SPL PATIENT PACKAGE INSERT SECTION.

SUPPLEMENTAL PATIENT MATERIAL. Patient InformationOnce Weekly FOSAMAX(R) (FOSS-ah-max) (alendronate sodium) Tablets and Oral SolutionRead this information before you start taking FOSAMAX2. Also, read the leaflet each time you refill your prescription, just in case anything has changed. This leaflet does not take the place of discussions with your doctor. You and your doctor should discuss FOSAMAX when you start taking your medicine and at regular checkups.2Registered trademark of MERCK CO., Inc.COPYRIGHT (C) 2000 MERCK CO., Inc.All rights reservedWhat is the most important information should know about once weekly FOSAMAXYou must take once weekly FOSAMAX exactly as directed to help make sure it works and to help lower the chance of problems in your esophagus (the tube that connects your mouth and stomach). (See How should take once weekly FOSAMAX).If you have chest pain, new or worsening heartburn, or have trouble or pain when you swallow, stop taking FOSAMAX and call your doctor. (See What are the possible side effects of FOSAMAX).What is FOSAMAXFOSAMAX is prescription medicine for: The treatment or prevention of osteoporosis (thinning of bone) in women after menopause. It reduces the chance of having hip or spinal fracture (break). Treatment to increase bone mass in men with osteoporosis. FOSAMAX tablets are for treatment and prevention of osteoporosis. FOSAMAX oral solution is for treatment of osteoporosis. Improvement in bone density may be observed as early as months after you start taking FOSAMAX even though you wont see or feel difference. For FOSAMAX to continue to work, you need to keep taking it.FOSAMAX is not hormone.There is more information about osteoporosis at the end of this leaflet. Who should not take FOSAMAXDo not take FOSAMAX (tablets or oral solution) if you:Have certain problems with your esophagus, the tube that connects your mouth with your stomach Cannot stand or sit upright for at least 30 minutes Have low levels of calcium in your blood Are allergic to FOSAMAX or any of its ingredients. list of ingredients is at the end of this leaflet. Do not take FOSAMAX oral solution if you have trouble swallowing liquids. What should tell my doctor before using FOSAMAXTell your doctor about all of your medical conditions, including if you:have problems with swallowinghave stomach or digestive problemshave kidney problemsare pregnant or planning to become pregnant. It is not known if FOSAMAX can harm your unborn baby. are breastfeeding. It is not known if FOSAMAX passes into your milk and if it can harm your baby. Tell your doctor about all medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Know the medicines you take. Keep list of them and show it to your doctor and pharmacist each time you get new medicine.How should take once weekly FOSAMAXChoose the day of the week that best fits your schedule. Take dose of FOSAMAX every week on your chosen day after you get up for the day and before taking your first food, drink, or other medicine Take FOSAMAX while you are sitting or standing. Take your FOSAMAX with plain water only as follows: TABLETS: Swallow one tablet with full glass (6-8 oz) of plain water. ORAL SOLUTION: Drink one entire bottle of solution followed by at least ounces (a quarter of cup) of plain water. Do not take FOSAMAX with:Mineral waterCoffee or teaJuiceFOSAMAX works only if it is taken on an empty stomach.Do not chew or suck on tablet of FOSAMAX.After taking your FOSAMAX, wait at least 30 minutes:before you lie down. You may sit, stand or walk, and do normal activities like reading. before you take your first food or drink except for plain water. before you take other medicines, including antacids, calcium, and other supplements and vitamins. Do not lie down until after your first food of the day.It is important that you keep taking FOSAMAX for as long as your doctor says to take it. For FOSAMAX to continue to work, you need to keep taking it. What should do if miss dose of FOSAMAX or if take too manyIf you miss dose, take only dose of FOSAMAX on the morning after you remember. Do not take doses on the same day. Continue your usual schedule of dose once week on your chosen day. If you think you took more than the prescribed dose of FOSAMAX, drink full glass of milk and call your doctor right away. Do not try to vomit. Do not lie down. What should avoid while taking FOSAMAXDo not eat, drink, or take other medicines or supplements before taking FOSAMAX. Wait for at least 30 minutes after taking FOSAMAX to eat, drink, or take other medicines or supplements. Do not lie down for at least 30 minutes after taking FOSAMAX. Do not lie down until after your first food of the day. What are the possible side effects of FOSAMAXFOSAMAX may cause problems in your esophagus (the tube that connects the mouth and stomach). (See What is the most important information should know about once weekly FOSAMAX.) These problems include irritation, inflammation, or ulcers of the esophagus, which may sometimes bleed. This may occur especially if you do not drink full glass of water with FOSAMAX or if you lie down in less than 30 minutes or before your first food of the day.Stop taking FOSAMAX and call your doctor right away if you get any of these signs of possible serious problems of the esophagus: Chest painNew or worsening heartburnTrouble or pain when swallowingEsophagus problems may get worse if you continue to take FOSAMAX. Mouth sores (ulcers) may occur if the FOSAMAX tablet is chewed or dissolved in the mouth. You may get flu-like symptoms, typically at the start of treatment with FOSAMAX. You may get allergic reactions, such as hives or, in rare cases, swelling of your face, lips, tongue, or throat. FOSAMAX may cause jaw-bone problems in some people. Jaw-bone problems may include infection, and delayed healing after teeth are pulled. The most common side effect is stomach area (abdominal) pain. Less common side effects are nausea, vomiting, full or bloated feeling in the stomach, constipation, diarrhea, black or bloody stools (bowel movements), gas, eye pain, rash that may be made worse by sunlight, hair loss, headache, dizziness, changed sense of taste, joint swelling or swelling in the hands or legs, and bone, muscle, or joint pain. Call your doctor if you develop severe bone, muscle, or joint pain. Tell your doctor about any side effect that bothers you or that does not go away.These are not all the side effects with FOSAMAX. Ask your doctor or pharmacist for more information.How do store FOSAMAXStore at room temperature, 59 to 86F (15 to 30C). Safely discard FOSAMAX that is out-of-date or no longer needed. Keep FOSAMAX and all medicines out of the reach of children.General information about using FOSAMAX safely and effectivelyMedicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Do not use FOSAMAX for condition for which it was not prescribed. Do not give FOSAMAX to other people, even if they have the same symptoms you have. It may harm them.FOSAMAX is not indicated for use in children.This leaflet is summary of information about FOSAMAX. If you have any questions or concerns about FOSAMAX or osteoporosis, talk to your doctor, pharmacist, or other health care provider. You can ask your doctor or pharmacist for information about FOSAMAX written for health care providers. For more information, call 1-877-408-4699 (toll-free) or visit the following website: www.fosamax.com.What are the ingredients in FOSAMAXTabletsFOSAMAX tablets contain alendronate sodium as the active ingredient and the following inactive ingredients: cellulose, lactose, croscarmellose sodium and magnesium stearate.Oral SolutionFosamax oral solution contains alendronate sodium as the active ingredient and the following inactive ingredients: sodium citrate, citric acid, sodium saccharin, artificial raspberry flavor, purified water, sodium propylparaben and sodium butylparaben.What should know about osteoporosisNormally your bones are being rebuilt all the time. First, old bone is removed (resorbed). Then similar amount of new bone is formed. This balanced process keeps your skeleton healthy and strong.Osteoporosis is thinning and weakening of the bones. It is common in women after menopause, and may also occur in men. In osteoporosis, bone is removed faster than it is formed, so overall bone mass is lost and bones become weaker. Therefore, keeping bone mass is important to keep your bones healthy. In both men and women, osteoporosis may also be caused by certain medicines called corticosteroids.At first, osteoporosis usually has no symptoms, but it can cause fractures (broken bones). Fractures usually cause pain. Fractures of the bones of the spine may not be painful, but over time they can make you shorter. Eventually, your spine can curve and your body can become bent over. Fractures may happen during normal, everyday activity, such as lifting, or from minor injury that would normally not cause bones to break. Fractures most often occur at the hip, spine, or wrist. This can lead to pain, severe disability, or loss of ability to move around (mobility).Who is at risk for osteoporosisMany things put people at risk of osteoporosis. The following people have higher chance of getting osteoporosis: Women who:Are going through or who are past menopause Men who:Are elderly People who:Are white (Caucasian) or oriental (Asian) Are thin Have family member with osteoporosis Do not get enough calcium or vitamin Do not exercise Smoke Drink alcohol often Take bone thinning medicines (like prednisone or other corticosteroids) for long time What can do to help prevent or treat osteoporosisIn addition to FOSAMAX, your doctor may suggest one or more of the following lifestyle changes:Stop smoking. Smoking may increase your chance of getting osteoporosis. Reduce the use of alcohol. Too much alcohol may increase the risk of osteoporosis and injuries that can cause fractures. Exercise regularly. Like muscles, bones need exercise to stay strong and healthy. Exercise must be safe to prevent injuries, including fractures. Talk with your doctor before you begin any exercise program. Eat balanced diet. Having enough calcium in your diet is important. Your doctor can advise you whether you need to change your diet or take any dietary supplements, such as calcium or vitamin D. Rx onlyMERCK CO., INC.Whitehouse Station, NJ 08889, USAIssued February 20089635608Patient InformationFOSAMAX(R) (FOSS-ah-max)(alendronate sodium) TabletsRead this information before you start taking FOSAMAX3. Also, read the leaflet each time you refill your prescription, just in case anything has changed. This leaflet does not take the place of discussions with your doctor. You and your doctor should discuss FOSAMAX when you start taking your medicine and at regular checkups.3Registered trademark of MERCK CO., Inc.COPYRIGHT (C) 1995, 1997, 2000 MERCK CO., Inc. All rights reservedWhat is the most important information should know about FOSAMAXYou must take FOSAMAX exactly as directed to help make sure it works and to help lower the chance of problems in your esophagus (the tube that connects your mouth and stomach). (See How should take FOSAMAX).If you have chest pain, new or worsening heartburn, or have trouble or pain when you swallow, stop taking FOSAMAX and call your doctor. (See What are the possible side effects of FOSAMAX).What is FOSAMAXFOSAMAX is prescription medicine for: The treatment or prevention of osteoporosis (thinning of bone) in women after menopause. It reduces the chance of having hip or spinal fracture (break). Treatment to increase bone mass in men with osteoporosis. The treatment of osteoporosis in either men or women who are taking corticosteroid medicines (for example, prednisone). Improvement in bone density may be observed as early as months after you start taking FOSAMAX even though you wont see or feel difference. For FOSAMAX to continue to work, you need to keep taking it.FOSAMAX is not hormone.There is more information about osteoporosis at the end of this leaflet.Who should not take FOSAMAXDo not take FOSAMAX if you:Have certain problems with your esophagus, the tube that connects your mouth with your stomach Cannot stand or sit upright for at least 30 minutes Have low levels of calcium in your blood Are allergic to FOSAMAX or any of its ingredients. list of ingredients is at the end of this leaflet. What should tell my doctor before using FOSAMAXTell your doctor about all of your medical conditions, including if you:have problems with swallowinghave stomach or digestive problemshave kidney problemsare pregnant or planning to become pregnant. It is not known if FOSAMAX can harm your unborn baby. are breastfeeding. It is not known if FOSAMAX passes into your milk and if it can harm your baby. Tell your doctor about all medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements.Know the medicines you take. Keep list of them and show it to your doctor and pharmacist each time you get new medicine.How should take FOSAMAXTake FOSAMAX tablet once day, every day after you get up for the day and before taking your first food, drink, or other medicine. Take FOSAMAX while you are sitting or standing. Swallow your FOSAMAX tablet with full glass (6-8 oz) of plain water only. Do not take FOSAMAX with:Mineral waterCoffee or teaJuiceFOSAMAX works only if taken on an empty stomach.Do not chew or suck on tablet of FOSAMAX.After swallowing your FOSAMAX tablet, wait at least 30 minutes:before you lie down. You may sit, stand or walk, and do normal activities like reading. before you take your first food or drink except for plain water. before you take other medicines, including antacids, calcium, and other supplements and vitamins. Do not lie down until after first food of the day.It is important that you keep taking FOSAMAX for as long as your doctor says to take it. For FOSAMAX to continue to work, you need to keep taking it. What should do if miss dose of FOSAMAX or if take too manyIf you miss dose, do not take it later in the day. Continue your usual schedule of tablet once day the next morning. If you think you took more than the prescribed dose of FOSAMAX, drink full glass of milk and call your doctor right away. Do not try to vomit. Do not lie down. What should avoid while taking FOSAMAXDo not eat, drink, or take other medicines or supplements before taking FOSAMAX. Wait for at least 30 minutes after taking FOSAMAX to eat, drink, or take other medicines or supplements. Do not lie down for at least 30 minutes after taking FOSAMAX. Do not lie down until after your first food of the day. What are the possible side effects of FOSAMAXFOSAMAX may cause problems in your esophagus (the tube that connects the mouth and stomach). (See What is the most important information should know about FOSAMAX.) These problems include irritation, inflammation, or ulcers of the esophagus, which may sometimes bleed. This may occur especially if you do not drink full glass of water with FOSAMAX or if you lie down in less than 30 minutes or before your first food of the day.Stop taking FOSAMAX and call your doctor right away if you get any of these signs of possible serious problems of the esophagus:Chest painNew or worsening heartburnTrouble or pain when swallowingEsophagus problems may get worse if you continue to take FOSAMAX. Mouth sores (ulcers) may occur if the FOSAMAX tablet is chewed or dissolved in the mouth. You may get flu-like symptoms typically at the start of treatment with FOSAMAX. You may get allergic reactions, such as hives or, in rare cases, swelling of your face, lips, tongue, or throat. FOSAMAX may cause jaw-bone problems in some people. Jaw-bone problems include infection, and delayed healing after teeth are pulled. The most common side effect is stomach area (abdominal) pain. Less common side effects are nausea, vomiting, full or bloated feeling in the stomach, constipation, diarrhea, black or bloody stools (bowel movements), gas, eye pain, rash that may be made worse by sunlight, hair loss, headache, dizziness, changed sense of taste, joint swelling or swelling in the hands or legs, and bone, muscle, or joint pain. Call your doctor if you develop severe bone, muscle, or joint pain.Tell your doctor about any side effect that bothers you or that does not go away.These are not all the side effects with FOSAMAX. Ask your doctor or pharmacist for more information.How do store FOSAMAXStore FOSAMAX at room temperature, 59 to 86F (15 to 30C). Safely discard FOSAMAX that is out-of-date or no longer needed. Keep FOSAMAX and all medicines out of the reach of children.General information about using FOSAMAX safely and effectivelyMedicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Do not use FOSAMAX for condition for which it was not prescribed. Do not give FOSAMAX to other people, even if they have the same symptoms you have. It may harm them.FOSAMAX is not indicated for use in children.This leaflet is summary of information about FOSAMAX. If you have any questions or concerns about FOSAMAX or osteoporosis, talk to your doctor, pharmacist, or other health care provider. You can ask your doctor or pharmacist for information about FOSAMAX written for health care providers. For more information, call 1-877-408-4699 (toll-free) or visit the following website: www.fosamax.com.What are the ingredients in FOSAMAXFOSAMAX contains alendronate sodium as the active ingredient and the following inactive ingredients: cellulose, lactose, croscarmellose sodium and magnesium stearate. The 10 mg tablet also contains carnauba wax.What should know about osteoporosisNormally your bones are being rebuilt all the time. First, old bone is removed (resorbed). Then similar amount of new bone is formed. This balanced process keeps your skeleton healthy and strong.Osteoporosis is thinning and weakening of the bones. It is common in women after menopause, and may also occur in men. In osteoporosis, bone is removed faster than it is formed, so overall bone mass is lost and bones become weaker. Therefore, keeping bone mass is important to keep your bones healthy. In both men and women, osteoporosis may also be caused by certain medicines called corticosteroids. At first, osteoporosis usually has no symptoms, but it can cause fractures (broken bones). Fractures usually cause pain. Fractures of the bones of the spine may not be painful, but over time they can make you shorter. Eventually, your spine can curve and your body can become bent over. Fractures may happen during normal, everyday activity, such as lifting, or from minor injury that would normally not cause bones to break. Fractures most often occur at the hip, spine, or wrist. This can lead to pain, severe disability, or loss of ability to move around (mobility).Who is at risk for osteoporosisMany things put people at risk of osteoporosis. The following people have higher chance of getting osteoporosis:Women who:Are going through or who are past menopause Men who: Are elderly People who:Are white (Caucasian) or oriental (Asian) Are thin Have family member with osteoporosis Do not get enough calcium or vitamin Do not exercise Smoke Drink alcohol often Take bone thinning medicines (like prednisone or other corticosteroids) for long time What can do to help prevent or treat osteoporosisIn addition to FOSAMAX, your doctor may suggest one or more of the following lifestyle changes:Stop smoking. Smoking may increase your chance of getting osteoporosis. Reduce the use of alcohol. Too much alcohol may increase the risk of osteoporosis and injuries that can cause fractures. Exercise regularly. Like muscles, bones need exercise to stay strong and healthy. Exercise must be safe to prevent injuries, including fractures. Talk with your doctor before you begin any exercise program. Eat balanced diet. Having enough calcium in your diet is important. Your doctor can advise you whether you need to change your diet or take any dietary supplements, such as calcium or vitamin D. Rx OnlyMERCK CO., INC.Whitehouse Station, NJ 08889, USAIssued February 20089636808. You must take once weekly FOSAMAX exactly as directed to help make sure it works and to help lower the chance of problems in your esophagus (the tube that connects your mouth and stomach). (See How should take once weekly FOSAMAX).. If you have chest pain, new or worsening heartburn, or have trouble or pain when you swallow, stop taking FOSAMAX and call your doctor. (See What are the possible side effects of FOSAMAX).. The treatment or prevention of osteoporosis (thinning of bone) in women after menopause. It reduces the chance of having hip or spinal fracture (break). Treatment to increase bone mass in men with osteoporosis. FOSAMAX tablets are for treatment and prevention of osteoporosis. FOSAMAX oral solution is for treatment of osteoporosis. Have certain problems with your esophagus, the tube that connects your mouth with your stomach Cannot stand or sit upright for at least 30 minutes Have low levels of calcium in your blood Are allergic to FOSAMAX or any of its ingredients. list of ingredients is at the end of this leaflet. have problems with swallowing. have stomach or digestive problems. have kidney problems. are pregnant or planning to become pregnant. It is not known if FOSAMAX can harm your unborn baby. are breastfeeding. It is not known if FOSAMAX passes into your milk and if it can harm your baby. Choose the day of the week that best fits your schedule. Take dose of FOSAMAX every week on your chosen day after you get up for the day and before taking your first food, drink, or other medicine Take FOSAMAX while you are sitting or standing. Take your FOSAMAX with plain water only as follows: TABLETS: Swallow one tablet with full glass (6-8 oz) of plain water. ORAL SOLUTION: Drink one entire bottle of solution followed by at least ounces (a quarter of cup) of plain water. TABLETS: Swallow one tablet with full glass (6-8 oz) of plain water. ORAL SOLUTION: Drink one entire bottle of solution followed by at least ounces (a quarter of cup) of plain water. before you lie down. You may sit, stand or walk, and do normal activities like reading. before you take your first food or drink except for plain water. before you take other medicines, including antacids, calcium, and other supplements and vitamins. It is important that you keep taking FOSAMAX for as long as your doctor says to take it. For FOSAMAX to continue to work, you need to keep taking it. If you miss dose, take only dose of FOSAMAX on the morning after you remember. Do not take doses on the same day. Continue your usual schedule of dose once week on your chosen day. If you think you took more than the prescribed dose of FOSAMAX, drink full glass of milk and call your doctor right away. Do not try to vomit. Do not lie down. Do not eat, drink, or take other medicines or supplements before taking FOSAMAX. Wait for at least 30 minutes after taking FOSAMAX to eat, drink, or take other medicines or supplements. Do not lie down for at least 30 minutes after taking FOSAMAX. Do not lie down until after your first food of the day. Stop taking FOSAMAX and call your doctor right away if you get any of these signs of possible serious problems of the esophagus: Chest painNew or worsening heartburnTrouble or pain when swallowing. Chest pain. New or worsening heartburn. Trouble or pain when swallowing. Esophagus problems may get worse if you continue to take FOSAMAX. Mouth sores (ulcers) may occur if the FOSAMAX tablet is chewed or dissolved in the mouth. You may get flu-like symptoms, typically at the start of treatment with FOSAMAX. You may get allergic reactions, such as hives or, in rare cases, swelling of your face, lips, tongue, or throat. FOSAMAX may cause jaw-bone problems in some people. Jaw-bone problems may include infection, and delayed healing after teeth are pulled. The most common side effect is stomach area (abdominal) pain. Less common side effects are nausea, vomiting, full or bloated feeling in the stomach, constipation, diarrhea, black or bloody stools (bowel movements), gas, eye pain, rash that may be made worse by sunlight, hair loss, headache, dizziness, changed sense of taste, joint swelling or swelling in the hands or legs, and bone, muscle, or joint pain. Call your doctor if you develop severe bone, muscle, or joint pain. Store at room temperature, 59 to 86F (15 to 30C). Safely discard FOSAMAX that is out-of-date or no longer needed. Keep FOSAMAX and all medicines out of the reach of children.. Are going through or who are past menopause Are elderly Are white (Caucasian) or oriental (Asian) Are thin Have family member with osteoporosis Do not get enough calcium or vitamin . Do not exercise Smoke Drink alcohol often Take bone thinning medicines (like prednisone or other corticosteroids) for long time Stop smoking. Smoking may increase your chance of getting osteoporosis. Reduce the use of alcohol. Too much alcohol may increase the risk of osteoporosis and injuries that can cause fractures. Exercise regularly. Like muscles, bones need exercise to stay strong and healthy. Exercise must be safe to prevent injuries, including fractures. Talk with your doctor before you begin any exercise program. Eat balanced diet. Having enough calcium in your diet is important. Your doctor can advise you whether you need to change your diet or take any dietary supplements, such as calcium or vitamin D. You must take FOSAMAX exactly as directed to help make sure it works and to help lower the chance of problems in your esophagus (the tube that connects your mouth and stomach). (See How should take FOSAMAX).. If you have chest pain, new or worsening heartburn, or have trouble or pain when you swallow, stop taking FOSAMAX and call your doctor. (See What are the possible side effects of FOSAMAX).. The treatment or prevention of osteoporosis (thinning of bone) in women after menopause. It reduces the chance of having hip or spinal fracture (break). Treatment to increase bone mass in men with osteoporosis. The treatment of osteoporosis in either men or women who are taking corticosteroid medicines (for example, prednisone). Have certain problems with your esophagus, the tube that connects your mouth with your stomach Cannot stand or sit upright for at least 30 minutes Have low levels of calcium in your blood Are allergic to FOSAMAX or any of its ingredients. list of ingredients is at the end of this leaflet. have problems with swallowing. have stomach or digestive problems. have kidney problems. are pregnant or planning to become pregnant. It is not known if FOSAMAX can harm your unborn baby. are breastfeeding. It is not known if FOSAMAX passes into your milk and if it can harm your baby. Take FOSAMAX tablet once day, every day after you get up for the day and before taking your first food, drink, or other medicine. Take FOSAMAX while you are sitting or standing. Swallow your FOSAMAX tablet with full glass (6-8 oz) of plain water only. before you lie down. You may sit, stand or walk, and do normal activities like reading. before you take your first food or drink except for plain water. before you take other medicines, including antacids, calcium, and other supplements and vitamins. It is important that you keep taking FOSAMAX for as long as your doctor says to take it. For FOSAMAX to continue to work, you need to keep taking it. If you miss dose, do not take it later in the day. Continue your usual schedule of tablet once day the next morning. If you think you took more than the prescribed dose of FOSAMAX, drink full glass of milk and call your doctor right away. Do not try to vomit. Do not lie down. Do not eat, drink, or take other medicines or supplements before taking FOSAMAX. Wait for at least 30 minutes after taking FOSAMAX to eat, drink, or take other medicines or supplements. Do not lie down for at least 30 minutes after taking FOSAMAX. Do not lie down until after your first food of the day. Stop taking FOSAMAX and call your doctor right away if you get any of these signs of possible serious problems of the esophagus:Chest painNew or worsening heartburnTrouble or pain when swallowing. Chest pain. New or worsening heartburn. Trouble or pain when swallowing. Esophagus problems may get worse if you continue to take FOSAMAX. Mouth sores (ulcers) may occur if the FOSAMAX tablet is chewed or dissolved in the mouth. You may get flu-like symptoms typically at the start of treatment with FOSAMAX. You may get allergic reactions, such as hives or, in rare cases, swelling of your face, lips, tongue, or throat. FOSAMAX may cause jaw-bone problems in some people. Jaw-bone problems include infection, and delayed healing after teeth are pulled. The most common side effect is stomach area (abdominal) pain. Less common side effects are nausea, vomiting, full or bloated feeling in the stomach, constipation, diarrhea, black or bloody stools (bowel movements), gas, eye pain, rash that may be made worse by sunlight, hair loss, headache, dizziness, changed sense of taste, joint swelling or swelling in the hands or legs, and bone, muscle, or joint pain. Call your doctor if you develop severe bone, muscle, or joint pain.. Store FOSAMAX at room temperature, 59 to 86F (15 to 30C). Safely discard FOSAMAX that is out-of-date or no longer needed. Keep FOSAMAX and all medicines out of the reach of children.. Are going through or who are past menopause Are elderly Are white (Caucasian) or oriental (Asian) Are thin Have family member with osteoporosis Do not get enough calcium or vitamin . Do not exercise Smoke Drink alcohol often Take bone thinning medicines (like prednisone or other corticosteroids) for long time Stop smoking. Smoking may increase your chance of getting osteoporosis. Reduce the use of alcohol. Too much alcohol may increase the risk of osteoporosis and injuries that can cause fractures. Exercise regularly. Like muscles, bones need exercise to stay strong and healthy. Exercise must be safe to prevent injuries, including fractures. Talk with your doctor before you begin any exercise program. Eat balanced diet. Having enough calcium in your diet is important. Your doctor can advise you whether you need to change your diet or take any dietary supplements, such as calcium or vitamin D.

ADVERSE REACTIONS SECTION.

ADVERSE REACTIONS. Clinical StudiesIn clinical studies of up to five years in duration adverse experiences associated with FOSAMAX usually were mild, and generally did not require discontinuation of therapy.FOSAMAX has been evaluated for safety in approximately 8000 postmenopausal women in clinical studies.Treatment of osteoporosisPostmenopausal womenIn two identically designed, three-year, placebo-controlled, double-blind, multicenter studies (United States and Multinational; n=994), discontinuation of therapy due to any clinical adverse experience occurred in 4.1% of 196 patients treated with FOSAMAX 10 mg/day and 6.0% of 397 patients treated with placebo. In the Fracture Intervention Trial (n=6459), discontinuation of therapy due to any clinical adverse experience occurred in 9.1% of 3236 patients treated with FOSAMAX mg/day for years and 10 mg/day for either one or two additional years and 10.1% of 3223 patients treated with placebo. Discontinuations due to upper gastrointestinal adverse experiences were: FOSAMAX, 3.2%; placebo, 2.7%. In these study populations, 49-54% had history of gastrointestinal disorders at baseline and 54-89% used nonsteroidal anti-inflammatory drugs or aspirin at some time during the studies. Adverse experiences from these studies considered by the investigators as possibly, probably, or definitely drug related in >=1% of patients treated with either FOSAMAX or placebo are presented in the following table.Osteoporosis Treatment Studies in Postmenopausal Women: Adverse Experiences Considered Possibly, Probably, or Definitely Drug Related by the Investigators and Reported in >=1% of Patients United States/Studies Multinational FractureTrial Intervention FOSAMAX (n=196) Placebo%(n=397)FOSAMAX+ (n=3236) Placebo%(n=3223)Gastrointestinal abdominal pain 6.6 4.8 1.5 1.5 nausea 3.6 4.0 1.1 1.5 dyspepsia 3.6 3.5 1.1 1.2 constipation 3.1 1.8 0.0 0.2 diarrhea 3.1 1.8 0.6 0.3 flatulence 2.6 0.5 0.2 0.3 acid regurgitation 2.0 4.3 1.1 0.9 esophageal ulcer 1.5 00 0.1 0.1 vomiting 1.0 1.5 0.2 0.3 dysphagia 1.0 0.0 0.1 0.1 abdominal distention 1.0 0.8 0.0 0.0 gastritis 0.5 1.3 0.6 0.7 Musculoskeletal musculoskeletal (bone, muscle or joint) pain 4.1 2.50.4 0.3 muscle cram 0.0 1.0 0.2 0.1 Nervous System/Psychiatric headache 2.6 1.5 0.2 0.2 dizziness 0.0 1.0 0.0 0.1 Special Senses taste perversion 0.5 1.0 0.1 0.0 10 mg/day for three years 5 mg/day for years and 10 mg/day for either or additional years Rarely, rash and erythema have occurred. One patient treated with FOSAMAX (10 mg/day), who had history of peptic ulcer disease and gastrectomy and who was taking concomitant aspirin developed an anastomotic ulcer with mild hemorrhage, which was considered drug related. Aspirin and FOSAMAX were discontinued and the patient recovered. The adverse experience profile was similar for the 401 patients treated with either or 20 mg doses of FOSAMAX in the United States and Multinational studies. The adverse experience profile for the 296 patients who received continued treatment with either or 10 mg doses of FOSAMAX in the two-year extension of these studies (treatment years and 5) was similar to that observed during the three-year placebo-controlled period. During the extension period, of the 151 patients treated with FOSAMAX 10 mg/day, the proportion of patients who discontinued therapy due to any clinical adverse experience was similar to that during the first three years of the study. In one-year, double-blind, multicenter study, the overall safety and tolerability profiles of once weekly FOSAMAX 70 mg and FOSAMAX 10 mg daily were similar. The adverse experiences considered by the investigators as possibly, probably, or definitely drug related in >=1% of patients in either treatment group are presented in the following table. Osteoporosis Treatment Studies in Postmenopausal Women: Adverse Experiences Considered Possibly, Probably, or Definitely Drug Related by the Investigators and Reported in >=1% of PatientsOnce Weekly FOSAMAX70 mg %(n=519)FOSAMAX10 mg/day%(n=370)Gastrointestinal abdominal pain dyspepsia acid regurgitation nausea abdominal distention constipation flatulence gastritis gastric ulcer3.72.71.91.91.00.80.40.20.03.02.22.42.41.41.61.61.11.1Musculoskeletal musculoskeletal (bone, muscle, joint) pain muscle cramp2.90.23.21.1 MenIn two placebo-controlled, double-blind, multicenter studies in men (a two-year study of FOSAMAX 10 mg/day and one-year study of once weekly FOSAMAX 70 mg) the rates of discontinuation of therapy due to any clinical adverse experience were 2.7% for FOSAMAX 10 mg/day vs. 10.5% for placebo, and 6.4% for once weekly FOSAMAX 70 mg vs. 8.6% for placebo. The adverse experiences considered by the investigators as possibly, probably, or definitely drug related in >=2% of patients treated with either FOSAMAX or placebo are presented in the following table. Osteoporosis Studies in Men: Adverse Experiences Considered Possibly, Probably, or Definitely Drug Related by the Investigators and Reported in >=2% of PatientsTwo-year StudyOne-year StudyFOSAMAX10 mg/day%(n=146)Placebo%(n=95)Once Weekly FOSAMAX 70 mg%(n=109)Placebo%(n=58)Gastrointestinal acid regurgitation flatulence gastroesophageal reflux disease dyspepsia diarrhea abdominal pain nausea4.14.10.73.41.42.12.13.21.13.20.01.11.10.00.00.02.82.82.80.90.00.00.00.01.70.03.40.0 Prevention of osteoporosis in postmenopausal womenThe safety of FOSAMAX mg/day in postmenopausal women 40-60 years of age has been evaluated in three double-blind, placebo-controlled studies involving over 1,400 patients randomized to receive FOSAMAX for either two or three years. In these studies the overall safety profiles of FOSAMAX mg/day and placebo were similar. Discontinuation of therapy due to any clinical adverse experience occurred in 7.5% of 642 patients treated with FOSAMAX mg/day and 5.7% of 648 patients treated with placebo. In one-year, double-blind, multicenter study, the overall safety and tolerability profiles of once weekly FOSAMAX 35 mg and FOSAMAX mg daily were similar. The adverse experiences from these studies considered by the investigators as possibly, probably, or definitely drug related in >=1% of patients treated with either once weekly FOSAMAX 35 mg, FOSAMAX mg/day or placebo are presented in the following table. Osteoporosis Prevention Studies in Postmenopausal Women: Adverse Experiences Considered Possibly, Probably, or Definitely Drug Related by the Investigators and Reported in >=1% of PatientsTwo/Three-Year StudiesOne-Year StudyFOSAMAX5 mg/day%(n=642) Placebo%(n=648)FOSAMAX5 mg/day%(n=361)Once Weekly FOSAMAX35 mg% (n=362) Gastrointestinal dyspepsia abdominal pain acid regurgitation nausea diarrhea constipation abdominal distention1.91.71.41.41.10.90.21.43.42.51.41.70.50.32.24.24.22.51.11.71.41.72.24.71.40.60.31.1Musculoskeletal musculoskeletal (bone, muscle or joint) pain0.80.91.92.2 Concomitant use with estrogen/hormone replacement therapyIn two studies (of one and two years duration) of postmenopausal osteoporotic women (total: n=853), the safety and tolerability profile of combined treatment with FOSAMAX 10 mg once daily and estrogen +- progestin (n=354) was consistent with those of the individual treatments. Treatment of glucocorticoid-induced osteoporosisIn two, one-year, placebo-controlled, double-blind, multicenter studies in patients receiving glucocorticoid treatment, the overall safety and tolerability profiles of FOSAMAX and 10 mg/day were generally similar to that of placebo. The adverse experiences considered by the investigators as possibly, probably, or definitely drug related in >=1% of patients treated with either FOSAMAX or 10 mg/day or placebo are presented in the following table. One-Year Studies in Glucocorticoid-Treated Patients: Adverse Experiences Considered Possibly, Probably, or Definitely Drug Related by the Investigators and Reported in >=1% of PatientsFOSAMAX10 mg/day% (n=157) FOSAMAX5 mg/day%(n=161) Placebo %(n=159) Gastrointestinal abdominal pain acid regurgitation constipation melena nausea diarrhea Nervous System/Psychiatric headache3.22.51.31.30.60.00.61.91.90.60.01.20.00.00.01.30.00.00.61.31.3 The overall safety and tolerability profile in the glucocorticoid-induced osteoporosis population that continued therapy for the second year of the studies (FOSAMAX: n=147) was consistent with that observed in the first year. Pagets disease of boneIn clinical studies (osteoporosis and Pagets disease), adverse experiences reported in 175 patients taking FOSAMAX 40 mg/day for 3-12 months were similar to those in postmenopausal women treated with FOSAMAX 10 mg/day. However, there was an apparent increased incidence of upper gastrointestinal adverse experiences in patients taking FOSAMAX 40 mg/day (17.7% FOSAMAX vs. 10.2% placebo). One case of esophagitis and two cases of gastritis resulted in discontinuation of treatment. Additionally, musculoskeletal (bone, muscle or joint) pain, which has been described in patients with Pagets disease treated with other bisphosphonates, was considered by the investigators as possibly, probably, or definitely drug related in approximately 6% of patients treated with FOSAMAX 40 mg/day versus approximately 1% of patients treated with placebo, but rarely resulted in discontinuation of therapy. Discontinuation of therapy due to any clinical adverse experience occurred in 6.4% of patients with Pagets disease treated with FOSAMAX 40 mg/day and 2.4% of patients treated with placebo. Osteogenesis Imperfecta FOSAMAX is not indicated for use in children. The overall safety profile of FOSAMAX in OI patients treated for up to 24 months was generally similar to that of adults with osteoporosis treated with FOSAMAX. However, there was an increased occurrence of vomiting in OI patients treated with FOSAMAX compared to placebo. During the 24-month treatment period, vomiting was observed in 32 of 109 (29.4%) patients treated with FOSAMAX and of 30 (10%) patients treated with placebo. In pharmacokinetic study, of 24 pediatric OI patients who received single oral dose of FOSAMAX 35 or 70 mg developed fever, flu-like symptoms, and/or mild lymphocytopenia within 24 to 48 hours after administration. These events, lasting no more than to days and responding to acetaminophen, are consistent with an acute-phase response that has been reported in patients receiving bisphosphonates, including FOSAMAX. See ADVERSE REACTIONS, Post-Marketing Experience, Body as Whole. Laboratory Test FindingsIn double-blind, multicenter, controlled studies, asymptomatic, mild, and transient decreases in serum calcium and phosphate were observed in approximately 18% and 10%, respectively, of patients taking FOSAMAX versus approximately 12% and 3% of those taking placebo. However, the incidences of decreases in serum calcium to less than 8.0 mg/dL (2.0 mM) and serum phosphate to less than or equal to 2.0 mg/dL (0.65 mM) were similar in both treatment groups. Post-Marketing ExperienceThe following adverse reactions have been reported in post-marketing use: Body as Whole: hypersensitivity reactions including urticaria and rarely angioedema. Transient symptoms of myalgia, malaise, asthenia and rarely, fever have been reported with FOSAMAX, typically in association with initiation of treatment. Rarely, symptomatic hypocalcemia has occurred, generally in association with predisposing conditions. Rarely, peripheral edema. Gastrointestinal: esophagitis, esophageal erosions, esophageal ulcers, rarely esophageal stricture or perforation, and oropharyngeal ulceration. Gastric or duodenal ulcers, some severe and with complications have also been reported (see WARNINGS, PRECAUTIONS, Information for Patients, and DOSAGE AND ADMINISTRATION). Localized osteonecrosis of the jaw, generally associated with tooth extraction and/or local infection, often with delayed healing, has been reported rarely (see PRECAUTIONS, Dental). Musculoskeletal: bone, joint, and/or muscle pain, occasionally severe, and rarely incapacitating (see PRECAUTIONS, Musculoskeletal Pain); joint swelling. Nervous system: dizziness and vertigo. Skin: rash (occasionally with photosensitivity), pruritus, alopecia, rarely severe skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis. Special Senses: rarely uveitis, scleritis or episcleritis.

CLINICAL PHARMACOLOGY SECTION.

CLINICAL PHARMACOLOGY. Mechanism of ActionAnimal studies have indicated the following mode of action. At the cellular level, alendronate shows preferential localization to sites of bone resorption, specifically under osteoclasts. The osteoclasts adhere normally to the bone surface but lack the ruffled border that is indicative of active resorption. Alendronate does not interfere with osteoclast recruitment or attachment, but it does inhibit osteoclast activity. Studies in mice on the localization of radioactive [3H]alendronate in bone showed about 10-fold higher uptake on osteoclast surfaces than on osteoblast surfaces. Bones examined and 49 days after [3H]alendronate administration in rats and mice, respectively, showed that normal bone was formed on top of the alendronate, which was incorporated inside the matrix. While incorporated in bone matrix, alendronate is not pharmacologically active. Thus, alendronate must be continuously administered to suppress osteoclasts on newly formed resorption surfaces. Histomorphometry in baboons and rats showed that alendronate treatment reduces bone turnover (i.e., the number of sites at which bone is remodeled). In addition, bone formation exceeds bone resorption at these remodeling sites, leading to progressive gains in bone mass.PharmacokineticsAbsorptionRelative to an intravenous (IV) reference dose, the mean oral bioavailability of alendronate in women was 0.64% for doses ranging from to 70 mg when administered after an overnight fast and two hours before standardized breakfast. Oral bioavailability of the 10 mg tablet in men (0.59%) was similar to that in women when administered after an overnight fast and hours before breakfast.FOSAMAX 70 mg oral solution and FOSAMAX 70 mg tablet are equally bioavailable.A study examining the effect of timing of meal on the bioavailability of alendronate was performed in 49 postmenopausal women. Bioavailability was decreased (by approximately 40%) when 10 mg alendronate was administered either 0.5 or hour before standardized breakfast, when compared to dosing hours before eating. In studies of treatment and prevention of osteoporosis, alendronate was effective when administered at least 30 minutes before breakfast.Bioavailability was negligible whether alendronate was administered with or up to two hours after standardized breakfast. Concomitant administration of alendronate with coffee or orange juice reduced bioavailability by approximately 60%.DistributionPreclinical studies (in male rats) show that alendronate transiently distributes to soft tissues following mg/kg IV administration but is then rapidly redistributed to bone or excreted in the urine. The mean steady-state volume of distribution, exclusive of bone, is at least 28 in humans. Concentrations of drug in plasma following therapeutic oral doses are too low (less than ng/mL) for analytical detection. Protein binding in human plasma is approximately 78%.MetabolismThere is no evidence that alendronate is metabolized in animals or humans.ExcretionFollowing single IV dose of [14C]alendronate, approximately 50% of the radioactivity was excreted in the urine within 72 hours and little or no radioactivity was recovered in the feces. Following single 10 mg IV dose, the renal clearance of alendronate was 71 mL/min (64, 78; 90% confidence interval [CI]), and systemic clearance did not exceed 200 mL/min. Plasma concentrations fell by more than 95% within hours following IV administration. The terminal half-life in humans is estimated to exceed 10 years, probably reflecting release of alendronate from the skeleton. Based on the above, it is estimated that after 10 years of oral treatment with FOSAMAX (10 mg daily) the amount of alendronate released daily from the skeleton is approximately 25% of that absorbed from the gastrointestinal tract.Special PopulationsPediatric:The oral bioavailability in children was similar to that observed in adults; however, FOSAMAX is not indicated for use in children (see PRECAUTIONS, Pediatric Use).Gender:Bioavailability and the fraction of an IV dose excreted in urine were similar in men and women.Geriatric:Bioavailability and disposition (urinary excretion) were similar in elderly and younger patients. No dosage adjustment is necessary (see DOSAGE AND ADMINISTRATION).Race:Pharmacokinetic differences due to race have not been studied.Renal Insufficiency:Preclinical studies show that, in rats with kidney failure, increasing amounts of drug are present in plasma, kidney, spleen, and tibia. In healthy controls, drug that is not deposited in bone is rapidly excreted in the urine. No evidence of saturation of bone uptake was found after weeks dosing with cumulative IV doses of 35 mg/kg in young male rats. Although no clinical information is available, it is likely that, as in animals, elimination of alendronate via the kidney will be reduced in patients with impaired renal function. Therefore, somewhat greater accumulation of alendronate in bone might be expected in patients with impaired renal function.No dosage adjustment is necessary for patients with mild-to-moderate renal insufficiency (creatinine clearance 35 to 60 mL/min). FOSAMAX is not recommended for patients with more severe renal insufficiency (creatinine clearance less than 35 mL/min) due to lack of experience with alendronate in renal failure. Hepatic Insufficiency:As there is evidence that alendronate is not metabolized or excreted in the bile, no studies were conducted in patients with hepatic insufficiency. No dosage adjustment is necessary.Drug Interactions(also see PRECAUTIONS, Drug Interactions)Intravenous ranitidine was shown to double the bioavailability of oral alendronate. The clinical significance of this increased bioavailability and whether similar increases will occur in patients given oral H2-antagonists is unknown.In healthy subjects, oral prednisone (20 mg three times daily for five days) did not produce clinically meaningful change in the oral bioavailability of alendronate (a mean increase ranging from 20 to 44%).Products containing calcium and other multivalent cations are likely to interfere with absorption of alendronate.PharmacodynamicsAlendronate is bisphosphonate that binds to bone hydroxyapatite and specifically inhibits the activity of osteoclasts, the bone-resorbing cells. Alendronate reduces bone resorption with no direct effect on bone formation, although the latter process is ultimately reduced because bone resorption and formation are coupled during bone turnover.Osteoporosis in postmenopausal womenOsteoporosis is characterized by low bone mass that leads to an increased risk of fracture. The diagnosis can be confirmed by the finding of low bone mass, evidence of fracture on x-ray, history of osteoporotic fracture, or height loss or kyphosis, indicative of vertebral (spinal) fracture. Osteoporosis occurs in both males and females but is most common among women following the menopause, when bone turnover increases and the rate of bone resorption exceeds that of bone formation. These changes result in progressive bone loss and lead to osteoporosis in significant proportion of women over age 50. Fractures, usually of the spine, hip, and wrist, are the common consequences. From age 50 to age 90, the risk of hip fracture in white women increases 50-fold and the risk of vertebral fracture 15- to 30-fold. It is estimated that approximately 40% of 50-year-old women will sustain one or more osteoporosis-related fractures of the spine, hip, or wrist during their remaining lifetimes. Hip fractures, in particular, are associated with substantial morbidity, disability, and mortality.Daily oral doses of alendronate (5, 20, and 40 mg for six weeks) in postmenopausal women produced biochemical changes indicative of dose-dependent inhibition of bone resorption, including decreases in urinary calcium and urinary markers of bone collagen degradation (such as deoxypyridinoline and cross-linked N-telopeptides of type collagen). These biochemical changes tended to return toward baseline values as early as weeks following the discontinuation of therapy with alendronate and did not differ from placebo after months.Long-term treatment of osteoporosis with FOSAMAX 10 mg/day (for up to five years) reduced urinary excretion of markers of bone resorption, deoxypyridinoline and cross-linked N-telopeptides of type collagen, by approximately 50% and 70%, respectively, to reach levels similar to those seen in healthy premenopausal women. Similar decreases were seen in patients in osteoporosis prevention studies who received FOSAMAX mg/day. The decrease in the rate of bone resorption indicated by these markers was evident as early as one month and at three to six months reached plateau that was maintained for the entire duration of treatment with FOSAMAX. In osteoporosis treatment studies FOSAMAX 10 mg/day decreased the markers of bone formation, osteocalcin and bone specific alkaline phosphatase by approximately 50%, and total serum alkaline phosphatase by approximately 25 to 30% to reach plateau after to 12 months. In osteoporosis prevention studies FOSAMAX mg/day decreased osteocalcin and total serum alkaline phosphatase by approximately 40% and 15%, respectively. Similar reductions in the rate of bone turnover were observed in postmenopausal women during one-year studies with once weekly FOSAMAX 70 mg for the treatment of osteoporosis and once weekly FOSAMAX 35 mg for the prevention of osteoporosis. These data indicate that the rate of bone turnover reached new steady-state, despite the progressive increase in the total amount of alendronate deposited within bone.As result of inhibition of bone resorption, asymptomatic reductions in serum calcium and phosphate concentrations were also observed following treatment with FOSAMAX. In the long-term studies, reductions from baseline in serum calcium (approximately 2%) and phosphate (approximately to 6%) were evident the first month after the initiation of FOSAMAX 10 mg. No further decreases in serum calcium were observed for the five-year duration of treatment; however, serum phosphate returned toward prestudy levels during years three through five. Similar reductions were observed with FOSAMAX mg/day. In one-year studies with once weekly FOSAMAX 35 and 70 mg, similar reductions were observed at and 12 months. The reduction in serum phosphate may reflect not only the positive bone mineral balance due to FOSAMAX but also decrease in renal phosphate reabsorption.Osteoporosis in menTreatment of men with osteoporosis with FOSAMAX 10 mg/day for two years reduced urinary excretion of cross-linked N-telopeptides of type collagen by approximately 60% and bone-specific alkaline phosphatase by approximately 40%. Similar reductions were observed in one-year study in men with osteoporosis receiving once weekly FOSAMAX 70 mg.Glucocorticoid-induced OsteoporosisSustained use of glucocorticoids is commonly associated with development of osteoporosis and resulting fractures (especially vertebral, hip, and rib). It occurs both in males and females of all ages. Osteoporosis occurs as result of inhibited bone formation and increased bone resorption resulting in net bone loss. Alendronate decreases bone resorption without directly inhibiting bone formation.In clinical studies of up to two years duration, FOSAMAX and 10 mg/day reduced cross-linked N-telopeptides of type collagen (a marker of bone resorption) by approximately 60% and reduced bone-specific alkaline phosphatase and total serum alkaline phosphatase (markers of bone formation) by approximately 15 to 30% and to 18%, respectively. As result of inhibition of bone resorption, FOSAMAX and 10 mg/day induced asymptomatic decreases in serum calcium (approximately to 2%) and serum phosphate (approximately to 8%).Pagets disease of bonePagets disease of bone is chronic, focal skeletal disorder characterized by greatly increased and disorderly bone remodeling. Excessive osteoclastic bone resorption is followed by osteoblastic new bone formation, leading to the replacement of the normal bone architecture by disorganized, enlarged, and weakened bone structure.Clinical manifestations of Pagets disease range from no symptoms to severe morbidity due to bone pain, bone deformity, pathological fractures, and neurological and other complications. Serum alkaline phosphatase, the most frequently used biochemical index of disease activity, provides an objective measure of disease severity and response to therapy.FOSAMAX decreases the rate of bone resorption directly, which leads to an indirect decrease in bone formation. In clinical trials, FOSAMAX 40 mg once daily for six months produced significant decreases in serum alkaline phosphatase as well as in urinary markers of bone collagen degradation. As result of the inhibition of bone resorption, FOSAMAX induced generally mild, transient, and asymptomatic decreases in serum calcium and phosphate.Clinical StudiesTreatment of Osteoporosis Postmenopausal womenEffect on bone mineral densityThe efficacy of FOSAMAX 10 mg once daily in postmenopausal women, 44 to 84 years of age, with osteoporosis (lumbar spine bone mineral density [BMD] of at least standard deviations below the premenopausal mean) was demonstrated in four double-blind, placebo-controlled clinical studies of two or three years duration. These included two three-year, multicenter studies of virtually identical design, one performed in the United States (U.S.) and the other in 15 different countries (Multinational), which enrolled 478 and 516 patients, respectively. The following graph shows the mean increases in BMD of the lumbar spine, femoral neck, and trochanter in patients receiving FOSAMAX 10 mg/day relative to placebo-treated patients at three years for each of these studies. Osteoporosis Treatment Studies in Postmenopausal Women: Increase in BMD: FOSAMAX 10mg/day at Three YearsAt three years significant increases in BMD, relative both to baseline and placebo, were seen at each measurement site in each study in patients who received FOSAMAX 10 mg/day. Total body BMD also increased significantly in each study, suggesting that the increases in bone mass of the spine and hip did not occur at the expense of other skeletal sites. Increases in BMD were evident as early as three months and continued throughout the three years of treatment. (See figures below for lumbar spine results.) In the two-year extension of these studies, treatment of 147 patients with FOSAMAX 10 mg/day resulted in continued increases in BMD at the lumbar spine and trochanter (absolute additional increases between years and 5: lumbar spine, 0.94%; trochanter, 0.88%). BMD at the femoral neck, forearm and total body were maintained. FOSAMAX was similarly effective regardless of age, race, baseline rate of bone turnover, and baseline BMD in the range studied (at least standard deviations below the premenopausal mean). Thus, overall FOSAMAX reverses the loss of bone mineral density, central factor in the progression of osteoporosis. Osteoporosis Treatment Studies in Postmenopausal Women: Time Course of Effect of FOSAMAX 10 mg/day Versus Placebo: Lumbar Spine BMD Percent Change From BaselineIn patients with postmenopausal osteoporosis treated with FOSAMAX 10 mg/day for one or two years, the effects of treatment withdrawal were assessed. Following discontinuation, there were no further increases in bone mass and the rates of bone loss were similar to those of the placebo groups. These data indicate that continued treatment with FOSAMAX is required to maintain the effect of the drug.The therapeutic equivalence of once weekly FOSAMAX 70 mg (n=519) and FOSAMAX 10 mg daily (n=370) was demonstrated in one-year, double-blind, multicenter study of postmenopausal women with osteoporosis. In the primary analysis of completers, the mean increases from baseline in lumbar spine BMD at one year were 5.1% (4.8, 5.4%; 95% CI) in the 70-mg once-weekly group (n=440) and 5.4% (5.0, 5.8%; 95% CI) in the 10-mg daily group (n=330). The two treatment groups were also similar with regard to BMD increases at other skeletal sites. The results of the intention-to-treat analysis were consistent with the primary analysis of completers.. image of figure 1(Osteoporosis Treatment Studies in Postmenopausal Women). image of figure 2(Osteoporosis Treatment Studies in Postmenopausal Women).

PRECAUTIONS SECTION.

PRECAUTIONS. GeneralCauses of osteoporosis other than estrogen deficiency, aging, and glucocorticoid use should be considered.Hypocalcemia must be corrected before initiating therapy with FOSAMAX (see CONTRAINDICATIONS). Other disorders affecting mineral metabolism (such as vitamin deficiency) should also be effectively treated. In patients with these conditions, serum calcium and symptoms of hypocalcemia should be monitored during therapy with FOSAMAX.Presumably due to the effects of FOSAMAX on increasing bone mineral, small, asymptomatic decreases in serum calcium and phosphate may occur, especially in patients with Pagets disease, in whom the pretreatment rate of bone turnover may be greatly elevated and in patients receiving glucocorticoids, in whom calcium absorption may be decreased.Ensuring adequate calcium and vitamin intake is especially important in patients with Pagets disease of bone and in patients receiving glucocorticoids.Musculoskeletal PainIn post marketing experience, severe and occasionally incapacitating bone, joint, and/or muscle pain has been reported in patients taking bisphosphonates that are approved for the prevention and treatment of osteoporosis (see ADVERSE REACTIONS). However, such reports have been infrequent. This category of drugs includes FOSAMAX (alendronate). Most of the patients were postmenopausal women. The time to onset of symptoms varied from one day to several months after starting the drug. Discontinue use if severe symptoms develop. Most patients had relief of symptoms after stopping. subset had recurrence of symptoms when rechallenged with the same drug or another bisphosphonate.In placebo-controlled clinical studies of FOSAMAX, the percentages of patients with these symptoms were similar in the FOSAMAX and placebo groups.DentalOsteonecrosis of the jaw, generally associated with tooth extraction and/or local infection, often with delayed healing, has been reported in patients taking bisphosphonates. Most reported cases of bisphosphonate-associated osteonecrosis have been in cancer patients treated with intravenous bisphosphonates, but some have occurred in patients with postmenopausal osteoporosis. Known risk factors for osteonecrosis include 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).Patients who develop osteonecrosis of the jaw (ONJ) while on bisphosphonate therapy should receive care by an oral surgeon. Dental surgery may exacerbate the condition. For patients requiring dental procedures, there are no data available to suggest whether discontinuation of bisphosphonate treatment reduces the risk for ONJ. Clinical judgment of the treating physician should guide the management plan of each patient based on individual benefit/risk assessment.Renal insufficencyFOSAMAX is not recommended for patients with renal insufficiency (creatinine clearance less than 35 mL/min). (See DOSAGE AND ADMINISTRATION.)Glucocorticoid-induced osteoporosisThe risk versus benefit of FOSAMAX for treatment at daily dosages of glucocorticoids less than 7.5 mg of prednisone or equivalent has not been established (see INDICATIONS AND USAGE). Before initiating treatment, the hormonal status of both men and women should be ascertained and appropriate replacement considered.A bone mineral density measurement should be made at the initiation of therapy and repeated after to 12 months of combined FOSAMAX and glucocorticoid treatment.The efficacy of FOSAMAX for the treatment of glucocorticoid-induced osteoporosis has been shown in patients with median bone mineral density which was 1.2 standard deviations below the mean for healthy young adults.The efficacy of FOSAMAX has been established in studies of two years duration. The greatest increase in bone mineral density occurred in the first year with maintenance or smaller gains during the second year. Efficacy of FOSAMAX beyond two years has not been studied.The efficacy of FOSAMAX in respect to fracture prevention has been demonstrated for vertebral fractures. However, this finding was based on very few fractures that occurred primarily in postmenopausal women. The efficacy for prevention of non-vertebral fractures has not been demonstrated.Information for PatientsGeneralPhysicians should instruct their patients to read the patient package insert before starting therapy with FOSAMAX and to reread it each time the prescription is renewed.Patients should be instructed to take supplemental calcium and vitamin D, if daily dietary intake is inadequate. Weight-bearing exercise should be considered along with the modification of certain behavioral factors, such as cigarette smoking and/or excessive alcohol consumption, if these factors exist.Dosing InstructionsPatients should be instructed that the expected benefits of FOSAMAX may only be obtained when it is taken with plain water the first thing upon arising for the day at least 30 minutes before the first food, beverage, or medication of the day. Even dosing with orange juice or coffee has been shown to markedly reduce the absorption of FOSAMAX (see CLINICAL PHARMACOLOGY, Pharmacokinetics, Absorption).To facilitate delivery to the stomach and thus reduce the potential for esophageal irritation patients should be instructed to swallow each tablet of FOSAMAX with full glass of water (6-8 oz). To facilitate gastric emptying patients should drink at least oz (a quarter of cup) of water after taking FOSAMAX oral solution. Patients should be instructed not to lie down for at least 30 minutes and until after their first food of the day. Patients should not chew or suck on the tablet because of potential for oropharyngeal ulceration. Patients should be specifically instructed not to take FOSAMAX at bedtime or before arising for the day. Patients should be informed that failure to follow these instructions may increase their risk of esophageal problems. Patients should be instructed that if they develop symptoms of esophageal disease (such as difficulty or pain upon swallowing, retrosternal pain or new or worsening heartburn) they should stop taking FOSAMAX and consult their physician.Patients should be instructed that if they miss dose of once weekly FOSAMAX, they should take one dose on the morning after they remember. They should not take two doses on the same day but should return to taking one dose once week, as originally scheduled on their chosen day.Drug Interactions (also see CLINICAL PHARMACOLOGY, Pharmacokinetics, Drug Interactions)Estrogen/hormone replacement therapy (HRT)Concomitant use of HRT (estrogen +- progestin) and FOSAMAX was assessed in two clinical studies of one or two years duration in postmenopausal osteoporotic women. In these studies, the safety and tolerability profile of the combination was consistent with those of the individual treatments; however, the degree of suppression of bone turnover (as assessed by mineralizing surface) was significantly greater with the combination than with either component alone. The long-term effects of combined FOSAMAX and HRT on fracture occurrence have not been studied (see CLINICAL PHARMACOLOGY, Clinical Studies, Concomitant use with estrogen/hormone replacement therapy (HRT) and ADVERSE REACTIONS, Clinical Studies, Concomitant use with estrogen/hormone replacement therapy).Calcium Supplements/AntacidsIt is likely that calcium supplements, antacids, and some oral medications will interfere with absorption of FOSAMAX. Therefore, patients must wait at least one-half hour after taking FOSAMAX before taking any other oral medications.AspirinIn clinical studies, the incidence of upper gastrointestinal adverse events was increased in patients receiving concomitant therapy with daily doses of FOSAMAX greater than 10 mg and aspirin-containing products.Nonsteroidal Anti-inflammatory Drugs (NSAIDs)FOSAMAX may be administered to patients taking NSAIDs. In 3-year, controlled, clinical study (n=2027) during which majority of patients received concomitant NSAIDs, the incidence of upper gastrointestinal adverse events was similar in patients taking FOSAMAX or 10 mg/day compared to those taking placebo. However, since NSAID use is associated with gastrointestinal irritation, caution should be used during concomitant use with FOSAMAX.Carcinogenesis, Mutagenesis, Impairment of FertilityHarderian gland (a retro-orbital gland not present in humans) adenomas were increased in high-dose female mice (p=0.003) in 92-week oral carcinogenicity study at doses of alendronate of 1, 3, and 10 mg/kg/day (males) or 1, 2, and mg/kg/day (females). These doses are equivalent to 0.12 to 1.2 times maximum recommended daily dose of 40 mg (Pagets disease) based on surface area, mg/m2. The relevance of this finding to humans is unknown. Parafollicular cell (thyroid) adenomas were increased in high-dose male rats (p=0.003) in 2-year oral carcinogenicity study at doses of and 3.75 mg/kg body weight. These doses are equivalent to 0.26 and times 40 mg human daily dose based on surface area, mg/m2. The relevance of this finding to humans is unknown. Alendronate was not genotoxic in the in vitro microbial mutagenesis assay with and without metabolic activation, in an in vitro mammalian cell mutagenesis assay, in an in vitro alkaline elution assay in rat hepatocytes, and in an in vivo chromosomal aberration assay in mice. In an in vitro chromosomal aberration assay in Chinese hamster ovary cells, however, alendronate gave equivocal results. Alendronate had no effect on fertility (male or female) in rats at oral doses up to mg/kg/day (1.3 times 40 mg human daily dose based on surface area, mg/m2). Pregnancy Pregnancy Category C:Reproduction studies in rats showed decreased postimplantation survival at mg/kg/day and decreased body weight gain in normal pups at mg/kg/day. Sites of incomplete fetal ossification were statistically significantly increased in rats beginning at 10 mg/kg/day in vertebral (cervical, thoracic, and lumbar), skull, and sternebral bones. The above doses ranged from 0.26 times (1 mg/kg) to 2.6 times (10 mg/kg) maximum recommended daily dose of 40 mg (Pagets disease) based on surface area, mg/m2. No similar fetal effects were seen when pregnant rabbits were treated at doses up to 35 mg/kg/day (10.3 times 40 mg human daily dose based on surface area, mg/m2). Both total and ionized calcium decreased in pregnant rats at 15 mg/kg/day (3.9 times 40 mg human daily dose based on surface area, mg/m2) resulting in delays and failures of delivery. Protracted parturition due to maternal hypocalcemia occurred in rats at doses as low as 0.5 mg/kg/day (0.13 times 40 mg human daily dose based on surface area, mg/m2) when rats were treated from before mating through gestation. Maternotoxicity (late pregnancy deaths) occurred in the female rats treated with 15 mg/kg/day for varying periods of time ranging from treatment only during pre-mating to treatment only during early, middle, or late gestation; these deaths were lessened but not eliminated by cessation of treatment. Calcium supplementation either in the drinking water or by minipump could not ameliorate the hypocalcemia or prevent maternal and neonatal deaths due to delays in delivery; calcium supplementation IV prevented maternal, but not fetal deaths. Bisphosphonates are incorporated into the bone matrix, from which they are gradually released over period of years. The amount of bisphosphonate incorporated into adult bone, and hence, the amount available for release back into the systemic circulation, is directly related to the dose and duration of bisphosphonate use. There are no data on fetal risk in humans. However, there is theoretical risk of fetal harm, predominantly skeletal, if woman becomes pregnant after completing course of bisphosphonate therapy. The impact of variables such as time between cessation of bisphosphonate therapy to conception, the particular bisphosphonate used, and the route of administration (intravenous versus oral) on the risk has not been studied. There are no studies in pregnant women. FOSAMAX should be used during pregnancy only if the potential benefit justifies the potential risk to the mother and fetus. Nursing MothersIt is not known whether alendronate is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when FOSAMAX is administered to nursing women. Pediatric UseThe efficacy and safety of FOSAMAX were examined in randomized, double-blind, placebo-controlled two-year study of 139 pediatric patients, aged 4-18 years, with severe osteogenesis imperfecta. One-hundred-and-nine patients were randomized to mg FOSAMAX daily (weight less than 40 kg) or 10 mg FOSAMAX daily (weight greater than or equal to 40 kg) and 30 patients to placebo. The mean baseline lumbar spine BMD Z-score of the patients was -4.5. The mean change in lumbar spine BMD Z-score from baseline to Month 24 was 1.3 in the FOSAMAX-treated patients and 0.1 in the placebo-treated patients. Treatment with FOSAMAX did not reduce the risk of fracture. Sixteen percent of the FOSAMAX patients who sustained radiologically-confirmed fracture by Month 12 of the study had delayed fracture healing (callus remodeling) or fracture non-union when assessed radiographically at Month 24 compared with 9% of the placebo-treated patients. In FOSAMAX-treated patients, bone histomorphometry data obtained at Month 24 demonstrated decreased bone turnover and delayed mineralization time; however, there were no mineralization defects. There were no statistically significant differences between the FOSAMAX and placebo groups in reduction of bone pain. FOSAMAX is not indicated for use in children. (For clinical adverse experiences in children, see ADVERSE REACTIONS, Clinical Studies, Osteogenesis Imperfecta.) Geriatric UseOf the patients receiving FOSAMAX in the Fracture Intervention Trial (FIT), 71% (n=2302) were greater than or equal to 65 years of age and 17% (n=550) were greater than or equal to 75 years of age. Of the patients receiving FOSAMAX in the United States and Multinational osteoporosis treatment studies in women, osteoporosis studies in men, glucocorticoid-induced osteoporosis studies, and Pagets disease studies (see CLINICAL PHARMACOLOGY, Clinical Studies), 45%, 54%, 37%, and 70%, respectively, were 65 years of age or over. No overall differences in efficacy or safety were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

SPL UNCLASSIFIED SECTION.

Effect on fracture incidenceData on the effects of FOSAMAX on fracture incidence are derived from three clinical studies: 1) U.S. and Multinational combined: study of patients with BMD T-score at or below minus 2.5 with or without prior vertebral fracture, 2) Three-Year Study of the Fracture Intervention Trial (FIT): study of patients with at least one baseline vertebral fracture, and 3) Four-Year Study of FIT: study of patients with low bone mass but without baseline vertebral fracture.To assess the effects of FOSAMAX on the incidence of vertebral fractures (detected by digitized radiography; approximately one third of these were clinically symptomatic), the U.S. and Multinational studies were combined in an analysis that compared placebo to the pooled dosage groups of FOSAMAX (5 or 10 mg for three years or 20 mg for two years followed by mg for one year). There was statistically significant reduction in the proportion of patients treated with FOSAMAX experiencing one or more new vertebral fractures relative to those treated with placebo (3.2% vs. 6.2%; 48% relative risk reduction). reduction in the total number of new vertebral fractures (4.2 vs. 11.3 per 100 patients) was also observed. In the pooled analysis, patients who received FOSAMAX had loss in stature that was statistically significantly less than was observed in those who received placebo (-3.0 mm vs. -4.6 mm).The Fracture Intervention Trial (FIT) consisted of two studies in postmenopausal women: the Three-Year Study of patients who had at least one baseline radiographic vertebral fracture and the Four-Year Study of patients with low bone mass but without baseline vertebral fracture. In both studies of FIT, 96% of randomized patients completed the studies (i.e., had closeout visit at the scheduled end of the study); approximately 80% of patients were still taking study medication upon completion.Fracture Intervention Trial: Three-Year Study (patients with at least one baseline radiographic vertebral fracture)This randomized, double-blind, placebo-controlled, 2027-patient study (FOSAMAX, n=1022; placebo, n=1005) demonstrated that treatment with FOSAMAX resulted in statistically significant reductions in fracture incidence at three years as shown in the table below.Effect of FOSAMAX on Fracture Incidence in the Three-Year Study of FIT (patients with vertebral fracture at baseline)FOSAMAX(n=1022)Percent of Patients Placebo(n=1005) AbsoluteReductionin FractureIncidenceRelativeReduction inFractureRisk %Patients with:Vertebral fractures (diagnosed by X-ray) >= new vertebral fracture7.915.07.147+ >= new vertebral fractures0.5 4.9 4.4 90+ Clinical (symptomatic) fractures Any clinical (symptomatic) fracture13.818.14.326 >= clinical (symptomatic) vertebral fracture2.3 5.0 2.7 54 Hip fracture 1.1 2.2 1.1 51 Wrist (forearm) fracture 2.2 4.1 1.9 48 Number evaluable for vertebral fractures: FOSAMAX, n=984; placebo, n=966 p less than 0.001 p=0.007 less than 0.01 less than 0.05 Furthermore, in this population of patients with baseline vertebral fracture, treatment with FOSAMAX significantly reduced the incidence of hospitalizations (25.0% vs. 30.7%). In the Three-Year Study of FIT, fractures of the hip occurred in 22 (2.2%) of 1005 patients on placebo and 11 (1.1%) of 1022 patients on FOSAMAX, p=0.047. The figure below displays the cumulative incidence of hip fractures in this study. Cumulative Incidence of Hip Fractures in the Three-Year Study of FIT (patients with radiographic vertebral fracture at baseline) Fracture Intervention Trial: Four-Year Study (patients with low bone mass but without baseline radiographic vertebral fracture)This randomized, double-blind, placebo-controlled, 4432-patient study (FOSAMAX, n=2214; placebo, n=2218) further investigated the reduction in fracture incidence due to FOSAMAX. The intent of the study was to recruit women with osteoporosis, defined as baseline femoral neck BMD at least two standard deviations below the mean for young adult women. However, due to subsequent revisions to the normative values for femoral neck BMD, 31% of patients were found not to meet this entry criterion and thus this study included both osteoporotic and non-osteoporotic women. The results are shown in the table below for the patients with osteoporosis. Effect of FOSAMAX on Fracture Incidence in Osteoporotic Patients in the Four-Year Study of FIT (patients without vertebral fracture at baseline)FOSAMAX(n=1545)Percent of Patients Placebo(n=1521) AbsoluteReductionin FractureIncidenceRelativeReduction inFracture Risk(%)Patients with: Vertebral fractures (diagnosed by X-ray)+ >= new vertebral fracture2.5 4.8 2.3 48 >= new vertebral fractures0.1 0.6 0.5 78 Clinical (symptomatic) fractures Any clinical (symptomatic) fracture 12.9 16.2 3.3 22 >= clinical (symptomatic) vertebral fracture1.0 1.6 0.6 41(NS) Hip fracture 1.0 1.4 0.4 29(NS) Wrist (forearm) fracture 3.9 3.8 -0.1 NS Baseline femoral neck BMD at least SD below the mean for young adult women Number evaluable for vertebral fractures: FOSAMAX, n=1426; placebo, n=1428 less than 0.001 p=0.035 p=0.01 Not significant. This study was not powered to detect differences at these sites. Fracture results across studiesIn the Three-Year Study of FIT, FOSAMAX reduced the percentage of women experiencing at least one new radiographic vertebral fracture from 15.0% to 7.9% (47% relative risk reduction, less than 0.001); in the Four-Year Study of FIT, the percentage was reduced from 3.8% to 2.1% (44% relative risk reduction, p=0.001); and in the combined U.S./Multinational studies, from 6.2% to 3.2% (48% relative risk reduction, p=0.034). FOSAMAX reduced the percentage of women experiencing multiple (two or more) new vertebral fractures from 4.2% to 0.6% (87% relative risk reduction, less than 0.001) in the combined U.S./Multinational studies and from 4.9% to 0.5% (90% relative risk reduction, less than 0.001) in the Three-Year Study of FIT. In the Four-Year Study of FIT, FOSAMAX reduced the percentage of osteoporotic women experiencing multiple vertebral fractures from 0.6% to 0.1% (78% relative risk reduction, p=0.035). Thus, FOSAMAX reduced the incidence of radiographic vertebral fractures in osteoporotic women whether or not they had previous radiographic vertebral fracture. FOSAMAX, over three- or four-year period, was associated with statistically significant reductions in loss of height vs. placebo in patients with and without baseline radiographic vertebral fractures. At the end of the FIT studies the between-treatment group differences were 3.2 mm in the Three-Year Study and 1.3 mm in the Four-Year Study. Bone histologyBone histology in 270 postmenopausal patients with osteoporosis treated with FOSAMAX at doses ranging from to 20 mg/day for one, two, or three years revealed normal mineralization and structure, as well as the expected decrease in bone turnover relative to placebo. These data, together with the normal bone histology and increased bone strength observed in rats and baboons exposed to long-term alendronate treatment, support the conclusion that bone formed during therapy with FOSAMAX is of normal quality. MenThe efficacy of FOSAMAX in men with hypogonadal or idiopathic osteoporosis was demonstrated in two clinical studies. two-year, double-blind, placebo-controlled, multicenter study of FOSAMAX 10 mg once daily enrolled total of 241 men between the ages of 31 and 87 (mean, 63). All patients in the trial had either: 1) BMD T-score less than or equal to -2 at the femoral neck and <=-1 at the lumbar spine, or 2) baseline osteoporotic fracture and BMD T-score less than or equal to -1 at the femoral neck. At two years, the mean increases relative to placebo in BMD in men receiving FOSAMAX 10 mg/day were significant at the following sites: lumbar spine, 5.3%; femoral neck, 2.6%; trochanter, 3.1%; and total body, 1.6%. Treatment with FOSAMAX also reduced height loss (FOSAMAX, -0.6 mm vs. placebo, -2.4 mm). one-year, double-blind, placebo-controlled, multicenter study of once weekly FOSAMAX 70 mg enrolled total of 167 men between the ages of 38 and 91 (mean, 66). Patients in the study had either: 1) BMD T-score less than or equal to -2 at the femoral neck and less than or equal to -1 at the lumbar spine, 2) BMD T-score less than or equal to -2 at the lumbar spine and less than or equal to -1 at the femoral neck, or 3) baseline osteoporotic fracture and BMD T-score less than or equal to -1 at the femoral neck. At one year, the mean increases relative to placebo in BMD in men receiving FOSAMAX 70 mg once weekly were significant at the following sites: lumbar spine, 2.8%; femoral neck, 1.9%; trochanter, 2.0%; and total body, 1.2%. These increases in BMD were similar to those seen at one year in the 10 mg once-daily study. In both studies, BMD responses were similar regardless of age (greater than or equal to 65 years vs. less than 65 years), gonadal function (baseline testosterone less than ng/dL vs. greater than or equal to ng/dL), or baseline BMD (femoral neck and lumbar spine T-score less than or equal to -2.5 vs. greater than -2.5). Prevention of osteoporosis in postmenopausal women Prevention of bone loss was demonstrated in two double-blind, placebo-controlled studies of postmenopausal women 40-60 years of age. One thousand six hundred nine patients (FOSAMAX mg/day; n=498) who were at least six months postmenopausal were entered into two-year study without regard to their baseline BMD. In the other study, 447 patients (FOSAMAX mg/day; n=88), who were between six months and three years postmenopause, were treated for up to three years. In the placebo-treated patients BMD losses of approximately 1% per year were seen at the spine, hip (femoral neck and trochanter) and total body. In contrast, FOSAMAX mg/day prevented bone loss in the majority of patients and induced significant increases in mean bone mass at each of these sites (see figures below). In addition, FOSAMAX mg/day reduced the rate of bone loss at the forearm by approximately half relative to placebo. FOSAMAX mg/day was similarly effective in this population regardless of age, time since menopause, race and baseline rate of bone turnover. Osteoporosis Prevention Studies in Postmenopausal Women The therapeutic equivalence of once weekly FOSAMAX 35 mg (n=362) and FOSAMAX mg daily (n=361) was demonstrated in one-year, double-blind, multicenter study of postmenopausal women without osteoporosis. In the primary analysis of completers, the mean increases from baseline in lumbar spine BMD at one year were 2.9% (2.6, 3.2%; 95% CI) in the 35-mg once-weekly group (n=307) and 3.2% (2.9, 3.5%; 95% CI) in the 5-mg daily group (n=298). The two treatment groups were also similar with regard to BMD increases at other skeletal sites. The results of the intention-to-treat analysis were consistent with the primary analysis of completers. image of figure (Cumulative Incidence of Hip Fractures). image of figure (Osteoporosis Prevention Studies).