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This is the retyped text of a letter from Merck & Co., Inc. Contact the company for a copy of any referenced enclosures.

IMPORTANT INFORMATION

FOSAMAX (ALENDRONATE SODIUM TABLETS):
PROPER DOSING AND AVOIDANCE OF ESOPHAGEAL SIDE EFFECTS

Dear Doctor:

We would like to call your attention to esophageal side effects in patients taking FOSAMAX Since market introduction of the product, some of these side effects have been of greater severity than we observed in our controlled clinical trials. It is clear from the case reports received by Merck & Co., Inc. that FOSAMAX can be irritating to the esophagus but that careful adherence to the dosing instructions can reduce the potential for these side effects. In a large proportion of cases reported, there is evidence that FOSAMAX was not dosed in the manner recommended in the Product Circular. We have therefore made modifications to the Product Circular (and Patient Package Insert) that we believe will further reduce the risk of adverse reactions such as esophagitis, esophageal erosion or ulceration. Merck & Co., Inc. is writing to you directly as the most rapid way to bring this important information to your attention.

FOSAMAX is an aminobisphosphonate, a selective inhibitor of bone resorption that is the first nonhormonal therapy indicated for the treatment of osteoporosis in postmenopausal women (the daily oral dosage is 10 mg). FOSAMAX is also indicated for the treatment of Paget's disease of bone (the daily oral dosage is 40 mg for six months). In controlled clinical trials of three years' duration in postmenopausal women with osteoporosis, FOSAMAX was generally well tolerated. Like other bisphosphonates, however, FOSAMAX was recognized to have the potential to cause local irritation of the upper gastrointestinal mucosa. In ongoing, carefully-monitored studies of over 12,000 patients, esophageal irritation has been no different in incidence or severity than observed in the completed three-year trials. (As you know, esophageal ulcers, considered to be drug related, were reported in 1.5% of the patients taking FOSAMAX 10 mg in three-year trials.)

As part of our customary postmarketing surveillance, we have become aware of a number of case reports of esophagitis and esophageal ulceration in which patients have presented with difficulty or pain on swallowing, and/or retrosternal pain. When endoscopy has been performed, the findings have been consistent with a chemical irritation of the esophagus.

Although infrequent, the reports of esophagitis/ulceration have generally been of a more severe nature than observed in either previous clinical trials, or in ongoing studies of FOSAMAX (alendronate sodium tablets). In a large majority of the postmarketing reports, it appears patients were not compliant with our recommended dosing instructions (for example, patients were taking FOSAMAX with little or no water, taking it at bedtime and/or lying down within minutes after taking it, etc.). Several patients continued taking FOSAMAX after the occurrence of symptoms suggestive of esophageal irritation. In a few cases, patients have been found to have previously undiagnosed esophageal disorders.

We therefore strongly advise strict compliance with the dosing instructions, which have been updated in the Product Circular, and are summarized in the attachment. Please read them carefully, and in the case of any question contact the Merck National Service Center at (800) 672-6372. Enclosed is a copy of the revised Product Circular. Merck has been taking, and is continuing to take, a number of steps to ensure that physicians, pharmacists, and patients understand the importance of proper dosing of FOSAMAX. We believe that the risk of esophageal irritation can be substantially decreased with adherence to these recommendations.

At Merck, our primary concern remains the safety and well-being of the patients who use our products. We appreciate the continuing efforts of doctors, pharmacists and other healthcare professionals in communicating dosing information to patients. We truly value your trust in us and thank you very much for your time and attention to this matter.

Sincerely

Louis M. Sherwood, MD
Senior Vice President
Medical and Scientific Affairs
U.S. Human Health

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