COVID-19 Contributes to the Broken Supply Chain of Parenteral Opioids

There has been much discussion among healthcare clinicians regarding lack and diminishing availability of opioids fueled by COVID-19 and related expansive need for these medications during the pandemic.  Joining me today are guest bloggers Doctoral candidate Bethany Brown and Dr. Batista Quevedo. Here’s what they have to share…

The COVID -19 pandemic has resulted in many changes to how healthcare is provided in order to ensure that patients continue to receive uninterrupted quality medical care. As a recent article by Bettinger et al. highlighted providers have seen themselves racing to adapt, requiring additional support to continue provide “normal” standards of care.1 While in the outpatient setting this may mean enlisting telehealth services to allow care at a distance, for many inpatient facilities they face another obstacle of a dwindling supply of opioids needed to manage patients’ pain.  Inspired by a recent editorial in the Journal of Pain Research “The United States Drug Enforcement Administration and Prescription Opioid Production Quotas: An End Game of Eradication?” we decided to take a dive into this problematic supply chain. 2

While there are various non-opioid modalities to management pain, often times opioids are required for symptom relief. Even before the pandemic resulted in a redirected supply of available opioids, institutions caring for these patients began having difficulty obtaining parenteral opioids required for effective analgesia. Prior to COVID-19, we saw qualitative and quantitative restrictions by states, pharmacies, and/or third party payers.3 Notwithstanding, recent declining availability could be in large part be due to the steady reduction of the Aggregate Production Quota (APQ) since 2017, which was started by the Drug Enforcement Administration (DEA) as a means of counteracting the prescription opioid crisis, which as Dr. Susan Nesbit has pointed out resulted in development of alternative pain management recommendations that are being explored.4 The changes to the APQ  has steadily decreased the production of both parenteral and oral opioids.2 The 2020 APQ reduced the production of five commonly prescribed opioids – oxycodone, hydrocodone, oxymorphone, hydromorphone, and fentanyl- anywhere from 9 to 55 percent.2 With the DEA announcing even more decreases in the production for 2021 and no foreseeable end to the pandemic, where does this leave patients relying on this fragile supply chain?

A quick scan of the drug shortage list published by the American Society of Health System Pharmacists reveals current shortages of parenteral fentanyl, hydromorphone, meperidine, and morphine.5   While drug manufacturers and healthcare systems have been attempting to sound the alarm on these looming shortages for years, the onset of the pandemic has resulted in a new urgency to obtain these medications. The demand for injectable opioids more than doubled in the months between January and April of this year as hospitals were faced with increased need to keep patients on ventilators much longer than usual.6 Manufacturers have been left working at maximum capacity with limited ability or allowance to increase their production, resulting in hospitals being unable to provide patients with the accepted standards care. For years, providers faced with as shortage of parenteral opioids have been forced to implement less efficacious methods. Presently, with the novel coronavirus the use of inferior substitutes only continues to grow: ranging from using paralytic agents to keep patients who are on ventilators from pulling out their tubing to crushing opioids for administration through feeding tubes, and even utilizing alternative parenteral agents such as buprenorphine and nalbuphine in attempt to control pain.7  While these agents can be effective at managing pain, some clinicians are less familiar using them which can make their use complex, especially in patients who have been receiving other opioids as buprenorphine and nalbuphine can precipitate withdrawal symptoms in opioid tolerant patients.

Unfortunately, deficiency in the supply of opioids is not a new issue, but rather an ongoing problem that is amplified with the pandemic. As early as 2018, one year after the first cuts to the APQ, healthcare facilities across the United States started to report shortages of parenteral morphine, hydromorphone, and fentanyl.7   The tightened production regulations has created serious consequences for patients and their healthcare providers. With uncertainty in supply, many facilities are turning to less reliable alternatives.6 Parenteral opioids provide hospitalized patients, who have uncontrolled pain, with quick and reliable analgesia. Reducing the production of these agents is denying safe and effective care to those suffering with pain after undergoing major surgeries or those with inadequate oral intake. Switching to using less familiar drugs increases the risk of medication errors during administration and these patients may experience a delay in the onset of analgesia or even serious adverse events as not all opioids are metabolized the same way.8 It is noteworthy that healthcare systems are now facing clinically significant pharmacokinetic drug-drug interactions resulting from Phase 1 cytochrome P450 drug interactions which we believe in many cases are not considered. Morphine, hydromorphone, and oxymorphone all undergo phase II glucuronidation and avoid the CYP450 system, resulting in lower risk of interacting with other medications.8  Frequently the patients in need of parenteral opioids have the most complex medication regimens. Inability to provide these patients with the aforementioned opioids may place them at an elevated risk for dangerous and even fatal drug interactions.

The current actions of the DEA are reflective of their mission to protect the public and uphold the enforcement of controlled substances laws and regulations.9 But, the enforcement of  restrictions during the COVID-19 crisis may be causing more harm than good. There is no evidence opioid manufacturing reductions to the APQs is helping to curb overdose rates.2 However, there is considerable evidence that faced with production restrictions, manufacturers are turning away from their less lucrative products, such as parenteral medications with long expired patents, for product formulations with higher profit margins.5 The cost to manufacture  sterile products outweighs their market value, manufacturers are forced to compete for buyers by lowering the price while still maintaining the facilities and equipment needed to complete sterile preparations. This results in manufacturers who would prefer to focus on products with greater return and less difficulty to produce, such as the fentanyl citrate nasal spray, Lazanda or oral drug formulations.6 This again, leaves providers and patients without needed parenteral opioids. Sure, the morphine milligram equivalent is being reduced across the nation, but in turn both cancer and non-cancer pain patients are left with inadequate pain control. Palliative care specialists are convinced that the current mandate is harming patients and making their already complex care more difficult. The DEA’s role is to protect the public, but are they punishing its citizens instead?

The oath of a pharmacist promises to seek justice in the distribution of health resources, to be fair, treat patients equally, and balance the needs of patients and society. 10  So what happens when the needs of society and the individual cannot be met with current supply? This is a question many pharmacy and therapeutics committees across the country wrestle with daily with blinded insight to when, or even if, their needs will be met.

As always, comments and enthusiastically welcomed!

This post is written by the authors listed below. It was reviewed and edited by Dr. Jeffrey Fudin.




Bethany Brown is a PharmD Candidate, class of 2021 at Western New England University College of Pharmacy and Health Sciences in Springfield, MA. She received her B.S. in both Biology and Chemistry from Massachusetts College of Liberal Arts in 2016. She recently completed an advanced pharmacy rotation with the interdisciplinary pain clinic at Stratton VA Medical Center, Albany, NY.




Dr. Batista Quevedo is currently completing a PGY-2 Pain and Palliative Care Pharmacy Residency at the Stratton VA Medical Center, Albany, NY. She received her PharmD from Wilkes University Nesbitt School of Pharmacy Wilkes-Barre, PA and completed a PGY-1 residency at Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA




  1. Bettinger J, Cleary J, Fudin J. COVID-19 crisis, pain therapeutics telehealth services by pharmacist clinicians fill unique void and mitigate risk [Internet]. Medicine Access@ Point of Care. 2020. Available from:
  2. Schatman ME, Wegrzyn EL. The United States Drug Enforcement Administration and Prescription Opioid Production Quotas: An End Game of Eradication? Journal of Pain Research. 2020; 13: 2629-26. Available from:
  3. Gawdat M, Gawdat M, Bettinger JJ, Cleary JH, Fudin J. Analysis of variable morphine milligram equivalent (MME) threshold trends by state. Poster: (8-223). December 5, 2018. American Society of Health-System Pharmacists (ASHP) December 5, 2018. Midyear Clinical Meeting and Exhibition in Anaheim CA. Available from:
  4. Amato Nesbit S. Clinical pharmacy roles and disparities [Internet]. Practical Pain Management. 2020: 20(3) [cited 3 Nov 2020]. Available from:
  5. Drug Shortages List [Internet]. American Society of Health System Pharmacists; 2020 [cited 25 Oct 2020]. Available from:
  6. Girion L, Levin D, Respauit R. COVID deepens the other opioid crisis – a shortage of hospital painkiller [Internet]s. Reuters healthcare & pharma. 2020 [cited 25 Oct 2020]. Available from:
  7. Bruera E. Parenteral opioid shortage – treating pain during the opioid-overdose epidemic. N Engl J. Med. 2018; 379 (7): 601-603.
  8. Smith HS. Opioid metabolism. Mayo Clinic Proc. 2009; 84(7): 613-624.
  9. Mission [Internet] United States Drug Enforcement Administration. [Cited 25 Oct 2020]. Available from:,members%20of%20organizations%2C%20involved%20in
  10. Code of Ethics [Internet]. American Pharmacists Association. 1994 [cited 25 Oct 2020]. Available from:


5 thoughts on “COVID-19 Contributes to the Broken Supply Chain of Parenteral Opioids

  1. In 2012, the Food and Drug Administration Safety and Innovation Act (FDASIA) was enacted and among its many provisions was one requiring drug manufacturers to notify the FDA “of a permanent discontinuance or interruption in the production of certain prescription drugs that are life-saving, life-sustaining, or intended for use in the prevention or treatment of a debilitating disease or condition.” As soon as FDA is notified of a potential drug shortage, a special team moves quickly to prevent the shortage. If the drug in question is a controlled substance, the FDA and DEA have streamlined a procedure for adjusting the manufacturing quota to prevent any shortages from occurring. In 2011, a year before passage of the Act, there were 251 new shortages tracked by the FDA’s CDER and CBER. In 2019, there were 51 new shortages, two of which involved working with the DEA to adjust quota allotments for the industry. Drug shortages of controlled substances may result from causes that often have nothing to do with DEA quotas. As the authors above note, manufacturers are in the business of making money and many of our more common analgesic medications are generic and have slim profit margins despite a relatively high demand. The quota regulations are required by the federal Controlled Substances Act and Congress provided ample discretion to the Attorney General (delegated to the DEA administrator) to adjust a quota at any time if and when requested by a manufacturer based on a show of market need. Since passage of the FDASIA in 2012, FDA and DEA have worked closely to prevent shortages of controlled substances but the federal government, absent a national emergency, cannot force manufacturers to produce products they choose to discontinue or reduce production of for whatever reason. Finally, one inside baseball tip: Some years ago, after DEA levied multimillion dollar fines on some major drug distributors for failing to report suspicious orders as the law requires, the distributors agreed under threat of losing their DEA registrations to adopt suspicious order monitoring programs that, in effect, cut supplies of controlled substances, mostly opioids, to pill mills and pill mill pharmacies in Florida and elsewhere. As a result, some pharmacists were telling customers with prescriptions for large amounts of controlled substances that they could no longer fill the prescriptions because DEA restricted the amount they could buy. The DEA investigated these false claims and traced them back to a distributor that had been heavily fined and, as a result, no longer was simply filling orders regardless of size or frequency. The DEA chief counsel’s office issued a stern warning to the distributor whose representatives were spreading this falsehood to their pharmacy customers. The practice was halted. In 2011, the Florida legislature enacted emergency legislation that overnight closed up about half of Florida’s estimated 1,000 pill mills. The new law also changed some minor pharmacy law violations to third class felonies. While these changes dramatically reduced opioid-related mortality in the short-term, it did not occur without depriving some legitimate patients, especially those who used the pill mills for their drugs, from being accepted as new patients by local practitioners. Likewise, when some of these patients tried to get prescriptions filled at local pharmacies, they sometimes were told the drug in question – usually an opioid – was unavailable or restricted by DEA. This situation eventually abated after about six months or a year. Faced with a possible criminal violation, some pharmacists were fearful of dispensing controlled substances to patients they didn’t know or trust. Citing DEA as the “cause” was common, although as in the case of the errant distributor, it was not the DEA but the state Department of Health cracking down on the pill mills. There are millions of stories in the naked city; occasionally some are true! 🙂

    1. John, It’s been way to long since I’ve seen you. I can’t thank you enough for this comprehensive response. I love it when you write an entire blog in a single response. Stay safe my friend!

  2. “The current actions of the DEA are reflective of their mission to protect the public and uphold the enforcement of controlled substances laws and regulations.”

    Why does the false narrative of RX Opioids being the issue persist despite overwhelming evidence to the contrary?

    It just continues, on and on, the DEA has made RX opioids nearly impossible to obtain at the expense of unprecedented overdose death rates largely due to heroin (although practically obsolete, in 2020) and largely, but still incresing– illicit fentanyls, the suffering of pain patients, some who have been driven to suicide, and severe COVID-19 pstients unfortunate enough to wake up in the ICU hooked up to a ventilator with a hard plastic endotracheal tube sitting in their throat for weeks on end without adequate iv hospital drugs.

    Which portion of the public is being protected,? I dont get it.

    Oh, and they want to FURTHER restrict access. Brilliant. I’m sure if you eliminate s substance that is not killing many the substances that are killing mawill stop killing people ‍♀️

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