英文药名:Auryxia(Ferric Citrate Tablets) 中文药名:柠檬酸铁片 生产厂家:Keryx生物制药
There are no empirical data on avoiding drug interactions between Auryxia and most concomitant oral drugs. For oral medications where a reduction in the bioavailability of that medication would have a clinically significant effect on its safety or efficacy, consider separation of the timing of the administration of the two drugs. The duration of separation depends upon the absorption characteristics of the medication concomitantly administered, such as the time to reach peak systemic levels and whether the drug is an immediate release or an extended release product. Consider monitoring clinical responses or blood levels of concomitant medications that have a narrow therapeutic range. 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Category B: There are no adequate and well-controlled studies in pregnant women. It is not known whether Auryxia can cause fetal harm when administered to a pregnant woman. Animal reproduction studies have not been conducted. The effect of Auryxia on the absorption of vitamins and other nutrients has not been studied in pregnant women. Requirements for vitamins and other nutrients are increased in pregnancy. An overdose of iron in pregnant women may carry a risk for spontaneous abortion, gestational diabetes and fetal malformation [see Nonclinical Toxicology (13.1)]. 8.2 Labor and Delivery The effects of Auryxia on labor and delivery are unknown. 8.3 Nursing Mothers Data from rat studies have shown the transfer of iron into milk by divalent metal transporter-1 (DMT-1) and ferroportin-1 (FPN-1). Hence, there is a possibility of infant exposure when Auryxia is administered to a nursing woman. 8.4 Pediatric Use The safety and efficacy of Auryxia have not been established in pediatric patients. 8.5 Geriatric Use Clinical studies of Auryxia included 106 subjects aged 65 years and older (33 subjects aged 75 years and older). Overall, the clinical study experience has not identified any obvious differences in responses between the elderly and younger patients in the tolerability or efficacy of Auryxia. 10 OVERDOSAGE No data are available regarding overdose of Auryxia in patients. In patients with chronic kidney disease on dialysis, the maximum dose studied was 2,520 mg ferric iron (12 tablets of Auryxia) per day. Iron absorption from Auryxia may lead to excessive elevations in iron stores, especially when concomitant IV iron is used [see Warnings and Precautions [see Warnings and Precautions (5.1)]. In clinical trials, one case of elevated iron in the liver as confirmed by biopsy was reported in a patient administered IV iron and Auryxia. Because accidental overdose of iron-containing products is a leading cause of fatal poisoning in children under 6 years of age, this product must be kept out of the reach of children. In case of accidental overdose, a doctor or poison control center should be contacted immediately [see Warnings and Precautions (5.2)]. 11 DESCRIPTION Auryxia (ferric citrate) is known chemically as iron (+3), x (1, 2, 3-propanetricarboxylic acid, 2 hydroxy-), y (H2O) Auryxia 210 mg ferric iron tablets, equivalent to 1g ferric citrate, are film-coated, peach-colored, and oval-shaped tablets embossed with “KX52”. The inactive ingredients are pregelatinized starch and calcium stearate. In addition, the film-coating contains the following inactive ingredients; hypromellose, titanium dioxide, triacetin, and FD&C Yellow #6/Sunset Yellow FCF Aluminum Lake, FD&C Red #40/Allura Red AC Aluminum Lake, and FD&C Blue #2/Indigo Carmine Aluminum Lake. 12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Ferric iron binds dietary phosphate in the GI tract and precipitates as ferric phosphate. This compound is insoluble and is excreted in the stool. By binding phosphate in the GI tract and decreasing absorption, ferric citrate lowers the phosphate concentration in the serum. 12.2 Pharmacodynamics In addition to effects on serum phosphorus levels, Auryxia has been shown to increase serum iron parameters, including ferritin, iron and TSAT. In dialysis patients treated with Auryxia in a 52-week study in which IV iron could also be administered, mean (SD) ferritin levels rose from 593 (293) ng/mL to 895 (482) ng/mL, mean (SD) TSAT levels rose from 31% (11) to 39% (17) and mean (SD) iron levels rose from 73 (29) mcg/dL to 88 (42) mcg/dL. In contrast, in patients treated with active control, these parameters remained relatively constant [see Contraindications (4) and Warnings and Precautions (5.1)]. 12.3 Pharmacokinetics Absorption and Distribution Formal pharmacokinetic studies have not been performed with Auryxia. Examination of serum iron parameters has shown that there is systemic absorption of iron from Auryxia [see Contraindications (4), Warnings and Precautions (5.1) and Clinical Pharmacology (12.2)]. Drug Interaction Studies In vitro Of the drugs screened for an interaction with ferric citrate in vitro, only doxycycline showed the potential for interaction with at least 70% decrease in its concentration. This interaction can be avoided by spacing the administration of doxycycline and ferric citrate [see Drug Interactions (7)]. 13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Data from carcinogenesis studies have shown that ferric citrate is not carcinogenic in mice and rats when administered intramuscularly or subcutaneously. Ferric citrate was neither mutagenic in the bacterial reverse mutation assay (Ames test) nor clastogenic in the chromosomal aberration test in Chinese hamster fibroblasts. 14 CLINICAL STUDIES The ability of Auryxia to lower serum phosphorus in patients with CKD on dialysis was demonstrated in randomized clinical trials: one 56-week, safety and efficacy trial, consisting of a 52-week active-controlled phase and a 4-week, placebo-controlled, randomized withdrawal period, and one 4-week open-label trial of different fixed doses of Auryxia. Both trials excluded subjects who had an absolute requirement for aluminum containing drugs with meals. 14.1 Long-term, Randomized, Controlled, Safety and Efficacy Trial After the 2-week washout period during which phosphate binders were held, patients with a mean serum phosphorus of 7.5 mg/dL during washout were randomized 2:1 to Auryxia (N=292) or active control (calcium acetate and/or sevelamer carbonate; N=149). The majority (>96%) of subjects were on hemodialysis. The starting dose of Auryxia was 6 tablets/day, divided with meals. The starting dose of active control was the patient’s dose prior to the washout period. The dose of phosphate binder was increased or decreased as needed to maintain serum phosphorus levels between 3.5 and 5.5 mg/dL, to a maximum of 12 tablets/day. As shown in the figure below, serum phosphorus levels declined following initiation of therapy. The phosphorus lowering effect was maintained over 52 weeks of treatment. Figure 1: Serum Phosphorus Control over 52 Weeks Following completion of the 52-week active-controlled phase, Auryxia-treated patients were eligible to enter a 4-week placebo-controlled randomized withdrawal phase, in which patients were re-randomized in a 1:1 ratio to receive Auryxia (N=96) or placebo (N=96). During the placebo-controlled period, the serum phosphorus concentration rose by 2.2 mg/dL on placebo relative to patients who remained on Auryxia. Table 2: Effect of Auryxia on serum phosphorus during randomized withdrawal
Note: Analyses using ANCOVA with last observation carried forward. ANCOVA=analysis of covariance; CI=confidence interval. 14.2 Fixed-Dose Trial Following a 1- to 2-week washout from all phosphate-binding agents, 154 patients with hyperphosphatemia (mean serum phosphorus of 7.5 mg/dL) and CKD on dialysis were randomized in a 1:1:1 ratio to 1, 6, or 8 tablets/day of Auryxia for 4 weeks. Auryxia was administered with meals; subjects receiving 1 tablet/day were instructed to take it with their largest meal of the day, and subjects on 6 or 8 tablets/day took divided doses in any distribution with meals. Dose-dependent decreases in serum phosphorus were observed by Day 7 and remained relatively stable for the duration of treatment. The demonstrated reductions from baseline to Week 4 in mean serum phosphorus were significantly greater with 6 and 8 tablets/day than with 1 tablet/day (p<0.0001). Mean reduction in serum phosphorus at Week 4 was 0.1 mg/dL with 1 tablet/day, 1.9 mg/dL with 6 tablets/day, and 2.1 mg/dL with 8 tablets/day. 16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied Tablets: Auryxia 210 mg ferric iron tablets equivalent to 1 g of ferric citrate are supplied as 200 tablets in 400-cc high-density polyethylene bottles. The 210 mg ferric iron tablets are film-coated, peach-colored, and oval-shaped tablets embossed with “KX52.” 1 Bottle of 200-count 210 mg ferric iron tablets (NDC 59922-631-01) 16.2 Storage and Handling Storage: Store at 20 to 25°C (68 to 77°F): excursions permitted to 15° to 30°C (59°F to 86°F) [See USP controlled room temperature]. Protect from moisture. 17 PATIENT COUNSELING INFORMATION 17.1 Dosing Recommendations Inform patients to take Auryxia as directed with meals and adhere to their prescribed diets. Instruct patients on concomitant medications that should be dosed apart from Auryxia. 17.2 Adverse Reactions Advise patients that Auryxia may cause discolored (dark) stools, but this staining of the stool is considered normal with oral medications containing iron. Auryxia may cause diarrhea, nausea, constipation and vomiting. Advise patients to report severe or persistent gastrointestinal symptoms to their physician. Manufactured for and Distributed by: Keryx Biopharmaceuticals, Inc. 750 Lexington Avenue, 20th Floor New York, NY 10022 US Patents Nos 5,753,706; 6,903,235; 7,767,851; 8,093,423; 8,299,298; 8,338,642; 8,609,896; 8,754,257 and pending, comparable and/or related patents. Issued 11/2014 Rev 2 17 PATIENT COUNSELING INFORMATION 17.1 Dosing Recommendations Inform patients to take Auryxia as directed with meals and adhere to their prescribed diets. Instruct patients on concomitant medications that should be dosed apart from Auryxia. 17.2 Adverse Reactions Advise patients that Auryxia may cause discolored (dark) stools, but this staining of the stool is considered normal with oral medications containing iron. Auryxia may cause diarrhea, nausea, constipation and vomiting. Advise patients to report severe or persistent gastrointestinal symptoms to their physician. Manufactured for and Distributed by: Keryx Biopharmaceuticals, Inc. 750 Lexington Avenue, 20th Floor New York, NY 10022 |
柠檬酸铁片|Auryxia(Ferric Citrate Tablets)简介:
英文药名:Auryxia(Ferric Citrate Tablets)
中文药名:柠檬酸铁片
生产厂家:Keryx生物制药药品介绍Auryxia™(柠檬酸铁)是一种口服,为基础的磷酸盐结合剂。在美国,Auryxia™已于2014年 ... 责任编辑:admin |
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