NEW YORK (AP) _ Call it the battle of the bellyache.

Three of the world's most popular prescription drugs _ ulcer medicines called Zantac, Tagamet and Pepcid _ are being reintroduced as a powerful new generation of over-the-counter stomach acid blockers.

They have the potential to revolutionize the $1 billion-per-year market for antacids, which hasn't seen a major innovation since the last century. Their fight for supremacy promises to be one of the drug industry's most tenacious.

The drugs promise a significant breakthrough _ they block production of stomach acid, providing all-day relief from indigestion, heartburn and sour stomach.

That's welcome news for the millions of Americans who have spent a day popping Tums or slugging Mylanta after a hefty serving of spicy meatballs.

By late this year or early next, industry analysts predict the trio of new products will be common sights on television, magazines and billboards as manufacturers gear up advertising campaigns expected to cost at least $100 million each.

``I think we will be blitzed,'' said Mariola Haggar of C.J. Lawrence-Deutsche Bank in New York.

And for good reason.

``We're talking about three gladiators here,'' said David Saks of Gruntal & Co. ``It would be a major disappointment if they, as a combined group, didn't double the size of the gastrointestinal therapy market,'' within three years, he said.

Drug companies often get their latest over-the-counter products from the ranks of their prescription medicines and these entries are the biggest ever to make the switch.

Tagamet, introduced by Britain's SmithKline Beecham PLC in 1977, became the first drug in history to sell $1 billion a year. Zantac is now the best selling drug in the world, with annual sales of about $3.6 billion.

The drugs are the best-known members of a family called H2 blockers. As prescriptions, these pills have treated hundreds of millions of patients with gastric ulcers or other gastrointestinal diseases. They work quite differently than antacids.

Antacids, typically made from chemicals like calcium carbonate or magnesium hydroxide, neutralize stomach acid that has already been produced. While they go to work in a few minutes, they only last about two hours _ the time they stay in the stomach.

H2 blockers must be absorbed into the bloodstream, so the onset of relief is longer, perhaps up to an hour. Once there, however, they slow down or stop acid from being produced for six to 12 hours, doctors say.

They act by blocking proteins called H2 receptors in the stomach's acid-producing cells from triggering a chemical reaction that causes the cells to secrete acid. The effect is similar to the antihistamines people commonly take for a stuffy nose to cut the production of mucus.

While Tagamet, Pepcid and Zantac vary widely in potency, the non-prescription dosages are being structured so all three will have about the same effectiveness, doctors say. Therefore, their success depends largely on the timing of their introduction and how they're promoted.

On that score, Pepcid has an obvious lead. The drug's creator, Merck & Co., in partnership with its New Jersey neighbor Johnson & Johnson, persuaded the Food and Drug Administration to approve non-prescription Pepcid AC (for acid controller) in April and rushed it to market by early June.

J&J-Merck is doing saturation advertising, hoping to ingrain Pepcid's name in the minds of consumers before the others even hit the market.

SmithKline Beecham got approval for Tagamet HB (for heartburn) in June and expects to begin selling it in the early fall.

Zantac, made by Britain's Glaxo Wellcome PLC, hasn't gotten FDA approval yet and won't be introduced until late this year at the earliest, analysts say.

However, that delay may be irrelevant once Zantac arrives. As a prescription drug, Zantac outsells the others by more than 4-to-1, a market dominance guaranteed to make its non-prescription version a major player.

Nonetheless, Pepcid has other advantages besides timing. J&J-Merck did extra studies on humans and got permission to sell Pepcid for a new use _ preventing indigestion, not just curing it.

``Every consumer can relate to certain foods that always cause them heartburn _ chili, Mexican or spicy food,'' said Merck spokesman Gary Lachow. ``We believe people can prudently eat meals they once were unable to, by taking a Pepcid AC an hour prior,'' he said.

Although doctors say Zantac and Tagamet will do the same, Glaxo and SmithKline never asked that their drugs be used that way.

It's a decision that SmithKline vice president Jack Ziegler, for one, said he doesn't regret. ``Very few consumers can actually predict when they're going to get heartburn,'' said Ziegler.

Pepcid's other advantage concerns safety _ or at least the perception of it.

On rare occasions, some H2 blockers have interfered with other medicines. The FDA required SmithKline to include a warning on Tagamet HB's label telling people who take three other drugs to consult their doctors before taking it. The drugs are warfarin, a blood thinner used mostly by heart patients; theophylline, an asthma drug; and phenytoin, an epilepsy drug whose most popular brand name is Dilantin.

Zantac may also be required to make such warnings, but the FDA didn't require them for Pepcid because the risks are considered smaller.

``I'm not making a claim that Pepcid is safer, but we do have the tremendous benefit of not having any warnings vis a vis Tagamet and I assume we'll have the same benefit vis a vis Zantac,'' said Dr. Patrick Ciccone, a J&J-Merck vice president.

Doctors, however, dismiss any safety concerns as extremely minor. Robert Fisher, chairman of the gastroenterology section at the Temple University School of Medicine in Philadelphia, said Tagamet in particular has gotten a ``bum rap.''

``The truth is those effects haven't bothered a lot of people. It's one of the safest medications ever introduced. (Pepcid) may be a little safer.''

Despite their blockbuster potential, analysts point out that profits from these drugs probably won't come for two years. The biggest reason is the tremendous start-up and promotional costs.

In addition, Stephen Gerber, an analyst for Oppenheimer & Co., expects some consumers may get turned off by the drugs' slow-acting nature compared to current over-the-counter remedies.

If the drugs do sell well, they will steal sales of antacids made by the same companies. SmithKline, for instance, makes Tums and J&J-Merck makes Mylanta.

In coming years, there will be other competitors, including cheaper generic versions and perhaps other brand names like Eli Lilly & Co.'s H2 blocker, Axid.

The drugs will also be expensive. A box of 12 Pepcid sells for $5.50 at a discount drug chain in New York City, while 75 Tums go for $2.39.

Analyst Haggar doubts however that consumers will be bothered by sticker shock when they see the drugs on store shelves.

``Pepcid costs about 45 cents a pill, but it may provide relief for a whole day. That's less than a cup of coffee,'' she said.

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