Risedronate

283.11

283.11

1592732-453-0

KM2Z91756Z

DTXSID2023563

M05BA07|M - Musculo-skeletal system

2933399090

148

-3.6

Solid

1.870±0.06 g/cm3(Predicted)

252-262

692.3±65.0 °C(Predicted)

372.5±34.3 °C

1.651

1.04e+01 g/L

2.1X10-11 mm Hg at 25 deg C /Estimated/

Henry's Law constant = 1.0X10-29 atm-cu m/mol at 25 °C /Estimated/

pKa1 = 2.9 phosphoric acid moiety based on etidronic acid; pKa2= 7 phosphoric acid moiety based on etidronic acid /Etidronic acid/

Hydroxyl radical reaction rate constant = 5.2X10-12 cu cm/molecule-sec at 25 °C /Estimated/|Fine, white to off-white crystalline powder; odorless; MW 305.09. Occurs as hemi-pentahydrate. Soluble in water. Essentially insoluble in common organic solvents. /Monosodium salt/|Soluble in aqueous solutions. /Sodium/

P261, P264, P270, P271, P280, P301+P312, P302+P352, P304+P312, P304+P340, P305+P351+P338, P312, P321, P322, P330, P332+P313, P337+P313, P362, P363, P403+P233, P405, P501

H302+H312+H332

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl risedronate sodium, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Risedronate Sodium/

|Warning|H302+H312+H332 (86.36%): Harmful if swallowed, in contact with skin or if inhaled [Warning Acute toxicity, oral; acute toxicity, dermal; acute toxicity, inhalation]|P261, P264, P270, P271, P280, P301+P312, P302+P352, P304+P312, P304+P340, P312, P322, P330, P363, and P501|Aggregated GHS information provided by 44 companies from 7 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|Danger|H290 (60%): May be corrosive to metals [Warning Corrosive to Metals]|P201, P202, P234, P260, P261, P263, P264, P270, P271, P280, P281, P301+P312, P301+P330+P331, P302+P352, P303+P361+P353, P304+P340, P305+P351+P338, P308+P313, P310, P312, P314, P321, P330, P332+P313, P337+P313, P362, P363, P390, P403+P233, P404, P405, and P501|Aggregated GHS information provided by 5 companies from 5 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H319 (100%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]|P264, P280, P305+P351+P338, and P337+P313|The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

In clinical trials, over 10% of patients experienced back pain, arthralgia, abdominal pain, and dyspepsia. Less commonly, patients experience angioedema, generalized rash, bullous skin reactions, iritis, and uveitis. Patients experiencing an overdose may experience a decrease in serum calcium and phosphorus. Patients can be given milk or antacids to bind the drug and reduce its absorption. In more severe cases, patients may require gastric lavage and intravenous calcium. A lethal dose in rats is equivalent to 320 to 620 times the human dose based on surface area.

Antacids or Mineral Supplements Containing Divalent Cations: Pharmacokinetic interaction (decrease risedronate absorption) when risedronate is used concomitantly with antacids or mineral supplements containing divalent cations (e.g. aluminum, calcium, magnesium). /Risedronate/|Nonsteroidal Anti-inflammatory Agents /(SRP: NSAIDs)/: No evidence of increased adverse upper GI effects. /Risedronate/|Histamine H2 Receptor Antagonists, Proton Pump Inhibitors: No evidence of increased adverse upper GI effects. /Risedronate/

~24%.

Risedronic acid's production and use as a bone resorption inhibitor(1) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 2,400(SRC), determined from a structure estimation method(2), indicates that anagrelide is expected to have slight mobility in soil(SRC). The pKa of the phosphoric acid moiety of risedronic acid is estimated to be about 2.8 based on the pKa of etidronic acid(3), an analogous compound containing a similar functional group. The estimated pKa indicates that this compound will primarily exist in the anionic form and anions do not volatilize from moist soil surfaces. Anagrelide is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 6.8X10-10 mm Hg(SRC), determined from a fragment constant method(4). Biodegradation data were not available(SRC, 2005).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 10(SRC), determined from a structure estimation method(2), indicates that risedronic acid is not expected to adsorb to suspended solids and sediment(SRC). The pKa of the phosphoric acid moiety of risedronic acid is estimated to be about 2.8 based on the pKa of etidronic acid(3), an analogous compound containing a similar functional group. The estimated pKa indicates that this compound will primarily exist as an anion in the environment and anions generally do not adsorb more strongly to organic carbon and clay than their neutral counterparts(4) and do not volatilize from water surfaces. Hydrolysis is not expected to be an important environmental fate process since this compound lacks functional groups that are expected to hydrolyze under environmental conditions. According to a classification scheme(5), an estimated BCF of 3.2(SRC), from an estimated log Kow of -0.29(6) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data were not available(SRC, 2005).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), risedronic acid, which has an estimated vapor pressure of 2.1X10-11 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase risedronic acid may be removed from the air by wet and dry deposition(SRC). Risedronic acid does not contain chromophores that absorb light at wavelengths >290 nm and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

Hydrolysis is not expected to be an important environmental fate process since this compound lacks functional groups that hydrolyze under environmental conditions(1). Risedronic acid does not contain chromophores that to absorb light at wavelengths >290 nm and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 3.2 was calculated for risedronic acid(SRC), using an estimated log Kow of -0.29(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc for risedronic acid can be estimated to be 10(SRC). According to a classification scheme(2), this estimated Koc value suggests that risedronic acid is expected to have very high mobility in soil. The pKa of the phosphoric acid moiety of risedronic acid is estimated to be about 2.8 based on the pKa of etidronic acid(3), indicating that this compound will primarily exist in the dissociated form in the environment and anions generally do not adsorb more strongly to organic carbon and clay than their neutral counterparts(4).

The pKa of the phosphoric acid moiety of risedronic acid is estimated to be about 2.8 based on the pKa of etidronic acid(1), an analogous compound containing a similar functional group. The estimated pKa indicates that risedronic acid will exist predominantly in its anion form in the environment and anions do not volatilize from water or moist soil surfaces. Risedronic acid is not expected to volatilize from dry soil based on its estimated vapor pressure of 2.1X10-11 mm Hg(SRC), determined from a fragment constant method(2).

Risedronate was detected in feeding pups exposed to lactating rats for a 24-hour period postdosing, indicating a small degree of lacteal transfer. /Risedronate/

Occupational exposure to risedronic acid may occur through inhalation and dermal contact with this compound at workplaces where risedronic acid is produced or used. General population exposure would be restricted to those being administered this drug under medical supervision. (SRC)

Risedronate was detected in feeding pups exposed to lactating rats for a 24-hour period postdosing, indicating a small degree of lacteal transfer. /Risedronate/

Risedronic acid is indicated for the treatment of osteoperosis in men, treatment of Paget's disease, treatment and prevention of osteoperosis in postmenopausal women, and treatment and prevention of glucocorticoid-induced osteoperosis.|FDA Label

Bone resorption inhibitor.|Risedronate is indicated for the prevention and treatment of glucocorticoid-induction osteoporosis in men and women who are either initiating or continuing systemic glucocorticoid treatment for chronic diseases./Risedronate; Included in US product labeling/|Risedronate is indicated for the prevention of osteoporosis in postmenopausal women. It 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. /Risedronate; Included in US product labeling/|Risedronate is indicated for the treatment of post menopausal osteoporosis. It increases the bone mineral density and reduces the incidence of vertebral fractures and a composite endpoint of nonvertebral osteoporosis fractures. /Risedronate; Included in US product labeling/|Risedronate is indicated for the treatment of Paget's disease of bone (osteitis deformans) in patients with alkaline phosphatase concentrations that are at least two times the upper limit of normal, those who are symptomatic, or those at risk for future complications from the disease. Signs and symptoms of Paget's disease may include bone pain, deformity, and/or fractures; increased concentrations of N-telopeptide of I collagen, serum alkaline phosphatase, and/or urinary hydroxyproline; neurologic disorders associated with skull lesions and spinal deformities; and elevated cardiac output and other vascular disorders associated with increased vascularity of bones. /Risedronate; Included in US product labeling/

Risendronate should not be used in patients with severe renal impairment (creatinine clearance less than 30 mL/minute). Adjustments in risedronate sodium dosage are not necessary in patients with mild-to-moderate renal impairment (a creatinine clearance of 30 mL/minute or greater) or in patients with hepatic impairment. /Risedronate/|Adverse upper GI effects (e.g. dysphagia, esophagitis, esophageal or gastric ulcer) have been reported in patients receiving bisphosphonates. In clinical studies, the incidence of such adverse upper GI effects in patients receiving risedronate was similar to that in patients receiving placebo. Data from postmarketing surveillance have occurred, albeit rarely, in patients receiving risedronate sodium 4mg to take risedronate with 180-240 mL of plain water to avoid lying down for 30 minutes following administration of the drug. To minimize risk of adverse upper GI effects, patients should be advised to take risedronate with 180 to 240 mL of plain water and to avoid lying down for 30 minutes following administration of the drug. /Risedronate sodium/|Osteonecrosis and osteomyelitis of the jaws have been reported in patients, principally in these with cancer, who have received bisphosphonates.|Hypocalcemia and other disturbances of bone and mineral metabolism must be corrected before risedronate therapy is initiated, and patients with osteoporosis or Paget's disease of bone should receive supplemental calcium and vitamin D if their daily dietary intake is adequate. /Risedronate/|For more Drug Warnings (Complete) data for RISEDRONIC ACID (10 total), please visit the HSDB record page.

Risedronate is a pyridine-based bisphosphonate that inhibits bone resorption caused by osteoclasts.

Agents that inhibit BONE RESORPTION and/or favor BONE MINERALIZATION and BONE REGENERATION. They are used to heal BONE FRACTURES and to treat METABOLIC BONE DISEASES such as OSTEOPOROSIS. (See all compounds classified as Bone Density Conservation Agents.)|A class of drugs that act by selective inhibition of calcium influx through cellular membranes. (See all compounds classified as Calcium Channel Blockers.)

Oral bioavailability is 0.63% and maximum absorption is approximately 1 hour after dosing. Administration half and hour before a meal reduces bioavailability by 55% compared to fasting and dosing 1 hour before a meal reduces bioavailability by 30%.|Risedronate is excreted by the kidneys and the unabsorbed dose is eliminated in the feces.|13.8 L/kg.|Mean renal clearance was 52mL/min and mean total clearance was 73mL/min.|/Absorption is/ rapid and independent of dose, occurring throughout the upper gastrointestinal tract. Mean oral bioavailability is 0.63% and is decreased when administered with food. Administration either 0.5 hour before breakfast or 2 hours after dinner reduces the extent of absorption by 55% compared to the fasting state (no food or drink for 10 hours before or 4 hours after administration). Administration 1 hour before breakfast reduces the extent of absorption by 30% compared with the fasting state. /Risedronate/|Studies in rats and dogs with intravenously administered single doses of radiolabeled risedronate showed that approximately 60% of the dose was distributed to bone. The mean steady-state volume of distribution is 6.3 L/kg of body weight in humans. /Risedronate/|After multiple oral dosing in rats, the uptake of risedronate in soft tissues was in the range of 0.001% to 0.01%.|Risedronate was detected in feeding pups exposed to lactating rats for a 24-hour period postdosing, indicating a small degree of lacteal transfer. /Risedronate/|Elimination: Fecal, unabsorbed drug (unchanged). Renal, unchanged, approximately 50% of the absorbed dose within 24 hours, 85% over 28 days. Mean renal clearance is 105 mL/minute and mean total clearance is 122 mL/min, the difference primarily reflecting nonrenal clearance or clearance due to absorption to bone. Note: Renal clearance is not concentration dependent and there is a linear relationship between renal clearance and creatinine clearance. /Risedronate/

Risedronic acid is not likely not metabolized before elimination. The P-C-P group of bisphosphonates is resistant to chemical and enzymatic hydrolysis preventing metabolism of the molecule.|There is no evidence that risedronate is metabolized in humans or animals. /Risedronate/

The initial half life of risedronic acid is approximately 1.5 hours, with a terminal half life of 561 hours.|Initial: Approximately 1.5 hours; Terminal exponential: 480 hours (which may represent the dissociation of risedronate from the surface of bone). /Risedronate/

Risedronatic acid binds to bone hydroxyapatite. Bone resorption causes local acidification, releasing risedronic acid which is that taken into osteoclasts by fluid-phase endocytosis. Endocytic vesicles are acidified, releasing risedronic acid to the cytosol of osteoclasts where they induce apoptosis through inhbition of farnesyl pyrophosphate synthase. Inhibition of osteoclasts results in decreased bone resorption.|Risedronate binds to bone hydroxyapatite and, at the cellular level, inhibits osteoclasts. Although the osteoclasts adhere normally to the bone surface, they show evidence of reduced active resorption (e.g., lack of ruffled border). Evidence from studies in rats and dogs indicates that risedronate treatment reduces bone turnover (activation frequency, i.e., the number of sites at which bone is remodeled) and bone resorption at remodeling sites. /Risedronate/|Risedronate sodium, a synthetic pyridinyl bisphosphonate analog of pyrophosphate, is an inhibitor of osteoclast-mediated bone resorption. / Risedronate sodium/|... Nitrogen-containing bisphosphonates (such as pamidronate, alendronate, risedronate, ibandronate and zoledronate) appear to act as analogues of isoprenoid diphosphate lipids, thereby inhibiting FPP synthase, an enzyme in the mevalonate pathway. Inhibition of this enzyme in osteoclasts prevents the biosynthesis of isoprenoid lipids (FPP and GGPP) that are essential for the post-translational farnesylation and geranylgeranylation of small GTPase signalling proteins. Loss of bone-resorptive activity and osteoclast apoptosis is due primarily to loss of geranylgeranylated small GTPases. Identification of FPP synthase as the target of nitrogen-containing bisphosphonates has also helped explain the molecular basis for the adverse effects of these agents in the GI tract and on the immune system. /Risedronate/

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.|Basic treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poison A and B/|Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/

/SIGNS AND SYMPTOMS/ 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. /Risedronate/

1-Hydroxy-2-(3-pyridyl)ethylidene diphosphonate

Oral: Tablets, film-coated: 5 mg Actonel, (Procter & Gamble); 30 mg Actonel, (Procter & Gamble); 35 mg Actonel, (Procter & Gamble). /Risedronate sodium/

Bisphosphonate antiresorptive agent.|Information available in 2005 indicated that Risedronate sodium was used in the manufacture of pharmaceutical preparations in the following countries: Algeria, Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, Colombia, Costa Rica, Czech Republic, Dominican Republic, Ecuador, El Salvador, Finland, France, Germany, Greece, Guatemala, Honduras, Hong Kong, Hungary, Indonesia, Ireland, Israel, Italy, Japan, Netherlands, Nicaragua, Norway, Panama, Poland, Portugal, Romania, Singapore, Slovenia, South Africa, Spain, Sweden, Switzerland, Thailand, Turkey, United Kingdom, United States (1,2) /Risedronate Sodium/

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients