From prescription to over-the-counter: watered-down warnings.

A growing trend in pharmaceutical regulation is for the FDA drugs formerly requiring prescription to be sold directly to consumers as so-called over-the-counter (OTC) drugs. For example, today consumers can buy Tagamet HB or Pepcid AC--drugs commonly used to treat heartburn--off a drugstore shelf, but for many years only a doctor, acting as a "learned intermediary," could prescribe them.

The government and the drug industry have many motives to switch a drug from prescription to over-the-counter. From a public health standpoint, the government favors the change because it reduces medical costs. If sick people can treat what ails them with OTC drugs, they incur no physician bills. The drug industry's primary motive, of course, is to increase sales (witness the current mammoth ad campaigns for Tagamet and Pepcid). And consumers presumably benefit because the drug is generally much cheaper to buy over-the-counter than by prescription.

But the switch from prescription to over-the-counter status isn't entirely benign. Because consumers don't get the same information about possible adverse reactions from OTC drugs that doctors get about prescription drugs, OTC products can present hidden risks to users. This raises an important legal issue: What liability is created on the part of drug manufacturers when this switch occurs?

Look at the; labeling on a container of over-the-counter Tagamet (cimetidine). The information printed on the box provides just a few words of warning to the consumer, and there is not a single reference to possible adverse reactions.

Contrast that with what physicians are told about the same drug when they prescribe it. The Physicians' Desk Reference (PDR) write-up for prescription Tagamet, which is the same as the FDA-approved package insert, runs nine columns in small type. In the PDR, physicians can find everything they need to know about safe use of the drug, including side effects (dozens are fisted) and contraindications. A consumer will never find this information on an OTC drug label.

A person who sustains an injury due to lack of information on the OTC version of a drug--an injury that would likely have been avoided if a doctor had prescribed the medication and given the full warnings--may have a viable claim against the manufacturer. This is especially so so if the risks of using the product were increased because the user had a special medical condition or was taking another drug at the same time.

Another way of proving manufacturer liability is to show that the consumer, had he or she been armed with adequate warnings about adverse reactions, would have stopped using the drug early enough to avoid permanent injury.

We recently settled a case where the prescription form of phenylpropanolamine (PPA), a drug used to treat a runny nose, had extensive warnings against using the product with an antidepressant. Doctors were warned in the prescription version that the combination could cause hypertensive crisis (sudden very high blood pressure). We represented the family of a man who bought the drag over-the-counter with no such warnings and took it while he was on Nardil, an antidepressant. He was dead in one hour. The defendant agreed to a satisfactory out-of-court settlement.(1)

Some products include labeling for both the general public and physicians. This situation highlights the stark difference between the warnings given to consumers and those given to doctors. For example, the labeling on Fleet enemas has the usual simplified warnings--discontinue use if nausea develops, do not use the drug for prolonged periods of time--for consumers. The same labeling includes a message for doctors: "Professional Use Warnings: Consult Physicians' Desk Reference for complete professional labeling." The doctor's section of the label also lists warnings for physicians about use by patients with impaired renal function or those taking certain other medications.

When confronted with facts like these, jurors are likely to wonder why physicians receive more medical information than lay users of pharmaceutical products. It seems logical that consumers need as much information--if not more--about risks and contraindications than doctors do.

Liability

The law relating to prescription drugs is well known. The so-called black letter law, accepted in most states, is that the drug manufacturer has no obligation to issue warnings to the pub]ic.(2) The manufacturer's only duty is to inform the doctor, who, as the "learned intermediary," decides what information to pass on to the patient. Exceptions to this rule have been made by the courts for drugs that come with package inserts for patients or for drugs distributed in public health programs, such as vaccines.(3)

When it comes to OTC drugs, the case law recognizes the manufacturer's obligation to give warnings directly to the user.(4) In other words, the general rules of negligence and strict liability apply, with liability based on warning and labeling defects.

For example, in a leading New Jersey case the manufacturer of Anacin was held liable for failure to warn about gastrointestinal bleeding as a risk of the long-term use of aspirin. The court affirmed findings against the manufacturer based on both strict liability and negligence for not warning of risks known to the seller but not likely to be known to the user.(5)

In cases involving over-the-counter drugs previously available only by prescription, the attorney has a powerful weapon for proving what the manufacturer knew about the drug's risks. The attorney can easily show what the manufacturer knew by pointing out what the manufacturer told physicians but withheld from consumers.

FDA Review

More than 50 prescription drugs have become OTC products in the past decade. The FDA must approve a manufacturer's request to make the switch. Understanding the agency's role will help the attorney combat the industry's standard defenses in failure-to-warn cases involving these drugs.

In 1962, the FDA began a review of OTC products' efficacy and safety. By 1981, the agency had classified these drugs into various categories, one of which was "generally recognized as safe and effective" or "GRAS/E."

The FDA then began reviewing the OTC drugs on the market in a series of "monographs," examining the drugs according to the medical conditions for which they were used or treatment categories. Examples are antacids, antihistamines, bronchodilators, expectorants, and sleep aids.

The agency plans to publish 81 monographs because the FDA decided that there are 81 OTC-suitable medical conditions. In the past 15 years, 18 have been completed; the others are in draft stages. Each monograph covers regulations common to all OTCs; testing procedures; well-recognized indications; and labeling requirements, including directions for use, dosages, and warnings. Monographs operate legally as federal regulations. The OTC monograph system applies only to the older drugs, like PPA, that were grandfathered in when the system was established in 1981. There are a number of mechanisms in place now that are used to switch a prescription product to OTC status.

The primary process for switching a prescription drug to OTC status is to gain the approval of the appropriate FDA advisory panel for that type drug. The panel studies the data it has on file from the original new drug application (NDA) submission for the drug in deciding whether to grant its approval. If the panel approves the drug for OTC status and the FDA concurs, the FDA then tells the manufacturer what should be put on its labeling. Over 75 percent of the drugs switched in the past 15 years have undergone this type of review.

Another method manufacturers use to switch a drug is to file a full NDA--the same document that a company files when it seeks approval to market a new prescription drug. In certain circumstances, the manufacturer may file a supplemental or an abbreviated NDA. One advantage of submitting the full NDA is that the seller gets a period of exclusive sale.(6)

The agency's required warnings for OTC drugs seem deficient in several respects. OTC address how to avoid acute injuries. The FDA has placed much less emphasis on labeling about the risks of long-term use, even though long-term use of many products, such as pain relievers, is likely.(7) The minimal labeling rules also do not seem to require adequate warnings about adverse reactions that might occur in specific users (for example, people with high blood pressure or diabetes) and about adverse reactions between the OTC drug and other drugs.

Combating the Defenses

Despite their deficiencies, the requirements for proper labeling listed in the monographs are usually cited by OTC drug manufacturers as their first line of defense in suits involving drug-related injuries. If a drug's labeling complies with the monograph or if it was approved by the advisory panel, the defense commonly asserted is that the FDA approved the labeling.

The attorney should respond first that this is not a preemption issue, as in the case of medical devices. In our opinion, preemption is not an issue here because the Food, Drug and Cosmetics Act contains no preemption provision for drug labeling regulations. On the other hand, state laws on medical devices are expressly preempted by the act. The common law applies to set the duty to warn, and at most compliance with regulations is only some evidence of due care.(8)

A second argument for plaintiffs is that nothing prevented the manufacturer from enhancing the warnings or at least seeking FDA approval to do so. Additional warnings may be given as long as they appear in a different place on the label than the required warnings.(9)

Courts have ruled that compliance with FDA regulations is not a complete defense. An example is a New Mexico case involving a man's regular use of Sinutab (containing phenacetin) and its generic equivalent over an eight-year period. The plaintiff was diagnosed with kidney failure and alleged that the warnings on the labeling were inadequate. The defendant argued that it was not liable because its label warnings fully complied with the Food, Drug and Cosmetics Act.

The court rejected this defense, stating that a warning label adopted verbatim from a state or federal regulation does not constitute an adequate warning as a matter of law, but merely sets minimum standards.(10)

Another fine of argument useful in opposing the "government knows best" position is that the OTC industry has a trade group involved in label review and improvement. The Nonprescription Drug Manufacturers Association has issued numerous voluntary guidelines that counsel should obtain to determine if the labeling in question met them.

Some states may also have regulations for specific types of products or users, an issue that may raise preemption problems of a different sort. For example, Texas and Florida have authorized the prescription use of the unapproved drug dimethyl sulfoxide so long as certain warnings are given to patients. Similarly, Colorado and New Jersey both permit the prescription use of the unapproved Laetrile (amygdalin) provided warnings are given to patients. Thus, it is important to check your state law for specific regulations that can both help and hurt your case and that can turn the preemption issue around entirely.

Another favorite defense is consumer "abuse." The manufacturer argues that the user took the product at a higher strength than the labeling advises or took it for too long a time. Counsel should look to see how clear the labeling and directions actually are and may find that there is no warning at all or a misleading one about the consequences of taking an overdose. In products law generally, a warning of the consequences of misuse may well be required.(11)

Further, an OTC drug is almost always sold to be used at less strength than the prescription version, so the alleged "abuse" is often well within the permitted safe prescription dosage. For example, Motrin (ibuprofen) is sold as a prescription at 400 mg strength, and doctors often advise their patients to take two pills at a time. Motrin IB and other OTC forms of ibuprofen are sold at 200 mg strength, and users are advised to take two pills at most. However, even if a user took four OTC ibuprofen pills, the user would still not exceed the allowed safe prescription dosage. Under circumstances like these, the "abuse" defense can be easily deflected.

Other common defenses include:

* The package was too small to include all the warnings found in the PDR.

* Users don't read or heed labeling.

* A label with too many warnings dilutes the significance of the warnings.

Each of these defenses is defeated by simply appealing to the jurors' common sense and the facts of your case. Since each of these defenses is within the exclusive control of the manufacturers, they are in a bind if they suggest that they don't have the space or the ability to convey complete warnings to the public. After all, they run ads for prescription drugs in the public press, trying to stir up demand so that patients will ask their doctors for a prescription. In compliance with FDA rules, they run the full PDR data in these ads in fine print--something they say they can't do when the drug is sold over-the-counter.(12)

Pharmacist Liability

Another party who assumes greater responsibility when a prescription drug switches to over-the-counter is the pharmacist. Studies have shown that many people ask their local pharmacist what to take for what ails them.(13)

When pharmacists give advice, they act as professionals and must use due care. They may be held responsible for knowing that the customer is taking a drug (perhaps a prescription they filled) that might react adversely with an OTC drug. The pharmacist may know, or, at least should ask, whether the consumer has conditions that would increase the risks associated with taking the OTC drug. Even if there is a warning about side effects on the container, this might not relieve the pharmacist of a duty to emphasize the warnings and caution the consumer to stop taking the product if certain early signs appear.

A source of proof for the duties of pharmacists is the Physicians' Desk Reference for Nonprescription Drugs It warns pharmacists that poor communications can cause injuries.(14) It lists rules like keeping up to date on OTC product risks, making sure consumers understand what they are being told, and repeating directions to them.

If the trend toward converting prescription drugs to over-the-counter products continues, and if drug manufacturers do not change their current practice of giving fewer warnings to consumers than they do to physicians, this area of litigation is likely to grow. Drug companies and pharmacists must. either give proper warnings or be held accountable for failing to do so while they cash in on the OTC boom.

The bottom fine is this: Without the benefit of a doctor's advice, consumers need more information about their medicine, not less.

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Notes

(1) The case cite is unavailable because the settlement is subject to a confidentiality agreement. (2) See, e.g., RESTATEMENT (SECOND) OF TORTS [sections] 388 (1965); Swayze v. McNeil Lab., Inc., 807 F.2d 464 (5th Cir. 1987); Felix v. Hoffman-LaRoche, Inc., 540 So. 2d 102 (Fla. 1989). (3) See generally Reyes v. Wyeth Lab., Inc., 498 F.2d 1264 (5th Cir. , cert. denied, 419 U.S. 1096 (1974); Davis v. Wyeth Lab.,, Inc., 399 F.2d 121 (9th Cir. 1968); Givens v. Lederle, 556 F.2d 1341 (5th Cir. 1977). (4) See, e.g., Michael v. Warner/Chilcott, 579 P.2d 183 (N.M. Ct. App.), cert. denied, 577 P.2d 1256 (N.M. 1978). (5) Torsiello v. Whitehall Labs., 398 A.2d 132 (N.J. Super. Ct. App. Div. 1979). (6) PHYSICIANS' DESK REFERENCE FOR NONPRESCRIPTION DRUGS 412 (1995). (7) Lars Noah, The Imperative to Warn: Disentangling the "Right to Know" from the "Need to Know" About Consumer Product Hazards, 11 YALE J. ON REG. 293, 324 (1994). (8) Michael, 579 P.2d 183,186. (9) Noah, supra note 7, at 321. (10) Michael 579 P.2d 183, 186. See generally RESTATEMENT (SECOND) OF TORIS [subsections] 388,402A, Hawkins v. Richardson-Merrell, Inc., 249 S.E.2d 286 (Ga. Ct. App. 1978). (12) The pharmaceutical industry has recently been suggesting that when a drug switches from prescription to OTC, the manufacturer should be immune from strict liability. See, eg., Thomas M. Moore & Scott L. Hengsbach, Comment K: A Prescription for the Over-the-Counter Drug Industry, 22 PAC. L.J. 943 (1990). (13) PHYSICIANS' DESK REFERENCE FOR NONPRESCRIPTION DRUGS, supra note 6, at 418. (14) Id. at 416.

Terrence E. McCartney and Paul D. Rheingold practice in the law office of Paul D. Rheingold in New York City.