Article, Emergency Medicine

Resurgence of intravenous Opana as a cause of secondary thrombotic thrombocytopenic purpura

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American Journal of Emergency Medicine

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Resurgence of intravenous Opana as a cause of secondary thrombotic thrombocytopenic purpura?,??

Abstract

Opana or oxymorphone is a drug introduced into the American market in 1955 by Endo Pharmaceuticals. Soon after, oxymorphone became a popular drug of abuse by easily changing the route of administration from oral to intravenous (IV), therefore increasing bioavailability tenfold. In 1972, the formulation was changed rendering the process of conversion time intensive. Oxymorphone fell out of use and was quickly replaced by oxycodone and later oxycontin as it was easier to obtain and convert to an injectable form for recreation. In 2010, the manufacturer of oxycodone and oxycontin, Perdue Pharma LP, changed the formulation of their drug to become crush resistant, rendering it unfit for IV use to deter misuse1. This led to a resurgence of interest in Opana by the recreational drug community, now with newer techniques to overcome its safety barriers put forth 40 years back. IV use of Opana has been shown be to be a secondary cause of thrombotic thrombocytopenic purpura (TTP) as several cases in the past few years have indicate. We present a case of 37-year-old patient presenting with a constellation of clinical and lab abnormalities with history of IV Opana use and no other identifiable cause of TTP. This patient was successfully treated with plasmapheresis. Hence, we want to report this case to increase awareness among the medical community (1) to advise patients being prescribed Opana about the risks involved if abused intravenously and

(2) recognize Opana IV use as a possible cause of TTP when encountered in the inpatient setting.

Opana, Numorphan, Numorphone (registered trade names), or oxymorphone became a popular drug of abuse by changing the route of administration from oral to intravenous (IV), increasing bioavail- ability 10-fold. Oxymorphone was quickly replaced by oxycodone and later oxycontin as it was easier to obtain and convert to an injectable form for recreation. In 2010, the formulation of oxycontin was changed to become crush resistant, rendering it unfit for IV use to deter misuse [1]. This led to a resurgence of interest in Opana by the recreational drug community. Recently, Opana has been linked to cases of thrombotic thrombocytopenic purpura (TTP) [2]. TTP classically includes thrombocytopenia, fever, AKI, microangiopathic hemolytic anemia and neurologic symptoms manifesting as altered mental status, hallucinations, stroke, or headache [3].

A 37-year-old female presented with complaints of a severe, constant, non-radiating, stabbing pain in the chest, back and abdomen, worse on inspiration that had been ongoing for the last

? Funding source: None.

?? Conflicts of interest: Meghan Rane: None. Aakash Aggarwal: None. Emerald Banas: None. Amit Sharma: None.

6 hours. Social history revealed IV Opana use. Within the hour she became disoriented and oxygen saturation, initially 95%, rapidly fell with increasing tachypnea; eventually the patient was intubated. On physical examination, she was febrile at 38.5?C with a blood pressure of 142/108 mmHg, equal in both arms, tachycardic at 139 beats per minute, and tachypneic at 36 breaths per minute with 95% oxygen saturation on room air. Her pupils were dilated and urine was red tinged but without any sediment. Labs included WBC-16.4×10 [3] cells/mL, Hb-6.4 g/dL, platelets 13×10 [3], BUN 33 mg/dL, creatinine

1.7 mg/dL, indirect bilirubin of 2 mg/dL and a low bicarbonate with an anion gap of 25. ABG showed metabolic acidosis with well compensated PCO2 and hypoxemia. Lactic acid was 7.7 mEq/L, lactic dehydrogenase N 4000 IU/L, and drug screen positive for opiates only. Electrocardiogram showed sinus tachycardia and chest radiograph was clear. ADAMTS13 was within normal limits. Given the clinical picture, and history of IV Opana a diagnosis of secondary TTP due to IV Opana was made, and the patient was treated with plasmapheresis with return to baseline state of health in 1 week. The diagnosis, was one of exclusion since Detailed history did not reveal any other cause of TTP (eg, other drugs, infections, pregnancy, etc.) other than Opana.

Unlike in the past, the classic pentad of TTP is rarely seen and it has transitioned from a deadly illness to a treatable entity. With treatment plasma exchange, mortality is estimated to be reduced to less than 29% [4]. Criteria for TTP do not have to be met to diagnose this disorder, if there is a high index of suspicion. Here history of intravenous injection of Opana and drug screen positive for only opiates helped in clinching the diagnosis.

TTP is a rare disorder with reported incidence of 11/1,000,000 persons [5].TTP can be divided into primary where ADAMTS13 activity is suppressed by antibodies (congenital TTP or Upshaw-Schulman syndrome) [6] or secondary where the ADAMSTS13 activity is normal. Etiologies for secondary TTP are pretty varied and include various drugs, infections etc.

Amongst the drugs classically implicated are anti-platelet agents, immunosuppressants, and dose dependent toxicity of chemotherapy, and they are thought to invoke direct endothelial damage causing auto-cycling thrombus formation. Quinine is actually thought to cause TTP via an antibody mechanism. Various infections may also trigger TTP. The most common is enterohemorrhagic Escherichia coli infection due to Shiga Toxin (O157:H7), while other infections like HIV and pneumococcal infection have also been implicated rarely. TTP is often a multifactorial disease and can occur or re-occur after Systemic conditions like pregnancy, surgery or pancreatitis. Also sometimes other autoimmune disorders like SLE can mimic TTP.

In 2012, 15 cases of TTP like illness were identified in Tennessee among IV Drug users [7] (of which 14 of them admitted to use of

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reformulated Opana intravenously). The sudden emergence of drug induced TTP is due to Intravenous use of oral Opana ER (oxymor- phone) which gained popularity in 2010. Opana is meant to be used orally only. The euphoric action of Opana can be produced by crushing, dissolving, and injecting the medication intravenously, thus producing a rapid high rather than sustained oral absorption. The side effects of IV Opana ER include hypotension, apnea, cardiac arrest and TTP like illness. TTP has been shown to occur with Opana abuse when injected intravenously and Food and Drug Administration has warned against use of this drug intravenously [8].

It is important to understand that physicians are distributing this drug as insurance companies are no longer paying for oxycontin, and Opana is just as powerful in pain control. It is therefore very important to make patients aware regarding serious adverse events in case Opana ER is used via non-indicated route of administration. Also, IV drug abuse with Opana should be suspected in patients presenting with TTP like illness of unknown cause.

Meghan Rane, MB, BS Aakash Aggarwal, MB, BS Emerald Banas, MD

Amit Sharma, MB, BS, MPH

Internal Medicine, SUNY Upstate Medical University, Syracuse, NY

E-mail address: [email protected] http://dx.doi.org/10.1016/j.ajem.2014.01.058

References

  1. FDA Approves New Formulation for OxyContin. http://www.fda.gov/newsevents/ newsroom/PressAnnouncements/ucm207480.htm.
  2. Cluster of Cases of Thrombotic Thrombocytopenic Purpura (TTP) Associated with Intravenous Nonmedical Use of Opana ER(R). http://www.bt.cdc.gov/han/ han00331.asp.
  3. Amorosi E, Ultmann J. Thrombotic thrombocytopenic purpura: report of 16 cases and review of the literature. Medicine 1966;45:139.
  4. Rock GA, Shumak KH, Buskard NA, et al. Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura. Canadian Apheresis Study Group. N Engl J Med 1991;325:393.
  5. Moake JL. Thrombotic microangiopathies. N Engl J Med 2002;347(8):589-600.
  6. Levy GG, Nichols WC, Lian EC, et al. Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura. Nature 2001;413:488.
  7. Marder E, Kirschke D, Robbins D, Dunn J, Jones T, Racoosin J, Paulozzi L, Chang A. Thrombotic Thrombocytopenic purpura (TTP)-like illness associated with intra- venous opana ER abuse Tennessee, 2012. MMWR Morb Mortal Wkly Rep 2013;62 (1):1-4.
  8. U.S. Food and Drug 7.Administration. FDA warns about serious blood disorder resulting from misuse of Opana(R) ER. U.S. Department of Health & Human Services. Available at: http://www.fda.gov/drugs/drugsafety/ucm322432.htm.

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