By Victoria Houghton, managing editor

A patient taking a blood thinner is unable to have a suspicious skin lesion biopsied. A skin cancer patient’s surgery is delayed indefinitely. Why? Lidocaine with epinephrine is in shortage and these procedures are simply too risky to perform without it.

Unfortunately, these scenarios are not all that uncommon in physicians’ offices across the country, as lidocaine with epinephrine is only available in limited quantities and in some cases has been on back order for months. Indeed, the issue of drug shortages in the United States has been an escalating challenge for dermatologists. “Drug shortages remain an ongoing public health concern in the United States,” said dermatologist Jack Resneck Jr., MD, chair of the American Medical Association’s Board of Trustees. “Over the last few years, shortages of injectable lidocaine (with and without epinephrine) and of sodium bicarbonate for buffering lidocaine have been the most noticeable for dermatologists. We’ve also seen shortages of injectable methotrexate, mupirocin ointment, sterile water for diluting medications, injectable bleomycin, and oral chloroquine.” As a result, “These shortages have an incredible impact on quality of patient care and safety of patient care,” said CDR Josephine Nguyen, MD, chair of the Academy’s Regulatory Policy Committee.

With so much at stake for patients, Dermatology World talks with experts about the effects these shortages have on patient care, the reasons behind the shortages, and what’s being done to put an end to the drought. 

The effects

For physicians who perform the more than 100 diagnostic, reconstructive, and other therapeutic procedures that utilize lidocaine with epinephrine, this shortage is undeniably a problem. “The lidocaine with epinephrine shortage is truly a patient safety issue,” said Ashley John, the American Academy of Dermatology Association’s (AADA) senior specialist of advocacy and policy. Without it, “There is a risk of increased bleeding at the surgical site and potential post-operative complications.”

For Joerg Albrecht, MD, chair of the Academy’s Drug Pricing and Transparency Task Force, these shortages, particularly sodium bicarbonate, often put him and his colleagues at Chicago’s Cook County Health and Hospital Systems in a bind. “As dermatologists we are usually in the privileged position that our patients do not die of their skin disease due to drug shortages. However, this is different for inpatient care. For cancer treatments, our preferred regimen may just not be available. We have also seen dramatic shortages of normal saline, and currently, IV morphine.”

As a result of the current dermatologic drug shortages, in 2017, the AADA’s Drug Pricing Task Force recommended potential alternatives to lidocaine that include bupivacaine and ropivacaine. While these alternatives may not pose major safety issues, the lack of epinephrine may not offer clinically significant vasoconstriction/hemostasis to limit blood loss. Additionally, the hit to patients’ wallets can be painful. The task force warned that these alternatives may be cost prohibitive.

Similarly, when a drug does come back from shortage, a new access challenge may materialize. “Usually shortages make drugs more expensive,” said Dr. Albrecht. “It can normalize, but often remains higher than it used to be for a long period of time.” Dr. Albrecht recalls that clobetasol was once in limited supply and when it was widely available again, the price changed drastically. “The shortage of clobetasol led to price increases where tube prices reached $500 — up from about $50 — that put the drug out of reach for many patients.” Fortunately, with the current shortage of sodium bicarbonate and lidocaine with epinephrine, “While physicians have called the AADA with concerns about this, we have not heard of specific examples of price increases due to these shortages,” said Dr. Nguyen.

The cause?

While it’s clear that drug shortages are affecting patient access to care, what’s not so obvious is: Why are these drug shortages occurring in the first place? “It depends on who you ask,” said Dr. Nguyen. “No one wants to take ownership of this issue and there’s minimal accountability.”

Indeed, the causes of these shortages are ambiguous and are often justified in general terms, if at all. According to the U.S. Food and Drug Administration (FDA), 37% of drug shortages are due to quality and safety violations related to manufacturing; 27% are due to a shortage of raw materials needed to produce the drug; 27% are caused by delays from natural events that affect capacity (such as hurricanes); 5% are caused by increased demand; 2% are caused by a loss of the manufacturing site (from a fire or natural disaster); and 2% are caused by discontinuation of a drug (www.fda.gov/Drugs/DrugSafety/DrugShortages/ucm441579.htm). According to John, “the manufacturers of sodium bicarbonate and lidocaine have explained that an increase in demand for the drugs is one of the causes of the shortage.”

Get updates on drug shortages

Visit staging.aad.org/drugshortages.

Certainly, the reasons behind these shortages remain vague at best as the FDA cannot require manufacturers to disclose the specific details regarding a shortage other than “manufacturing delay” or “increased demand,” for example, or adhere to a plan to resolve the issue. However, “The Food and Drug Administration Safety and Innovation Act of 2012 generally requires manufacturers to notify the FDA of any disruptions, such as manufacturing changes, production or shipping delays, and product discontinuations likely to affect their supplies,” said Natasha Pattanshetti, JD, MPH, the AADA’s manager of regulatory policy. However, said Dr. Resneck, “Although this warning requirement has played a significant role in reducing the number of drug shortages, it has not solved the problem.”

When the FDA is notified of these shortages, it does have the authority to take steps to help mitigate the impact of the shortages. “The FDA responds to potential drug shortages by taking actions to address their underlying causes and to enhance product availability,” said Jeremy Kahn, from the division of health communications at the FDA’s Center for Drug Evaluation and Research. “The FDA determines how best to address each shortage situation based on its cause and the public health risk associated with the shortage.”

For example, according to Kahn, the FDA can work with other manufacturers that have the capacity to make the drug in shortage and help them ramp up production if the manufacturer is willing. “Often they need new production lines approved or need new raw material sources approved to help increase supplies. FDA can and does expedite review of these to help resolve shortages of medically necessary drugs,” said Kahn. However, the “FDA can’t require the other firms to increase production.”

Addressing the shortage

Given that patient safety and quality of care are on the line, what is the AADA doing to address drug shortages?

Manufacturers: First and foremost, the Academy has not been shy about addressing the issue at the source. “The AADA has continued contact with manufacturers Pfizer and Fresenius Kabi to ensure that they are aware that access to lidocaine with epinephrine and even lidocaine and bupivacaine are extremely important to physicians and patients,” said Dr. Nguyen.

Additionally, the Academy has also reached out to the suppliers, as many physicians have noticed delays in their orders being filled. “The supplier explained that they fill orders on a first-come, first-serve basis, but they continue to receive sporadic shipments of the drug to fulfill the orders,” said John.

FDA: The Academy also continues to work with FDA staff, participating in regular conference calls with other specialty groups where the FDA gives updates on the shortages and provides an opportunity for questions. Additionally, through letters and phone calls, the AADA has called on the FDA to create incentives for manufacturers to produce drugs in shortage, allow for temporary importation of some drugs such as lidocaine with epinephrine, and require manufacturers to have plans in place for when shortages do occur.

As a result of the Academy’s advocacy efforts, the FDA recently issued a statement indicating that the agency will be evaluating its current authorities, likely with the U.S. Congress, to see if there are better ways it can mitigate and prevent shortages. “One consideration might be to expand the FDA’s existing authority to require applicants of certain drugs to conduct a risk assessment to identify the vulnerabilities in their drug supply, including vulnerabilities that could cause a shortage, and establish risk mitigation plans to address those risks,” said FDA Commissioner Scott Gottlieb, MD. Additionally, the FDA has announced the formation of a drug shortages task force that will include representatives from the FDA, CMS, and the U.S. Department of Veterans Affairs to address ongoing shortages of medically necessary products. The AADA is planning to participate in the agency’s stakeholder meetings.

“It is promising to see the FDA’s recent efforts to address drug shortages as they commit to exploring additional ways to work with manufacturers to help mitigate shortages,” said John. However, the fight isn’t nearly over. “All of us must keep up our efforts to raise the seriousness of the shortage to all stakeholders.”

Federal Trade Commission: The AADA has also been addressing the potential for price gouging with the FTC. “Last year the FTC held a public meeting to explore the drug supply chain and seek recommendations for how to improve competition,” said John. “The AADA submitted comments in response to the meeting that specifically call on the FTC to monitor the price of drugs during and after a shortage. There is concern that the price will increase with such limited supply available.”

Academy members: While the Academy has a seat at the table on many fronts, internally, it has developed several resources to help physicians not only navigate these drug shortages, but get involved as well. The AADA regularly provides updates to its members on drugs shortages in its weekly e-newsletters Dermatology World Weekly and Dermatology World Academy Insider.

Additionally, a new drug shortage web page on the AAD website has information available on the expected resupply dates, manufacturer contact information, alternatives for local anesthetics, and advocacy resources such as template letters physicians can use to call on their elected officials to identify solutions. Visit staging.aad.org/drugshortages.

While the current drug shortage challenges are dire for patients and physicians alike, Dr. Resneck argues that the issue will likely come to a head, as stakeholders and policymakers begin to evaluate what needs to be done to prepare for future shortages. All told, he maintains, the drug shortage issue may eventually be elevated from a mere health care concern to a larger issue with national implications. “There is growing recognition that drug shortages should be examined as a national security initiative.” 

Get the latest in shortage news

To get the latest news on drug shortages, subscribe to the ‘Advocacy’ section of the Academy’s new DW Academy Insider e-newsletter.

Visit staging.aad.org/account/communication/ and select ‘Advocacy’ under Dermatology World Academy Insider.