Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/3290
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Risedronate Sodium (Tablet, Film Coated)
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Risedronate sodium tablets should be taken at least 30 minutes before the first food or drink of the day other than water. To facilitate delivery to the stomach, risedronate sodium tablets should be swallowed while the patient is in an upright position and with a full glass of plain water (6 to 8 oz). Patients should not lie down for 30 minutes after taking the medication (see PRECAUTIONS, Upper Gastrointestinal Effects). Patients should receive supplemental calcium and vitamin D if dietary intake is inadequate (see PRECAUTIONS, Mineral Metabolism). Calcium supplements and calcium-, aluminum-, and magnesium-containing medications may interfere with the absorption of risedronate and should be taken at a different time of the day. Risedronate sodium tablets are not recommended for use in patients with severe renal impairment (creatinine clearance<30 mL/min). No dosage adjustment is necessary in patients with a creatinine clearance���30 mL/min or in the elderly.<br/>Treatment of Postmenopausal Osteoporosis (see INDICATIONS AND USAGE): The recommended regimen is: or<br/>Prevention of Postmenopausal Osteoporosis (see INDICATIONS AND USAGE): The recommended regimen is: or<br/>Treatment and Prevention of Glucocorticoid-Induced Osteoporosis (see INDICATIONS AND USAGE): The recommended regimen is:<br/>Paget's Disease (see INDICATIONS AND USAGE): The recommended treatment regimen is 30 mg orally once daily for 2 months. Retreatment may be considered (following post-treatment observation of at least 2 months) if relapse occurs, or if treatment fails to normalize serum alkaline phosphatase. For retreatment, the dose and duration of therapy are the same as for initial treatment. No data are available on more than 1 course of retreatment.
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Risedronate sodium tablets are a pyridinyl bisphosphonate that inhibits osteoclast-mediated bone resorption and modulates bone metabolism. Each risedronate sodium tablet for oral administration contains the equivalent of 5, 30, or 35 mg of anhydrous risedronate sodium in the form of the monohydrate. The chemical name of risedronate sodium is [1-hydroxy-2-(3-pyridinyl)ethylidene]bis[phosphonic acid] monosodium salt. The chemical structure of risedronate sodium monohydrate is the following: CHNOPNa��HO M.W. Monohydrate: 323.10 Anhydrous: 305.10 Risedronate sodium monohydrate is a white to off-white powder. It is soluble in water and in aqueous solutions, and essentially insoluble in common organic solvents.<br/>Inactive Ingredients: Colloidal silicon dioxide, D&C yellow #10 lake (5 mg tablets only), FD&C yellow #6 aluminum lake (35 mg tablets only), hypromellose, iron oxide red (35 mg tablets only), iron oxide yellow (5 and 35 mg tablets only), lactose monohydrate, magnesium stearate, polyethylene glycol, polysorbate 80, pregelatinized starch, sodium stearyl fumarate, starch, and titanium dioxide.
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Mechanism of Action: Risedronate has an affinity for hydroxyapatite crystals in bone and acts as an antiresorptive agent. At the cellular level, risedronate inhibits osteoclasts. The osteoclasts adhere normally to the bone surface, but show evidence of reduced active resorption (e.g., lack of ruffled border). Histomorphometry in rats, dogs, and minipigs showed that risedronate treatment reduces bone turnover (activation frequency, i.e., the rate at which bone remodeling sites are activated) and bone resorption at remodeling sites.<br/>Pharmacokinetics:<br/>Absorption: Absorption after an oral dose is relatively rapid (t~1 hour) and occurs throughout the upper gastrointestinal tract. The fraction of the dose absorbed is independent of dose over the range studied (single dose, from 2.5 to 30 mg; multiple dose, from 2.5 to 5 mg). Steady-state conditions in the serum are observed within 57 days of daily dosing. Mean absolute oral bioavailability of the 30 mg tablet is 0.63% (90% CI: 0.54% to 0.75%) and is comparable to a solution. The extent of absorption of a 30 mg dose (three 10 mg tablets) when administered 0.5 hours before breakfast is reduced by 55% compared to dosing inthe fasting state (no food or drink for 10 hours prior to or 4 hours after dosing). Dosing 1 hour prior to breakfast reduces the extent of absorption by 30% compared to dosing in the fasting state. Dosing either 0.5 hours prior to breakfast or 2 hours after dinner (evening meal) results in a similar extent of absorption. Risedronate is effective when administered at least 30 minutes before breakfast.<br/>Distribution: The mean steady-state volume of distribution is 6.3 L/kg in humans. Human plasma protein binding of drug is about 24%. Preclinical studies in rats and dogs dosed intravenously with single doses of [C] risedronate indicate that approximately 60% of the dose is distributed to bone. The remainder of the dose is excreted in the urine. After multiple oral dosing in rats, the uptake of risedronate in soft tissues was in the range of 0.001% to 0.01%.<br/>Metabolism: There is no evidence of systemic metabolism of risedronate.<br/>Elimination: Approximately half of the absorbed dose is excreted in urine within 24 hours, and 85% of an intravenous dose is recovered in the urine over 28 days. Mean renal clearance is 105 mL/min (CV = 34%) and mean total clearance is 122 mL/min (CV = 19%), with the difference primarily reflecting nonrenal clearance or clearance due to adsorption to bone. The renal clearance is not concentration dependent, and there is a linear relationship between renal clearance and creatinine clearance. Unabsorbed drug is eliminated unchanged in feces. Once risedronate is absorbed, the serum concentration-time profile is multi-phasic, with an initial half-life of about 1.5 hours and a terminal exponential half-life of 480 hours. This terminal half-life is hypothesized to represent the dissociation of risedronate from the surface of bone.<br/>Special Populations:<br/>Pediatric: Risedronate pharmacokinetics have not been studied in patients<18 years of age.<br/>Gender: Bioavailability and pharmacokinetics following oral administration are similar in men and women.<br/>Geriatric: Bioavailability and disposition are similar in elderly (>60 years of age) and younger subjects. No dosage adjustment is necessary.<br/>Race: Pharmacokinetic differences due to race have not been studied.<br/>Renal Insufficiency: Risedronate is excreted unchanged primarily via the kidney. As compared to persons with normal renal function, the renal clearance of risedronate was decreased by about 70% in patients with creatinine clearance of approximately 30 mL/min. Risedronate is not recommended for use in patients with severe renal impairment (creatinine clearance<30 mL/min) because of lack of clinical experience. No dosage adjustment is necessary in patients with a creatinine clearance���30 mL/min.<br/>Hepatic Insufficiency: No studies have been performed to assess risedronate's safety or efficacy in patients with hepatic impairment. Risedronate is not metabolized in rat, dog, and human liver preparations. Insignificant amounts (<0.1% of intravenous dose) of drug are excreted in the bile in rats. Therefore, dosage adjustment is unlikely to be needed in patients with hepatic impairment.<br/>Pharmacodynamics:<br/>Treatment and Prevention of Osteoporosis in Postmenopausal Women: Osteoporosis is characterized by decreased bone mass and increased fracture risk, most commonly at the spine, hip, and wrist. The diagnosis can be confirmed by the finding of low bone mass, evidence of fracture on x-ray, a history of osteoporotic fracture, or height loss or kyphosis indicative of vertebral fracture. Osteoporosis occurs in both men and women but is more common among women following menopause. In healthy humans, bone formation and resorption are closely linked; old bone is resorbed and replaced by newly-formed bone. In postmenopausalosteoporosis, bone resorption exceeds bone formation, leading to bone loss and increased risk of bone fracture. After menopause, the risk of fractures of the spine and hip increases; approximately 40% of 50 year-old women will experience an osteoporosis-related fracture during their remaining lifetimes. After experiencing 1 osteoporosis-related fracture, the risk of future fracture increases 5 fold compared to the risk among a non-fractured population. Risedronate treatment decreases the elevated rate of bone turnover that is typically seen in postmenopausal osteoporosis. In clinical trials, administration of risedronate to postmenopausal women resulted in decreases in biochemical markers of bone turnover, including urinary deoxypyridinoline/creatinine and urinary collagen cross-linked N-telopeptide (markers of bone resorption) and serum bone specific alkaline phosphatase (a marker of bone formation). At the 5 mg dose, decreases in deoxypyridinoline/creatinine were evident within 14 days of treatment. Changes in bone formation markers were observed later than changes in resorption markers, as expected, due to the coupled nature of bone resorption and bone formation; decreases in bone specific alkaline phosphatase of about 20% were evident within 3 months of treatment. Bone turnover markers reached a nadir of about 40% below baseline values by the sixth month of treatment and remained stable with continued treatment for up to 3 years. Bone turnover is decreased as early as 14 days and maximally within about 6 months of treatment, with achievement of a new steady state that more nearly approximates the rate of bone turnover seen in premenopausal women. In a 1 year study comparing daily versus weekly oral dosing regimens of risedronate for the treatment of osteoporosis in postmenopausal women, risedronate sodium tablets 5 mg daily and risedronate sodium tablets 35 mg once a week decreased urinary collagen cross-linked N-telopeptide by 60% and 61%,respectively. In addition, serum bone-specific alkaline phosphatase was also reduced by 42% and 41% in the risedronate sodium tablets 5 mg daily and risedronate sodium tablets 35 mg once a week groups, respectively. When postmenopausal women with osteoporosis were treated for 1 year with risedronate sodium tablets 5 mg daily, urinary collagen cross-linked N-telopeptide was decreased by 54% and serum bone-specific alkaline phosphatase was reduced by 36%. Risedronate is not an estrogen and does not have the benefits and risks of estrogen therapy.<br/>Glucocorticoid-Induced Osteoporosis: Sustained use of glucocorticoids is commonly associated with development of osteoporosis and resulting fractures (especially vertebral, hip, and rib). It occurs in both males and females of all ages. The relative risk of a hip fracture in patients on>7.5 mg/day prednisone is more than doubled (RR = 2.27); the relative risk of vertebral fracture is increased 5 fold (RR = 5.18). Bone loss occurs most rapidly during the first 6 months of therapy with persistent but slowing bone loss for as long as glucocorticoid therapy continues. Osteoporosis occurs as a result of inhibited bone formation and increased bone resorption resulting in net bone loss. Risedronate decreases bone resorption without directly inhibiting bone formation. In two 1 year clinical trials in the treatment and prevention of glucocorticoid-induced osteoporosis, risedronate sodium tablets 5 mg decreased urinary collagen cross-linked N-telopeptide (a marker of bone resorption), and serum bone specific alkaline phosphatase (a marker of bone formation) by 50% to 55% and 25% to 30%, respectively, within 3 to 6 months after initiation of therapy.<br/>Paget's Disease: Paget's disease of bone is a chronic, focal skeletal disorder characterized by greatly increased and disordered 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 Paget's disease range from no symptoms to severe bone pain, bone deformity, pathological fractures, and neurological disorders. Serum alkaline phosphatase, the most frequently used biochemical marker of disease activity, provides an objective measure of disease severity and response to therapy. In pagetic patients treated with risedronate sodium tablets 30 mg daily for 2 months, bone turnover returned to normal in a majority of patients as evidenced by significant reductions in serum alkaline phosphatase (a marker of bone formation), and in urinary hydroxyproline/creatinine and deoxypyridinoline/creatinine (markers of bone resorption). Radiographic structural changes of bone lesions, especially improvement of a majority of lesions with an osteolytic front in weight-bearing bones, were also observed after risedronate treatment. In addition, histomorphometric data provide further support that risedronate can lead to a more normal bone structure in these patients. Radiographs taken at baseline and after 6 months from patients treated with risedronate sodium tablets 30 mg daily demonstrate that risedronate decreases the extent of osteolysis in both the appendicular and axial skeleton. Osteolytic lesions in the lower extremities improved or were unchanged in 15/16 (94%) of assessed patients; 9/16 (56%) patients showed clear improvement in osteolytic lesions. No evidence of new fractures was observed.
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Risedronate sodium tablets are available as: 5 mg: yellow, round, standard convex coated tablets, debossed with���93���on one side and���7390���on the other side, in bottles of 30, 100, and 1000. 30 mg: white, round, standard convex coated tablets, debossed with���93���on one side and���7391���on the other side, in bottles of 30, 100, and 1000. 35 mg: orange, round, standard convex coated tablets, debossed with���93���on one side and���7389���on the other side, in bottles of 1000 and in blister package of 4 x 1 card in a carton. Store at 20��to 25��C (68��to 77��F) [See USP Controlled Room Temperature]. Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).
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dailymed-ingredient:D&C_yellow_#10_lake,
dailymed-ingredient:colloidal_silicon_dioxide,
dailymed-ingredient:hypromellose,
dailymed-ingredient:iron_oxide_yellow,
dailymed-ingredient:lactose_monohydrate,
dailymed-ingredient:magnesium_stearate,
dailymed-ingredient:polyethylene_glycol,
dailymed-ingredient:polysorbate_80,
dailymed-ingredient:pregelatinized_starch,
dailymed-ingredient:sodium_stearyl_fumarate,
dailymed-ingredient:starch,
dailymed-ingredient:titanium_dioxide
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Mineral Metabolism: Hypocalcemia and other disturbances of bone and mineral metabolism should be effectively treated before starting risedronate therapy. Adequate intake of calcium and vitamin D is important in all patients, especially in patients with Paget's disease in whom bone turnover is significantly elevated. Risedronate is not recommended for use in patients with severe renal impairment (creatinine clearance<30 mL/min).<br/>Upper Gastrointestinal Effects: Bisphosphonates have been associated with gastrointestinal disorders such as dysphagia, esophagitis, and esophageal or gastric ulcers. This association has been reported for bisphosphonates in postmarketing experience, but has not been found in most pre-approval clinical trials, including those conducted with risedronate. Patients should be advised that taking the medication according to the instructions is important to minimize the risk of these events. They should take risedronate with sufficient plain water (6 to 8 oz) to facilitate delivery to the stomach, and should not lie down for 30 minutes after taking the drug.<br/>Jaw Osteonecrosis: Osteonecrosis, primarily in the jaw, has been reported in patients treated with bisphosphonates. Most cases have been in cancer patients undergoing dental procedures such as tooth extraction, but some have occurred in patients with postmenopausal osteoporosis or other diagnoses. Most reported cases have been in patients treated with bisphosphonates intravenously but some have been in patients treated orally. For patients requiring dental procedures, there are no data available to suggest whether discontinuation of bisphosphonate treatment, prior to the procedure, reduces the risk of osteonecrosis of the jaw. Clinical judgment should guide the management plan of each patient based on individual benefit/risk assessment.<br/>Musculoskeletal Pain: In postmarketing experience, there have been infrequent reports of severe and occasionally incapacitating bone, joint, and/or muscle pain in patients taking bisphosphonates (see ADVERSE REACTIONS). The time to onset of symptoms varied from one day to several months after starting the drug. Most patients had relief of symptoms after stopping medication. A subset had recurrence of symptoms when rechallenged with the same drug or another bisphosphonate.<br/>Glucocorticoid-Induced Osteoporosis: The risk versus benefit of risedronate for the prevention and treatment of glucocorticoid-induced osteoporosis at daily doses of glucocorticoids<7.5 mg of prednisone or equivalent has not been established. Before initiating treatment, the hormonal status of both men and women should be ascertained and appropriate replacement considered. The efficacy of risedronate for this indication has been established in studies of 1 year duration. The efficacy of risedronate beyond 1 year has not been studied.<br/>Information for Patients: The patient should be informed to pay particular attention to the dosing instructions as clinical benefits may be compromised by failure to take the drug according to instructions. Specifically, risedronate should be taken at least 30 minutes before the first food or drink of the day other than water. To facilitate delivery to the stomach, and thus reduce the potential for esophageal irritation, patients should take risedronate while in an upright position (sitting or standing) with a full glass of plain water (6 to 8 oz). Patients should not lie down for 30 minutes after taking the medication (see PRECAUTIONS, Upper Gastrointestinal Effects). Patients should not chew or suck onthe tablet because of a potential for oropharyngeal irritation. Patients should be instructed that if they develop symptoms of esophageal disease (such as difficulty or pain upon swallowing, retrosternal pain or severe persistent or worsening heartburn) they should consult their physician before continuing risedronate. Patients should be instructed that if they miss a dose of risedronate sodium tablets 35 mg once a week, they should take 1 tablet on the morning after they remember and return to taking 1 tablet once a week, as originally scheduled on their chosen day. Patients should not take 2 tablets on the same day. Patients should receive supplemental calcium and vitamin D if dietary intake is inadequate (see PRECAUTIONS, Mineral Metabolism). Calcium supplements or calcium-, aluminum-, and magnesium-containing medications may interfere with the absorption of risedronate and should be taken at a different time of the day, as with food. Weight-bearing exercise should be considered along with the modification of certain behavioral factors, such as excessive cigarette smoking, and/or alcohol consumption, if these factors exist. Physicians should instruct their patients to read the Patient Information before starting therapy with risedronate sodium tablets 5 mg or 35 mg and to re-read it each time the prescription is renewed. Patients should be reminded to give all of their health care providers an accurate medication history. Instruct patients to tell all of their health care providers that they are taking risedronate. Patients should be instructed that any time they have a medical problem they think may be from risedronate, they should talk to their doctor.<br/>Drug Interactions: No specific drug-drug interaction studies were performed. Risedronate is not metabolized and does not induce or inhibit hepatic microsomal drug-metabolizing enzymes (Cytochrome P450).<br/>Calcium Supplements/Antacids: Coadministration of risedronate and calcium, antacids, or oral medications containing divalent cations will interfere with the absorption of risedronate.<br/>Hormone Replacement Therapy: One study of about 500 early postmenopausal women has been conducted to date in which treatment with risedronate sodium tablets (5 mg daily) plus estrogen replacement therapy was compared to estrogen replacement therapy alone. Exposure to study drugs was approximately 12 to 18 months and the primary endpoint was change in BMD. If considered appropriate, risedronate may be used concomitantly with hormone replacement therapy.<br/>Aspirin/Non-steroidal Anti-Inflammatory Drugs (NSAIDs): Of over 5700 patients enrolled in the Risedronate Phase 3 osteoporosis studies, aspirin use was reported by 31% of patients, 24% of whom were regular users (3 or more days per week). Forty-eight percent of patients reported NSAID use, 21% of whom were regular users. Among regular aspirin or NSAID users, the incidence of upper gastrointestinal adverse experiences in risedronate-treated patients (24.5%) was similar to that in placebo-treated patients (24.8%).<br/>HBlockers and Proton Pump Inhibitors (PPIs): Of over 5700 patients enrolled in the Risedronate Phase 3 osteoporosis studies, 21% used Hblockers and/or PPIs. Among these patients, the incidence of upper gastrointestinal adverse experiences in the risedronate-treated patients was similar to that in placebo-treated patients.<br/>Drug/Laboratory Test Interactions: Bisphosphonates are known to interfere with the use of bone-imaging agents. Specific studies with risedronate have not been performed.<br/>Carcinogenesis, Mutagenesis, Impairment of Fertility:<br/>Carcinogenesis: In a 104 week carcinogenicity study, rats were administered daily oral doses up to 24 mg/kg/day (approximately 7.7 times the maximum recommended human daily dose of 30 mg based on surface area, mg/m). There were no significant drug-induced tumor findings in male or female rats. The high dose male group of 24 mg/kg/day was terminated early in the study (Week 93) due to excessive toxicity, and data from this group were not included in the statistical evaluation of the study results. In an 80 week carcinogenicity study, mice were administered daily oral doses up to 32 mg/kg/day (approximately 6.4 times the 30 mg/day human dose based on surface area, mg/m). There were no significant drug-induced tumor findings in male or female mice.<br/>Mutagenesis: Risedronate did not exhibit genetic toxicity in the following assays: in vitro bacterial mutagenesis in Salmonella and E. coli (Ames assay), mammalian cell mutagenesis in CHO/HGPRT assay, unscheduled DNA synthesis in rat hepatocytes and an assessment of chromosomal aberrations in vivo in rat bone marrow. Risedronate was positive in a chromosomal aberration assay in CHO cells at highly cytotoxic concentrations (>675 mcg/mL, survival of 6% to 7%). When the assay was repeated at doses exhibiting appropriate cell survival (29%), there was no evidence of chromosomal damage.<br/>Impairment of Fertility: In female rats, ovulation was inhibited at an oral dose of 16 mg/kg/day (approximately 5.2 times the 30 mg/day human dose based on surface area, mg/m). Decreased implantation was noted in female rats treated with doses���7 mg/kg/day (approximately 2.3 times the 30 mg/day human dose based on surface area, mg/m). In male rats, testicular and epididymal atrophy and inflammation were noted at 40 mg/kg/day (approximately 13 times the 30 mg/day human dose based on surface area, mg/m). Testicular atrophy was also noted in male rats after 13 weeks of treatment at oral doses of 16 mg/kg/day (approximately 5.2 times the 30 mg/day human dose based on surface area, mg/m). There was moderate-to-severe spermatid maturation block after 13 weeks in male dogs at an oral dose of 8 mg/kg/day (approximately 8 times the 30 mg/day human dose based on surface area, mg/m). These findings tended to increase in severity with increased dose and exposure time.<br/>Pregnancy:<br/>Teratogenic Effects:<br/>Nursing Women: Risedronate was detected in feeding pups exposed to lactating rats for a 24 hour period post-dosing, indicating a small degree of lacteal transfer. It is not known whether risedronate is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from bisphosphonates, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.<br/>Pediatric Use: Safety and effectiveness in pediatric patients have not been established.<br/>Geriatric Use: Of the patients receiving risedronate in postmenopausal osteoporosis studies (see CLINICAL STUDIES), 47% were between 65 and 75 years of age, and 17% were over 75. The corresponding proportions were 26% and 11% in glucocorticoid-induced osteoporosis trials, and 40% and 26% in Paget's disease trials. No overall differences in efficacy between geriatric and younger patients were observed in these studies. No overall differences in safety between geriatric and younger patients were observed in the risedronate trials, but greater sensitivity of some older individuals cannot be ruled out.
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Decreases in serum calcium and phosphorus following substantial overdose may be expected in some patients. Signs and symptoms of hypocalcemia may also occur in some of these patients. Milk or antacids containing calcium should be given to bind risedronate and reduce absorption of the drug. In cases of substantial overdose, gastric lavage may be considered to remove unabsorbed drug. Standard procedures that are effective for treating hypocalcemia, including the administration of calcium intravenously, would be expected to restore physiologic amounts of ionized calcium and to relieve signs and symptoms of hypocalcemia. Lethality after single oral doses was seen in female rats at 903 mg/kg and male rats at 1703 mg/kg. The minimum lethal dose in mice and rabbits was 4000 mg/kg and 1000 mg/kg. These values represent 320 to 620 times the 30 mg human dose based on surface area (mg/m).
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Risedronate Sodium
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Risedronate Sodium (Tablet, Film Coated)
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Daily Dosing:<br/>Osteoporosis: Risedronate 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 risedronate sodium tablets 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 risedronate sodium tablets 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 risedronate sodium tablets 5 mg groups, respectively. Table 5 lists adverse events from the Phase 3 osteoporosis trials reported in���2% of patients and in more risedronate-treated patients than placebo-treated patients. Adverse events are shown without attribution of causality. Duodenitis and glossitis have been reported uncommonly (0.1% to 1%). There have been rare reports (<0.1%) of abnormal liver function tests.<br/>Laboratory Test Findings: Throughout the Phase 3 studies, transient decreases from baseline in serum calcium (<1%) and serum phosphate (<3%) and compensatory increases in serum PTH levels (<30%) were observed within 6 months in patients in osteoporosis clinical trials treated with risedronate sodium tablets 5 mg once daily. There were no significant differences in serum calcium, phosphate, or PTH levels between risedronate sodium tablets 5 mg once daily and placebo at 3 years. Serum calcium levels below 8 mg/dL were observed in 18 patients, 9 (0.5%) in each treatment arm (risedronate sodium tablets 5 mg once daily and placebo). Serum phosphorus levels below 2 mg/dL were observed in 14 patients, 11 (0.6%) treated with risedronate sodium tablets 5 mg once daily and 3 (0.2%) treated with placebo.<br/>Endoscopic Findings: Risedronate clinical studies enrolled over 5700 patients, many with preexisting 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%) risedronate]. Across treatment groups, the percentage of patients with normal esophageal, gastric, and duodenal mucosa on endoscopy was similar (20% placebo, 21% risedronate). 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 risedronate 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% risedronate).<br/>Once-A-Week Dosing: In a 1 year, double-blind, multicenter study comparing risedronate sodium tablets 5 mg daily and risedronate sodium tablets 35 mg once a week in postmenopausal women, the overall safety and tolerability profiles of the 2 oral dosing regimens were similar. Table 6 lists the adverse events in���2% of patients from this trial. Events are shown without attribution of causality.<br/>Laboratory Test Findings: In a 1 year study comparing daily versus weekly oral dosing regimens of risedronate sodium tablets in postmenopausal women, the mean percent changes from baseline at 12 months were similar between the risedronate sodium tablets 5 mg daily and risedronate sodium tablets 35 mg once a week groups, respectively, for serum calcium (0.4% and 0.7%), phosphate (- 3.8% and - 2.6%) and PTH (6.4% and 4.2%).<br/>Paget's Disease: Risedronate has been studied in 392 patients with Paget's disease of bone. As in trials of risedronate for other indications, the adverse experiences reported in the Paget's disease trials have generally been mild or moderate, have not required discontinuation of treatment, and have not appeared to be related to patient age, gender, or race. In a double-blind, active-controlled study, the adverse event profile was similar for risedronate and etidronate disodium: 6.6% (4/61) of patients treated with risedronate sodium tablets 30 mg daily for 2 months discontinued treatment due to adverse events, compared to 8.2% (5/61) of patients treated with etidronate disodium tablets 400 mg daily for 6 months.<br/>Ocular Adverse Events: Three patients who received risedronate sodium tablets 30 mg daily experienced acute iritis in 1 supportive study. All 3 patients recovered from their events; however, in 1 of these patients, the event recurred during risedronate treatment and again during treatment with pamidronate. All patients were effectively treated with topical steroids.<br/>Postmarketing Experience: Very rare hypersensitivity and skin reactions have been reported, including angioedema, generalized rash and bullous skin reactions, some severe. Musculoskeletal: bone, joint, or muscle pain, rarely described as severe or incapacitating (see PRECAUTIONS, Musculoskeletal Pain). Very rare reactions of eye inflammation including iritis and uveitis have been reported. Osteonecrosis of the jaw has been reported very rarely (see PRECAUTIONS, Jaw Osteonecrosis).
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Bisphosphonates may cause upper gastrointestinal disorders such as dysphagia, esophagitis, and esophageal or gastric ulcer (see PRECAUTIONS).
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Postmenopausal Osteoporosis: Risedronate sodium tablets are indicated for the treatment and prevention of osteoporosis in postmenopausal women.<br/>Treatment of Osteoporosis: In postmenopausal women with osteoporosis, risedronate sodium tablets increase BMD and reduce the incidence of vertebral fractures and a composite endpoint of nonvertebral osteoporosis-related fractures (see CLINICAL STUDIES). Osteoporosis may be confirmed by the presence or history of osteoporotic fracture, or by the finding of low bone mass (for example, at least 2 SD below the premenopausal mean).<br/>Prevention of Osteoporosis: Risedronate sodium tablets may be considered in postmenopausal women who are at risk of developing osteoporosis and for whom the desired clinical outcome is to maintain bone mass and to reduce the risk of fracture. Factors such as family history of osteoporosis, previous fracture, smoking, BMD (at least 1 SD below the premenopausal mean), high bone turnover, thin body frame, Caucasian or Asian race, and early menopause are associated with an increased risk of developing osteoporosis and fractures. The presence of these risk factors may be important when considering the use of risedronate sodium tablets for prevention of osteoporosis.<br/>Glucocorticoid-Induced Osteoporosis: Risedronate sodium tablets are indicated for the prevention and treatment of glucocorticoid-induced osteoporosis in men and women who are either initiating or continuing systemic glucocorticoid treatment (daily dosage equivalent to 7.5 mg or greater of prednisone) for chronic diseases. Patients treated with glucocorticoids should receive adequate amounts of calcium and vitamin D.<br/>Paget's Disease: Risedronate sodium tablets are indicated for treatment of Paget's disease of bone in men and women. Treatment is indicated in patients with Paget's disease of bone (1) who have a level of serum alkaline phosphatase at least 2 times the upper limit of normal, or (2) who are symptomatic, or (3) who are at risk for future complications from their disease, to induce remission (normalization of serum alkaline phosphatase).
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Risedronate Sodium
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