CMX-020 can be delivered intravenously in a hospital setting and orally

THE OPIOID CRISIS

The use of opioids in the United States (and around the world) has created a serious condition, indeed an epidemic of opioid addiction and abuse.  According to the National Institutes of Health (NIH), over 49,068 people died in the United States from the use of opioids in 2017 (NIH, 2017).  The number of yearly overdose deaths in the United States from opioids now exceeds the yearly deaths from breast cancer (41,070 in 2016) (American Cancer Society, 2017) and are near the level of yearly deaths from HIV/AIDs at the peak of its epidemic (50,610 in 1995) (CDC, 2000). Most deaths associated with the use of opioids are caused by opioid’s adverse event of respiratory depression or apnea.  As a pain therapy, death from respiratory depression is just one of many potential adverse events associated with opioids – in addition to nausea, vomiting, itching, constipation, and addiction, which collectively hinder recovery in a hospital setting and potentially lead to dependency. 

Opioid use often starts intravenously in a hospital setting to manage acute pain associated with accidents and injuries. Intravenous opioids are used to manage severe acute pain associated with peri- or post-operative medical procedures.  For severe acute pain, the most effective pain therapies are currently intravenous opioids, including fentanyl, sufentanil, hydromorphone, meperidine, methadone, morphine, and tramadol. Opioid use may continue outside of the hospital setting with an oral or transdermal patch opioid prescription from a medical practitioner to treat residual or chronic pain at home.  Common oral opioids include: codeine, fentanyl, hydrocodone, hydromorphone, meperidine, methadone, morphine, oxycodone, propoxyphene, sufentanil, and tramadol.   Patch opioids include:  buprenorphine and fentanyl

In a hospital setting, physicians understandably have a conundrum. They know intravenous opioids are the most effective pain therapies in managing acute pain.  They understand the potential risks of respiratory depression, constipation, nausea, vomiting, and addiction. From their perspective, any adverse event associated with intravenous opioids can be generally well managed in a hospital setting.  If there were other equally effective non-narcotic intravenous options, physicians would certainly use them; indeed, opioids are commonly used with other much less effective non-narcotic pain adjuvants, commonly acetaminophen and ketorolac.  But there is currently no intravenous non-narcotic pain therapy available with the analgesic efficacy to replace opioids. 

The distribution of opioids to the masses often starts in a closely monitored hospital setting with intravenous opioids. With continuing pain management at home, oral opioids are prescribed to patients who then self-administer them unmonitored at home over longer periods of time.  Anyone who takes opioids is at risk of developing addiction and tolerance leading to drug seeking behavior. Personal history and the length of time that one uses opioids play a role, but it is impossible to predict who is vulnerable to eventual dependence, abuse, and death from opioids. 

Hospital-based opioid use is a known source of the growing opioid overdose epidemic, with studies demonstrating increased risk of chronic opioid use following low-risk surgery with intravenous opioids in both opioid-naive patients and patients with a history of drug abuse (Alam et al, 2012, Clark et al, 2014, Sun et al, 2016).

However, there is also a significant mortality rate associated with the direct use of intravenous opioids for medical procedures in hospital settings.   A study published in JAMA on May 23, 2018 (Shafi et al, 2018) identified the costs of using intravenous opioids in a hospital setting for endoscopic procedures.  In this study, opioid-related adverse drug events (ORADEs) were common after endoscopic procedures and were associated with significantly worse clinical and cost outcomes, including:   

  • Opioid medications increased risk adjusted mortality by 2.9%
  • Opioid medications increased costs by over $8,000
  • Opioid medications increased hospital stays by 1.6 days

There was a total of 135,379 patients included in this study.  Of these, approximately 88% received opioids, 14,386 patients (10.6%) experienced at least one ORADE, and of those patients, a total of 747 patients died.  More than 7.3 million patients undergo inpatient surgical and endoscopic procedures in the United States each year (Steiner et al, 2014).  With 7.3 million patients, assuming 10.6% of patients experience ORADEs and 2.9% risk-adjusted mortality percentage from ORADEs, we estimate that over 22,000 patients die every year in hospitals from the direct use of intravenous opioids in surgical and endoscopic procedures.

Conclusion:  The epidemic death rates from opioid use in the United States is a serious condition that starts with intravenous opioid use that begins in a hospital setting and directly kills an estimated 22,000 people yearly.  Opioid use begins in hospitals, expands through use with prescription opioids, and often culminates with opioid addiction and drug seeking.  Yearly overdose deaths from opioids were 49,068 in 2017. The use of intravenous opioids in hospitals is a serious condition that has an unmet medical need in the United States. The ideal solution is a non-narcotic intravenous pain therapy that produces the analgesic levels of opioids.  With the recently completed maximum tolerated dose (MTD) clinical study of intravenous CMX-020, CMX-020 shows potential to replace intravenous opioids by matching the highest analgesic levels of intravenous remifentanil.

Author:  Lane Brostrom, CEO
January 2019

REFERENCES

  1. Alam, Asim, et al. “Long-term analgesic use after low-risk surgery: a retrospective cohort study.” Archives of Internal Medicine 172.5 (2012): 425-430.
  2. American Cancer Society, 2017 Breast Cancer Death Rates available at: https://www.beaumont.org/conditions/breast-cancer, accessed October 23, 2018.
  3. Center for Disease and Control, HIV/AIDS surveillance report, 2000;12(no. 1), HIV/AIDS Death Rate in 1995 (Table 27), available at: https://www.cdc.gov/hiv/pdf/library/reports/surveillance/cdc-hiv-surveillance-report-2000-vol-12-1.pdf., accessed October 23, 2018.
  4. Clarke, Hance, et al. “Rates and risk factors for prolonged opioid use after major surgery: population based cohort study.” BMJ 348 (2014): g1251.
  5. Shafi, Shahid, et al. “Association of Opioid-Related Adverse Drug Events With Clinical and Cost Outcomes Among Surgical Patients in a Large Integrated Health Care Delivery System.” JAMA surgery (2018).
  6. Steiner, C. A., et al. “Surgeries in Hospital-Based Ambulatory Surgery and Hospital Inpatient Settings, 2014: Statistical Brief # 223.” Available at: https://www.hcup-us.ahrq.gov/reports/statbriefs/sb223-Ambulatory-Inpatient-Surgeries-2014.jsp .
  7. Sun, Eric C., et al. “Incidence of and risk factors for chronic opioid use among opioid-naive patients in the postoperative period.” JAMA Internal Medicine 176.9 (2016): 1286-1293.

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