Common use of Safety of Alendronate Sodium Clause in Contracts

Safety of Alendronate Sodium. According to the US package insert for Fosamax® (alendronate sodium), in studies of up to five years duration, adverse experiences usually were mild and generally did not require discontinuation of therapy. In a three-year, placebo-controlled, double blind study in which 196 subjects were treated with 10 mg/day, discontinuation due to any adverse experience occurred in 4.1% of subjects treated with alendronate, and 6% of 397 subjects treated with placebo. The most frequently reported adverse event (occurring in >2% of subjects treated with alendronate) in this study were abdominal pain, musculoskeletal pain, nausea, dyspepsia, constipation, diarrhea, flatulence, headache and acid regurgitation. Alendronate may cause local irritation of the upper gastrointestinal mucosa. Esophageal adverse experiences, such as esophagitis, esophageal ulcers and esophageal erosions occasionally with bleeding and rarely followed by esophageal stricture or perforation have been reported. Osteonecrosis of the jaw (ONJ), which can occur spontaneously, is generally associated with tooth extraction and/or local infection with delayed healing, has been reported in subjects taking alendronate. For subjects requiring dental procedures, discontinuation of alendronate therapy may reduce the risk for ONJ. Atypical, low-energy, or low trauma fractures of the femoral shaft have been reported in bisphosphonate-treated patients. These fractures can occur anywhere in the femoral shaft from just below the lesser trochanter to above the supracondylar flare and are transverse or short oblique in orientation without evidence of comminution. Causality has not been established as these fractures also occur in osteoporotic patients who have not been treated with bisphosphonates. Atypical femur fractures most commonly occur with minimal or no trauma to the affected area. They may be bilateral and many patients report prodromal pain in the affected area, usually presenting as dull, aching thigh pain, weeks to months before a complete fracture occurs. A number of reports note that patients were also receiving treatment with glucocorticoids (e.g. prednisone) at the time of fracture. Any patient with a history of bisphosphonate exposure who presents with thigh or groin pain should be suspected of having an atypical fracture and should be evaluated to rule out an incomplete femur fracture. Patients presenting with an atypical fracture should also be assessed for symptoms and signs of fracture in the contralateral limb. Interruption of bisphosphonate therapy should be considered, pending a risk/benefit assessment, on an individual basis. According to the Summary of Product Characteristics for alendronate from the EMA, the following adverse experiences have been reported in alendronate treated subject during clinical trials and/or post-marketing use: Common: Headache, abdominal pain, dyspepsia, constipation, diarrhea, flatulence, esophageal ulcer, dysphagia, abdominal distension, acid regurgitation and musculoskeletal pain. Uncommon: Nausea, vomiting, gastritis, esophagitis, esophageal erosions, melena, rash, pruritus and erythema. Rare: Hypersensitivity reactions including urticarial and angioedema, symptomatic hypocalcemia (often in association with predisposing conditions), uveitis, scleritis, episcleritis, esophageal stricture, oropharyngeal ulceration, upper gastrointestinal perforations, ulcers and bleeds (PUBs), rash with photosensitivity, osteonecrosis of the jaw, atypical subtrochanteric and diaphyseal femoral fractures and transient symptoms as in an acute-phase response (myalgia, malaise and rarely, fever), typically associated with initiation of treatment.

Safety of Alendronate Sodium. According to the US package insert for Fosamax® (alendronate sodium), in studies of up to five years duration, adverse experiences usually were mild and generally did not require discontinuation of therapy. In a three-year, placebo-controlled, double blind study in which 196 subjects were treated with 10 mg/day, discontinuation due to any adverse experience occurred in 4.1% of subjects treated with alendronate, and 6% of 397 subjects treated with placebo. The most frequently reported adverse event (occurring in >2% of subjects treated with alendronate) in this study were abdominal pain, musculoskeletal pain, nausea, dyspepsia, constipation, diarrhea, flatulence, headache and acid regurgitation. Alendronate may cause local irritation of the upper gastrointestinal mucosa. Esophageal adverse experiences, such as esophagitis, esophageal ulcers and esophageal erosions occasionally with bleeding and rarely followed by esophageal stricture or perforation have been reported. Osteonecrosis of the jaw (ONJ), which can occur spontaneously, is generally associated with tooth extraction and/or local infection with delayed healing, has been reported in subjects taking alendronate. For subjects requiring dental procedures, discontinuation of alendronate therapy may reduce the risk for ONJ. Atypical, low-energy, or low trauma fractures of the femoral shaft have been reported in bisphosphonate-treated patients. These fractures can occur anywhere in the femoral shaft from just below the lesser trochanter to above the supracondylar flare and are transverse or short oblique in orientation without evidence of comminution. Causality has not been Radius Health, Inc. Confidential established as these fractures also occur in osteoporotic patients who have not been treated with bisphosphonates. Atypical femur fractures most commonly occur with minimal or no trauma to the affected area. They may be bilateral and many patients report prodromal pain in the affected area, usually presenting as dull, aching thigh pain, weeks to months before a complete fracture occurs. A number of reports note that patients were also receiving treatment with glucocorticoids (e.g. prednisone) at the time of fracture. Any patient with a history of bisphosphonate exposure who presents with thigh or groin pain should be suspected of having an atypical fracture and should be evaluated to rule out an incomplete femur fracture. Patients presenting with an atypical fracture should also be assessed for symptoms and signs of fracture in the contralateral limb. Interruption of bisphosphonate therapy should be considered, pending a risk/benefit assessment, on an individual basis. According to the Summary of Product Characteristics for alendronate from the EMA, the following adverse experiences have been reported in alendronate treated subject during clinical trials and/or post-marketing use: Common: Headache, abdominal pain, dyspepsia, constipation, diarrhea, flatulence, esophageal ulcer, dysphagia, abdominal distension, acid regurgitation and musculoskeletal pain. Uncommon: Nausea, vomiting, gastritis, esophagitis, esophageal erosions, melena, rash, pruritus and erythema. Rare: Hypersensitivity reactions including urticarial and angioedema, symptomatic hypocalcemia (often in association with predisposing conditions), uveitis, scleritis, episcleritis, esophageal stricture, oropharyngeal ulceration, upper gastrointestinal perforations, ulcers and bleeds (PUBs), rash with photosensitivity, osteonecrosis of the jaw, atypical subtrochanteric and diaphyseal femoral fractures and transient symptoms as in an acute-phase response (myalgia, malaise and rarely, fever), typically associated with initiation of treatment.