This case study of one drug label will show you that:
• Drug labels are designed for marketing and sales purposes, not to inform the user of the risks and benefits of the drug.
• Unless you do some questioning, checking, and research on your own, you’re likely to get some bad advice, if you follow the label.
• The label doesn’t tell you that it communicates only a small portion of the risks of the drug and other information you should have about it.
• You should be aware that the risks of drugs are not fully understood, and it may take many years or even decades for them to be revealed. So you have to take that unknown factor into account when you calculate the risk and benefit of any drug.
• You could read a dozen books, and still get only a small slice of the important information on a drug. But to protect yourself, it pays to be as informed as reasonably possible.
• An over-the-counter (OTC) drug can be just as dangerous as a prescription drug. Don’t assume that because it is an over-the-counter drug it is somehow benign.
• Finally, as this column has frequently documented in the past, not only labeling but also drug research even in academic medicine is largely controlled by the drug companies, so disinterested advice is hard to come by but is essential.
For this case study, I’ve selected ibuprofen, a widely used drug for the management of pain, fever, and inflammation. Some of the brand names of ibuprofen are Advil, Medipren, Motrin, and Nuprin. It is one of the class of drugs called nonsteroidal anti-inflammatory drugs (NSAIDs) that includes aspirin, ketoprofen, meloxicam, naproxen (Aleve), piroxicam (Feldene) and many others. These are drugs that almost everyone takes at one time or another, and much of the information on ibuprofen applies to other NSAIDs as well.
Let’s get down to how the label gives bad advice. I’m using CVS’s housebrand of ibuprofen but that is representative of the labels on most of the generic and brand-names of that drug. The label warns that if you take three or more drinks of alcoholic beverages every day while using ibuprofen, then you are at increased risk of stomach bleeding. Compare that with the advice offered by The Johns Hopkins Consumer Guide to Drugs: “Avoid alcohol, as it may increase the risk of stomach irritation.” The PDR Pocket Guide to Prescription Drugs states: “Avoid the use of alcohol while taking this drug.” Mosby’s Drug Guide for Nurses (8th ed.) has this advice: “Caution the patient to avoid alcohol ingestion…GI bleeding may occur.” The makers of ibuprofen would have the person taking two drinks of an alcohol beverage every day use the drug despite that risk of stomach irritation and worse. Wouldn’t you think the drug companies and the FDA (that regulates the labels) would want to be on the side of safety and caution, not on the side of marketing, sales, and profits? Bleeding in the GI tract, which can be fatal, is more likely when alcohol is used in combination with the drug.
Another piece of wise advice omitted from the label: Don’t smoke while taking ibuprofen. Smoking can increase stomach irritation and increase the chance of damage. This advice is offered in The AARP Guide to Pills.
Here’s another bit of label advice, which is even more foolish and dangerous: “Do not use right before or after heart surgery.” That would suggest it’s OK to use the drug before brain surgery, dental surgery, back surgery and every other kind of surgery. You don’t have to be a Philadelphia pharmacologist to figure out the stupidity of that advice. The Johns Hopkins book gets it right: “Because NSAIDs can interfere with blood coagulation they should be stopped at least 3 days prior to any surgery.” When the FDA and the drug companies get around to revising that label, perhaps they ought to add consult your doctor or other health care provider about when to stop the drug before any surgery including dental procedures. The label on drug interactions is too weak. It simply advises the user to tell your doctor or pharmacist if you are taking other drugs. One of the drug interactions it should warn against taking ibuprofen when also on drugs used for high blood pressure. Ibuprofen and other NSAIDs can increase blood pressure and make blood it hard to control. This is discussed at length in the current issue of the newsletter, Worst Pills, Best Pills (February 2009).
Still another piece of foolish and dangerous advice relates to allergy warnings. The label enumerates symptoms of an allergic reaction, but fails to name difficulty in breathing and swelling of the tongue or throat. Perhaps the sales department thought that was too scary for sales purposes. So it was omitted. It should have been included and what’s more, the advice in case of such an allergic reaction should be call 9-1-1 immediately, and not — as the label advises — “seek medical help right away.”
Here’s the label advice on how to avoid stomach irritation when taking ibuprofen: “Take with food or milk if stomach upset occurs.” What about taking with food or milk routinely to avoid the stomach upset in the first place? The Hopkins book says, “Take ibuprofen with food.” The AARP Guide to Pills has even more specific and sensible advice: “Swallow tablets whole with a full glass of water; take tablets in an upright or sitting position. Taking a sip of water first, before taking the tablets, may help you swallow them. If possible take bedtime tablets at least 10 minutes before lying down.”
The stomach bleeding warning on the label states, “This product contains a nonsteroidal anti-inflammatory drug (NSAID), which may cause stomach bleeding.” It adds that if you have stomach ulcers or bleeding problems, you are at higher risk of the drug-induced bleeding. Consumer Reports on Health offers a more cautious approach: “If you have a stomach ulcer or bleeding, or at high risk of either, avoid using NSAIDs.” The label does advise asking your doctor about using the drug if you have ulcers, bleeding problems, and a fairly long list of other conditions.
The Web site Drugs.com has even more specific and informative information on the GI risks of this drug: “This medicine can also increase your risk of serious effects on the stomach or intestines, including bleeding or perforation (forming of a hole). These conditions can be fatal and gastrointestinal effects can occur without warning at any time when you are taking ibuprofen. Older adults may have an even greater risk of these serious gastrointestinal side effects. Call your doctor at once if you have symptoms of bleeding in your stomach or intestines. This includes black, bloody, or tarry stools, or coughing up blood or vomit that looks like coffee grounds.”
The label, again for marketing and sales reasons, has none of the general warnings that should be communicated to any user: “All NSAIDs should be used with caution. All can have dangerous side effects, especially stomach ulcers and gastrointestinal bleeding.” That’s the warning from Consumer Reports on Health.
The label goes soft on the heart disease and kidney disease warning: “Ask a doctor before use if you have heart or kidney disease.” Here is the Consumer Reports on Health warning on heart disease: “The FDA has warned that prolonged use at high doses of any NSAID may raise the risk or heart attack or stroke. NSAIDs (except low-dose aspirin) may not be appropriate for people already at risk of heart disease or stroke.” The label comes up short on directions of dosage and duration. It simply states, “The smallest effective dose should be used.” Consumer Reports on Health takes into account duration as well as dose: “Take the lowest dose of an NSAID that brings relief, for the shortest period.”
The label has no listing of adverse effects, something that I would expect on any drug label. Here are just a few of them listed in Mosby’s Drug Guide for Nurses: Headache, dizziness, drowsiness, fatigue, tremors, confusion, insomnia, anxiety and depression. One other caution on adverse effects in general: Some reference books only list certain adverse effects. For example, one reference indicates it lists only those occurring in 1 percent or more of the population. What’s more, all the adverse effects may not yet be discovered. So a good rule is to assume that any new symptom you develop right after taking a new drug may be a side effect. Make sure your doctor rules it in or out as a side effect.
The ibuprofen label, like most drug labels, has no information about how soon the drug acts and how long it provides relief. The Hopkins book includes this information: “Onset of effect. For pain and fever 30 minutes. For arthritis, up to 3 weeks. Duration of action. 4 hours or more.” Mosby’s Drug Guide for Nurses agrees that it takes a half-hour for the onset of the drug’s effect, adds it reaches a peak in one to two hours, and has duration of action of four to six hours. Most references indicate that relief from arthritis may take much longer use of the drug, such as two weeks to a month.
The label is incomplete in providing information on storage. It says store at “controlled room temperature.” But what is controlled room temperature? A label should tell you that and many do. The AARP book has more complete instructions for storage: “Store at room temperature between 15 and 30 C (59 and 86 degrees F). Keep container tightly closed.” Incidentally, I think it is strange to give the Centigrade temperature first, when the Fahrenheit is the one almost universally understood in the U.S.
The label’s advice on telling your doctor of other medications and related products you’re taking also is deficient. It simply advises to tell the doctor of any drug you’re taking. It should say advise the doctor of any drug (both prescription and OTC), herbal supplement, nutritional supplement, vitamin or mineral you’re taking. This can be important, as, for example, there are herbal products that interact with ibuprofen such as feverfew, garlic, ginger, ginkgo biloba, and many more. I should add if your doctor prescribes without asking you what other drugs you’re taking, that is usually a signal to get another doctor who is smart enough to ask that important question. Perhaps the label advice should read: If your doctor isn’t smart enough to ask you about other drugs, herbal supplements, nutritional supplements, vitamin and minerals you’re taking, you better volunteer the information. But to test his competence, wait until he asks.
The label has a much shorter list of conditions that should be known to your doctor before taking ibuprofen than most good drug books and other references. Among those omitted on the label, but included on the list of Drug.com are asthma, polyps in your nose, if you smoke, and systemic lupus erythematosus (SLE). Drugs.com states, “If you have any of these conditions [it lists 9 altogether], you may need a dose adjustment or special tests to safely take ibuprofen.”
The dosing warning on the label might also be beefed up. It simply says, “Do not take more than directed.” Drugs.com is more persuasive: “Do not take more of this medication than is recommended. An overdose of ibuprofen can cause damage to your stomach or intestines.” The overdose warning on the label is also defective in that it is found under the heading “Keep out of reach of children.” So an adult taking the drug might skip that section, which also states: “In case of overdose, get medical help or contact a Poison Control Center right away.” It is also defective as it does not give the universal number for Poison Control, which is 800-222-1222. It also fails to give the symptoms of overdose, which is something Drugs.com does. Among other more compelling reasons for not taking more of the drug than directed, there is this bit of information on the Web site of Wyeth (makers of Advil, a brand-name of ibuprofen): Whether you take 400, 600, or 800 milligrams of ibuprofen, the pain relief is about the same. The usual over-the-counter dose is 200 milligrams. The drug is also sold in larger doses by prescription.
They’re some things that will never appear on the label, but which the user should be aware of. Consumer Reports on Health says taking effectiveness, safety and cost into account, it has chosen three generic NSAIDs as Consumer Reports Best Buy Drugs:
• Ibuprofen – costing an average $26 to $30 per month.
• Naproxen – costing an average $44 to $50 per month.
• Salsalate – costing an average $26 to $25 per month.
There’s one other kind of information that would appear on an ideal label in an ideal world: the non-drug approaches to treating pain (or whatever other condition the drug is being taken for). You may want to try a non-drug approach as the first step or along with the drug. Here are a few examples of the non-drug approach to the management of acute pain, recommended in The Nurse’s Pocket Guide: Diagnoses, Prioritized Interventions and Rationales: “Provide comfort measures (e.g., touch, repositioning, use of heat/cold packs, nurse’s presence), quiet environment, and calm activities to promote nonpharmacological pain management. Instruct in/encourage use of relaxation techniques, such as focused breathing, imaging, CDs/tapes (e.g., ‘white’ noise, music, instructional), to distract attention and reduce tension. Encourage diversional activities (e.g., TV/radio socialization with others).” I’d be curious about how the nurse is supposed to provide a “quiet environment” — as recommended above — in a hospital, where patients hear an endless series of medical equipment beeping and buzzing, where hospital personnel are constantly being paged, where personnel and others are running in and out of the room, etc. It’s almost impossible to get a quiet environment at night, and during the day — forget about it. Try some of those diversional activities recommended above for acute pain; maybe they work for acute noise.
The ideal label might also advise the user to question both his doctor and pharmacist (or other health care provider) about the drug and ask for any information that they might make available on the drug. Despite the impressive deficiencies of drug labels, you should read them. This is the classic case where what you don’t know may hurt you … or even kill you. So you should try to be informed as possible. And you should also appreciate the limits of drug labels in particular and drug material in general.
Drugs can deliver miracles or death warrants. You can influence which of the two you are more likely to get by proceeding with due care when using prescription or over-the-counter drugs, and by not taking them casually or without due diligence.
Don’t expect these or other drug labeling problems to be corrected anytime soon. I’ve been complaining about many drug labeling and regulation for many years, and I’ve seen the same problems continue for decades uncorrected. Under both Democratic and Republican administrations, the FDA — The Foot Dragging Administration — lives up to its name and reputation. And all this leads me to a little poem I wrote, with the first two lines borrowed from Gilbert and Sullivan:
Things are seldom what they seem;
Skim milk masquerades as cream.
If product labels had a nose,
They’d all be Pinocchio’s.
Herb Denenberg is a former Pennsylvania Insurance Commissioner, Pennsylvania Public Utility Commissioner, and professor at the Wharton School. He is a longtime Philadelphia journalist and consumer advocate. He is also a member of the Institute of Medicine of the National Academy of the Sciences. His column appears daily in The Bulletin. You can reach him at advocate@thebulletin.us