| 英文药名: Phoslo(Calcium Acetate Tablets)
中文药名: 醋酸钙片 药品说明 常用名：醋酸钙片 【注意事项】 【孕妇及哺乳期妇女用药】 孕妇，哺乳期妇女使用本品的安全性尚未确定。 【药物相互作用】 【包装规格】667mg*200 片 Phoslo DOSAGE & ADMINISTRATION DOSAGE FORMS & STRENGTHS Capsule: 667 mg calcium acetate per gelcap. CONTRAINDICATIONS Patients with hypercalcemia. WARNINGS AND PRECAUTIONS Hypercalcemia Patients with end stage renal disease may develop hypercalcemia when treated with calcium, including calcium acetate (Phoslo®). Avoid the use of calcium supplements, including calcium-based nonprescription antacids, concurrently with Phoslo®. An overdose of Phoslo may lead to progressive hypercalcemia, which may require emergency measures. Therefore, early in the treatment phase during the dosage adjustment period, monitor serum calcium levels twice weekly. Should hypercalcemia develop, reduce the Phoslo® dosage or discontinue the treatment, depending on the severity of hypercalcemia. More severe hypercalcemia (Ca>12 mg/dL) is associated with confusion, delirium, stupor and coma. Severe hypercalcemia can be treated by acute hemodialysis and discontinuing Phoslo® therapy. Mild hypercalcemia (10.5 to 11.9 mg/dL) may be asymptomatic or manifest as constipation, anorexia, nausea, and vomiting. Mild hypercalcemia is usually controlled by reducing the Phoslo® dose or temporarily discontinuing therapy. Decreasing or discontinuing Vitamin D therapy is recommended as well. Chronic hypercalcemia may lead to vascular calcification and other soft-tissue calcification. Radiographic evaluation of suspected anatomical regions may be helpful in early detection of soft tissue calcification. The long term effect of Phoslo® on the progression of vascular or soft tissue calcification has not been determined. Hypercalcemia (>11 mg/dL) was reported in 16% of patients in a 3-month study of a solid dose formulation of calcium acetate; all cases resolved upon lowering the dose or discontinuing treatment. Maintain the serum calcium-phosphorus (Ca x P) product below 55 mg2/dL2. Concomitant Use with Medications Hypercalcemia may aggravate digitalis toxicity. ADVERSE REACTIONS Hypercalcemia is discussed elsewhere [see Warnings and Precautions (5.1)]. Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In clinical studies, calcium acetate has been generally well tolerated. Phoslo® was studied in a 3-month, open-label, non-randomized study of 98 enrolled ESRD hemodialysis patients and in a two week double-blind, placebo-controlled, cross-over study with 69 enrolled ESRD hemodialysis patients. Adverse reactions (>2% on treatment) from these trials are presented in Table 1.
Mild hypercalcemia may be asymptomatic or manifest itself as constipation, anorexia, neusea, and vomiting. More severe hypercalcemia is associated with confusion, delirium, stupor, and coma. Decreasing dialysate calcium concentration could reduce the incidence and severity of Phoslo®-induced hypercalcemia. Isolated cases of pruritus have been reported, which may represent allergic reactions. Postmarketing Experience Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency or to establish a causal relationship to drug exposure. The following additional adverse reactions have been identified during post-approval of calcium acetate: dizziness, edema, and weakness. DRUG INTERACTIONS The drug interaction of Phoslo® is characterized by the potential of calcium to bind to drugs with anionic functions (e.g., carboxyl and hydroxyl groups). Phoslo® may decrease the bioavailability of tetracyclines or fluoroquinolones via this mechanism. There are no empirical data on avoiding drug interactions between calcium acetate or Phoslo® and most concomitant drugs. When administering an oral medication with Phoslo® where a reduction in the bioavailability of that medication would have a clinically significant effect on its safety or efficacy, administer the drug one hour before or three hours after Phoslo® or calcium acetate. Monitor blood levels of the concomitant drugs that have a narrow therapeutic range. Patients taking anti-arrhythmic medications for the control of arrhythmias and anti-seizure medications for the control of seizure disorders were excluded from the clinical trials with all forms of calcium acetate. Ciprofloxacin In a study of 15 healthy subjects, a co-administered single dose of 4 calcium acetate tablets approximately 2.7 g, decreased the bioavailability of ciprofloxacin by approximately 50%. USE IN SPECIFIC POPULATIONS PREGNANCY Pregnancy Category C Phoslo® contains calcium acetate. Animal reproduction studies have not been conducted with Phoslo®, and there are no adequate and well controlled studies of Phoslo® use in pregnant women. Patients with end stage renal disease may develop hypercalcemia with calcium acetate treatment [see Warnings and Precautions (5.1)]. Maintenance of normal serum calcium levels is important for maternal and fetal well being. Hypercalcemia during pregnancy may increase the risk for maternal and neonatal complications such as stillbirth, preterm delivery, and neonatal hypocalcemia and hypoparathyroidism. Phoslo® treatment, as recommended, is not expected to harm a fetus if maternal calcium levels are properly monitored during and following treatment. LABOR & DELIVERY The effects of Phoslo® on labor and delivery are unknown. NURSING MOTHERS Phoslo® contains calcium acetate and is excreted in human milk. Human milk feeding by a mother receiving Phoslo® is not expected to harm an infant, provided maternal serum calcium levels are appropriately monitored. PEDIATRIC USE Safety and effectiveness in pediatric patients have not been established. GERIATRIC USE Clinical studies of calcium acetate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. OVERDOSAGE Administration of Phoslo® in excess of the appropriate daily dosage may result in hypercalcemia [see Warnings and Precautions (5.1)]. DESCRIPTION Phoslo® acts as a phosphate binder. Its chemical name is calcium acetate. Its molecular formula is C4H6CaO4, and its molecular weight is 158.17. Its structural formula is:
Each opaque gelcap with a blue cap and white body is spin printed in blue and white ink with “Phoslo®” printed on the cap and “667 mg” printed on the body. Each gelcap contains 667 mg calcium acetate, USP (anhydrous; Ca(CH3COO)2; MW=158.17 grams) equal to 169 mg (8.45 mEq) calcium, and 10 mg of the inert binder, polyethylene glycol 8000 NF. The gelatin cap and body have the following inactive ingredients: FD&C blue #1, D&C red #28, titanium dioxide, USP and gelatin, USP. CLINICAL PHARMACOLOGY Patients with ESRD retain phosphorus and can develop hyperphosphatemia. High serum phosphorus can precipitate serum calcium resulting in ectopic calcification. Hyperphosphatemia also plays a role in the development of secondary hyperparathyroidism in patients with ESRD. MECHANISM OF ACTION Calcium acetate, (Phoslo®) when taken with meals, combines with dietary phosphate to form an insoluble calcium phosphate complex, which is excreted in the feces, resulting in decreased serum phosphorus concentration. PHARMACODYNAMICS Orally administered calcium acetate from pharmaceutical dosage forms is systemically absorbed up to approximately 40% under fasting conditions and up to approximately 30% under non-fasting conditions. This range represents data from both healthy subjects and renal dialysis patients under various conditions. NONCLINICAL TOXICOLOGY CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY No carcinogenicity, mutagenicity, or fertility studies have been conducted with calcium acetate. CLINICAL STUDIES Effectiveness of calcium acetate in decreasing serum phosphorus has been demonstrated in two studies of the calcium acetate solid dosage form. Ninety-one patients with end-stage renal disease who were undergoing hemodialysis and were hyperphosphatemic (serum phosphorus >5.5 mg/dL) following a 1-week phosphate binder washout period contributed efficacy data to an open-label, non-randomized study. The patients received calcium acetate 667 mg tablets at each meal for a period of 12 weeks. The initial starting dose was 2 tablets per meal for 3 meals a day, and the dose was adjusted as necessary to control serum phosphorus levels. The average final dose after 12 weeks of treatment was 3.4 tablets per meal. Although there was a decrease in serum phosphorus, in the absence of a control group the true magnitude of effect is uncertain. The data presented in Table 2 demonstrate the efficacy of calcium acetate in the treatment of hyperphosphatemia in end-stage renal disease patients. The effects on serum calcium levels are also presented.
There was a 30% decrease in serum phosphorus levels during the 12 week study period (p<0.01). Two-thirds of the decline occurred in the first month of the study. Serum calcium increased 9% during the study mostly in the first month of the study. Treatment with the phosphate binder was discontinued for patients from the open-label study, and those patients whose serum phosphorus exceeded 5.5 mg/dL were eligible for entry into a double-blind, placebo-controlled, cross-over study. Patients were randomized to receive calcium acetate or placebo, and each continued to receive the same number of tablets as had been individually established during the previous study. Following 2 weeks of treatment, patients switched to the alternative therapy for an additional 2 weeks. The phosphate binding effect of calcium acetate is shown in the Table 3.
Overall, 2 weeks of treatment with calcium acetate statistically significantally (p<0.01) decreased serum phosphorus by a mean of 19% and increased serum calcium by a statistically significant (p<0.01) but clinically unimportant mean of 7%. HOW SUPPLIED/STORAGE AND HANDLING Gelcap A white and blue gelcap for oral administration containing 667 mg calcium acetate (anhydrous Ca(CH3COO)2; MW=158.17 grams) equal to 169 mg (8.45 mEq) calcium. Gelcap NDC 49230-640-21 Bottles of 200 STORAGE: Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [See USP “Controlled Room Temperature”]. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
