4/14/2006
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 in response to news reports 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 bisphosphonate-associated osteonecrosis have been in cancer patients treated with intravenous bisphosphonates, but cases have occurred in patients with postmenopausal osteoporosis and other diagnoses. Known risk factors for osteonecrosis include a diagnosis of cancer, concomitant therapies (e.g., chemotherapy, radiotherapy, corticosteroids), poor oral hygiene, and co-morbid disorders (e.g., pre-existing dental disease, anemia, coagulopathy, infection).
In controlled clinical trials involving more than 17,000 patients, 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 191 million total prescriptions have been dispensed for FOSAMAX/FOSAMAX Plus D, Actonel (risedronate) and Boniva (ibandronate) in the U.S. and 77% of these have been dispensed as FOSAMAX/FOSAMAX Plus D.
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 March 31, 2006 , Merck estimates the worldwide, cumulative reporting rate of osteonecrosis of the jaw to be <1/100,000 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.
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" section of their respective package circular:
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.
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 & Co, Inc., 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.
This article was originally published by www.merck.com
Dead Jaw is also known as ONJ or Osteonecrosis of the jaw. Osteonecrosis of the jaw is an uncommon condition that involves the loss or breakdown of the jaw bone. Symptoms include pain, swelling, or infection of the gums, loosening of the teeth, poor healing of the gums, and numbness or feeling of heaviness in the jaw.
If you experience any of the symptoms of Osteonecrosis of the jaw, contact your oncologist and dentist immediately.
Merck & Co., which faces more than 9,000 lawsuits over its Vioxx® painkiller, misrepresented the safety of its osteoporosis drug Fosamax® by withholding warnings that it could kill jawbone tissue, according to a lawsuit filed Monday.
Linda Secrest, 59, sued Merck, accusing it of failing to warn doctors and patients that Fosamax® could hamper blood flow to the jaw. Secrest, who began taking the drug in 2000, says she was diagnosed with jawbone tissue death in 2005. The condition is irreversible.
Merck should be ordered to change the Fosamax® prescribing information given to doctors and pay the cost of medical monitoring for users, Secrest says.
The complaint, in federal court in Fort Myers , Fla. , seeks to represent more than 10 million Fosamax® users. It is the second of about 200 suits that Secrest's attorney, Tim O'Brien, said he planned to file.
Merck spokesman Chris Loder said claims of jawbone tissue death caused by Fosamax® were "exceedingly rare." A warning notice was added to the drug's label in July 2005 at the Food and Drug Administration's request, he said.
Fosamax® and Fosamax® Plus D together are the most-prescribed medicine for osteoporosis in post-menopausal women.
This article was originally published by
Over a three-year period, the jaws of dozens of patients who had undergone oral surgery at his hospital had failed to heal properly. Part of the jawbone had died and become exposed.
"We never saw this before in the jaw" except in patients who had received radiation therapy to that part of the face, says Ruggiero, chief of oral and maxillofacial surgery at Long Island Jewish Medical Center. "It just never existed."
Further investigation revealed one common thread: All of the patients had been treated with at least one of a class of drugs called bisphosphonates, like Fosamax®.
Most were cancer patients who had received the intravenous bisphosphonates Zometa or Aredia or both for excessive calcium in their blood or bone tumors.
But about 10% were osteoporosis patients who had taken an oral bisphosphonate, mainly Fosamax®.
In May, Ruggiero co-wrote a report on 63 patients with osteonecrosis — or bone death — of the jaw in the Journal of Oral and Maxillofacial Surgery . Six had taken Fosamax, and a seventh had taken Actonel, another oral bisphosphonate for osteoporosis.
The problem doesn't appear to be as severe with oral bisphosphonates as it is with the IV drugs, Ruggiero notes. Patients who have been receiving IV bisphosphonates should avoid having teeth pulled "at all costs," he says.
Based on his cases, a Food and Drug Administration review posted last week on the agency's Web site suggests that osteonecrosis of the jaw (ONJ) is a risk of all bisphosphonates, not just the IV drugs.
Bisphosphonates remain in bone indefinitely. Ruggiero speculates that their long-term use could upset the delicate balance between cells that put calcium in bone and cells that take calcium away.
The FDA review concluded that all bisphosphonate labels should mention osteonecrosis.
Novartis, maker of Zometa and Aredia, added a precaution about ONJ to their package inserts in August, although the inserts note that cancer patients have other osteonecrosis risk factors, such as their malignancies.
Merck spokesman Tony Plohoros says his company is in the process of adding information about the ONJ cases to the Fosamax® label. And Terri Pedone, spokeswoman for Sanofi-Aventis, which markets Actonel with Procter & Gamble, says, "We are currently addressing the FDA's request to update the label" with information about ONJ.
Rugierro says he has now seen a total of 12 or 13 cases of ONJ in patients treated with an oral bisphosphonate. Robert Marx, chairman of the division of oral and maxillofacial surgery at Florida 's University of Miami , says he's aware of at least 40 or 50 cases of ONJ nationwide in patients who had taken Fosamax®.
That's a infinitely small fraction of the approximately 3 million women in the USA who are taking the drug, although most experts agree that only 1% to 10% of adverse events linked to drugs are reported.
Interestingly, some doctors have prescribed IV bisphosphonates "off label" for osteoporosis. And Roche and GlaxoSmithKline announced in December that they are seeking FDA permission to market an IV form of their oral bisphosphonate, Boniva, for osteoporosis.
This article was originally published by http://www.usatoday.com/news/health/2005-03-13-jawbone-deaths_x.htm
NOTICE: www.fosamax-information.com is solely to be used as an informational resource and should never be used to replace contact with your licensed healthcare provider. Always consult you physician before taking any medication, including Fosamax®.