For years the pharmaceutical industry has been cashing in on “blockbuster” drugs.¹ Big Pharma spends billions of dollars on advertising and marketing these drugs but unfortunately they often times don’t conduct the necessary safety testing to determine the dangers of a drug PRIOR to marketing them. Consequently, dangerous drugs are consumed by millions of Americans who are unknowingly participating in what is essentially a large clinical trial. While most people put faith in the FDA to protect the public, the reality is that the FDA is woefully understaffed and political pressures force them to quickly approve medications for sale. While we can all agree on the necessity for new and innovative drugs to help fight cancer, AIDS, and other serious disease, the fact is that more and more frequently drug companies are rushing medications to market for much less serious illnesses or for ailments where there are already several alternative medications available. The Vioxx “debacle” ² has brought many of these problems to light in the mainstream media, but this continues to be a widespread problem. Over the past two decades, more than twenty prescription drugs and medical devices have been withdrawn from the market for safety reasons.³ Over fifty drugs acquired black box warnings, used to inform physicians of serious and fatal risks after initially being marketed to the American public and physicians without these warnings.⁴ Litigation concerning prescription drugs continues to grow, and plaintiffs’ attorneys should continue to stay informed in this area to help maximize recoveries for their respective clients.

II. What to Look for When a Client Calls

When a client calls in with a particular illness or injury, the attorney should immediately obtain a complete list of ALL medications the client is taking or was taking for the last five years. Don’t limit this information to only those medications the client was on at the time of the illness or the injury as many latent injuries do not manifest themselves for years after the client has taken the drug.⁵
The adequacy or inadequacy of the warning is almost always at issue in pharmaceutical litigation. Therefore, once you have the list of medications, a good place to start any investigation of prescription medication is the Physicians Desk Reference (PDR).This is in every doctor’s office (or should be) and is an invaluable tool for the plaintiff’s attorney. The PDR contains the product inserts (warnings, precautions, contraindications, etc.) for all the prescription medication.⁶ The plaintiff’s attorney must carefully evaluate what information was available to the doctor when the client was prescribed the drug. Was there a warning? If so, was it adequate? While most people are under the impression that the warnings are dictated by the FDA, the FDA is essentially powerless to mandate what goes into the label. Rather, the system that is in place allows the drug companies to “negotiate”what information goes into the product insert (label).⁷ There is an obvious and inherent conflict in this process. The fewer warnings/precautions there are, the more likely the doctor is to prescribe that medication over a competitor. So, the drug companies have a direct and SIGNIFICANT motive to try and downplay the risks inherent in many medications. This is one of the reasons there continue to be reports of more and more drugs or medical devices being removed from the market after the FDA has approved them. Some of these recent drugs or medical devices are discussed below.

III. Current Litigation

A. Antibiotics

Two clear examples of the lack of appropriate safety testing and adequate warnings arise with the antibiotic drugs Ketek and Tequin.
Ketek was approved in April 2004 and brought in more than $193 million to its manufacturer in one year. Ketek could cause people being treated for everyday bronchitis to die from liver failure. In an effort to compile the data necessary to get the drug approved, the manufacturer enlisted a product development company wherein doctors prescribing Ketek would be paid a graduated fee based on the level of evaluation and reporting performed, a common research tool used by drug companies. During the process, the manufacturer, managers of the study process, and, allegedly, members of the FDA became aware that physicians were simply fabricating patient data and, as of today, at least one of those physicians has been jailed for fraud.⁸ Still, armed with this knowledge, the manufacturer pushed the drug for approval and the FDA actually approved the drug in April 2004. Within the following year, many cases of liver failure and liver death surfaced. Incredibly, liver failure was not added to the label until the end of 2006.

Tequin was developed in Japan and licensed to a manufacturer in the United States in 1999. It was approved to treat similar infections as those with Ketek. Tequin has been associated with new onset diabetes, severe cases of hypoglycemia and hyperglycemia, and other complicating conditions requiring hospitalization. After at least four inadequate changes to the drug label regarding blood sugar events, the drug manufacturer ceased production in May 2006. While the Japanese contraindicated Tequin for diabetics in 2003, it actually took the United States until 2006 to do the same.⁹

B. Trasylol

Trasylol (also known as aprotonin) was approved for use by the FDA in 1993 and is commonly used during major heart surgery to control bleeding. Trasylol has been linked to serious complications including kidney damage, increased risk of heart attack, heart failure, and stroke. It is used during as many as one million heart and bypass surgeries per year.

Studies now show that Trasylol doubles the risk of kidney damage and also increases the risk of heart attack by 48 percent.¹⁰ Furthermore, studies suggest there are safer alternatives, including the less expensive generics. Unlike a typical prescription medication, most of the time plaintiffs will have no idea whether or not they received Trasylol because it is given intravenously during administration of the anesthesia. Therefore, plaintiff’s counsel should immediately obtain medical records in order to confirm the type of medication administered during the surgery.

C. Gadolinium

Gadolinium is used as a contrast agent in MRIs and MRAs. Gadolinium has been linked to Nephrogenic Systemic Fibrosis (NSF), also known as nephrogenic fibrosing dermopathy (NFD), which is a condition that, so far, has occurred only in people with kidney disease.¹¹ NSF is a systemic disorder with its most prominent and visible effects in the skin — particularly, swelling and tightening of the skin, usually limited to the extremities but sometimes involving other areas of the body. Plaintiffs with severe cases may be unable to walk, or fully extend the joints of their arms, hands, legs, and feet. The skin changes may start as reddened or darkened patches and, in time, the skin may resemble the texture of the peel of an orange. There is no consistently successful treatment for NSF, although improving renal function (by any means) seems to slow NSF (and in many cases allows for gradual reversal of the process over time).

At this time, the only people known to be at risk for NSF are those who had gadolinium injected in connection with an MRI (magnetic resonance imaging) scan or an MRA (magnetic resonance angiography) and who also, at the time of MRI or MRA, had kidney failure or impaired kidney function.

D. Fosamax

Fosamax is a blockbuster osteoporosis drug manufactured by Merck, generating more than $3.5 billion in annual revenue. Despite having one of the highest side effect profiles of any drug in the U.S. prescription database, Fosamax remains on the market and available by prescription. Fosamax causes osteonecrosis of the jaw — literally, rotting of the jaw bone. There is very little debate in the oral surgery community about the link between Fosamax and osteonecrosis. Osteonecrosis of the jaw (“ONJ”) is a disfiguring and disabling condition through which the jaw bones — the maxilla and the mandible — suffer literal bone death and, in some cases, rotting of the bone. This is an exceedingly rare disease, the causes of which are very few. The disease typically is manifested by loosening of teeth, or lesions on the gums, and advances to osteomyelitis — literally, infected jaw bone marrow. This disease process can advance to the point where entire sections of necrotic bone require removal, rendering the patient unable to chew solid food. Left untreated, the process can cause infection in the blood — septicemia — and even result in death.

For years, physicians and dentists in the oncologic and dental communities have acknowledged the observed risk of osteonecrosis of the jaw caused by the adjunct chemotherapy agents, Zometa and Aredia. These drugs are in the same class of drugs as Fosamax, but are administered intravenously. Additionally, in August 2004, the United States Food & Drug Administration Office of Drug Safety (“ODS”) issued a report based upon its review of post-marketing reports of Fosamax-associated ONJ. The ODS found the risk of ONJ to be a class effect common to the nitrogenous bisphosphonates, including Fosamax. The FDA observed that the risk of ONJ extended to the oral bisphosphonates, chiefly Merck’s Fosamax, and that Merck should proactively advise prescribers and patients of the risk.¹²

Merck has yet to include any information in its “Warnings” section about the risk of osteonecrosis of the jaw and Fosamax use. Rather, Merck has indicated in its “Precautions” section that osteoporosis (rather than osteoporosis medication) is a risk factor for ONJ.

IV. Conclusion

These are just a few examples of ongoing or emerging drug or medical device litigation. As with any products liability case, a thorough pre-suit investigation is critical. When a client calls in, whether it is in a medical malpractice case or any other type of case, the attorney should determine whether or not a pharmaceutical product is implicated.

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1. In 2002, national drug expenditures totaled over $160 billion and in 2003, Florida ranked number four in the country with $10.57 billion in prescription drug sales. Kershaw, JM, “Prescription Drug Recalls on Florida’s Medicaid Preferred Drug List.” Florida Public Health Review, 2005; 2:108-114.
2. Topol, EJ. “Failing the Public Health — Rofecoxib, Merck, and the FDA.” N ENGL J MED 2004; 351:17:1707-9.
3. Lasser, K., Allen, P., Woolhandler, S.. Timing of New Black Box Warnings & Withdrawal for Prescription Medications. JAMA 2002; 287:17:2215-20.
4. Report to the Chairman, Committee on Health, Education, Labor & Pension, U.S. Senate, Food & Drug Administration: “Effect of User Fees on Drug Approval Times, Withdrawals and Other Agency Activities”, September 2002; GAO-02-958.
5. For example, it is important for the plaintiff’s attorney to know that Fosamax (which is discussed below) has a half-life in bone of greater than 10 years. As a result, clients may still be at risk for developing ONJ for years after the discontinuation of Fosamax therapy.
6. Because of the learned intermediary doctrine, the duty to warn extends to the prescribing doctor, rather than the patient. Therefore, the plaintiff’s attorney must look at the information provided to the prescribing doctor. Felix v. Hoffman-LaRoche, 540 So.2d 102, 104 (Fla.1989). When a physician has been fully and accurately informed of all the risks of a particular drug, the learned intermediary doctrine may be pled as an affirmative defense.
7. Dr. Sandra Kweder, an FDA Official being questioned about Vioxx testified before the Committee on Health, Education, Labor, and Pensions, U.S. Senate Hearing 109-67, on March 1, 2005, that, “Well, what caused the delay [in changing the Vioxx label] is that we don’t have the authority to tell a company, this is how your label has to look. This is the language that needs to go into your label. Here is where it goes, end of story. We have to negotiate with the company the specific language of how things should be worded, placement, those kinds of things.”
8. Anna Wilde Mathews, Wall Street Journal Online, May 1, 2006. “Infected Data: Fraud, Errors Taint Key Study of Widely Used Sanofi Drug Despite Some Faked Results, FDA Approves Antibiotic; One Doctor’s Cocaine Use; Company Defends Safety.”
9. Petition to the FDA to Immediately Ban the Antibiotic Gatifoxin (Tequin)(HRG Publications #1768) Available at http://www.citizen.org/publicationsrelease.cfm? ID=7430
10. Dennis T. Mangano, Ph.D., et al. “The Risk Associated with Aprotinin in Cardian Surgery.” N ENGL J MED 2006; 354:353-65
11. http://www.fda.gov/cder/drug/InfoSheets/HCP/gcca_200705HCP.pdf
12. United States Food & Drug Administration, Office of Drug Safety, Division of Drug Risk Evaluation, ODS Postmarketing Safety Review, ODS PID# D040283, 08/25/04.