Alendronic acid

249.1

249.10

204-352-8

X1J18R4W8P

DTXSID5022568

C61625

Fine white powder

M05BB03|M05BA04|M - Musculo-skeletal system

2931900090

161

-0.50 (est)

Solid

1.857 g/cm3

234 °C (decomp)

616.7ºC at 760 mmHg

326.7ºC

H2O: 1mg/L

Store at 20 to 25 deg C (68 to 77 deg F); excursions permitted to 15 to 30 deg C (59 to 86 deg F).

4.90X10-13 mm Hg at 25 deg C (est)

2.72(at 25 °C)

2.72 (at 25 °C)|pKa1 = 2.72; pKa2 = 8.73; pKa3 = 10.5; pKa4 = 11.6 (all at 25 °C)

Hydroxyl radical reaction rate constant = 3.82X10-11 cu cm/molec-sec at 25 °C (est)

III

8

1759

SZ6521833

P234, P260, P264, P280, P301+P330+P331, P303+P361+P353, P304+P340, P305+P351+P338, P310, P321, P363, P390, P404, P405, P501

H290

SRP: At the time of review, regulatory criteria for small quantity disposal are subject to significant revision, however, household quantities of waste pharmaceuticals may be managed as follows: Mix with wet cat litter or coffee grounds, double bag in plastic, discard in trash.|SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.

|Danger|H290 (20%): May be corrosive to metals [Warning Corrosive to Metals]|P201, P202, P234, P260, P264, P270, P280, P281, P301+P312, P301+P330+P331, P302+P352, P303+P361+P353, P304+P340, P305+P351+P338, P308+P313, P309+P311, P310, P321, P330, P332+P313, P337+P313, P362, P363, P390, P404, P405, and P501|Aggregated GHS information provided by 6 companies from 5 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|Warning|H315 (100%): Causes skin irritation [Warning Skin corrosion/irritation]|P201, P202, P261, P264, P271, P280, P281, P302+P352, P304+P340, P305+P351+P338, P308+P313, P312, P321, P332+P313, P337+P313, P362, P403+P233, P405, and P501|The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

In clinical studies, ≥3% of patients experience abdominal pain, acid regurgitation, constipation, diarrhea, dyspepsia, musculoskeletal pain, and nausea. No information for treatment of overdose is available, however patients should be given milk or antacids to bind alendronic acid and vomiting should not be induced. Patients may experience hypocalcemia, hypophosphatemia, and upper gastrointestinal events.. There are currently no studies for safety and efficacy in pregnancy, though studies in pregnant rats show fetal and maternal complications at 4 times the clinical dose and pregnant rabbits do not show complications at as high as 10 times the clincal dose. Excretion in breast milk, and therefore safety in lactation, is unknown. Alendronic acid has been studied for use in pediatric patients. The oral bioavailability is similar to that in adult patients, but an increase in the portion of patients experiencing vomiting. There is no significant difference in efficacy or safety of alendronic acid in geriatric populations, though there is potential for even greater sensitivity in patients at a further advanced age than those in the study. Alendronic acid is not recommended for patients with creatinine clearance <35mL/min, but no dosage adjustment is necessary in hepatic impairment.

Intravenous ranitidine was shown to double the bioavailability of oral alendronate. The clinical significance of this increased bioavailability and whether similar increases will occur in patients given oral H2-antagonists is unknown.|In healthy subjects, oral prednisone (20 mg three times daily for five days) did not produce a clinically meaningful change in the oral bioavailability of alendronate (a mean increase ranging from 20 to 44%).|It is likely that calcium supplements, antacids, and some oral medications will interfere with absorption of alendronate sodium. Therefore, patients must wait at least one-half hour after taking alendronate sodium before taking any other oral medications.|Concomitant administration of alendronate with coffee or orange juice reduced bioavailability by approximately 60%.|For more Interactions (Complete) data for Alendronic acid (8 total), please visit the HSDB record page.

Hypocalcemia must be corrected before initiating therapy with. Other disorders affecting mineral metabolism (such as vitamin D deficiency) should also be effectively treated. In patients with these conditions, serum calcium and symptoms of hypocalcemia should be monitored during therapy with alendronate sodium.|No dosage adjustment is necessary for patients with mild-to-moderate renal insufficiency (creatinine clearance 35 to 60 mL/min). Alendronate sodium is not recommended for patients with more severe renal insufficiency (creatinine clearance <35 mL/min) due to lack of experience with alendronate in renal failure.|Presumably due to the effects of alendronate sodium on increasing bone mineral, small, asymptomatic decreases in serum calcium and phosphate may occur, especially in patients with Paget's disease, in whom the pretreatment rate of bone turnover may be greatly elevated and in patients receiving glucocorticoids, in whom calcium absorption may be decreased. Ensuring adequate calcium and vitamin D intake is especially important in patients with Paget's disease of bone and in patients receiving glucocorticoids.|Osteonecrosis of the jaw, generally associated with tooth extraction and/or local infection, often with delayed healing, has been reported in patients taking bisphosphonates. Most reported cases of bisphosphonate-associated osteonecrosis have been in cancer patients treated with intravenous bisphosphonates, but some have occurred in patients with postmenopausal osteoporosis. Known risk factors for osteonecrosis include a diagnosis of cancer, concomitant therapies (e.g., chemotherapy, radiotherapy, corticosteroids), poor oral hygiene, and co-morbid disorders (e.g., pre-existing dental disease, anemia, coagulopathy, infection).

78%. Studies in rats show that plasma protein binding increases with decreasing alendronic acid plasma concentration and increasing pH.

Alendronic 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 10(SRC), determined from a structure estimation method(2), indicates that alendronic acid is expected to have very high mobility in soil(SRC). The pKa values of alendronic acid are pKa1 2.72, pKa2 8.73, pKa3 10.5 and pKa4 11.6(3), indicating that this compound will almost entirely exist in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization from moist soil is not expected because the compound exists as an anion and anions do not volatilize. Alendronic acid is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 4.9X10-13 mm Hg at 25 °C(SRC), determined from a fragment constant method(5). Biodegradation data in soil were not available(SRC, 2011).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 10(SRC), determined from a structure estimation method(2), indicates that alendronic acid is not expected to adsorb to suspended solids and sediment(SRC). The pKa values of alendronic acid are pKa1 2.72, pKa2 8.73, pKa3 10.5 and pKa4 11.6(3) indicate alendronic acid will exist almost entirely in the anion form at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process. According to a classification scheme(4), an estimated BCF of 5(SRC), from an estiamted log Kow of -0.50(5) and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data in water were not available(SRC, 2011).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), alendronic acid, which has an estimated vapor pressure of 4.9X10-13 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 alendronic acid may be removed from the air by wet or dry deposition(SRC). Alendronic acid does not contain chromophores that absorb at wavelengths >290 nm(3), and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

Alendronic acid is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(1). Alendronic acid does not contain chromophores that absorb at wavelengths >290 nm(1), and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 3 was calculated in fish for alendronic acidl(SRC), using an estimated log Kow of -0.50(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 of alendronic acid can be estimated to be 10(SRC). According to a classification scheme(2), this estimated Koc value suggests that alendronic acid is expected to have very high mobility in soil. The pKa values of alendronic acid are pKa1 2.72, pKa2 8.73, pKa3 10.5 and pKa4 11.6(3), indicating that this compound will almost entirely exist in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).

The pKa values of pKa1 2.72, pKa2 8.73, pKa3 10.5 and pKa4 11.6(1) indicate alendronic acid will exist almost entirely in the anion form at pH values of 5 to 9 and therefore volatilization from water surfaces and moist soil is not expected to be an important fate process. Alendronic acid is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 4.9X10-13 mm Hg(SRC), determined from a fragment constant method(2).

While data specific to alendronic acid were not located(SRC, 2011), the literature suggests that some pharmaceutically active compounds originating from human and veterinary therapy are not eliminated completely in municipal sewage treatment plants and are therefore discharged into receiving waters(1). Wastewater treatment processes often were not designed to remove them from the effluent(2). Selected organic waste compounds may be degrading to new and more persistent compounds that may be released instead of or in addition to the parent compound(2). Studies have indicated that several polar pharmaceutically active compounds can leach through soils(1).

Occupational exposure to alendronic acid may occur through inhalation and dermal contact with this compound at workplaces where alendronic acid is produced or used. Exposure to alendronic acid among the general population may be limited to those administered the drug Fosamax, a bone resorption inhibitor. (SRC)

Alendronic acid is indicated for the treatment and prevention of osteoporosis in men and postmenopausal women, treatment of glucocorticoid-induced osteoporosis, and Paget's disease of bone. However, alendronic acid is not indicated for use in pediatric populations or patients with a creatinine clearance <35mL/min.|FDA Label|Treatment of postmenopausal osteoporosis in patients at risk of vitamin-D insufficiency., , Fosavance reduces the risk of vertebral and hip fractures.,|Treatment of postmenopausal osteoporosis in patients at risk of vitamin-D insufficiency.Vantavo reduces the risk of vertebral and hip fractures.Treatment of postmenopausal osteoporosis in patients who are not receiving vitamin-D supplementation and are at risk of vitamin-D insufficiency.Vantavo reduces the risk of vertebral and hip fractures.|Treatment of osteoporosis

Bone Density Conservation Agents|Alendronate sodium tablets are indicated for the treatment of osteoporosis, alendronate sodium tablets increases bone mass and reduce the incidence of fractures, including those of the hip and spine (vertebral compression fractures). Osteoporosis may be confirmed by the finding of low bone mass (for example, at least 2 standard deviations below the premenopausal mean) or by the presence or history of osteoporotic fracture. /Included in US product label/|Alendronate sodium tablets are indicated for the prevention of osteoporosis, alendronate 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 future fracture. /Included in US product label/|Alendronate sodium tablets are indicated for treatment to increase bone mass in men with osteoporosis. /Included in US product label/|For more Therapeutic Uses (Complete) data for Alendronic acid (7 total), please visit the HSDB record page.

FDA notified healthcare professionals and patients about its ongoing review of data from published studies to evaluate whether use of oral bisphosphonate drugs is associated with an increased risk of cancer of the esophagus. FDA has not concluded that taking an oral bisphosphonate drug increases the risk of esophageal cancer. There are insufficient data to recommend endoscopic screening of asymptomatic patients. FDA will continue to evaluate all available data supporting the safety and effectiveness of bisphosphonate drugs and will update the public when more information becomes available.|Bone loss is particularly rapid in postmenopausal women younger than age 60. Risk factors often associated with the development of postmenopausal osteoporosis include early menopause; moderately low bone mass (for example, at least 1 standard deviation below the mean for healthy young adult women); thin body build; Caucasian or Asian race; and family history of osteoporosis. The presence of such risk factors may be important when considering the use of alendronate sodium tablets for prevention of osteoporosis.|/Alendronate sodium is contraindicated in the presence of/: Abnormalities of the esophagus which delay esophageal emptying such as stricture or achalasia; inability to stand or sit upright for at least 30 minutes; hypersensitivity to any component of this product; hypocalcemia.|Alendronate sodium, like other bisphosphonates, may cause local irritation of the upper gastrointestinal mucosa. Esophageal adverse experiences, such as esophagitis, esophageal ulcers and esophageal erosions, occasionally with bleeding and rarely followed by esophageal stricture or perforation, have been reported in patients receiving treatment with alendronate sodium. In some cases these have been severe and required hospitalization. Physicians should therefore be alert to any signs or symptoms signaling a possible esophageal reaction and patients should be instructed to discontinue alendronate sodium and seek medical attention if they develop dysphagia, odynophagia, retrosternal pain or new or worsening heartburn.|For more Drug Warnings (Complete) data for Alendronic acid (18 total), please visit the HSDB record page.

Alendronic acid tablets have a very low oral bioavialability. After administration it distributes into soft tissue and bone or is excreted in the urine. Alendronic acid does not undergo metabolism.

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.)

Mean oral bioavailability of alendronic acid in women is 0.64% and in men is 0.59%. Bioavailability of alendronic acid decreases by up to 40% if it is taken within an hour of a meal.|Administration of radiolabeled alendronic acid results in 50% recovery in urine within 72 hours. No alendronic acid is recovered in the feces. Men excrete less alendronic acid than women, though race and advanced age do not affect elimination.|28L.|71mL/min.|Relative to an intravenous iv reference dose, the mean oral bioavailability of alendronate in women was 0.64% for doses ranging from 5 to 70 mg when administered after an overnight fast and two hours before a standardized breakfast. Oral bioavailability of the 10 mg tablet in men (0.59%) was similar to that in women when administered after an overnight fast and 2 hours before breakfast.|Alendronate sodium 70 mg oral solution and alendronate sodium 70 mg tablet are equally bioavailable.|A study examining the effect of timing of a meal on the bioavailability of alendronate was performed in 49 postmenopausal women. Bioavailability was decreased (by approximately 40%) when 10 mg alendronate was administered either 0.5 or 1 hour before a standardized breakfast, when compared to dosing 2 hours before eating. In studies of treatment and prevention of osteoporosis, alendronate was effective when administered at least 30 minutes before breakfast.|Bioavailability was negligible whether alendronate was administered with or up to two hours after a standardized breakfast.|For more Absorption, Distribution and Excretion (Complete) data for Alendronic acid (10 total), please visit the HSDB record page.

Urinary excretion is the sole method of elimination of alendronic acid and no metabolites are detected upon urine collection.|There is no evidence that alendronate is metabolized in animals or humans.

Due to alendronic acid being incorporated into the skeleton, the terminal half life is estimated to be over 10 years.|The terminal half-life in humans is estimated to exceed 10 years, probably reflecting release of alendronate from the skeleton. Based on the above, it is estimated that after 10 years of oral treatment with alendronate sodium (10 mg daily) the amount of alendronate released daily from the skeleton is approximately 25% of that absorbed from the gastrointestinal tract.

Alendronic acid binds to bone hydroxyapatite. Bone resorption causes local acidification, releasing alendronic acid which is that taken into osteoclasts by fluid-phase endocytosis. Endocytic vesicles are acidified, releasing alendronic acid to the cytosol of osteoclasts where they induce apoptosis. Inhibition of osteoclasts results in decreased bone resorption which is shown through decreased urinary calcium, deoxypyridinoline and cross-linked N-telopeptidases of type I collagen.|Animal studies have indicated the following mode of action. At the cellular level, alendronate shows preferential localization to sites of bone resorption, specifically under osteoclasts. The osteoclasts adhere normally to the bone surface but lack the ruffled border that is indicative of active resorption. Alendronate does not interfere with osteoclast recruitment or attachment, but it does inhibit osteoclast activity. Studies in mice on the localization of radioactive (3)H-alendronate in bone showed about 10-fold higher uptake on osteoclast surfaces than on osteoblast surfaces. Bones examined 6 and 49 days after (3)H-alendronate administration in rats and mice, respectively, showed that normal bone was formed on top of the alendronate, which was incorporated inside the matrix. While incorporated in bone matrix, alendronate is not pharmacologically active. Thus, alendronate must be continuously administered to suppress osteoclasts on newly formed resorption surfaces. Histomorphometry in baboons and rats showed that alendronate treatment reduces bone turnover (i.e., the number of sites at which bone is remodeled). In addition, bone formation exceeds bone resorption at these remodeling sites, leading to progressive gains in bone mass.|Alendronate (alendronate sodium hydrate) is a nitrogen-containing bisphosphonate, which combines with the bone surface and reduces osteoclast-mediated bone resorption. It is a third-generation bisphosphonate compound, specifically distributed on the surface of bone resorption and taken into osteoclasts. Under the closed circumstances which is formed with osteoclast and the bone surface, alendronate becomes detached from the bone surface and taken into osteoclast since acid released from osteoclast leads to pH decrease (acidified). The uptaken alendronate blocks the pathway of mevalonic acid synthesis, which is cholesteric synthesis, inhibits the prenylation of GTP binding protein, and decreases the osteoclast's function by influencing the cytoskeleton. This restraint of alendronate in bone resorption against osteoclasts is reversible, showing no cytotoxicity at more than hundredfold concentration level at which action occurs. ...|The differences that exist among individual BPs in terms of mineral binding and biochemical actions may explain differences in their clinical behavior and effectiveness. The classical pharmacological effects of bisphosphonates (BPs) appear to be the result of two key properties: their affinity for bone mineral and their inhibitory effects on osteoclasts. There is new information about both properties. Mineral binding affinities differ among the clinically used BPs and may influence their differential distribution within bone, their biological potency, and their duration of action. The antiresorptive effects of the nitrogen-containing BPs (including alendronate, risedronate, ibandronate, and zoledronate) appear to result from their inhibition of the enzyme farnesyl pyrophosphate synthase (FPPS) in osteoclasts. FPPS is a key enzyme in the mevalonate pathway, which generates isoprenoid lipids utilized for the post-translational modification of small GTP-binding proteins that are essential for osteoclast function. Effects on other cellular targets, such as osteocytes, may also be important. BPs share several common properties as a drug class. However, as with other families of drugs, there are obvious chemical, biochemical, and pharmacological differences among the individual BPs. Each BP has a unique profile that may help to explain potential clinical differences among them, in terms of their speed and duration of action, and effects on fracture reduction.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). 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 0.9% saline (NS) 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 ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/HUMAN EXPOSURE STUDIES/ ... The aim of this study was to investigate whether alendronate and naproxen are synergistic as causes of gastric ulcers. /Investigaors/ performed an endoscopist-blind, randomized, crossover, single-center comparison of 10 mg/d of alendronate sodium, 500 mg of naproxen sodium twice daily, or the combination taken orally for 10 days in volunteers aged 30 years or older. Videoendoscopy was used to evaluate the presence and degree of mucosal damage to the esophagus, stomach, or duodenal bulb before and after each treatment. There was a 1- to 4-week washout between evaluations. Twenty-six healthy volunteers participated (18 women and 8 men), aged 30 to 50 years. Gastric ulcers were present in 2 subjects receiving alendronate (8%), in 3 receiving naproxen (12%), and in 10 receiving both (38%) (P<0.05 for the combination vs either drug alone). Both alendronate and naproxen can cause gastric ulcers. The combination appears synergistic. Alendronate should be used with caution in those who simultaneously require nonsteroidal anti-inflammatory drugs.|/CASE REPORTS/ Alendronate sodium, an aminobiphosphonate used primarily to treat osteoporosis in postmenopausal women, is known to cause esophagitis. A 71-year-old woman experienced severe, acute esophagitis and severe stricture of the esophagus due to oral alendronate therapy. Unlike in previous cases, she had taken alendronate for 10 months before the onset of complications and the stricture proved resistant to dilation.|/CASE REPORTS/ ... A 63-year-old woman started medical therapy with alendronate in a dose of 10 mg daily. After a period of one month of medical treatment with this drug she began to complain of dysphagic symptoms and abdominal pain. She was submitted to endoscopic examination that showed an esophageal ulceration, an enteric ulceration of the anastomosis and an esophageal stenosis. Medical treatment with alendronate was discontinued and the symptom of abdominal pain disappeared. The intensity of dysphagia has decreased. The ulcerated lesion remitted although esophageal stenosis did not. The patient was subsequently treated with esophagus-enteric anastomosis dilation. She improved in her general state and nowadays she is free of symptoms. Alendronate sodium could cause lesions of the inferior esophageal portion or in distal segments of the gastrointestinal tube, in patients with a fast gastrointestinal transit. Special attention must be given to gastrectomized patients that use this drug because of the possibility to develop mucosal lesions in the enteric anastomosed part and its fearful complications as stenosis.|/CASE REPORTS/ ... /Investigators/ present a 74-year-old woman with a stage 0 chronic lymphocytic leukemia who developed acute renal failure following the initiation of alendronate. The renal biopsy revealed an acute granulomatous interstitial nephritis. Infectious and inflammatory etiologies were ruled out. Hemodialysis was required despite discontinuation of all medications. Partial recovery of renal function occurred after 6 weeks of prednisone therapy and cyclophosphamide. This report describes a unique case of acute granulomatous interstitial nephritis and leukemic cell kidney infiltration by CLL.|For more Human Toxicity Excerpts (Complete) data for Alendronic acid (15 total), please visit the HSDB record page.

4-Amino-1-Hydroxybutylidene 1,1-Biphosphonate

Alendronate Sodium preparations: (AHFS, 2011)

Determination by ion chromatography in pharmaceutical formulations.

Determination by HPLC in urine.

Human drugs -> Fosavance -> EMA Drug Category|Drugs for treatment of bone diseases -> Human pharmacotherapeutic group|Human drugs -> Vantavo (previously Alendronate sodium and colecalciferol, MSD) -> EMA Drug Category|Human Drugs -> EU pediatric investigation plans|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients