Molecular structure of cimetidine
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Tagamet

Cimetidine is a histamine H2-receptor antagonist that inhibits the production of acid in the stomach. It is largely used in the treatment of heartburn and peptic ulcers. It is marketed by GlaxoSmithKline under the trade name Tagamet®, and was approved by the Food & Drug Administration for prescriptions starting January 1, 1979. more...

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Clinical Use

History and development

Cimetidine was the prototypical histamine H2-receptor antagonist from which the later members of the class were developed. Cimetidine was the culmination of a project at Smith, Kline & French (SK&F; now GlaxoSmithKline) to develop a histamine receptor antagonist to suppress stomach acid secretion.

At the time (1964) it was known that histamine was able to stimulate the secretion of stomach acid, but also that traditional antihistamines had no effect on acid production. In the process, the SK&F scientists also proved the existence of histamine H2-receptors.

The SK&F team used a rational drug-design structure starting from the structure of histamine - the only design lead, since nothing was known of the then hypothetical H2-receptor. Hundreds of modified compounds were synthesised in an effort to develop a model of the receptor. The first breakthrough was Nα-guanylhistamine, a partial H2-receptor antagonist. From this lead the receptor model was further refined and eventually led to the development of burimamide - the first H2-receptor antagonist. Burimamide, a specific competitive antagonist at the H2-receptor 100-times more potent than Nα-guanylhistamine, proved the existence of the H2-receptor.

Burimamide was still insufficiently potent for oral administration and further modification of the structure, based on modifying the pKa of the compound, lead to the development of metiamide. Metiamide was an effective agent, however it was associated with unacceptable nephrotoxicity and agranulocytosis. It was proposed that the toxicity arose from the thiourea group, and similar guanidine-analogues were investigated until the ultimate discovery of cimetidine.

Shortcomings

Cimetidine is a known inhibitor of many isozymes of the cytochrome P450 enzyme system (specifically CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4). This inhibition forms the basis of the numerous drug interactions that occur between cimetidine and other drugs. For example, cimetidine may decrease metabolism of some drugs, such as oral contraceptives.

Adverse drug reactions were also found to be relatively common with cimetidine.

The development of longer-acting H2-receptor antagonists with reduced adverse effects such as ranitidine proved to be the downfall of cimetidine and, whilst it is still used, it is no longer amongst the more widely used H2-receptor antagonists.

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Tag, You're It - Tagamet - Statistical Data Included
From Brandweek, 9/20/99 by Christine Bittar

SmithKline's Tagamet Ups Ante with Liquid, $29M Ads

Looking to give its Tagamet antacid brand a much-needed boost, SmithKline Beecham will invest $29 million on a television ad campaign to kick off the introduction of Tagamet HB 200 Liquid, the first second-generation antacid, or H2 blocker, to become available in liquid form. It will launch in a 12-oz. bottle in Cool Mint flavor, per trade sources.

Tagamet has been one of the suffering brands in the intense inter-category war between immediate-action and preventative antacids, spurred by Rx-to-over-the-counter H2 blocker switches and, more recently, the rise of private label brands.

Pittsburgh-based SmithKline's effort is anchored by consumer research indicating that antacid form is one of the highest purchase priorities for consumers, with liquid fans currently forced to settle for immediate-relief products only. SmithKline is hoping that by being the first manufacturer to get an OTC liquid H2 blocker out, it can reverse the brand's erosion even while capturing a higher price on a per-dose basis.

While sales in the stomach remedies category have risen slightly this year, Tagamet sales have dropped by almost 17% as of April 25, putting it behind all the modestly performing liquid brands like Mylanta and Maalox, per scanner data from Information Resources Inc. At the same time, SmithKline has done an exceptional job with Tums, No. 2 in the category and up 15%, while J&J/Merck's category-leading Pepcid brand has eased off by 2%. In response to essentially flat sales of Pepcid over the past several years, J&J rolled out a chewable form last year, and a gelcap is expected to come next.

TV spots, likely playing up the soothing feeling of a liquid in contrast to a tablet and the medicine's ability to offer "long-lasting relief," break around Nov. 28, likely via Jordan McGrath, New York, the brand's lead agency. In sales materials, SmithKline claimed consumers reported that Tagamet Liquid provided relief lasting five times longer than Mylanta, and a soothing feeling at the onset of symptoms.

The heavy ad support will be buttressed by unusually generous consumer sampling inducements, as SmithKline looks to get the liquid into as many hands as possible by eliminating price as an obstacle. All initial shipments will have a $5 mail-in refund on the box, worth more than half the shelf price of the product. Rolling in a 12-oz. bottle containing about 18 doses, Tagamet Liquid will be line priced with the 30-count tablet at about $8.50. Full-and half-page national FSIs offering $2 off liquid and $1 off the tablets are scheduled for Nov. 14, Jan 2, April 2, June 25, Aug. 27 and Nov. 11. In addition, during the launch SmithKline will also offer $1 coupons in stores at national food and mass outlets, along with POP at food, drug and mass stores.

The Food and Drug Administration has not approved Tagamet Liquid for children under 12, and is requiring that the product carry a bold warning to emphasize that its safety for children has not been determined. If Tagmet Liquid later wins approval for children, it would more directly compete with traditional over-the-counter stomach liquids, such as Procter & Gamble's Pepto-Bismol and Mylanta, that can be used by children.

Putting the most into media for its premier brand, Tums, SmithKline committed only $20 million to Tagamet in 1998 and $10 million in the first six months of this year. By contrast, Tums received $39 million and $24 million in spending, respectively, according to Competitive Media Reporting.

COPYRIGHT 1999 BPI Communications, Inc.
COPYRIGHT 2000 Gale Group

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