Lanthanum carbonate

457.84

457.76700

209-599-5

0M78EU4V9H

White powder

V - Various

2846904100

189.57000

-7.34100

DryPowder; OtherSolid

2.6

333.6ºC at 760 mmHg

169.8ºC

Practically insoluble in water

Store at 25 deg C (77 deg F): excursions permitted to 15-30 deg C (59-86 deg F)

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

H315

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

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

|Warning|H315 (100%): Causes skin irritation [Warning Skin corrosion/irritation]|P261, P264, P271, P280, P302+P352, P304+P340, P305+P351+P338, P312, P321, P332+P313, P337+P313, P362, P403+P233, P405, and P501|Aggregated GHS information provided by 47 companies from 4 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|Aggregated GHS information provided by 10 companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

The symptoms associated with overdose are adverse reactions such as headache, nausea and vomiting. Lanthanum carbonate was not acutely toxic in animals by the oral route. No deaths and no adverse effects occurred in mice, rats or dogs after single oral doses of 2000 mg/kg.

Drugs known to interact with antacids should not be administered within 2 hours of a lanthanum carbonate dose. Potential pharmacokinetic interaction (insoluble complex formation).|... Twelve patients randomly received in a crossover manner a single oral dose of ciprofloxacin 750 mg alone and plus lanthanum carbonate 1 g three times daily with meals for six doses, with a washout interval of 7 to 14 d. Serial blood and urine samples were collected for 24 hr after ciprofloxacin administration, and ciprofloxacin concentrations were determined using reverse-phase HPLC. Pharmacokinetic parameters of ciprofloxacin were calculated by noncompartmental methods, and the effect of lanthanum on ciprofloxacin pharmacokinetic parameters was assessed using ANOVA. Lanthanum decreased (P < 0.001) the mean ciprofloxacin area under the plasma concentration-time curve by 54% and the maximum plasma concentration by 56%. The 24-hr urinary recovery of ciprofloxacin was reduced by 52% by lanthanum (P < 0.001). No statistically significant differences in ciprofloxacin time to maximum plasma concentration, elimination half-life, and renal clearance occurred between the two arms. Lanthanum carbonate significantly reduces the systemic exposure to orally administered ciprofloxacin. Concomitant administration of both drugs should be avoided to prevent possible suboptimal response to ciprofloxacin.

While growth abnormalities were not identified in long-term animal studies, lanthanum was deposited into developing bone including growth plate. The consequences of such deposition in developing bone in pediatric patients are unknown. Therefore, the use of lanthanum carbonate in this population is not recommended.

In vitro, lanthanum is highly bound (>99%) to human plasma proteins, including human serum albumin, α1-acid glycoprotein, and transferrin.

Used to reduce serum phosphate in patients with end stage renal disease (ESRD).|FDA Label

Lanthanum; Kidney Failure, Chronic|Lanthanum carbonate is indicated to reduce serum phosphate in patients with end stage renal disease. /Included in US product label/

Adverse effects reported in 5% or more of patients receiving lanthanum carbonate and more frequently than with placebo include nausea, vomiting, dialysis graft occlusion, and abdominal pain.|Patients with acute peptic ulcer, ulcerative colitis, Crohn's disease or bowel obstruction were not included in lanthanum carbonate clinical studies. Caution should be used in patients with these conditions.|While growth abnormalities were not identified in long-term animal studies, lanthanum was deposited into developing bone including growth plate. The consequences of such deposition in developing bone in pediatric patients are unknown. Therefore, the use of lanthanum carbonate in this population is not recommended.|/Patients taking lanthanum carbonate should be advised of the/ importance of taking lanthanum carbonate with or immediately after meals.|For more Drug Warnings (Complete) data for Lanthanum Carbonate (9 total), please visit the HSDB record page.

In clinical trials, daily doses up to 4718 mg/day of lanthanum were well tolerated in healthy adults when administered with food, with the exception of GI symptoms.

In vitro studies have shown that lanthanum binds phosphate in the physiologically relevant pH range of 3 to 7. In simulated gastric fluid, lanthanum binds approximately 97% of the available phosphate at pH 3-5 and 67% at pH 7, when lanthanum is present in a two-fold molar excess to phosphate. Bile acids have not been shown to affect the phosphate binding affinity of lanthanum. In order to bind dietary phosphate, lanthanum carbonate must be administered with or immediately after meals.

Bioavailability very low (<0.002%) following single or multiple dose oral administration.|No information is available regarding the mass balance of lanthanum in humans after oral administration. In rats and dogs, the mean recovery of lanthanum after an oral dose was about 99% and 94%, respectively, and was essentially all from feces. Biliary excretion is the predominant route of elimination for circulating lanthanum in rats.|In healthy volunteers administered intravenous lanthanum as the soluble chloride salt (120 μg), renal clearance was less than 2% of total plasma clearance.|Lanthanum is minimally absorbed from the GI tract following oral administration; bioavailability is less than 0.002%. In patients receiving therapeutic dosages of lanthanum for up to 2 years, mean plasma concentrations of the drug remained low (ie, 1.1 ng/mL or less).|Following single or multiple dose oral administration of lanthanum carbonate to healthy subjects, the concentration of lanthanum in plasma was very low. Following oral administration in ESRD patients, the mean lanthanum Cmax was 1.0 ng/mL. During long-term administration (52 weeks) in ESRD patients, the mean lanthanum concentration in plasma was approximately 0.6 ng/mL. There was minimal increase in plasma lanthanum concentrations with increasing doses within the therapeutic dose range. The effect of food on the bioavailability of lanthanum carbonate has not been evaluated, but the timing of food intake relative to lanthanum administration (during and 30 minutes after food intake) has a negligible effect on the systemic level of lanthanum|In vitro, lanthanum is highly bound (>99%) to human plasma proteins, including human serum albumin, alpha1-acid glycoprotein, and transferrin. Binding to erythrocytes in vivo is negligible in rats.|In studies in mice, rats and dogs, lanthanum concentrations in many tissues increased over time and were several orders of magnitude higher than plasma concentrations (particularly in the GI tract, bone and liver). Steady state tissue concentrations in bone and liver were achieved in dogs between 4 and 26 weeks. Relatively high levels of lanthanum remained in these tissues for longer than 6 months after cessation of dosing in dogs. There is no evidence from animal studies that lanthanum crosses the blood-brain barrier.|For more Absorption, Distribution and Excretion (Complete) data for Lanthanum Carbonate (13 total), please visit the HSDB record page.

Lanthanum is not metabolized.|Lanthanum is not metabolized and is not a substrate of CYP450. In vitro metabolic inhibition studies showed that lanthanum at concentrations of 10 and 40 ug/mL does not have relevant inhibitory effects on any of the CYP450 isoenzymes tested (1A2, 2C9/10, 2C19, 2D6, and 3A4/5).

Elimination half-life of 53 hours.|Lanthanum was cleared from plasma following discontinuation of therapy with an elimination half-life 53 hours.|... Estimates of elimination half-life from bone ranged from 2.0 to 3.6 years.

Lanthanum carbonate is a phosphate binder that reduces absorption of phosphate by forming insoluble lanthanum phosphate complexes that pass through the gastrointestinal (GI) tract unabsorbed. Both serum phosphate and calcium phosphate product are reduced as a consequence of the reduced dietary phosphate absorption.|Lanthanum carbonate dissociates in the acid environment of the upper GI tract to release lanthanum ions that bind dietary phosphate released from food during digestion. Lanthanum carbonate inhibits absorption of phosphate by forming highly insoluble lanthanum phosphate complexes, consequently reducing both serum phosphate and calcium phosphate product.|The carbonate salt of lanthanum is practically insoluble in water but dissociates in the acidic environment of the upper GI tract to release trivalent lanthanum ions, which bind dietary phosphates released during digestion, thereby forming highly insoluble lanthanum phosphate complexes. Consequently, phosphate absorption, serum phosphorus concentrations, and serum calcium times phosphorus product (Ca X P) are reduced. Lanthanum ions have a high affinity for phosphate; in vitro studies indicate that when lanthanum is present at pH 3-5 (pH corresponding to that of gastric fluid) in twofold molar excess to phosphates, the drug binds about 97% of available phosphates.

/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/

/CASE REPORTS/ A 75-year-old woman was admitted with febrile confusion and abdominal pain. She was taking medications that included lanthanum carbonate. Examination, biology, a cerebral scan, and a review of her medications could not explain the confusion. The plain film of the abdomen revealed multiple diffuse calcium-like deposits throughout the digestive tract. The plasma levels of lanthanum were higher than normal. The confusion resolved after discontinuation of the lanthanum carbonate. This case raises the problem of the potential role played by lanthanum tablet residue in the genesis or aggravation of diverticular flare-up and the problem of the potential permeability of the blood-brain barrier with lanthanum use in case of its digestive accumulation, leading to increased serum concentrations.|/CASE REPORTS/ ... A 77-year-old man was admitted to a hospital for renal failure caused by complete obstructive ureterolithiasis in the solitary kidney. Hemodialysis was indicated due to elevated renal parameters (urea 28.0 mmol/L, serum creatinine 1079 umol/L, phosphorus 2.45 mmol/L). Treatment with lanthanum carbonate was started in order to normalize serum phosphate levels. Surgical treatment of ureteral obstruction was necessary but the patient presented with hemodynamically significant supraventricular tachycardia. The ECG proved atrial flutter that was the indication to electrical cardioversion by cardiologists. Therefore, transesophageal echocardiography had to be carried out to exclude intracardial thrombi; these were not detected. The echocardiography also demonstrated an inexplicable finding on the thoracic aorta, and thus, computed tomography of the aorta was performed. The CT scan did not reveal any significant pathology of the aorta. However, a high-contrast substance of unknown origin and significance was captured in the stomach. /Investigators/ performed an X-ray of lanthanum pills in a vial and detected the radio-opacity of lanthanum itself, even without calcium and phosphate. This confirmed our suspicion that the high-contrast metallic-like substance in the stomach was a tablet of lanthanum. ...|/EPIDEMIOLOGY STUDIES/ A specified subset of data from four Phase III clinical trials and subsequent extension studies is presented, in order to assess the effects of lanthanum carbonate on the liver. Hepatic biochemical tests for alanine transaminase, aspartate aminotransferase, alkaline phosphatase and bilirubin were performed. Adverse events classified as "liver and biliary system events" were recorded. In the four initial clinical trials, lanthanum carbonate was not associated with any adverse changes in transaminases or bilirubin. The incidence and nature of adverse events associated with the liver during lanthanum carbonate treatment was similar to that in the comparator groups. For patients who enrolled into the subsequent long-term follow-up study (up to 6 years of treatment), changes in transaminases were not clinically relevant and mean values were similar to those observed in the earlier trials. Overall, there was no increase in the incidence of adverse events associated with the liver reported after up to 6 years of treatment when compared with the results of the initial studies. There was no evidence of adverse effects of lanthanum carbonate on the liver in patients who received treatment for up to 6 years.

Fosrenol

Formulations: (AHFS, 2009)

All other basic inorganic chemical manufacturing|Carbonic acid, lanthanum(3+) salt (3:2): ACTIVE

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