Here’s an all too common scenario in health care today: Dehydrated from a severe stomach flu, you’re admitted to a hospital. Your doctor wants to order medication to relieve your nausea and vomiting. A savvy user of Electronic Health Records (EHRs), she enters an order for prochlorperazine, a generic drug in use for over 30 years. The electronic response from the pharmacy is: “This product currently unavailable from the manufacturer.” So, your doctor orders another antiemetic, ondansetron, medication that became generic more recently. The same message returns from the pharmacy: “Unavailable…”
What’s behind the shortage of common generic medications? The number of reported prescription drug shortages in the United States nearly tripled between 2005 and 2010. At the same time that new and expensive drugs are dominating the market, proven workhorse drugs with a long history of successful use — like the two your doctor tried to order for you — are becoming harder to obtain.
Recent shortages include cytarabine, which can be life-saving in certain types of leukemia; 28 cancer drugs that are used by more than half a million patients; important injected drugs like lorazepam, a sedative that is the most common drug used to treat alcoholic withdrawal; many antibiotics; metformin, which is arguably the best drug to treat diabetes; methotrexate, which is used to treat some cancers, rheumatoid arthritis, and other autoimmune diseases; and even vitamins.
Part of the problem is that older, less expensive drugs are not very profitable. Once drugs go generic, the profit margin drops. The less profit there is, the less production there is, and fewer companies manufacture the drug. The fewer companies there are making a drug, the greater the chance that a production problems can cripple the drug supply. The Food and Drug Administration (FDA) notes that industry consolidation (i.e., fewer manufacturers) contributes to drug shortages. For example, only 5 manufacturers supply 80% of our injectible generic drugs.
When familiar medications are unavailable, physicians and patients are forced to use alternative drugs, which are often less desirable and more expensive. And, the potential for mistakes can increase dramatically. For example, during a recent morphine shortage, other opioids were used to treat patients. One opioid that was available during the shortage, hydromorphone, is seven times more potent than morphine. Fatal errors occurred when doctors who were unfamiliar with hydromorphone ordered it at the same dose as they use for morphine.
Drug shortages can also lead to unsafe practices such as using drugs past their expiration date or using a “single patient” vial for multiple patients. During a recent severe shortage of propofol (a drug made infamous by Michael Jackson’s overdose), anesthesiologists were reusing single dose vials for more than one patient. This can lead to serious infection outbreaks, such as a recent hepatitis outbreak at a Nevada endoscopy clinic.
When hospitals cannot get medications from their usual suppliers, they may turn to the “grey market” to obtain drugs. In pharmaceuticals, the “grey market” refers to the trade of prescription drugs through distribution channels that, while legal, are unofficial, unauthorized, or unintended by the original manufacturer. It can also refer to the manufacture of drugs in factories with lower safety and quality controls. In March 2012, the FDA recalled lots of Brilliant Blue, an injection used in eye surgeries; Brilliant Blue manufactured by one Florida pharmacy has caused fungal eye infections in some patients. (Not so brilliant, after all!)
Shortages also lead to price gouging. A 2011 Premier Healthcare Alliance report estimated that the typical grey market vendor marks up prices by 650 percent. In one extreme example, a blood pressure drug that usually costs $25.90 was being sold at $1,200 due to a drug shortage. The U.S. House Committee on Oversight and Government Reforms investigated “grey markets” and found that a leukemia drug with a typical contract price of $12 per vial was being sold at $999 per vial.
This is dismaying. In many cases, the best drug is an older, inexpensive, time-tested drug, which may soon become endangered species in the U.S. and internationally. Is there a link between drug shortages and pharmaceutical promotion of new products that may have no advantage over existing products? Although we are unaware of proof of such a direct link, pharmaceutical companies spend an estimated $60 billion a year to promote expensive new pharmaceuticals and influence many streams of information about drugs that go to prescribers and consumers.
A recent paper in the American Journal of Public Health raised the intriguing point that the most highly promoted drugs may be the least useful drugs. The authors call this the “Inverse Benefit Law”, which states that the ratio of benefits to harm among patients taking new drugs tends to vary inversely with how extensively the drugs are marketed. In other words, safe and effective drugs don’t need a lot of marketing, but a new drug with no advantage over older drugs will need a lot of marketing.
The FDA is taking this problem seriously and has joined with the Department of Justice to help prevent drug shortages and price gouging. New legislation may help, too. In February, Senators Amy Klobuchar (D-MN) and Bob Casey (D-PA) introduced the “Preserving Access to Life-Saving Medications Act” (S 296), which would require manufacturers to notify the FDA when a product is discontinued or production is interrupted. Similar legislation (HR 2245) has been introduced in the House of Representatives.
Back to you in the hospital, vomiting. Fortunately, your doctor remembers another old workhorse drug, promethazine, and she feels like she’s won the lottery when the good news comes back from the pharmacy: “Promethazine available.” You’re safe… for now.
Charlea T. Massion, MD, is a family physician and co-founder of the American College of Women’s Health Physicians; she teaches at Stanford University School of Medicine’s Center for Education in Family Medicine. Adriane Fugh-Berman, MD, is an associate professor in the Georgetown University Medical Center, a former chair of the NWHN, and director of Pharmedout, which educates prescribers about pharmaceutical marketing techniques.
Abramowitz PW, “Drug Shortages Impede Care, Threaten lives”, Drug Topics, March 5, 2012 . Available online at: http://drugtopics.modernmedicine.com/drugtopics/Modern+Medicine+Now/Drug-shortages-impede-care-threaten-lives/ArticleStandard/Article/detail/764156?contextCategoryId=40159
American Society of Health-System Pharmacists, Current Drug Shortage Bulletins. Available athttp://www.ashp.org/DrugShortages/Current. Accessed March 17, 2012.
Brody H, Light DW. “The inverse benefit law: how drug marketing undermines patient safety and public health”, American Journal of Public Health 2010; epub Jan. 13, 2011.
CBS Evening News, “Twenty-eight cancer medications in dangerously short supply,” February 13, 2012. Available online at: http://www.cbsnews.com/8301-18563_162-57377020/28-cancer-medications-in-dangerously-short-supply/?tag=mncol;lst;1re
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Kweder S, “Prescription Drug Shortages: Examining a Public Health Concern and Potential Solutions”, Statement of Sandra Kweder, M.D., Deputy Director, Office of New Drugs Center for Drug Evaluation and Research, Food and Drug Administration, Department of Health and Human Services, Before the US Senate’s Committee on Health, Education, Labor and Pensions, December 15, 2011. Available online at: http://www.fda.gov/NewsEvents/Testimony/ucm282956.htm.
The White House, “We can’t wait: The Obama Administration takes action to reduce prescription drug shortages, fight price gouging (Press Release)”, Washington DC: Office of the White House Press Secretary, October 31, 2011.