By Nancy Goldstein, Esq.
In September of 1997, the United States Food and Drug Administration announced that the popular diet drugs Pondimin (fenfluramine-hydrochloride) and Redux (dexfenfluramine) had been voluntarily withdrawn from the marketplace. This unprecedented recall of the drugs followed the prepublication release of a New England Journal of Medicine article detailing the findings of a Mayo Clinic Study in which echocardiograms of twenty four women who had utilized Fen-Phen (Fenfluramine-Phentermine) were found to have valvular abnormalities.
The appetite suppressants, fenfluramine and dexfenfluramine, are selective serotonin reuptake inhibitors (SSRI). Pondimin has been marketed in this country since the early 1970’s whereas its chemical cousin, Redux, received FDA approval in 1996. Although-fenfluramine had been marketed in the United States since the early-1970’s, annual prescriptions through 1990 approximated 10,000. In-1992, results of studies performed by Michael Weintraub, M.D. were published. Dr. Weintraub concluded that the combination of fenfluramine with phentermine was beneficial as a weight control measure. Dr. Weintraub’s studies gave birth to the Fen-Phen combination and transformed the relatively obscure drugs into a household item. For example, Redux was approved by the FDA in April, 1996. By October of 1996, monthly Redux prescriptions totaled 407,000. American Home Product sales of Pondimin in 1996 (fenfluramine) were reported to be $173 million.
The events culminating in the FDA recall of Pondimin and Redux are now in the realm of the legal arena. Fen-Phen litigation has ramifications for physicians as well as the pharmaceutical companies which marketed the drugs. It is virtually certain that the litigation will engender claims regarding the learned intermediaries who prescribed the diet drugs.
As a general proposition, pharmaceutical liability cases focus upon the adequacy of the warnings which accompany the drug under Pennsylvania law. Prescription medications are regarded as unavoidably unsafe products and are deemed to be legally adequate when marketed with proper warnings. The seller of a pharmaceutical is required to warn of those risks which are not generally known and recognized. The Pennsylvania Supreme Court has ruled that the adequacy of the warning is not to be judged from the standpoint of the prescribing physician rather than that of the prescribing patient. Thus emerges the physician as the “learned intermediary.”
In the litigation involving Fen-Phen and Redux one can anticipate that the pharmaceutical company defendants will scrutinize the manner in which the drug was prescribed. For example, the widespread concomitant use of fexfluramine with phentermine is an off-label use, one which is not indicated in the product literature. Another area in which the actions of the prescribing physician are bound to be scrutized concerns the pattern of usage. In the case of Pondimin, the indications and usage section of the Physician’s Desk Reference (PDR) states: “Pondimin is indicated in the management of exogenous obesity as a short term (a few weeks) adjunct in a regiment of weight reduction based on caloric restriction.” However, many individuals who utilized Pondimin took the drug for considerably longer than a few weeks.
Similarly, in the case of Redux, the manufacturer’s prescribing information recommends Redux for obese patients with a specific body mass index (BMI). In certain cases however, Redux was prescribed to individuals who were not obese but wished to lose five or ten pounds. Under such circumstances, attention will likely become focused upon the “learned intermediary” who prescribed the medication.
If the prescribing doctor is to be regarded as a learned intermediary, what degree of knowledge is required? A 1973 Superior Court case discussed the learned intermediary doctrine as follows: “It is for the prescribing physician to use his own independent medical judgment, taking into account the data supplied to him from the drug manufacturer, other medical literature, and any other source available to him, and weighing the knowledge against the personal medical history of his patient.” Based upon this language, the Superior Court in a 1995 decision involving VSP bone plates and screws noted that the information supplied by the drug manufacturer is only one of the sources a physician must consult.
However, a 1996 Supreme Court case seemingly conflicts with this notion. In Green v. Dolsky (1996), a patient developed an autoimmune disorder following an injection of Zyderm Collagen Implant (Zyderm) from her physician, Dr. Dolsky. The patient claimed Dr. Dolsky was negligent in failing to educate himself and his staff with regard to proper methods of administering Zyderm. The patient also alleged negligence due to the physician’s failure to fully investigate the product’s potential side effects. The Court indicated the physician would not be held responsible for a failure to educate himself or provide warnings that which was contained in the accompanying product-information. Thus, Green v. Dolsky seems to suggest that the learned intermediary need only import that knowledge as he or she has derived from the manufacturer materials.
There are two recognized sets of circumstances under which a pharmaceutical manufacturer’s product warnings will not insulate it from liability. One such circumstance is when the seller’s production information is inadequate to properly inform the prescribing physician of proper usage and risks association with the drug. With regard to Fen-Phen and Redux, the parties will likely battle over the adequacy of the warnings for valvular heart disease and primary pulmonary hypertension (PPH). Another potential issue may likely engender the adequacy of the product warnings relative to neurotoxicity. Under Pennsylvania law, when product warnings are insufficient to apprise the prescribing physician, the physician cannot be deemed to be a learned intermediary.
The Pennsylvania Supreme Court in a 1971 decision recognized the important role of the pharmaceutical sellers’ marketing and sales efforts. In Incollingo v. Ewing (1971), the Court acknowledged the significance of information imparted to physicians by the company’s sales force. The Court ruled that the promotional efforts of detail men may render the PDR-product information meaningless. Thus, product overpromotion may well be found to cancel out the official product warnings information.
Incollingo v. Ewing involved the death of a child who developed aplastic anemia after having taken Chloromycetin. The child had been given the drug for acute catarrhal rhinopharyngo-tonsillitis and for a condition described as possible mesenteric-adenitis. The child then returned six months later with the same diagnosis and Chloromycetin was again prescribed. The prescriptions were later refilled by the child’s parent for treatment of an upper respiratory infection. The child was subsequently diagnosed with aplastic anemia.
Parke Davis pointed to written product warnings which indicated the product should not be used indiscriminately or for minor infections and its use had been associated with certain blood dyscrasias. Evidence concerning the promotion of the product suggested the sales force presentations were inconsistent with the written warnings, particulaly with regard to using the drug only for serious infections. The Court ruled that the jury was appropriately permitted to decide whether or not the printed words of warning were in effect cancelled out or rendered meaningless in light of the sales effort made by the detail men.
In the case of Fen-Phen and Redux, the promotional efforts of the drugs’ sponsors will likely be scrutinized. For example, it has been widely reported that sales of Pondimin in the United States remained at 50,000 prescriptions per year in 1993, 1994 and 1995. In 1995, Fenfluramine prescriptions doubled to one million and soared to 7,000,000 prescriptions written for 1996. In the case of Dexfenfluramine, 2,000,000 prescriptions were written during the six months of 1996 following market approval. An article appearing in the Newark Star Ledger attributed a statement to American Home Products Vice President, Fred Hassan, indicating a sales force of over 1000 people devoted to the launch of Redux and an advertising budget of millions. It can therefore be anticipated that the written product warnings will be juxtaposed with the marketing and promotional efforts to ascertain whether the written warnings were effectively nullified by the sales force.
Fen-Phen litigation in its nascent state and it is difficult to predict its course. Many unanswered questions remain, both with regard to legal and scientific issues.
Nancy Goldstein, Esq., is a partner with Anapol, Schwartz Weiss & Cohan, P.C. in Philadelphia.