The Eight Drug Shortages Putting Americans at Risk

President Obama this week signed an executive order directing federal regulators to address shortages of vital prescription drugs. According to the president, the order, which does not need congressional approval, was necessary to reduce patient risk and prevent price gouging.

The executive order is aimed at 232 drugs that are in short supply — up from 70 in 2006, according to the University of Utah’s Drug Information Service, which maintains the most comprehensive list of drug shortages in the country. Much of the attention has been focused on drugs used in hospital treatment, which account for 80% of the shortages experienced. While such drugs, like injected medicines used for chemotherapy, are critical to patient care, many Americans are unfamiliar with them.

Using data provided by the Drug Information Service, 24/7 Wall St. examined the shortages of drugs most likely to impact the general public — those prescribed outside hospitals. The severity of the shortage, the total number of people who take these drugs annually, the availability and efficacy of alternatives, and the cost of potential replacements was then measured to identify the drugs that put the most American patients at risk.

The drug shortages for common prescription drugs that 24/7 Wall St. has identified can present problems for consumers. For example, cilostazol, a drug for a specific subset of heart disease patients, is on the list due to supply constraints and increased demand. While there are similar drugs available, cilostazol is the only one proven to improve survival and quality of life with the highest medical evidence.

The good news is the vast majority of drug shortages will not pose a problem for the average consumer for a number of reasons: There are excellent alternatives, the shortages are constrained to one dose type or one manufacturer, or the drug has fallen out of favor in the medical field. Methylprednisolone, an oral drug for rheumatoid arthritis, is in short supply, but two equivalent drugs, prednisone and prednisolone, are widely available. Likewise, lansoprazole, a heartburn drug, is in short supply in the form of orally disintegrating tablets, but is readily available in regular capsule form.

Data on drug shortages is from the University of Utah’s Drug Information Service, prescription estimates are from the most recently published 2007 National Ambulatory Medical Care Survey from the Center for Disease Control. Several other medical databases and journals were reviewed to provide details on each drug on the list.

These are the eight drug shortages putting Americans at risk.

1) Acyclovir – Herpes
>Estimated Prescriptions: 2.4 million
>Severity of Shortage: Intermittent back-order
>Alternatives: Non-generic Zovirax, Valtrex, and valacyclovir

Acyclovir is used to treat herpes infections, to prevent cold sores from herpes, and to prevent the spread of the virus from one person to another. Well over half of the population will have been infected with oral herpes by age 60. The more worrisome form of the virus, genital herpes, infects one in six Americans. The vast majority of these people will need limited treatment, but there were still an estimated 1.8 million prescriptions for generic acyclovir in 2007. Other drugs, including the brand name Zovirax, are available and equally effective, but are much more expensive. Other generic versions that are still in supply are back-ordered due to increased demand. Unless production is able to be increased, the acyclovir shortage may only get worse.

2) Methylphenidate – ADHD
>Estimated Prescriptions: 5.2 million
>Severity of Shortage: Intermittent back order
>Alternatives: Adderall, Adderall XR, Ritalin, Ritalin LA, and Concerta

Attention-Deficit/Hyperactivity Disorder affects approximately 5% of children and adults, over 15 million in total. Various stimulants — including amphetamine salts, methylphenidate, and dextroamphetamine — are used to treat the condition with varying levels of success. Many people try several different combinations until they find what works best for them. As of 2007, there were an estimated 11.6 million prescriptions across the three major drug types, 5.2 million of methylphenidate alone. Several generic drug manufacturers are having trouble meeting demand due to shortages of raw materials, manufacturing difficulties, and issues with FDA compliance. While roughly 85% of patients were prescribed brand name versions of these drugs, the remaining 15% may see their monthly bills rise four- or five-fold because of the shortages.

3) Calcium Acetate – Renal Disease
>Estimated Prescriptions: 350,000
>Severity of Shortage: Severe
>Alternatives: Lanthanum carbonate and sevelamer carbonate

Calcium acetate, while also used as a calcium supplement, is widely used to correct metabolic imbalances in patients with end-stage renal (kidney) disease. In 2007, an estimated 350,000 prescriptions were written. Currently, three of the four manufacturers have supplies on back-order, and two have no estimated availability date. There are two alternatives, lanthanum carbonate and sevelamer carbonate, but they are several times more expensive and have much higher incidences of side effects, including nausea, vomiting, and joint pain. If shortages of calcium acetate are not tackled quickly, the lives of sick patients may become even more uncomfortable.

4) Cilostazol – Circulatory Disease
> Estimated prescriptions: 636,000
> Severity of Shortage: Moderate to severe
> Alternatives: Clopidogrel and aspirin

Diseases of circulation, including heart attacks, strokes, and peripheral artery disease are treated with combinations of anti-platelet drugs to help prevent and reverse the formation of clots within blood vessels. In peripheral artery disease, cilostazol is given to increase the distance patients can walk without pain, as well as to decrease the likelihood of more serious complications. In 2007, there were an estimated 636,000 prescriptions for this drug. In August, one manufacturer discontinued production, and three others have severe shortages, leaving few supplies available. While aspirin and clopidogrel are also helpful in this disease, many patients are already taking these in combination, so no good alternative is available. Similarly, ticlopidine is given to patients with heart disease usually after the placement of coronary stents.  While only 117,000 prescriptions were estimated in 2007, these patients were usually given this in lieu of clopidogrel due to adverse reactions. This drug is on long-term back-order, placing many patients in an untenable situation.

5) Metronidazole – Infection
>Estimated Prescriptions: 4.2 million
>Severity of Shortage: Moderate
>Alternatives: Vancomycin

Multiple out-patient antibiotic preparations appear on the drug shortage list. Metronidazole, the first line treatment for C. difficile infections and multiple parasitic infections, may be the most problematic. While several generic and non-generic dosages of the drug remain available, the overall supply will be seriously constrained. Worse, there are no appropriate alternatives, as the available ones should be reserved for resistant infections. Shortages of other antibiotics are less troubling: cefpodoxmine can be replaced by cefepime; Cipro, the brand version of ciprofloxacin was discontinued by Merck/Schering, but several equivalent antibiotics are still available; clarithromycin is on back-order, but can be effectively replaced by several similarly priced antibiotics; tetracycline, is on an indefinite back-order, but can be replaced by several equivalent products.

6) Scopolamine – Nausea
>Estimated Prescriptions: 28,000
>Severity of Shortage: Severe
>Alternatives: Injectable anti-nausea/anti-emetic drugs

Scopolamine is routinely prescribed for motion sickness and nausea. It is given in transdermal patch form to those who need to rest their digestive tracts, cannot tolerate drugs by mouth, or suffer from long-term intractable nausea. This is the best way to allow otherwise stable patients to return home. The patch provides drugs for three days, making it a very efficient and easy way to relieve long-term nausea in cancer patients. While other anti-nausea medications are available, including ondansetron and metoclopramide, they frequently do not provide the same consistent and long-standing relief. Both manufacturers of scopolamine transdermal patches currently have the product on back-order due to increasing demand.

7) Trazodone – Depression
>Estimated Prescriptions: 9.1 million
>Severity of Shortage: Mild
>Alternatives: Other antidepressants

Depression affects approximately 17% of Americans over the course of their lives. While there are many anti-depressant drugs available, a large proportion of depression patients do not respond to the first, second, or even third drug they try. Once patients find a drug or combination that works for them, they should continue to use it. According to the most recent CDC survey, approximately 8% of patients, or 9.1 million people, use Trazodone as part of their treatment regimen. Currently, multiple manufacturers are experiencing shortages due to increasing demand and importation bans.  While there are several preparations still available, another disruption may keep many people from getting the treatment they need.

8) Zoster Vaccine – Shingles
>Estimated Prescriptions: 237,000
>Severity of Shortage: Resolving
>Alternatives: None

Shingles, a disease of the elderly caused by the reactivation of the chickenpox virus, occurs in nearly 1 million Americans annually.  In 2006, the FDA approved Zoster Vaccine, or Zostavax, which can reduce its incidence by over 50% annually. In 2007, the first year it was fully available, 237,000 Americans were vaccinated. However, Merck, the only manufacturer, has been unable to meet demand since. Zostavax has been on continual back-order since and is not reaching nearly as many people as it could benefit. While shingles is not life-threatening, the pain associated with it can be completely debilitating.

There have been some issues with two other vaccines — inactivated hepatitis A vaccine and a combination vaccine for measles, mumps, rubella, and varicella — but supplies remain adequate and there are excellent alternatives so shortages do not pose a danger to public health.

Baxter B. Allen and Ashley C. Allen