MERCK WARNING

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

March 15, 1996

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

Merck & Co., Inc.
PO Box 4
Sumneytown Pike
West Point, PA 19486-0004

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

If you suffer from Osteonecrosis of the jaw (ONJ) or jaw death as a result of taking Fosamax you should contact an attorney. Please fill out the form below and your submission will be forwarded to an experienced attorney.

Free Merck Warning Consultation

Title:
First Name:	*
Middle Name:
Last Name:	*
Home Phone:	*
Cell Phone:
Work Phone:
Email Address:
Address:	*
City:	*
State, Zip:	* *
What is the best way to reach you? Please provide the best place, time and method for contacting you.

Alternate Contact Person (not living in same household)

Title:
First Name:
Last Name:
Home Phone:
Cell Phone:
Work Phone:
Address:
City:
State, Zip:
Relationship to Injured:

Was the patient prescribed Fosamax?	Yes No
For what condition was Fosamax prescribed?
When did Fosamax therapy start?	*
When did Fosamax therapy end?	*
Please list name and address of doctor who prescribed Fosamax:
What dental/jaw problems do you have?
What City/State did these occur in? *
Please list name and address of doctor/dentist who you have seen for these problems:

Has any doctor linked your dental/jaw problems to Fosamax?	Yes No
If so, please list the name and address of doctor/dentist:

Case Description*
Please explain exactly what happened, trying to state
as thoroughly as possible who you believe was responsible
and why you believe that person was negligent:

Comments / Additional Information
Is there anything else that would assist us in
understanding the facts of your case?

To Better Serve You:

Please tell us how you found us? If "other" please specify.

Please specify how you found us (if other than above):

If you found us using a search engine,
please tell us which search engine?

Please tell us exactly what terms you typed into the
search engine to find us? (i.e. Personal Injury Lawyers)

I understand that by filling out this free consultation form I am not forming an attorney client relationship. I understand that I may only retain an attorney by entering into a fee agreement and that by submitting this form I am not entering into a fee agreement. I understand that not all submissions may receive a response.
Yes No

I agree that the above does not constitute a request for legal advice. I agree that any information that I will receive in response to the above question is general information and I will not be charged for the response to this e-mail question. I further understand that the law for each state may vary, and therefore, I will not rely upon this information as legal advice. I agree that if this matter requires advice regarding my home state, local counsel may be contacted for referral of this matter. I understand that email is not secure and thus I am not forming a confidential relationship.
Yes No

I have read and agree with the TERMS AND CONDITIONS
Yes No

By Clicking the box below, I agree to submit my case for a free case evaluation:

* = Required Fields

MERCK WARNING

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

Free Merck Warning Consultation

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