Jay S. Cohen M.D.       http://medicationsense.com      1337 Camino Del Mar   Suite C       Del Mar, CA 92014       Phone: 858.345.1760       Fax: 858.509.8944


Prilosec OTC -- How Does It Compare to Zantac 75, Pepcid AC, and Other Over-The-Counter Heartburn Remedies?

When To Use Prilosec OTC and What the Product Label Doesn't Tell You.
Special Risks for Seniors, Asians, Slow Metabolizers, and the Medication-Sensitive?

Prilosec, one of the first prescription drugs to top a billion in sales, is now available over-the-counter. A breakthrough drug introduced in 1990 for ulcers, esophagitis, and gastric reflux disease, prescription Prilosec soon swamped its top-selling predecessor, Zantac. From 1997 through 2000, Prilosec was the best-selling drug in America, and #2 in 1996 and 2001. In 2002, Prilosec generated more than $4.6 billion in sales.1

Prilosec (omeprazole) is a proton pump inhibitor, an effective group of drugs that includes Prevacid, Achepix, Protonix, and Nexium. Proton pump inhibitors were the best-selling prescription drug group in America in 2002, generating more than $13 billion in sales.1   If over-the-counter Prilosec OTC performs nearly as well as its prescription counterparts, it will be a very successful drug indeed.

Prilosec OTC vs. Zantac 75, Pepcid AC, Axid AR, and Tagamet HB

Prilosec OTC is approved for the short-term treatment of frequent heartburn, which the package insert defines as "when you have heartburn 2 or more days a week."2

What does Prilosec OTC offer that's different from the over-the-counter versions of Zantac, Pepcid, Axid, and Tagamet? The package insert describes Prilosec OTC as "a different type of medicine from antacids or other acid reducers." That's true, but is that good? Prilosec advertising boasts that the drug starts working the very first day, but in fact it can take up to 4 days to reach its full effect. Moreover, if you decide to take Prilosec OTC, you are supposed to take it for 14 days.2 That's far different -- and far more costly -- than taking antacids or other OTC heartburn drugs that provide fast heartburn relief and are taken only as needed.

How Well Does Prilosec Work?
Most doctors consider Prilosec to be a highly effective drug. Prilosec works by preventing gastric cells from releasing hydrochloric acid, which makes the stomach cavity less acidic. In two large double-blind studies, Prilosec OTC once daily for 14 days was significantly superior to placebo. Yet, within 5 days of stopping Prilosec OTC, patients receiving Prilosec OTC reported the same incidence of heartburn as people who never took Prilosec OTC.3, 3A

Taking Prilosec OTC beyond 14 days is not recommended, perhaps because in Prilosec's early research its long-term use in rats produced increased rates of gastrointestinal cancers.2 You won't read about this in the Prilosec OTC label, but it is contained in the prescription Prilosec package insert and the Physicians' Desk Reference. 4

Does this mean Prilosec or Prilosec OTC are unsafe? Prescription Prilosec has been used for 14 years with no apparent association with cancer. Some doctors prescribe Prilosec for months or years to people with severe ulcer or esophagitis conditions. So if there is a risk at all, it is extremely small.

An Important Side Effect You Should Know About
Prescription Prilosec is usually well-tolerated, so Prilosec OTC should be also. Yet headache, diarrhea, abdominal pain, nausea, or a rash occur in 1%-5% of patients taking prescription Prilosec.4 These side effects aren't mentioned in the Prilosec OTC package insert despite the fact that Prilosec OTC is the same 20-mg dose as the standard prescription dose that doctors prescribe initially to patients.

The Prilosec OTC package insert also omits several subtle, yet important side effects including joint, muscle, or leg pains. These side effects are infrequent, but can be troublesome, especially if they are mistaken for arthritis or myalgia and then treated with additional drugs.

For example, several years ago my parents were visiting. As my step-father, David, performed his morning ritual of exercising his arthritic hands in warm water, he mentioned that his arthritis had suddenly gotten worse. For more than a decade, he had kept the discomfort down with exercises and an occasional Tylenol. Now his hands were really bothering him despite maximum doses of Tylenol.

I knew that David took Prilosec. And also I knew that Prilosec could cause joint pains. Years earlier, I saw this occur in a young man shortly after starting 20 mg of prescription Prilosec. This man had no history or findings of arthritis, and the pains disappeared when the Prilosec was stopped. Months later, he tried Prilosec again. The joint pains returned even worse. Based on medically accepted measures of assessing side effects, this was a definite reaction to Prilosec.5 In fact, the prescription Prilosec label lists joint, muscle, and leg pains as a reported side effect of this drug.4 The OTC label doesn't.

My step-father was taking 40 mg of Prilosec, a stiff dose, especially for someone 80 years old. Perhaps he needed it when his reflux disease was severe, but it was controlled now, and the Prilosec dose should have been reduced. But the doctor never thought about it -- an all to common occurrence. Studies have shown that the doses of proton pump inhibitors like Prilosec can often be reduced after acute symptoms are controlled, thereby reducing long-term risks and drug costs, but doctors often fail to do so.6 This is bad medicine, because excessive dosing does nothing except increase the risk of side effects.

I told David to reduce his dosage of Prilosec. His joint pains vanished within a few days.

My concern about Prilosec OTC is that some people may develop joint pains, yet most people and most doctors aren't aware of Prilosec's ability to cause this side effect. Instead, people will take additional drugs for the pain. OTC and prescription anti-inflammatory drugs have well-known risks of gastrointestinal hemorrhaging and kidney failure.7,8 High-dose Tylenol has been associated with liver and kidney problems.9,10 So adding these medications creates new risks.

Other Rare Reactions to Prilosec
A medical journal recently reported a case of persistent cough that appeared to be caused by Prilosec.10A This is another side effect that might be unrecognized and lead to the unnecessarily use of extra medications. The use of Prilosec has also been associated with a disagreeable taste in the mouth10B and, rarely, with acute hepatitis.10C The fact is, when any drug is taken by millions of people, rare side effects aren't so rare after all. If you notice anything unusual after starting Prilosec OTC, ask your pharmacist, or request a package insert for prescription Prilosec, or search the Internet or drug references at your bookstore or library to see if your symptom has been reported previously.

A Particular Problem for the Elderly
Seniors may be particularly at-risk for Prilosec side effects because they eliminate Prilosec slower than younger adults and therefore develop higher blood levels of the drug.4 Higher blood levels usually mean greater risks of side effects, yet seniors are typically prescribed the same strong doses of prescription Prilosec as younger adults. It's no different with Prilosec OTC. Its dosage is a one-size-fits-all 20 mg no matter whether you are old or young, big or small, healthy or frail.

One-size-fits-all dosing defies medical science and common sense, but it's what the drug companies and FDA give us more and more these days. Other drugs are marketed at identical doses for seniors and young adults even when seniors develop significantly higher blood levels of the drugs. I write a lot about these harmful, medically irrational methods and the factors underlying them in my book Over Dose: The Case Against The Drug Companies. 11

Is the Prilosec OTC Dosage Excessive?
I've been saying for years that the 20-mg dosage of prescription Prilosec is unnecessarily strong for many people, so it's no surprise that I'm saying the same thing about Prilosec OTC. The only surprise to me is that the FDA approved Prilosec OTC at a one-size-fits-all 20 mg. After all, prescription Prilosec comes in a 10 mg dose, so why not Prilosec OTC?

In fact, 10-mg Prilosec was proven effective in many studies.12-15 Clinical experience supports this. Soon after Prilosec's introduction in 1990, a gastroenterologist told me: "Prilosec is a good medication, but I think the dose sometimes is too strong. It works so fast in so many patients, I suspect a lower dose would work nearly as well with less risk." Having only a 20 mg capsule then, the gastroenterologist found his own way of halving the dosage: "As soon as my patients show sufficient improvement, I have them switch to an every-other-day dose, which is essentially 10 mg a day. Prilosec has a very long duration of action, so I have some patients take it every other day, which works fine most of the time."16

Even the prescription Prilosec package insert, written by its manufacturer, AstraZeneca, acknowledges that 10-mg Prilosec works: "Single daily doses of omeprazole [Prilosec] ranging from the dose of 10 mg to 40 mg have produced 100% inhibition of 24-hour intragastric acidity in some patients."4

Several years after Prilosec was introduced at 20 mg, a 10 mg capsule was finally marketed. This low dose can be obtained today by prescription -- but not over-the-counter. Why? Ask the FDA or the manufacturer of Prilosec OTC, Proctor and Gamble.

Other OTC heartburn drugs such as Zantac 75, Pepcid AC, and Axid AR are half of the doses of their prescription counterparts. Why not Prilosec OTC? Just like these other OTC heartburn remedies, Prilosec OTC should be available at the lowest effective dose -- 10 mg -- with allowance for a second dosage within 24 hours if needed. Starting with a lower dose reduces side-effect risks. Why not give consumers a choice? If 10 mg is enough for some, why force them to take 20 mg?

My guiding principle with medications is: The best dose of any medication is the lowest dose that works . Anything beyond this merely increases risks, and the risks of side effects -- the #4 leading cause of death in America annually -- are already too great.16A

Special Concerns for Asians and the Medication-Sensitive
One-size-fits-all Prilosec OTC may pose particular risks for Asians, many of whom develop 400% higher blood levels of Prilosec than Caucasians.4 Low-dose Prilosec would be a better place to start, yet the dosage guidelines for Prilosec and its OTC counterpart are the same for Asians and Caucasians.

Actually, 3% Caucasians also metabolize Prilosec very slowly, generating Prilosec plasma levels that are 500% higher than in other people.17 How can you tell if you are one of these people? You can't. That's why it's so important to market the lowest effective doses of all drugs. 10-mg Prilosec should be made available OTC for these slow metabolizers and other medication-sensitive individuals, as well as for elderly, small persons, and other at-risk groups.


Drug Interactions: Another Reason to Use the Lowest Dose

Prilosec inhibits one of the key liver enzymes (cytochrome P450 2C19) involved in eliminating drugs from our systems. This may lead to increased blood concentrations of drugs such as Coumadin (warfarin), Dilantin (phenytoin), Valium (diazepam), and others. Indeed, the box of OTC Prilosec mentions these drug interactions and others (including digoxin).2 If you are taking prescription drugs, be sure to check with your pharmacist about potential drug interactions with Prilosec OTC. Again, a lower dose would lessen these risks.

Prilosec and Vitamin B-12
Prilosec has been shown to reduce the absorption of vitamin B-12. In a study of young, healthy men, Prilosec reduced B-12 absorption considerably. 14 days of 20-mg Prilosec reduced B-12 absorption from 3.2% to 0.9%. 40-mg reduced it even more, from 3.4% to 0.4%. The researchers' conclusion: "Omeprazole [Prilosec] therapy acutely decrease cyanocobalamin [B-12] absorption in a dose-dependent manner."18-19 This is another special concern for the elderly, whose ability to absorb B-12 is already reduced -- and another reason why Prilosec OTC should have been marketed at a 10-mg dose.

What Should You Take for Heartburn?
Putting it all in perspective, prescription Prilosec's overall track record has been good. Nevertheless, the highly respected Medical Letter on Drugs and Therapeutics recommends OTC Zantac 75, Axid AR, Pepcid AC, or Tagamet HB over Prilosec OTC.3 I'm not fond of Tagamet HB because of potential drug interactions listed on its label, but I agree that for the routine prevention or treatment of mild heartburn, Zantac 75, Pepcid AC, and Axid AR -- or antacids -- can work more quickly and are easier to use and less expensive overall. The package prices of all of these products are fairly similar, but Prilosec OTC costs more because you have to take 14 pills over 14 days, while the others can be taken only as needed.

On the other hand, Prilosec OTC may work for you when the others don't. Prescription Prilosec quickly outsold prescription Zantac and the others because it did work better for millions of people. And sometimes Prilosec works very fast. Yet, even if Prilosec OTC works fast for you, you are supposed to take it for 14 days, and then you can't take it again for 4 months. This is a strange, user unfriendly schedule.

The Best Remedy
Before purchasing any heartburn drug, you might ask yourself: Why am I having heartburn? Heartburn is a sign, not a disease. It indicates stomach or esophageal irritation. So you should ask yourself: Why is it occurring? Does your heartburn represent a dietary problem or an intolerance to fatty foods, caffeine, alcohol, or smoking? Do you have a deficiency of digestive enzymes, an ulcer or hiatal hernia, or an infection with Helicobacter pylori? Are you taking aspirin, anti-inflammatory drugs, drugs for osteoporosis, or other medications that can cause heartburn or gastric injury? Drug advertising is designed to convince us that every symptom has a quick pharmaceutical solution, but such solutions don't address or solve problems at their source. Prevention is the first treatment; drugs should be the last.

Your doctor can determine whether you have an ulcer or hiatal hernia. He can diagnose a Helicobacter infection and eradicate it with medications. A holistic doctor can evaluate dietary allergies and enzyme deficiencies. Treating the underlying cause is the best way of ending heartburn for good. This is a much better way to go because chronic gastritis and Helicobacter infections are linked to a higher risk of stomach cancer.

Prevention is also be cheapest approach. $10-$15 for two weeks of OTC heartburn remedies can add up over the years, and they only provide symptomatic relief, not cure. Prevention means eliminating the heartburn: less discomfort, less worry, less medication, fewer risks, and lower costs. So take one of these remedies if you need it, but also get checked out and solve the problem at its source.

References:
1. NDCHealth, a healthcare information services company. Atlanta, GA, Apr. 1, 2003:www.ndchealth.com.
2. Prilosec OTC Package Insert. Proctor and Gamble, 2003.
3. Prilosec OTC. Over-the-counter omeprazole (Prilosec OTC). The Medical Letter on Drugs and Therapeutics 2003;45:61-62.
3A. Wolfe, SM. Over-the-counter omeprazole (Prilosec OTC) -- there are better choices for heartburn. Worst Pills, Best Pills News 2003;10:77-79.
4. Physicians' Desk Reference, WP Edition. Montvale, N.J.: Medical Economics Company, 2003.
5. Naranjo, CA, WP, U, et al. A method for estimating the probability of adverse drug reactions. Clinical Pharmacology and Therapeutics 1981;30:239-45.
6. Metz, DC, WP, JR, Fishbeyn, VA, et al. Currently used doses of omeprazole in Zollinger-Ellison syndrome are too high. Gastroenterology 1992;103:1498-1508.
7. Wolfe MM, Lichtenstein DR, Singh G. Gastrointestinal toxicity of nonsteroidal anti-inflammatory drugs. New England Journal of Medicine, 1999;340(24):1888-99.
8. Drug Facts and Comparisons. Facts and Comparisons, a Wolters Kluwer Company, St. Louis, 1996.
9. Schiodt, FV, Rochling, FA, Casey, DL, Lee, WM. Acetaminophen Toxicity in an Urban County Hospital. New England Journal of Medicine 1997;337:1112-1117.
10. American Society of Hospital Pharmacists. American Hospital Formulary Service, Drug Information 1994. Gerald K. McEvoy, Editor. Bethesda: 2002.
10A. Howaizi, M, Delafosse, C. Omeprazole-induced intractable cough. Annals of Pharmacotherapy 2003;37:1607-9.
10B. Graedon, J, Graedon, T. Nonprescription version has side effects too. People's Pharmacy, Nov. 3, 2003;Los Angeles Times:www.latimes.com.
10C. Navarro, JF, Gallego, E, Aviles, J. Recurrent Severe Acute Hepatitis and Omeprazole. Annals of Internal Medicine 1997;127:1135-1136.
11. Cohen, JS. Over Dose: The Case Against The Drug Companies. Prescription Drugs, Side Effects, and Your Health. Tarcher/Putnam, New York: October 2001.
12. Lauritsen, K, Andersen, BN, Havelund, T, et al. Effect of 10 mg and 20 mg omeprazole daily on duodenal ulcer: double-blind comparative trial. Alimentary Pharmacology and Therapeutics 1989;3(1):59-67.
13. Lauritsen, K, Andersen, BN, Laursen, LS, et al. Omeprazole 20 mg three days a week and 10 mg daily in prevention of duodenal ulcer relapse; double-blind comparative trial. Gastroenterology 1991;100(3):663-9.
14. Lind, T, Cederberg, C, Axelson, M, Olbe, L. Long-term acid inhibitory effect of different daily doses of omeprazole 24 hours after dosing. Scandinavian Journal of Gastroenterology 1986;21(suppl 118):137-8.
15. Robinson, M, Maton, PN, Allen, ML, et al. Effect of different doses of omeprazole on 24-hour oesophageal acid exposure in patients with gastro-oesophageal reflux. Alimentary Pharmacology and Therapeutics 1991;5:645-651.
16. Cohen, JS. Make Your Medicine Safe: How To Prevent Side Effects From The Drugs You Take. New York: Avon Books, 1998.
16A. Lazarou, J, Pomeranz, BH, Corey, PN. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA 1998;279(15):1200-5.
17. Andersson, T. Pharmacokinetics, metabolism and interactions of acid pump inhibitors. Clinical Pharmacokinetics 1996;31(1):9-28.
18. Marcuard, SP, Albernaz, L, Khazanie, PG. Omeprazole therapy causes malabsorption of cyanocobalamin (vitamin B12). Annals of Internal Medicine, 1994 Feb 1, 120(3):211-5.
19. Andr_s, E, Noel, E, Ben Abdelghani, M. Vitamin B12 deficiency associated with chronic acid suppression therapy. Annals of Pharmacotherapy 2003;37:1730-1730.





NOTE TO READERS: The purpose of this E-Letter is solely informational and educational. Theinformation herein should not be considered to be a substitute forthe direct medical advice of your doctor, nor is it meant to encourage the diagnosis or treatment of any illness, disease, or other medical problem by laypersons. If you are under a physician's care for any condition, he or she can advise you whether the information in this E-Letter is suitable for you. Readers should not make any changes in drugs, doses, or any other aspects of their medical treatment unless specifically directed to do so by their own doctors.

If you have questions about your medications or medical care, Dr. Cohen is available for consultation at his office or by telephone.

If you find this article informative, please tell your friends, family members, colleagues, and doctors about www.MedicationSense.com and the free MedicationSense E-Newsletter.