WHITEHOUSE STATION, N.J., March 9, 2010 - Merck is committed to putting patients first and providing accurate information regarding the efficacy, safety and tolerability of our medicines. Merck offers the following statement concerning the osteoporosis medication FOSAMAX® (alendronate sodium) and reports of jaw problems associated with delayed healing and infection of the jaw often following tooth extraction. The condition is known as osteonecrosis of the jaw (ONJ).
ONJ is not well understood and may occur for a number of reasons. Most reported cases of osteonecrosis in bisphosphonate users have been in cancer patients treated with intravenous bisphosphonates, but cases have also been reported in patients taking oral bisphosphonates, including FOSAMAX. Known risk factors for osteonecrosis of the jaw include invasive dental procedures (e.g., tooth extraction, dental implants, boney surgery), diagnosis of cancer, concomitant therapies (e.g., chemotherapy, radiotherapy, corticosteroids), poor oral hygiene, and co-morbid disorders (e.g., periodontal and/or other pre-existing dental disease, anemia, coagulopathy, infection, ill-fitting dentures).
In controlled clinical trials involving more than 28,000 patients (over 17,000 of whom were treated with FOSAMAX), contributing as much as 10 years' data with alendronate, there have been no reports of ONJ. This includes ~3000 osteoporosis patients taking alendronate for 3-5 years and ~800 patients taking alendronate for 8-10 years. Since their market introduction, over 225 million total prescriptions have been dispensed for FOSAMAX/FOSAMAX Plus D, Actonel (risedronate) and Boniva (ibandronate) in the U.S.
In worldwide post-marketing experience with FOSAMAX/FOSAMAX Plus D, rare reports consistent with osteonecrosis of the jaw have been received. Many of these reports lack sufficient clinical details to make definitive assessments and/or are confounded, particularly since a generally accepted definition of ONJ in the general population is unknown. As of January 15, 2009, Merck estimates the worldwide, cumulative reporting rate of osteonecrosis of the jaw to range between 1.6/100,000 patient-treatment-years and 3.84/100,000 patient-treatment-years, regardless of causality.
On January 31, 2005, Merck received a request dated January 24, 2005 from the Food and Drug Administration to update the label for FOSAMAX to include bisphosphonate class labeling for ONJ. Merck submitted a draft revised label to FDA on March 1, 2005. FDA comments on this draft revised label were received in June 2005, and the new label was made publicly available in July 2005. In March 2010, the FDA approved revisions to the label for FOSAMAX that added, updated, and reordered information regarding ONJ.
Rare cases of ONJ have also been reported in patients who do not have osteoporosis and who have not taken any bisphosphonate medicines. These cases have been discussed in articles that have been published in the medical literature.
All products containing FOSAMAX include the following language pertaining to ONJ in the "Precautions" or “Warnings and Precautions” section of their respective package circular:
Osteonecrosis of the jaw (ONJ), which can occur spontaneously, is generally associated with tooth extraction and/or local infection with delayed healing, and has been reported in patients taking bisphosphonates, including FOSAMAX [FOSAMAX PLUS D]. Known risk factors for osteonecrosis of the jaw include invasive dental procedures (e.g., tooth extraction, dental implants, boney surgery), diagnosis of cancer, concomitant therapies (e.g., chemotherapy, corticosteroids), poor oral hygiene, and co-morbid disorders (e.g., periodontal and/or other pre-existing dental disease, anemia, coagulopathy, infection, ill-fitting dentures).
For patients requiring invasive dental procedures, discontinuation of bisphosphonate treatment may reduce the risk for ONJ. Clinical judgment of the treating physician and/or oral surgeon should guide the management plan of each patient based on individual benefit/risk assessment.
Patients who develop osteonecrosis of the jaw while on bisphosphonate therapy should receive care by an oral surgeon. In these patients, extensive dental surgery to treat ONJ may exacerbate the condition. Discontinuation of bisphosphonate therapy should be considered based on individual benefit/risk assessment.
Information for ONJ is also provided in the "Adverse Reactions" section of the package circular as well as in the patient package insert for the products containing FOSAMAX. As part of a review of your medical history with your healthcare providers (such as dentists, physicians, oral surgeons or others), be sure to include any product containing FOSAMAX in your list of medicines and talk to your healthcare provider if you have any questions about FOSAMAX.
FOSAMAX is indicated for the treatment of osteoporosis in postmenopausal women. For the treatment of osteoporosis, FOSAMAX increases bone mass and reduces the incidence of fracture, including those of the hip and spine. FOSAMAX is also indicated to increase bone mass in men with osteoporosis.
Osteoporosis, the most prevalent bone disease in the U.S., can lead to bone loss and an increased risk of fractures. Over 10 million Americans over the age of 50 have osteoporosis and another 34 million have low bone mass. Osteoporosis is especially common in women after menopause, but also occurs in older men. Most often, it is due to an increase in the rate of resorption (breakdown) of bone tissue that is not matched by the rate of bone formation. The risk of having an osteoporosis-related fracture increases with age. According to the Surgeon General, osteoporosis is a national health threat and by 2020 one in two Americans over the age of 50 will be at risk for fractures from osteoporosis or low bone mass. In fact, one out of every two women over age 50 will have an osteoporosis-related fracture in their remaining lifetime, with the risk of fracture increasing with age.
Important Information About FOSAMAX
FOSAMAX, like other bisphosphonate containing products, should be used with caution in people with certain stomach or digestive problems. FOSAMAX should not be used if the patient has certain disorders of the esophagus that delay emptying or if the patient is unable to stand or sit upright for at least 30 minutes. In addition, FOSAMAX should not be used in patients with severe kidney disease or low levels of calcium in their blood, in patients who are allergic to FOSAMAX or in patients who are pregnant or nursing. Patients who have difficulty swallowing liquids should not take FOSAMAX oral solution.
Some patients may develop severe digestive reactions including irritation, inflammation or ulceration of the esophagus. The risk of severe esophageal experiences appears to be greater in patients who fail to follow dosing instructions (see prescribing information for more details). Patients who experience new or worsening heartburn, difficulty or pain when swallowing or chest pain should stop taking the drug and call their doctor right away. Patients who develop severe bone, joint and/or muscle pain at any time should contact their doctor.
The standard dosing regimen for FOSAMAX includes swallowing the tablet with six to eight ounces of plain water the first thing upon arising for the day and at least 30 minutes before the first food, beverage or medication of the day. After swallowing FOSAMAX, patients should not lie down for at least 30 minutes and not until after consuming their first food of the day. Patients should not chew or suck on a tablet of FOSAMAX.
For more information on products containing FOSAMAX, please see and read the prescribing information and patient package insert which are available at www.fosamax.com.
Addendum: Several independent organizations have published statements related to osteonecrosis of the jaw (ONJ). Merck does not necessarily endorse the perspectives or opinions expressed within these statements. Also, the prescribing information of currently available intravenous and oral bisphosphonates may provide information about ONJ. To help healthcare professionals in their efforts to understand ONJ, a non-exhaustive list of online addresses associated with independent organizations and available intravenous and oral bisphosphonates is provided as follows.
Information from the National Institutes of Health
Background from the American Dental Association
Statement from the National Osteoporosis Foundation
Statement from the American Association of Oral and Maxillofacial Surgeons
Statement from the European Society on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis
Statement from the American Society for Bone and Mineral Research
Statement from Canadian Task Force on ONJ, comprised of the Canadian Association of Oral and Maxillofacial Surgeons in association with national and international multidisciplinary societies
Prescribing Information for Oral Bisphosphonates
Prescribing Information for IV Bisphosphonates