FDA label f66b35ea-036c-445b-a2af-1bab3829b84e

WARNINGS Actonel Bisphosphonates may cause upper gastrointestinal disorders such as dysphagia, esophagitis, and esophageal or gastric ulcer (see PRECAUTIONS ). Calcium See PRECAUTIONS

ADVERSE REACTIONS Actonel Osteoporosis: Actonel has been studied in over 5700 patients enrolled in the Phase 3 glucocorticoid-induced osteoporosis clinical trials and in postmenopausal osteoporosis trials of up to 3-years duration. The overall adverse event profile of Actonel 5 mg in these studies was similar to that of placebo. Most adverse events were either mild or moderate and did not lead to discontinuation from the study. The incidence of serious adverse events in the placebo group was 24.9% and in the Actonel 5 mg group was 26.3%. The percentage of patients who withdrew from the study due to adverse events was 14.4% and 13.5% for the placebo and Actonel 5 mg groups, respectively. Table 4 lists adverse events from the Phase 3 osteoporosis trials reported in greater than or equal to 2% of patients and in more Actonel-treated patients than placebo-treated patients. Adverse events are shown without attribution of causality. Table 4 Adverse Events Occurring at a Frequency greater than or equal to 2% and in More Actonel-Treated Patients than Placebo-Treated Patients Combined Phase 3 Osteoporosis Trials Body System Placebo % (N = 1914) Actonel 5 mg % (N = 1916) Body as a Whole Infection 29.7 29.9 Back Pain 23.6 26.1 Pain 13.1 13.6 Abdominal Pain 9.4 11.6 Neck Pain 4.5 5.3 Asthenia 4.3 5.1 Chest Pain 4.9 5.0 Neoplasm 3.0 3.3 Hernia 2.5 2.9 Cardiovascular Hypertension 9.0 10.0 Cardiovascular Disorder 1.7 2.5 Angina Pectoris 2.4 2.5 Digestive Nausea 10.7 10.9 Diarrhea 9.6 10.6 Flatulence 4.2 4.6 Gastritis 2.3 2.5 Gastrointestinal Disorder 2.1 2.3 Rectal Disorder 1.9 2.2 Tooth Disorder 2.0 2.1 Hemic and Lymphatic Ecchymosis 4.0 4.3 Anemia 1.9 2.4 Musculoskeletal Arthralgia 21.1 23.7 Joint Disorder 5.4 6.8 Myalgia 6.3 6.6 Bone Pain 4.3 4.6 Bone Disorder 3.2 4.0 Leg Cramps 2.6 3.5 Bursitis 2.9 3.0 Tendon Disorder 2.5 3.0 Nervous Depression 6.2 6.8 Dizziness 5.4 6.4 Insomnia 4.5 4.7 Anxiety 3.0 4.3 Neuralgia 3.5 3.8 Vertigo 3.2 3.3 Hypertonia 2.1 2.2 Paresthesia 1.8 2.1 Respiratory Pharyngitis 5.0 5.8 Rhinitis 5.0 5.7 Dyspnea 3.2 3.8 Pneumonia 2.6 3.1 Skin and Appendages Rash 7.2 7.7 Pruritus 2.2 3.0 Skin Carcinoma 1.8 2.0 Special Senses Cataract 5.4 5.9 Conjunctivitis 2.8 3.1 Otitis Media 2.4 2.5 Urogenital Urinary Tract Infection 9.7 10.9 Cystitis 3.5 4.1 Duodenitis and glossitis have been reported uncommonly (0.1% to 1%). There have been rare reports (less than 0.1%) of abnormal liver function tests. Laboratory Test Findings: Asymptomatic and small decreases were observed in serum calcium and phosphorus levels. Overall, mean decreases of 0.8% in serum calcium and of 2.7% in phosphorus were observed at 6 months in patients receiving Actonel. Throughout the Phase 3 studies, serum calcium levels below 8 mg/dL were observed in 18 patients, 9 (0.5%) in each treatment arm (Actonel and placebo). Serum phosphorus levels below 2 mg/dL were observed in 14 patients, 11 (0.6%) treated with Actonel and 3 (0.2%) treated with placebo. Endoscopic Findings: Actonel clinical studies enrolled over 5700 patients, many with pre-existing gastrointestinal disease and concomitant use of NSAIDs or aspirin. Investigators were encouraged to perform endoscopies in any patients with moderate-to-severe gastrointestinal complaints, while maintaining the blind. These endoscopies were ultimately performed on equal numbers of patients between the treated and placebo groups [75 (14.5%) placebo; 75 (11.9%) Actonel]. Across treatment groups, the percentage of patients with normal esophageal, gastric, and duodenal mucosa on endoscopy was similar (20% placebo; 21% Actonel). The number of patients who withdrew from the studies due to the event prompting endoscopy was similar across treatment groups. Positive findings on endoscopy were also generally comparable across treatment groups. There was a higher number of reports of mild duodenitis in the Actonel group, however there were more duodenal ulcers in the placebo group. Clinically important findings (perforations, ulcers, or bleeding) among this symptomatic population were similar between groups (51% placebo; 39% Actonel). Once-a-week Dosing: In a 1-year, double-blind, multicenter study comparing Actonel 5 mg daily and Actonel 35 mg once-a-week in postmenopausal women, the overall safety and tolerability profiles of the 2 oral dosing regimens were similar. Table 5 lists the adverse events in greater than or equal to 2% of patients from this trial. Events are shown without attribution of causality. Table 5 Adverse Events Occurring in greater than or equal to 2% of Patients of Either Treatment Group in the Daily vs. Weekly Osteoporosis Treatment Study in Postmenopausal Women Body System 5 mg Daily Actonel % (N = 480) 35 mg Weekly Actonel % (N = 485) Body as a Whole Infection 19.0 20.6 Accidental Injury 10.6 10.7 Pain 7.7 9.9 Back Pain 9.2 8.7 Flu Syndrome 7.1 8.5 Abdominal Pain 7.3 7.6 Headache 7.3 7.2 Overdose 6.9 6.8 Asthenia 3.5 5.4 Chest Pain 2.3 2.7 Allergic Reaction 1.9 2.5 Neoplasm 0.8 2.1 Neck Pain 2.7 1.2 Cardiovascular System Hypertension 5.8 4.9 Syncope 0.6 2.1 Vasodilatation 2.3 1.4 Digestive System Constipation 12.5 12.2 Dyspepsia 6.9 7.6 Nausea 8.5 6.2 Diarrhea 6.3 4.9 Gastroenteritis 3.8 3.5 Flatulence 3.3 3.1 Colitis 0.8 2.5 Gastrointestinal Disorder 1.9 2.5 Vomiting 1.9 2.5 Dry Mouth 2.5 1.4 Metabolic and Nutritional Disorders Peripheral Edema 4.2 1.6 Musculoskeletal System Arthralgia 11.5 14.2 Traumatic Bone Fracture 5.0 6.4 Myalgia 4.6 6.2 Arthritis 4.8 4.1 Bursitis 1.3 2.5 Bone Pain 2.9 1.4 Nervous System Dizziness 5.8 4.9 Anxiety 0.6 2.7 Depression 2.3 2.3 Vertigo 2.1 1.6 Respiratory System Bronchitis 2.3 4.9 Sinusitis 4.6 4.5 Pharyngitis 4.6 2.9 Cough Increased 3.1 2.5 Pneumonia 0.8 2.5 Rhinitis 2.3 2.1 Skin and Appendages Rash 3.1 4.1 Pruritus 1.9 2.3 Special Senses Cataract 2.9 1.9 Urogenital System Urinary Tract Infection 2.9 5.2 Osteoporosis Prevention: There were no deaths in a 1-year, double-blind, placebo-controlled study of Actonel 35 mg once-a-week for prevention of bone loss in 278 postmenopausal women without osteoporosis. More treated subjects on risedronate experienced arthralgia (risedronate 13.9%; placebo 7.8%), myalgia (risedronate 5.1%; placebo 2.1%), and nausea (risedronate 7.3%; placebo 4.3%) than subjects on placebo. Post-marketing Experience: Hypersensitivity and skin reactions have been reported, including angioedema, generalized rash and bullous skin reactions, some severe. Musculoskeletal: bone, joint, or muscle pain, occasionally described as severe or incapacitating (see PRECAUTIONS, Musculoskeletal Pain ). Pulmonary: Asthma exacerbations Reactions of eye inflammation including iritis and uveitis have been reported. Osteonecrosis of the jaw has been reported (see PRECAUTIONS, General ). Calcium Calcium carbonate may cause gastrointestinal adverse effects such as constipation, flatulence, nausea, abdominal pain, and bloating. Administration of calcium may increase the risk of kidney stones, particularly in patients with a history of this condition (see PRECAUTIONS ).

<table width="554" ID="id_c9c6fb8a-d5c3-4059-aac0-085d733e732a"> <caption ID="id_64dc7e7d-f1b7-498c-8f23-9edde1f1b3af">Table 4 Adverse Events Occurring at a Frequency greater than or equal to 2% and in More Actonel-Treated Patients than Placebo-Treated Patients Combined Phase 3 Osteoporosis Trials </caption> <col width="42.6%"/> <col width="28.7%"/> <col width="28.7%"/> <thead> <tr ID="id_5adc33d1-3e12-4bdc-8447-74d7cdb34f64"> <td align="left" valign="bottom" styleCode="Botrule Toprule Rrule Lrule">Body System </td> <td align="center" valign="top" styleCode="Botrule Rrule">Placebo % (N = 1914) </td> <td align="center" valign="top" styleCode="Botrule Rrule">Actonel 5 mg % (N = 1916) </td> </tr> </thead> <tbody> <tr ID="id_297c8f55-e3da-4968-8330-fc2f45a5ba4c"> <td align="left" valign="top" styleCode="Lrule Toprule Rrule">Body as a Whole </td> <td align="center" valign="top" styleCode="Rrule"/> <td align="center" valign="top" styleCode="Rrule"/> </tr> <tr ID="id_6f94636c-e9ad-45e7-9302-07c598e40fd9"> <td align="left" valign="top" styleCode="Lrule Rrule"> Infection </td> <td align="center" valign="top" styleCode="Rrule">29.7 </td> <td align="center" valign="top" styleCode="Rrule">29.9 </td> </tr> <tr ID="id_c77ce711-639e-4153-bf23-9e7d28d3e1de"> <td align="left" valign="top" styleCode="Lrule Rrule"> Back Pain </td> <td align="center" valign="top" styleCode="Rrule">23.6 </td> <td align="center" valign="top" styleCode="Rrule">26.1 </td> </tr> <tr ID="id_1879ae2a-2a25-40c8-b04e-cf41fdacb3d5"> <td align="left" valign="top" styleCode="Lrule Rrule"> Pain </td> <td align="center" valign="top" styleCode="Rrule">13.1 </td> <td align="center" valign="top" styleCode="Rrule">13.6 </td> </tr> <tr ID="id_ae4fd52d-8be9-4349-843d-b8e798d14706"> <td align="left" valign="top" styleCode="Lrule Rrule"> Abdominal Pain </td> <td align="center" valign="top" styleCode="Rrule">9.4 </td> <td align="center" valign="top" styleCode="Rrule">11.6 </td> </tr> <tr ID="id_b8f3e8a8-ccd1-4b38-8347-86555f14e797"> <td align="left" valign="top" styleCode="Lrule Rrule"> Neck Pain </td> <td align="center" valign="top" styleCode="Rrule">4.5 </td> <td align="center" valign="top" styleCode="Rrule">5.3 </td> </tr> <tr ID="id_5da6105d-9cbe-46a1-bfbc-5efab9f9728c"> <td align="left" valign="top" styleCode="Lrule Rrule"> Asthenia </td> <td align="center" valign="top" styleCode="Rrule">4.3 </td> <td align="center" valign="top" styleCode="Rrule">5.1 </td> </tr> <tr ID="id_1fd4ae16-3f44-456a-962a-4c8a743649cb"> <td align="left" valign="top" styleCode="Lrule Rrule"> Chest Pain </td> <td align="center" valign="top" styleCode="Rrule">4.9 </td> <td align="center" valign="top" styleCode="Rrule">5.0 </td> </tr> <tr ID="id_da7f15f8-a9c3-4148-ae6c-fcc647302262"> <td align="left" valign="top" styleCode="Lrule Rrule"> Neoplasm </td> <td align="center" valign="top" styleCode="Rrule">3.0 </td> <td align="center" valign="top" styleCode="Rrule">3.3 </td> </tr> <tr ID="id_645967f4-4b19-4b92-acd0-cc4646cf7163"> <td align="left" valign="top" styleCode="Lrule Rrule"> Hernia </td> <td align="center" valign="top" styleCode="Rrule">2.5 </td> <td align="center" valign="top" styleCode="Rrule">2.9 </td> </tr> <tr ID="id_a2b69a68-19fa-463b-b81a-5708e421866f"> <td align="left" valign="top" styleCode="Lrule Rrule">Cardiovascular </td> <td align="center" valign="top" styleCode="Rrule"/> <td align="center" valign="top" styleCode="Rrule"/> </tr> <tr ID="id_784fd1a8-2b6c-4170-9b2f-c22b883962ef"> <td align="left" valign="top" styleCode="Lrule Rrule"> Hypertension </td> <td align="center" valign="top" styleCode="Rrule">9.0 </td> <td align="center" valign="top" styleCode="Rrule">10.0 </td> </tr> <tr ID="id_d533d37e-8f40-4588-b1b5-5166ad0ebb9f"> <td align="left" valign="top" styleCode="Lrule Rrule"> Cardiovascular Disorder </td> <td align="center" valign="top" styleCode="Rrule">1.7 </td> <td align="center" valign="top" styleCode="Rrule">2.5 </td> </tr> <tr ID="id_811680b9-4f20-4bcc-b054-9dbf9e6b7c65"> <td align="left" valign="top" styleCode="Lrule Rrule"> Angina Pectoris </td> <td align="center" valign="top" styleCode="Rrule">2.4 </td> <td align="center" valign="top" styleCode="Rrule">2.5 </td> </tr> <tr ID="id_c0f401fe-1b64-451d-8d6b-9a7cc411245d"> <td align="left" valign="top" styleCode="Lrule Rrule">Digestive </td> <td align="center" valign="top" styleCode="Rrule"/> <td align="center" valign="top" styleCode="Rrule"/> </tr> <tr ID="id_27aed8af-6e05-4bd9-9f4b-f428b6a251e3"> <td align="left" valign="top" styleCode="Lrule Rrule"> Nausea </td> <td align="center" valign="top" styleCode="Rrule">10.7 </td> <td align="center" valign="top" styleCode="Rrule">10.9 </td> </tr> <tr ID="id_83144adc-8e00-46cd-a639-5694bbfadcda"> <td align="left" valign="top" styleCode="Lrule Rrule"> Diarrhea </td> <td align="center" valign="top" styleCode="Rrule">9.6 </td> <td align="center" valign="top" styleCode="Rrule">10.6 </td> </tr> <tr ID="id_d71ae642-b76c-4ea7-ac5a-c691918b61dd"> <td align="left" valign="top" styleCode="Lrule Rrule"> Flatulence </td> <td align="center" valign="top" styleCode="Rrule">4.2 </td> <td align="center" valign="top" styleCode="Rrule">4.6 </td> </tr> <tr ID="id_0fcee0cb-c77c-436b-a54a-98a545567a22"> <td align="left" valign="top" styleCode="Lrule Rrule"> Gastritis </td> <td align="center" valign="top" styleCode="Rrule">2.3 </td> <td align="center" valign="top" styleCode="Rrule">2.5 </td> </tr> <tr ID="id_dfd95fa1-e26a-478c-bde0-556ac824c156"> <td align="left" valign="top" styleCode="Lrule Rrule"> Gastrointestinal Disorder </td> <td align="center" valign="top" styleCode="Rrule">2.1 </td> <td align="center" valign="top" styleCode="Rrule">2.3 </td> </tr> <tr ID="id_4351a04d-1b97-4f8f-b4ac-298bb1f80e32"> <td align="left" valign="top" styleCode="Lrule Rrule"> Rectal Disorder </td> <td align="center" valign="top" styleCode="Rrule">1.9 </td> <td align="center" valign="top" styleCode="Rrule">2.2 </td> </tr> <tr ID="id_11ba4d70-1610-4a92-a6f7-6f4680185122"> <td align="left" valign="top" styleCode="Lrule Rrule"> Tooth Disorder </td> <td align="center" valign="top" styleCode="Rrule">2.0 </td> <td align="center" valign="top" styleCode="Rrule">2.1 </td> </tr> <tr ID="id_15b1c5a0-1305-483a-90f3-0aa91e3181d1"> <td align="left" valign="top" styleCode="Lrule Rrule">Hemic and Lymphatic </td> <td align="center" valign="top" styleCode="Rrule"/> <td align="center" valign="top" styleCode="Rrule"/> </tr> <tr ID="id_09ca21ff-9e2e-4add-bb0b-5c3792bea3bc"> <td align="left" valign="top" styleCode="Lrule Rrule"> Ecchymosis </td> <td align="center" valign="top" styleCode="Rrule">4.0 </td> <td align="center" valign="top" styleCode="Rrule">4.3 </td> </tr> <tr ID="id_23234c48-abcd-4938-84f2-56fee041c427"> <td align="left" valign="top" styleCode="Lrule Rrule"> Anemia </td> <td align="center" valign="top" styleCode="Rrule">1.9 </td> <td align="center" valign="top" styleCode="Rrule">2.4 </td> </tr> <tr ID="id_d5d3b1af-31c5-4b1e-a8bd-c3ca76c01c79"> <td align="left" valign="top" styleCode="Lrule Rrule">Musculoskeletal </td> <td align="center" valign="top" styleCode="Rrule"/> <td align="center" valign="top" styleCode="Rrule"/> </tr> <tr ID="id_2d7ae79a-c2cf-4be5-ba3e-a111a7b656db"> <td align="left" valign="top" styleCode="Lrule Rrule"> Arthralgia </td> <td align="center" valign="top" styleCode="Rrule">21.1 </td> <td align="center" valign="top" styleCode="Rrule">23.7 </td> </tr> <tr ID="id_0112c0e8-303e-4cbb-abc4-3c17b9866d01"> <td align="left" valign="top" styleCode="Lrule Rrule"> Joint Disorder </td> <td align="center" valign="top" styleCode="Rrule">5.4 </td> <td align="center" valign="top" styleCode="Rrule">6.8 </td> </tr> <tr ID="id_e04e173d-2604-4628-9c0e-a02d1550847e"> <td align="left" valign="top" styleCode="Lrule Rrule"> Myalgia </td> <td align="center" valign="top" styleCode="Rrule">6.3 </td> <td align="center" valign="top" styleCode="Rrule">6.6 </td> </tr> <tr ID="id_48f6792a-11ce-4018-8207-0febdd2bbf3f"> <td align="left" valign="top" styleCode="Lrule Rrule"> Bone Pain </td> <td align="center" valign="top" styleCode="Rrule">4.3 </td> <td align="center" valign="top" styleCode="Rrule">4.6 </td> </tr> <tr ID="id_63ec967e-ef3e-48e7-b2d7-48760f6a75ca"> <td align="left" valign="top" styleCode="Lrule Rrule"> Bone Disorder </td> <td align="center" valign="top" styleCode="Rrule">3.2 </td> <td align="center" valign="top" styleCode="Rrule">4.0 </td> </tr> <tr ID="id_a476b2fe-6eaf-4aea-b716-c62cb9f19622"> <td align="left" valign="top" styleCode="Lrule Rrule"> Leg Cramps </td> <td align="center" valign="top" styleCode="Rrule">2.6 </td> <td align="center" valign="top" styleCode="Rrule">3.5 </td> </tr> <tr ID="id_480c8e32-d14d-478e-9ce8-afcb87b75019"> <td align="left" valign="top" styleCode="Lrule Rrule"> Bursitis </td> <td align="center" valign="top" styleCode="Rrule">2.9 </td> <td align="center" valign="top" styleCode="Rrule">3.0 </td> </tr> <tr ID="id_59fdc09b-d161-4f3a-8b0a-0d191f6c68a5"> <td align="left" valign="top" styleCode="Lrule Rrule"> Tendon Disorder </td> <td align="center" valign="top" styleCode="Rrule">2.5 </td> <td align="center" valign="top" styleCode="Rrule">3.0 </td> </tr> <tr ID="id_2e7b0065-3975-45b0-b8b9-c9a84ccc6dc9"> <td align="left" valign="top" styleCode="Lrule Rrule">Nervous </td> <td align="center" valign="top" styleCode="Rrule"/> <td align="center" valign="top" styleCode="Rrule"/> </tr> <tr ID="id_bc76f66a-6400-4fa4-8e8c-36c808203ceb"> <td align="left" valign="top" styleCode="Lrule Rrule"> Depression </td> <td align="center" valign="top" styleCode="Rrule">6.2 </td> <td align="center" valign="top" styleCode="Rrule">6.8 </td> </tr> <tr ID="id_b649c4c3-1ba3-47ad-95bd-36d5a3b95bd6"> <td align="left" valign="top" styleCode="Lrule Rrule"> Dizziness </td> <td align="center" valign="top" styleCode="Rrule">5.4 </td> <td align="center" valign="top" styleCode="Rrule">6.4 </td> </tr> <tr ID="id_c5366feb-2d4e-4aff-985c-ca794ef5beb5"> <td align="left" valign="top" styleCode="Lrule Rrule"> Insomnia </td> <td align="center" valign="top" styleCode="Rrule">4.5 </td> <td align="center" valign="top" styleCode="Rrule">4.7 </td> </tr> <tr ID="id_c50b07e4-7847-4458-bfa2-baf4df6327ff"> <td align="left" valign="top" styleCode="Lrule Rrule"> Anxiety </td> <td align="center" valign="top" styleCode="Rrule">3.0 </td> <td align="center" valign="top" styleCode="Rrule">4.3 </td> </tr> <tr ID="id_5fe3b69c-6d70-4b8e-bc12-fbebe2ec645d"> <td align="left" valign="top" styleCode="Lrule Rrule"> Neuralgia </td> <td align="center" valign="top" styleCode="Rrule">3.5 </td> <td align="center" valign="top" styleCode="Rrule">3.8 </td> </tr> <tr ID="id_06797e08-d3a1-4835-bf58-a979f9c8a90f"> <td align="left" valign="top" styleCode="Lrule Rrule"> Vertigo </td> <td align="center" valign="top" styleCode="Rrule">3.2 </td> <td align="center" valign="top" styleCode="Rrule">3.3 </td> </tr> <tr ID="id_b084b6da-3077-4dba-a3de-bf0170ba23b4"> <td align="left" valign="top" styleCode="Lrule Rrule"> Hypertonia </td> <td align="center" valign="top" styleCode="Rrule">2.1 </td> <td align="center" valign="top" styleCode="Rrule">2.2 </td> </tr> <tr ID="id_474f09dc-7c5b-42ad-905c-06209d3d11be"> <td align="left" valign="top" styleCode="Lrule Rrule"> Paresthesia </td> <td align="center" valign="top" styleCode="Rrule">1.8 </td> <td align="center" valign="top" styleCode="Rrule">2.1 </td> </tr> <tr ID="id_3c4ba4b1-a7b1-4950-b142-fb40b3c1430f"> <td align="left" valign="top" styleCode="Lrule Rrule">Respiratory </td> <td align="center" valign="top" styleCode="Rrule"/> <td align="center" valign="top" styleCode="Rrule"/> </tr> <tr ID="id_1afd1253-da43-404f-9d34-3db80cb2aa45"> <td align="left" valign="top" styleCode="Lrule Rrule"> Pharyngitis </td> <td align="center" valign="top" styleCode="Rrule">5.0 </td> <td align="center" valign="top" styleCode="Rrule">5.8 </td> </tr> <tr ID="id_352064c3-4664-4b7d-9a67-eaa5ab76be22"> <td align="left" valign="top" styleCode="Lrule Rrule"> Rhinitis </td> <td align="center" valign="top" styleCode="Rrule">5.0 </td> <td align="center" valign="top" styleCode="Rrule">5.7 </td> </tr> <tr ID="id_b0e2c2cb-ab46-482f-8bea-54845e293036"> <td align="left" valign="top" styleCode="Lrule Rrule"> Dyspnea </td> <td align="center" valign="top" styleCode="Rrule">3.2 </td> <td align="center" valign="top" styleCode="Rrule">3.8 </td> </tr> <tr ID="id_7bb58dcd-b020-4688-82ca-9b4b75bd485b"> <td align="left" valign="top" styleCode="Lrule Rrule"> Pneumonia </td> <td align="center" valign="top" styleCode="Rrule">2.6 </td> <td align="center" valign="top" styleCode="Rrule">3.1 </td> </tr> <tr ID="id_ebb715c1-57ec-4aea-a544-7166285c0de5"> <td align="left" valign="top" styleCode="Lrule Rrule">Skin and Appendages </td> <td align="center" valign="top" styleCode="Rrule"/> <td align="center" valign="top" styleCode="Rrule"/> </tr> <tr ID="id_96f44ad9-1307-400c-a3e7-8f4f8eca84d3"> <td align="left" valign="top" styleCode="Lrule Rrule"> Rash </td> <td align="center" valign="top" styleCode="Rrule">7.2 </td> <td align="center" valign="top" styleCode="Rrule">7.7 </td> </tr> <tr ID="id_0ffc531c-492b-4ecf-ac4f-2b2c19a75904"> <td align="left" valign="top" styleCode="Lrule Rrule"> Pruritus </td> <td align="center" valign="top" styleCode="Rrule">2.2 </td> <td align="center" valign="top" styleCode="Rrule">3.0 </td> </tr> <tr ID="id_3f810fc4-25aa-4fd3-a8ae-5caaf8afadd1"> <td align="left" valign="top" styleCode="Lrule Rrule"> Skin Carcinoma </td> <td align="center" valign="top" styleCode="Rrule">1.8 </td> <td align="center" valign="top" styleCode="Rrule">2.0 </td> </tr> <tr ID="id_a9ccf077-468e-4b2d-abae-b9a7104e970a"> <td align="left" valign="top" styleCode="Lrule Rrule">Special Senses </td> <td align="center" valign="top" styleCode="Rrule"/> <td align="center" valign="top" styleCode="Rrule"/> </tr> <tr ID="id_56160f8b-725f-4898-95ec-2376f960cc15"> <td align="left" valign="top" styleCode="Lrule Rrule"> Cataract </td> <td align="center" valign="top" styleCode="Rrule">5.4 </td> <td align="center" valign="top" styleCode="Rrule">5.9 </td> </tr> <tr ID="id_0784a608-ee7b-44ea-9674-1d7d5e3f3b36"> <td align="left" valign="top" styleCode="Lrule Rrule"> Conjunctivitis </td> <td align="center" valign="top" styleCode="Rrule">2.8 </td> <td align="center" valign="top" styleCode="Rrule">3.1 </td> </tr> <tr ID="id_9ca671e4-aade-493c-b7e4-daab8db0d233"> <td align="left" valign="top" styleCode="Lrule Rrule"> Otitis Media </td> <td align="center" valign="top" styleCode="Rrule">2.4 </td> <td align="center" valign="top" styleCode="Rrule">2.5 </td> </tr> <tr ID="id_71300ddd-e68c-4a3f-ba25-515e8083217f"> <td align="left" valign="top" styleCode="Lrule Rrule">Urogenital </td> <td align="center" valign="top" styleCode="Rrule"/> <td align="center" valign="top" styleCode="Rrule"/> </tr> <tr ID="id_044f69f5-4707-40ad-9b01-ee63a5b73308"> <td align="left" valign="top" styleCode="Lrule Rrule"> Urinary Tract Infection </td> <td align="center" valign="top" styleCode="Rrule">9.7 </td> <td align="center" valign="top" styleCode="Rrule">10.9 </td> </tr> <tr ID="id_02fe6481-dc27-4849-a33c-1e52db50f266"> <td align="left" valign="top" styleCode="Lrule Botrule Rrule"> Cystitis </td> <td align="center" valign="top" styleCode="Rrule">3.5 </td> <td align="center" valign="top" styleCode="Botrule Rrule">4.1 </td> </tr> </tbody> </table>

<table width="539" ID="id_ff2297f0-7c48-4fae-9ef4-3781ae5cc7cd"> <caption ID="id_2071ef54-2a5b-4b02-9a75-7feb62fa2d39">Table 5 Adverse Events Occurring in greater than or equal to 2% of Patients of Either Treatment Group in the Daily vs. Weekly Osteoporosis Treatment Study in Postmenopausal Women </caption> <col width="51.0%" align="left"/> <col width="24.5%" align="left"/> <col width="24.5%" align="left"/> <thead> <tr ID="id_3dd9a308-7359-4f5f-88d2-fa7fb3752bca"> <td align="left" valign="bottom" styleCode="Botrule Toprule Rrule">Body System </td> <td align="center" valign="bottom" styleCode="Botrule Rrule">5 mg Daily Actonel % (N = 480) </td> <td align="center" valign="bottom" styleCode="Botrule">35 mg Weekly Actonel % (N = 485) </td> </tr> </thead> <tbody> <tr ID="id_23faa818-0a68-4e01-89e5-d0044822bee7"> <td align="left" valign="bottom" styleCode="Botrule Toprule Rrule">Body as a Whole </td> <td align="center" valign="bottom" styleCode="Botrule Rrule"/> <td align="center" valign="bottom" styleCode="Botrule"/> </tr> <tr ID="id_4ac921b7-f00f-4703-b4b6-723b6311923c"> <td align="left" valign="bottom" styleCode="Botrule Rrule"> Infection </td> <td align="center" valign="bottom" styleCode="Botrule Rrule">19.0 </td> <td align="center" valign="bottom" styleCode="Botrule">20.6 </td> </tr> <tr ID="id_897b7735-ae44-4b2a-a618-083a49bd854c"> <td align="left" valign="bottom" styleCode="Botrule Rrule"> Accidental Injury </td> <td align="center" valign="bottom" styleCode="Botrule Rrule">10.6 </td> <td align="center" valign="bottom" styleCode="Botrule">10.7 </td> </tr> <tr ID="id_af295644-b79b-4c02-8a83-453e413a7bd4"> <td align="left" valign="bottom" styleCode="Botrule Rrule"> Pain </td> <td align="center" valign="bottom" styleCode="Botrule Rrule">7.7 </td> <td align="center" valign="bottom" styleCode="Botrule">9.9 </td> </tr> <tr ID="id_d485c4f9-5008-40fc-a435-fd26d0c3974d"> <td align="left" valign="bottom" styleCode="Botrule Rrule"> Back Pain </td> <td align="center" valign="bottom" styleCode="Botrule Rrule">9.2 </td> <td align="center" valign="bottom" styleCode="Botrule">8.7 </td> </tr> <tr ID="id_ad0f803f-17f8-4bae-a7a9-a7f70bed59c4"> <td align="left" valign="bottom" styleCode="Botrule Rrule"> Flu Syndrome </td> <td align="center" valign="bottom" styleCode="Botrule Rrule">7.1 </td> <td align="center" valign="bottom" styleCode="Botrule">8.5 </td> </tr> <tr ID="id_f5be9f48-7726-419d-af5f-072e5f00c592"> <td align="left" valign="bottom" styleCode="Botrule Rrule"> Abdominal Pain </td> <td align="center" valign="bottom" styleCode="Botrule Rrule">7.3 </td> <td align="center" valign="bottom" styleCode="Botrule">7.6 </td> </tr> <tr ID="id_7ff6772a-0417-4d3f-90ee-d51ac01c25ca"> <td align="left" valign="bottom" styleCode="Botrule Rrule"> Headache </td> <td align="center" valign="bottom" styleCode="Botrule Rrule">7.3 </td> <td align="center" valign="bottom" styleCode="Botrule">7.2 </td> </tr> <tr ID="id_cae1c6d6-6e55-47e2-aca1-e8bea73ce823"> <td align="left" valign="bottom" styleCode="Botrule Rrule"> Overdose </td> <td align="center" valign="bottom" styleCode="Botrule Rrule">6.9 </td> <td align="center" valign="bottom" styleCode="Botrule">6.8 </td> </tr> <tr ID="id_afb95767-516b-4df2-9be8-abaf40fb79bc"> <td align="left" valign="bottom" styleCode="Botrule Rrule"> Asthenia </td> <td align="center" valign="bottom" styleCode="Botrule Rrule">3.5 </td> <td align="center" valign="bottom" styleCode="Botrule">5.4 </td> </tr> <tr ID="id_d1baf7ca-9890-45bb-829c-e81052ae0b43"> <td align="left" valign="bottom" styleCode="Botrule Rrule"> Chest Pain </td> <td align="center" valign="bottom" styleCode="Botrule Rrule">2.3 </td> <td align="center" valign="bottom" styleCode="Botrule">2.7 </td> </tr> <tr ID="id_13c3bd41-8d75-4724-aa79-8e41a3a4b679"> <td align="left" valign="bottom" styleCode="Botrule Rrule"> Allergic Reaction </td> <td align="center" valign="bottom" styleCode="Botrule Rrule">1.9 </td> <td align="center" valign="bottom" styleCode="Botrule">2.5 </td> </tr> <tr ID="id_bad43a11-1ff7-49e4-a623-d8fd132468eb"> <td align="left" valign="bottom" styleCode="Botrule Rrule"> Neoplasm </td> <td align="center" valign="bottom" styleCode="Botrule Rrule">0.8 </td> <td align="center" valign="bottom" styleCode="Botrule">2.1 </td> </tr> <tr ID="id_fabfd8ee-ac06-44a0-843d-8ae6445b220e"> <td align="left" valign="bottom" styleCode="Botrule Rrule"> Neck Pain </td> <td align="center" valign="bottom" styleCode="Botrule Rrule">2.7 </td> <td align="center" valign="bottom" styleCode="Botrule">1.2 </td> </tr> <tr ID="id_dac9d358-76a0-4f6c-9d5d-40d414a59f0f"> <td align="left" valign="bottom" styleCode="Botrule Rrule">Cardiovascular System </td> <td align="center" valign="bottom" styleCode="Botrule Rrule"/> <td align="center" valign="bottom" styleCode="Botrule"/> </tr> <tr ID="id_6376a7f2-efa7-4f01-bfcb-a0d758eca40c"> <td align="left" valign="bottom" styleCode="Botrule Rrule"> Hypertension </td> <td align="center" valign="bottom" styleCode="Botrule Rrule">5.8 </td> <td align="center" valign="bottom" styleCode="Botrule">4.9 </td> </tr> <tr ID="id_c9dfee0c-27dc-4a54-b30e-8a30abc68afe"> <td align="left" valign="bottom" styleCode="Botrule Rrule"> Syncope </td> <td align="center" valign="bottom" styleCode="Botrule Rrule">0.6 </td> <td align="center" valign="bottom" styleCode="Botrule">2.1 </td> </tr> <tr ID="id_25ce7003-08b5-4c16-b831-a0530cad85f5"> <td align="left" valign="bottom" styleCode="Botrule Rrule"> Vasodilatation </td> <td align="center" valign="bottom" styleCode="Botrule Rrule">2.3 </td> <td align="center" valign="bottom" styleCode="Botrule">1.4 </td> </tr> <tr ID="id_788856bb-a04a-4e00-b26f-f17f7fd148f5"> <td align="left" valign="bottom" styleCode="Botrule Rrule">Digestive System </td> <td align="center" valign="bottom" styleCode="Botrule Rrule"/> <td align="center" valign="bottom" styleCode="Botrule"/> </tr> <tr ID="id_95650c7f-cdb0-4f7f-9dfe-0b3b35eb7798"> <td align="left" valign="bottom" styleCode="Botrule Rrule"> Constipation </td> <td align="center" valign="bottom" styleCode="Botrule Rrule">12.5 </td> <td align="center" valign="bottom" styleCode="Botrule">12.2 </td> </tr> <tr ID="id_b186885c-5e3b-4baa-86d0-418968956d25"> <td align="left" valign="bottom" styleCode="Botrule Rrule"> Dyspepsia </td> <td align="center" valign="bottom" styleCode="Botrule Rrule">6.9 </td> <td align="center" valign="bottom" styleCode="Botrule">7.6 </td> </tr> <tr ID="id_c1cb2106-7b7f-4e35-9dec-77a43fa7cad9"> <td align="left" valign="bottom" styleCode="Botrule Rrule"> Nausea </td> <td align="center" valign="bottom" styleCode="Botrule Rrule">8.5 </td> <td align="center" valign="bottom" styleCode="Botrule">6.2 </td> </tr> <tr ID="id_464ed235-8eb8-4853-96eb-54e39f75c305"> <td align="left" valign="bottom" styleCode="Botrule Rrule"> Diarrhea </td> <td align="center" valign="bottom" styleCode="Botrule Rrule">6.3 </td> <td align="center" valign="bottom" styleCode="Botrule">4.9 </td> </tr> <tr ID="id_bdc3b607-7b26-4fa2-8cd9-735b564b9f3f"> <td align="left" valign="bottom" styleCode="Botrule Rrule"> Gastroenteritis </td> <td align="center" valign="bottom" styleCode="Botrule Rrule">3.8 </td> <td align="center" valign="bottom" styleCode="Botrule">3.5 </td> </tr> <tr ID="id_2c580683-76c6-483a-89e9-002550115f6f"> <td align="left" valign="bottom" styleCode="Botrule Rrule"> Flatulence </td> <td align="center" valign="bottom" styleCode="Botrule Rrule">3.3 </td> <td align="center" valign="bottom" styleCode="Botrule">3.1 </td> </tr> <tr ID="id_63b8a6ef-c618-452b-9463-7c4d8c9b92ab"> <td align="left" valign="bottom" styleCode="Botrule Rrule"> Colitis </td> <td align="center" valign="bottom" styleCode="Botrule Rrule">0.8 </td> <td align="center" valign="bottom" styleCode="Botrule">2.5 </td> </tr> <tr ID="id_d8b83457-f73c-49d3-881f-8d7caa9de63f"> <td align="left" valign="bottom" styleCode="Botrule Rrule"> Gastrointestinal Disorder </td> <td align="center" valign="bottom" styleCode="Botrule Rrule">1.9 </td> <td align="center" valign="bottom" styleCode="Botrule">2.5 </td> </tr> <tr ID="id_f7d279ed-c32c-46ec-b998-ed5c0402e073"> <td align="left" valign="bottom" styleCode="Botrule Rrule"> Vomiting </td> <td align="center" valign="bottom" styleCode="Botrule Rrule">1.9 </td> <td align="center" valign="bottom" styleCode="Botrule">2.5 </td> </tr> <tr ID="id_9fef5ab7-ee7c-466e-9af7-56fc239569ff"> <td align="left" valign="bottom" styleCode="Botrule Rrule"> Dry Mouth </td> <td align="center" valign="bottom" styleCode="Botrule Rrule">2.5 </td> <td align="center" valign="bottom" styleCode="Botrule">1.4 </td> </tr> <tr ID="id_1cd4f532-7982-4253-b8c8-06aa1dab1351"> <td align="left" valign="bottom" styleCode="Botrule Rrule">Metabolic and Nutritional Disorders </td> <td align="center" valign="bottom" styleCode="Botrule Rrule"/> <td align="center" valign="bottom" styleCode="Botrule"/> </tr> <tr ID="id_f2eaeca0-73d7-4967-82dc-a2e16de55da3"> <td align="left" valign="bottom" styleCode="Botrule Rrule"> Peripheral Edema </td> <td align="center" valign="bottom" styleCode="Botrule Rrule">4.2 </td> <td align="center" valign="bottom" styleCode="Botrule">1.6 </td> </tr> <tr ID="id_ea938a52-a8c3-4749-b66a-07f3b8b15bea"> <td align="left" valign="bottom" styleCode="Botrule Rrule">Musculoskeletal System </td> <td align="center" valign="bottom" styleCode="Botrule Rrule"/> <td align="center" valign="bottom" styleCode="Botrule"/> </tr> <tr ID="id_f99d2829-34b1-43eb-87f7-f96648c96cda"> <td align="left" valign="bottom" styleCode="Botrule Rrule"> Arthralgia </td> <td align="center" valign="bottom" styleCode="Botrule Rrule">11.5 </td> <td align="center" valign="bottom" styleCode="Botrule">14.2 </td> </tr> <tr ID="id_370462e0-7c6f-4682-b86d-5f88f34d67fc"> <td align="left" valign="bottom" styleCode="Botrule Rrule"> Traumatic Bone Fracture </td> <td align="center" valign="bottom" styleCode="Botrule Rrule">5.0 </td> <td align="center" valign="bottom" styleCode="Botrule">6.4 </td> </tr> <tr ID="id_b6d50431-578c-4c18-9a79-fe92b0e40ba3"> <td align="left" valign="bottom" styleCode="Botrule Rrule"> Myalgia </td> <td align="center" valign="bottom" styleCode="Botrule Rrule">4.6 </td> <td align="center" valign="bottom" styleCode="Botrule">6.2 </td> </tr> <tr ID="id_5ea6914d-214d-411a-8273-1170f53b7596"> <td align="left" valign="bottom" styleCode="Botrule Rrule"> Arthritis </td> <td align="center" valign="bottom" styleCode="Botrule Rrule">4.8 </td> <td align="center" valign="bottom" styleCode="Botrule">4.1 </td> </tr> <tr ID="id_6d994c08-ebdb-42f6-a3aa-bf19f0224c98"> <td align="left" valign="bottom" styleCode="Botrule Rrule"> Bursitis </td> <td align="center" valign="bottom" styleCode="Botrule Rrule">1.3 </td> <td align="center" valign="bottom" styleCode="Botrule">2.5 </td> </tr> <tr ID="id_0afe35a9-b5d1-4e54-b475-fb16ce2bc3c6"> <td align="left" valign="bottom" styleCode="Botrule Rrule"> Bone Pain </td> <td align="center" valign="bottom" styleCode="Botrule Rrule">2.9 </td> <td align="center" valign="bottom" styleCode="Botrule">1.4 </td> </tr> <tr ID="id_c83f6e32-0e65-40bd-9c17-244baf0ac9f2"> <td align="left" valign="bottom" styleCode="Botrule Rrule">Nervous System </td> <td align="center" valign="bottom" styleCode="Botrule Rrule"/> <td align="center" valign="bottom" styleCode="Botrule"/> </tr> <tr ID="id_f304f05b-b07c-47aa-8b41-acf5a39ce693"> <td align="left" valign="bottom" styleCode="Botrule Rrule"> Dizziness </td> <td align="center" valign="bottom" styleCode="Botrule Rrule">5.8 </td> <td align="center" valign="bottom" styleCode="Botrule">4.9 </td> </tr> <tr ID="id_f7e439fa-f6e5-4cf1-ab13-5ff30d6aad75"> <td align="left" valign="bottom" styleCode="Botrule Rrule"> Anxiety </td> <td align="center" valign="bottom" styleCode="Botrule Rrule">0.6 </td> <td align="center" valign="bottom" styleCode="Botrule">2.7 </td> </tr> <tr ID="id_f3038f18-f680-427d-8ea1-8e462f445725"> <td align="left" valign="bottom" styleCode="Botrule Rrule"> Depression </td> <td align="center" valign="bottom" styleCode="Botrule Rrule">2.3 </td> <td align="center" valign="bottom" styleCode="Botrule">2.3 </td> </tr> <tr ID="id_d449a241-1704-4220-93fd-02814ad38bb9"> <td align="left" valign="bottom" styleCode="Botrule Rrule"> Vertigo </td> <td align="center" valign="bottom" styleCode="Botrule Rrule">2.1 </td> <td align="center" valign="bottom" styleCode="Botrule">1.6 </td> </tr> <tr ID="id_0c12b51d-d5da-465a-abc6-1213b6e99d2b"> <td align="left" valign="bottom" styleCode="Botrule Rrule">Respiratory System </td> <td align="center" valign="bottom" styleCode="Botrule Rrule"/> <td align="center" valign="bottom" styleCode="Botrule"/> </tr> <tr ID="id_6345b1c2-4584-4f27-a520-04d40861e5d7"> <td align="left" valign="bottom" styleCode="Botrule Rrule"> Bronchitis </td> <td align="center" valign="bottom" styleCode="Botrule Rrule">2.3 </td> <td align="center" valign="bottom" styleCode="Botrule">4.9 </td> </tr> <tr ID="id_014b9a81-0a1c-42f1-a3ce-590f49fbf89d"> <td align="left" valign="bottom" styleCode="Botrule Rrule"> Sinusitis </td> <td align="center" valign="bottom" styleCode="Botrule Rrule">4.6 </td> <td align="center" valign="bottom" styleCode="Botrule">4.5 </td> </tr> <tr ID="id_6182869c-d86d-46dc-ad43-c4c557675e27"> <td align="left" valign="bottom" styleCode="Botrule Rrule"> Pharyngitis </td> <td align="center" valign="bottom" styleCode="Botrule Rrule">4.6 </td> <td align="center" valign="bottom" styleCode="Botrule">2.9 </td> </tr> <tr ID="id_5c0c47d0-7d14-421a-afcc-610f2ee2321a"> <td align="left" valign="bottom" styleCode="Botrule Rrule"> Cough Increased </td> <td align="center" valign="bottom" styleCode="Botrule Rrule">3.1 </td> <td align="center" valign="bottom" styleCode="Botrule">2.5 </td> </tr> <tr ID="id_d4f1f82c-c6ab-4296-b715-e2a10a4f0cea"> <td align="left" valign="bottom" styleCode="Botrule Rrule"> Pneumonia </td> <td align="center" valign="bottom" styleCode="Botrule Rrule">0.8 </td> <td align="center" valign="bottom" styleCode="Botrule">2.5 </td> </tr> <tr ID="id_3f3a0988-582c-4eae-8a5f-0218f66d256f"> <td align="left" valign="bottom" styleCode="Botrule Rrule"> Rhinitis </td> <td align="center" valign="bottom" styleCode="Botrule Rrule">2.3 </td> <td align="center" valign="bottom" styleCode="Botrule">2.1 </td> </tr> <tr ID="id_f2a2e0d3-e74e-41f4-bba2-c2ea37347023"> <td align="left" valign="bottom" styleCode="Botrule Rrule">Skin and Appendages </td> <td align="center" valign="bottom" styleCode="Botrule Rrule"/> <td align="center" valign="bottom" styleCode="Botrule"/> </tr> <tr ID="id_91ac1eac-fc8f-4e27-93f0-c732f4a15ef5"> <td align="left" valign="bottom" styleCode="Botrule Rrule"> Rash </td> <td align="center" valign="bottom" styleCode="Botrule Rrule">3.1 </td> <td align="center" valign="bottom" styleCode="Botrule">4.1 </td> </tr> <tr ID="id_251f1287-6167-457c-92a8-4d1f34cb8728"> <td align="left" valign="bottom" styleCode="Botrule Rrule"> Pruritus </td> <td align="center" valign="bottom" styleCode="Botrule Rrule">1.9 </td> <td align="center" valign="bottom" styleCode="Botrule">2.3 </td> </tr> <tr ID="id_726552b1-d159-4cbc-83a6-5f2ce4930a90"> <td align="left" valign="bottom" styleCode="Botrule Rrule">Special Senses </td> <td align="center" valign="bottom" styleCode="Botrule Rrule"/> <td align="center" valign="bottom" styleCode="Botrule"/> </tr> <tr ID="id_cb562ef3-65a9-4940-b0b0-c99a8f8ee589"> <td align="left" valign="bottom" styleCode="Botrule Rrule"> Cataract </td> <td align="center" valign="bottom" styleCode="Botrule Rrule">2.9 </td> <td align="center" valign="bottom" styleCode="Botrule">1.9 </td> </tr> <tr ID="id_7f27a645-1e8c-4422-a9c5-e5eb4a66e7ce"> <td align="left" valign="bottom" styleCode="Botrule Rrule">Urogenital System </td> <td align="center" valign="bottom" styleCode="Botrule Rrule"/> <td align="center" valign="bottom" styleCode="Botrule"/> </tr> <tr ID="id_e6fd8e8f-e89b-443c-b7b7-d5fd702361ec"> <td align="left" valign="bottom" styleCode="Botrule Rrule"> Urinary Tract Infection </td> <td align="center" valign="bottom" styleCode="Rrule">2.9 </td> <td align="center" valign="bottom" styleCode="Botrule">5.2 </td> </tr> </tbody> </table>