathy characterized by severe arterial and arteriolar mucoid intimal edema with resultant glomerular and tubular ischemia. All 3 patients required hemodialysis and 2 also underwent therapeutic plasma exchange. Early follow-up suggests that kidney outcome is poor, with only partial recovery of function despite aggressive treatment. The specific component or components of this reformulated drug associated with endothelial injury is unknown. Most importantly, a high degree of clinical suspicion is needed when treating patients with a thrombotic thrombocytopenic purpura-like illness of unknown cause.

Topics: Acute Kidney Injury; Adult; Delayed-Action Preparations; Female; Humans; Kidney; Male; Oxymorphone; Plasma Exchange; Substance Abuse, Intravenous; Thrombotic Microangiopathies; Young Adult

We report the case of a 22 year-old-woman who presented with upper extremity cellulitis secondary to an infiltration of illicit intravenous drug use. She confessed to the intravenous use of Opana ER (an extended release oral formulation of oxymorphone) which is an opioid drug approved only for oral use. She was found to have clinical evidence of profound thrombotic microangiopathy which resulted due to the intravenous use of Opana ER. She showed full clinical improvement after withholding drug and supportive clinical care. Recent report of Opana ER intravenous abuse was published from Tennessee county and has now been increasingly recognised as one of the causes of thrombocytopenia which mimicks clinically as thrombotic thrombocytopenic purpura. Physicians should be aware of this association as the lack of familiarity to this can pose serious management dilemmas for our patients (especially the polysubstance abusers).

Topics: Analgesics, Opioid; Female; Humans; Opioid-Related Disorders; Oxymorphone; Purpura, Thrombotic Thrombocytopenic; Substance Abuse, Intravenous; Thrombotic Microangiopathies; Young Adult

In January 2013, the Centers for Disease Control and Prevention reported an illness associated with intravenous (IV) abuse of oral Opana ER (oxymorphone) in Tennessee. The clinical presentation of this syndrome was reported to resemble that of thrombotic thrombocytopenic purpura in the 15 patients reported; 12 were treated with plasma exchange. We report a similar case series of 15 patients with 18 episodes of thrombotic microangiopathy associated with recent IV abuse of oral Opana ER. In our series, we demonstrate that therapeutic plasma exchange is unnecessary; supportive care and treatment of underlying infections and renal dysfunction (without use of plasma exchange) resulted in clinical improvement in all patients. Thus, it appears that plasma exchange with associated costs and risks can be safely omitted in patients with thrombotic microangiopathy resulting from IV abuse of oral Opana ER.

Topics: Adult; Diagnosis, Differential; Female; Humans; Male; Middle Aged; Oxymorphone; Plasma Exchange; Purpura, Thrombotic Thrombocytopenic; Substance Abuse, Intravenous; Thrombotic Microangiopathies; Treatment Outcome; Young Adult