Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/94
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| dailymed-drugs:94 | rdf:type | http://www4.wiwiss.fu-berli... | lld:dailymed |
| dailymed-drugs:94 | rdf:type | dailymed-instance:drugs | lld:dailymed |
| dailymed-drugs:94 | rdfs:label | ARIXTRA (Injection, Solution) | lld:dailymed |
| dailymed-drugs:94 | dailymed-instance:dosage | ARIXTRA Injection is administered by subcutaneous injection once daily.<br/>Deep Vein Thrombosis Prophylaxis Following Hip Fracture, or Hip or Knee Replacement Surgeries: In patients undergoing hip fracture, hip replacement, or knee replacement surgery, the recommended dose of ARIXTRA is 2.5 mg administered by subcutaneous injection once daily. After hemostasis has been established, the initial dose should be given 6 to 8 hours after surgery. Administration before 6 hours after surgery has been associated with an increased risk of major bleeding. The usual duration of administration is 5 to 9 days, and up to 11 days administration has been tolerated. In patients undergoing hip fracture surgery, an extended prophylaxis course of up to 24 additional days is recommended. In patients undergoing hip fracture surgery, a total of 32 days (peri-operative and extended prophylaxis) has been tolerated. (See CLINICAL STUDIES, WARNINGS: Laboratory Testing and ADVERSE REACTIONS.)<br/>Deep Vein Thrombosis Prophylaxis Following Abdominal Surgery: In patients undergoing abdominal surgery, the recommended dose of ARIXTRA is 2.5 mg administered by subcutaneous injection once daily after hemostasis has been established. The initial dose should be given 6 to 8 hours after surgery. Administration before 6 hours after surgery has been associated with an increased risk of major bleeding. The usual duration of administration is 5 to 9 days, andup to 10 days of ARIXTRA injection has been administered.<br/>Deep Vein Thrombosis and Pulmonary Embolism Treatment: In patients with acute symptomatic DVT and in patients with acute symptomatic PE the recommended dose of ARIXTRA is 5 mg (body weight<50 kg), 7.5 mg (body weight 50-100 kg), or 10 mg (body weight>100 kg) by subcutaneous injection once daily (ARIXTRA treatment regimen). Treatment with ARIXTRA should be continued for at least 5 days and until a therapeutic oral anticoagulant effect is established (INR 2.0 to 3.0). Concomitant treatment with warfarin sodium should be initiated as soon as possible, usually within 72 hours. The usual duration of administration of ARIXTRA is 5 to 9 days; up to 26 days of ARIXTRA injection has been administered. (See CLINICAL STUDIES, WARNINGS: Laboratory Testing and ADVERSE REACTIONS.) | lld:dailymed |
| dailymed-drugs:94 | dailymed-instance:descripti... | ARIXTRA (fondaparinux sodium) Injection is a sterile solution containing fondaparinux sodium. It is a synthetic and specific inhibitor of activated Factor X (Xa). Fondaparinux sodium is methyl O-2-deoxy-6-O-sulfo-2-(sulfoamino)-��-D-glucopyranosyl-(1���4)-O-��-D-glucopyra-nuronosyl-(1���4)-O-2-deoxy-3,6-di-O-sulfo-2-(sulfoamino)-��-D-glucopyranosyl-(1���4)-O-2-O-sulfo-��-L-idopyranuronosyl-(1���4)-2-deoxy-6-O-sulfo-2-(sulfoamino)-��-D-glucopyranoside, decasodium salt. The molecular formula of fondaparinux sodium is CHNNaOSand its molecular weight is 1728. The structural formula is provided below: ARIXTRA is supplied as a sterile, preservative-free injectable solution for subcutaneous use. Each single dose, prefilled syringe of ARIXTRA, affixed with an automatic needle protection system, contains 2.5 mg of fondaparinux sodium in 0.5 mL, 5.0 mg of fondaparinux sodium in 0.4 mL, 7.5 mg of fondaparinux sodium in 0.6 mL, or 10.0 mg of fondaparinux sodium in 0.8 mL of an isotonic solution of sodium chloride and water for injection. The final drug product is a clear and colorless to slightly yellow liquid with a pH between 5.0 and 8.0. | lld:dailymed |
| dailymed-drugs:94 | dailymed-instance:clinicalP... | Pharmacodynamics:<br/>Mechanism of Action: The antithrombotic activity of fondaparinux sodium is the result of antithrombin III (ATIII)-mediated selective inhibition of Factor Xa. By selectively binding to ATIII, fondaparinux sodium potentiates (about 300 times) the innate neutralization of Factor Xa by ATIII. Neutralization of Factor Xa interrupts the blood coagulation cascade and thus inhibits thrombin formation and thrombus development. Fondaparinux sodium does not inactivate thrombin (activated Factor II) and has no known effect on platelet function. At the recommended dose, fondaparinux sodium does not affect fibrinolytic activity or bleeding time.<br/>Anti-Xa Activity: The pharmacodynamics/pharmacokinetics of fondaparinux sodium are derived from fondaparinux plasma concentrations quantified via anti-Factor Xa activity. Only fondaparinux can be used to calibrate the anti-Xa assay. (The international standards of heparin or LMWH are not appropriate for this use.) As a result, the activity of fondaparinux sodium is expressed as milligrams (mg) of the fondaparinux calibrator. The anti-Xa activity of the drug increases with increasing drug concentration, reaching maximum values in approximately 3 hours.<br/>Pharmacokinetics:<br/>Absorption: Fondaparinux sodium administered by subcutaneous injection is rapidly and completely absorbed (absolute bioavailability is 100%). Following a single subcutaneous dose of fondaparinux sodium 2.5 mg in young male subjects, Cof 0.34 mg/L is reached in approximately 2 hours. In patients undergoing treatment with fondaparinux sodium injection 2.5 mg, once daily, the peak steady-state plasma concentration is, on average, 0.39-0.50 mg/L and is reached approximately 3 hours post-dose. In these patients, the minimum steady-state plasma concentration is 0.14-0.19 mg/L. In patients with symptomatic deep vein thrombosis and pulmonary embolism undergoing treatment with fondaparinux sodium injection 5 mg (body weight<50 kg), 7.5 mg (body weight 50-100 kg) and 10 mg (body weight>100 kg) once daily, the body-weight-adjusted doses provide similar mean steady-state peaks and minimum plasma concentrations across all body weight categories. The mean peak steady-state plasma concentration is in the range of 1.20-1.26 mg/L. In these patients, the mean minimum steady-state plasma concentration is in the range of 0.46-0.62 mg/L.<br/>Distribution: In healthy adults, intravenously or subcutaneously administered fondaparinux sodium distributes mainly in blood and only to a minor extent in extravascular fluid as evidenced by steady state and non-steady state apparent volume of distribution of 7-11 L. Similar fondaparinux distribution occurs in patients undergoing elective hip surgery or hip fracture surgery. In vitro, fondaparinux sodium is highly (at least 94%) and specifically bound to antithrombin III (ATIII) and does not bind significantly to other plasma proteins (including platelet Factor 4 [PF4]) or red blood cells.<br/>Metabolism: In vivo metabolism of fondaparinux has not been investigated since the majority of the administered dose is eliminated unchanged in urine in individuals with normal kidney function.<br/>Elimination: In individuals with normal kidney function fondaparinux is eliminated in urine mainly as unchanged drug. In healthy individuals up to 75 years of age, up to 77% of a single subcutaneous or intravenous fondaparinux dose is eliminated in urine as unchanged drug in 72 hours. The elimination half-life is 17-21 hours.<br/>Special Populations:<br/>Renal Impairment: Fondaparinux elimination is prolonged in patients with renal impairment since the major route of elimination is urinary excretion of unchanged drug. In patients undergoing prophylaxis following elective hip surgery or hip fracture surgery, the total clearance of fondaparinux is approximately 25% lower in patients with mild renal impairment (creatinine clearance 50 to 80 mL/min), approximately 40% lower in patients with moderate renal impairment (creatinine clearance 30 to 50 mL/min), and approximately 55% lower in patients with severe renal impairment (<30 mL/min) compared to patients with normal renal function. A similar relationship between fondaparinux clearance and extent of renal impairment was observed in DVT treatment patients. (See CONTRAINDICATIONS and WARNINGS: Renal Impairment.)<br/>Hepatic Impairment: The pharmacokinetic properties of fondaparinux have not been studied in patients with hepatic impairment.<br/>Elderly Patients: Fondaparinux elimination is prolonged in patients older than 75 years. In studies evaluating fondaparinux sodium 2.5 mg prophylaxis in hip fracture surgery or elective hip surgery, the total clearance of fondaparinux was approximately 25% lower in patients older than 75 years as compared to patients younger than 65 years. A similar relationship between fondaparinux clearance and age was observed in DVT treatment patients.<br/>Patients Weighing Less Than 50 kg: Total clearance of fondaparinux sodium is decreased by approximately 30% in patients weighing less than 50 kg (see CONTRAINDICATIONS and DOSAGE AND ADMINISTRATION).<br/>Gender: The pharmacokinetic properties of fondaparinux sodium are not significantly affected by gender.<br/>Race: Pharmacokinetic differences due to race have not been studied prospectively. However, studies performed in Asian (Japanese) healthy subjects did not reveal a different pharmacokinetic profile compared to Caucasian healthy subjects. Similarly, no plasma clearance differences were observed between black and Caucasian patients undergoing orthopedic surgery.<br/>Drug Interactions: See PRECAUTIONS: Drug Interactions. | lld:dailymed |
| dailymed-drugs:94 | dailymed-instance:activeIng... | dailymed-ingredient:fondapa... | lld:dailymed |
| dailymed-drugs:94 | dailymed-instance:contraind... | ARIXTRA Injection is contraindicated in patients with severe renal impairment (creatinine clearance<30 mL/min). ARIXTRA is eliminated primarily by the kidneys, and such patients are at increased risk for major bleeding episodes (see WARNINGS: Renal Impairment). ARIXTRA prophylactic therapy is contraindicated in patients with body weight<50 kg undergoing hip fracture, hip replacement or knee replacement surgery, and abdominal surgery. During the randomized clinical trials of prophylaxis in the peri-operative period following hip fracture, hip replacement, or knee replacement surgery, occurrence of major bleeding was doubled in patients with a body weight<50 kg compared with those with a body weight���50 kg (5.4% versus 2.1%). In the clinical trial in patients undergoing abdominal surgery, the major bleeding rate was also higher in patients with a body weight<50 kg as compared to those with a body weight���50 kg (5.3% versus 3.3%), respectively. The use of ARIXTRA is contraindicated in patients with active major bleeding, bacterial endocarditis, in patients with thrombocytopenia associated with a positive in vitro test for anti-platelet antibody in the presence of fondaparinux sodium, or in patients with known hypersensitivity to fondaparinux sodium. | lld:dailymed |
| dailymed-drugs:94 | dailymed-instance:supply | ARIXTRA Injection is available in the following strengths and package sizes: 2.5 mg ARIXTRA in 0.5 mL single dose prefilled syringe, affixed with a 27-gauge x��-inch needle with a blue automatic needle protection system NDC 0007-3230-02 2 Single Unit Syringes NDC 0007-3230-1110 Single Unit Syringes 5 mg ARIXTRA in 0.4 mL single dose prefilled syringe, affixed with a 27-gauge x��-inch needle with an orange automatic needle protection system NDC 0007-3232-022 Single Unit Syringes NDC 0007-3232-1110 Single Unit Syringes 7.5 mg ARIXTRA in 0.6 mL single dose prefilled syringe, affixed with a 27-gauge x��-inch needle with a magenta automatic needle protection system NDC 0007-3234-022 Single Unit Syringes NDC 0007-3234-11 10 Single Unit Syringes 10 mg ARIXTRA in 0.8 mL single dose prefilled syringe, affixed with a 27-gauge x��-inch needle with a violet automatic needle protectionsystem NDC 0007-3236-02 2 Single Unit Syringes NDC 0007-3236-1110 Single Unit Syringes Store at 25��C (77��F); excursions permitted to 15���30��C (59���86��F) [See USP Controlled Room Temperature]. Keep out of the reach of children. Distributed by GlaxoSmithKline Research Triangle Park, NC 27709 ARIXTRA is a registered trademark of GlaxoSmithKline. ��2008, GlaxoSmithKline. All rights reserved. April 2008ARX:1PI | lld:dailymed |
| dailymed-drugs:94 | dailymed-instance:genericDr... | http://www4.wiwiss.fu-berli... | lld:dailymed |
| dailymed-drugs:94 | dailymed-instance:boxedWarn... | SPINAL/EPIDURAL HEMATOMAS: When neuraxial anesthesia (epidural/spinal anesthesia) or spinal puncture is employed, patients anticoagulated or scheduled to be anticoagulated with low molecular weight heparins, heparinoids, or fondaparinux sodium for prevention of thromboembolic complications are at risk of developing an epidural or spinal hematoma which can result in long-term or permanent paralysis. The risk of these events is increased by the use of indwelling epidural catheters for administration of analgesia or by the concomitant use of drugs affecting hemostasis such as non-steroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, or other anticoagulants. The risk also appears to be increased by traumatic or repeatedepidural or spinal puncture. Patients should be frequently monitored for signs and symptoms of neurologic impairment. If neurologic compromise is noted, urgent treatment is necessary. The physician should consider the potential benefit versus risk before neuraxial intervention in patients anticoagulated or to be anticoagulated for thromboprophylaxis (see also WARNINGS: Hemorrhage and PRECAUTIONS: Drug Interactions.) | lld:dailymed |
| dailymed-drugs:94 | dailymed-instance:activeMoi... | dailymed-ingredient:fondapa... | lld:dailymed |
| dailymed-drugs:94 | dailymed-instance:inactiveI... | dailymed-ingredient:sodium_... | lld:dailymed |
| dailymed-drugs:94 | dailymed-instance:possibleD... | diseasome-diseases:96 | lld:dailymed |
| dailymed-drugs:94 | dailymed-instance:precautio... | General: ARIXTRA Injection should be administered according to the recommended regimen, especially with respect to the timing of the first dose after surgery. In the hip fracture, hip replacement, knee replacement, or abdominal surgery clinical studies, the administration of ARIXTRA before 6 hours after surgery has been associated with an increased risk of major bleeding (see ADVERSE REACTIONS: Hemorrhage and DOSAGE AND ADMINISTRATION). ARIXTRA Injection should be used with care in patients with a bleeding diathesis, uncontrolled arterial hypertension, or a history of recent gastrointestinal ulceration, diabetic retinopathy, and hemorrhage. ARIXTRA Injection should be used with caution in elderly patients (see PRECAUTIONS: Geriatric Use). ARIXTRA should be used with caution in patients with a low body weight (<50 kg) for the treatment of PE and DVT. The needle guard of the prefilled syringe of ARIXTRA contains dry natural latex rubber that may cause allergic reactions in latex sensitive individuals. ARIXTRA Injection should not be mixed with other injections or infusions. If thrombotic events occur despite prophylaxis with ARIXTRA, appropriate therapy should be initiated.<br/>Laboratory Tests: Periodic routine complete blood counts (including platelet count), serum creatinine level, and stool occult blood tests are recommended during the course of treatment with ARIXTRA Injection. When administered at the recommended doses, routine coagulation tests such as Prothrombin Time (PT) and Activated Partial Thromboplastin Time (aPTT) are relatively insensitive measures of ARIXTRA activity, and are therefore, unsuitable for monitoring. The anti-Factor Xa activity of fondaparinux sodium can be measured by anti-Xa assay using the appropriate calibrator (fondaparinux). Since the international standards of heparin or LMWH are not appropriate calibrators, the activity of fondaparinux sodium is expressed in milligrams (mg) of the fondaparinux and cannot be compared with activities of heparin or low molecular weight heparins (see CLINICAL PHARMACOLOGY: Pharmacodynamics and Pharmacokinetics and WARNINGS: Laboratory Testing).<br/>Drug Interactions: In clinical studies performed with ARIXTRA, the concomitant use of oral anticoagulants (warfarin), platelet inhibitors (acetylsalicylic acid), NSAIDs (piroxicam), and digoxin did not significantly affect the pharmacokinetics/pharmacodynamics of fondaparinux sodium. In addition, ARIXTRA neither influenced the pharmacodynamics of warfarin, acetylsalicylic acid, piroxicam, and digoxin, nor the pharmacokinetics of digoxin at steady state. Agents that may enhance the risk of hemorrhage should be discontinued prior to initiation of therapy with ARIXTRA. If co-administration is essential, close monitoring may be appropriate. In an in vitro study in human liver microsomes, inhibition of CYP2A6 hydroxylation of coumarin by fondaparinux (200��M i.e., 350 mg/L) was 17-28%. Inhibition of the other isozymes evaluated (CYPs 2A1, 2C9, 2C19, 2D6, 3A4, and 3E1) was 0-16%. Since fondaparinux does not markedly inhibit CYP450s (CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, or CYP3A4) in vitro,fondaparinux sodium is not expected to significantly interact with other drugs in vivo by inhibition of metabolism mediated by these isozymes. Since fondaparinux sodium does not bind significantly to plasma proteins other than ATIII, no drug interactions by protein-binding displacement are expected.<br/>Carcinogenesis, Mutagenesis, Impairment of Fertility: No long-term studies in animals have been performed to evaluate the carcinogenic potential of fondaparinux sodium. Fondaparinux sodium was not genotoxic in the Ames test, the mouse lymphoma cell (L5178Y/TK) forward mutation test, the human lymphocyte chromosome aberration test, the rat hepatocyte unscheduled DNA synthesis (UDS) test, or the rat micronucleus test. At subcutaneous doses up to 10 mg/kg/day (about 32 times the recommended human dose based on body surface area), fondaparinux sodium was found to have no effect on fertility and reproductive performance of male and female rats.<br/>Pregnancy:<br/>Teratogenic Effects: Pregnancy Category B. Reproduction studies have been performed in pregnant rats at subcutaneous doses up to 10 mg/kg/day (about 32 times the recommended human dose based on body surface area) and pregnant rabbits at subcutaneous doses up to 10 mg/kg/day (about 65 times the recommended human dose based on body surface area) and have revealed no evidence of impaired fertility or harm to the fetus due to fondaparinux sodium. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.<br/>Nursing Mothers: Fondaparinux sodium was found to be excreted in the milk of lactating rats. However, it is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when fondaparinux sodium is administered to a nursing mother.<br/>Pediatric Use: Safety and effectiveness of ARIXTRA in pediatric patients have not been established.<br/>Geriatric Use: ARIXTRA should be used with caution in elderly patients. Over 3,000 patients, 65 years and older, have received ARIXTRA 2.5 mg in randomized clinical trials. Over 1,200 patients, 65 years and older, have received the ARIXTRA treatment regimen in the DVT and PE treatment clinical trials. The efficacy of ARIXTRA in the elderly (equal to or older than 65 years) was similar to that seen in younger patients (younger than65 years). In the peri-operative hip fracture, hip replacement, or knee replacement surgery clinical trials with patients receiving ARIXTRA 2.5 mg, the risk of major bleeding associated with use of ARIXTRA increased with age: 1.8% (23/1,253) in patients<65 years, 2.2% (24/1,111) in those 65-74 years, and 2.7% (33/1,227) in those���75 years. Serious adverse events increased with age for patients receiving ARIXTRA. In patients undergoing 3 weeks of extended prophylaxis following one week of peri-operative prophylaxis after hip fracture surgery, the incidence of major bleeding was: 1.9% (1/52) in patients<65 years, 1.4% (1/71) in those 65-74 years, and 2.9% (6/204) in those���75 years. In the abdominal surgery clinical trial, the risk of major bleeding associated with use of ARIXTRA increased with age: 3.0% (19/644) in patients<65 years, 3.2% (16/507) in those 65-74 years, and 5.0% (14/282) in those���75 years. In the DVT and PE treatment clinical trials with patients receiving the ARIXTRA treatment regimen, the risk of major bleeding associated with ARIXTRA increased with age: 0.6% (7/1,151) in patients<65 years, 1.6% (9/560) in those 65-74 years, and 2.1% (12/583) in those���75 years. Careful attention to dosing directions and concomitant medications (especially anti-platelet medication) is advised (see CLINICAL PHARMACOLOGY and PRECAUTIONS: General). Fondaparinux sodium is substantially excreted by the kidney, and the risk of toxic reactions to ARIXTRA may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, it may be useful to monitor renal function (see CONTRAINDICATIONS and WARNINGS: Renal Impairment). | lld:dailymed |
| dailymed-drugs:94 | dailymed-instance:overdosag... | Symptoms/Treatment: There is no known antidote for ARIXTRA Injection. Overdose of ARIXTRA may lead to hemorrhagic complications. Overdosage associated with bleeding complications should lead to treatment discontinuation and initiation of appropriate therapy. Data obtained in patients undergoing chronic intermittent hemodialysis suggest that clearance of ARIXTRA can increase by 20% during hemodialysis. | lld:dailymed |
| dailymed-drugs:94 | dailymed-instance:genericMe... | fondaparinux sodium | lld:dailymed |
| dailymed-drugs:94 | dailymed-instance:fullName | ARIXTRA (Injection, Solution) | lld:dailymed |
| dailymed-drugs:94 | dailymed-instance:adverseRe... | 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. The adverse reaction information from clinical trials does, however, provide a basis for identifying possible adverse events and for approximating rates. The data described below reflect exposure in 8,877 patients randomized to ARIXTRA Injection in controlled trials of hip fracture, hip replacement, major knee, or abdominal surgeries, and DVT and PE treatment. Patients received ARIXTRA primarily in 2 large peri-operative dose-response trials (n = 989), 4 active-controlled peri-operative trials with enoxaparin sodium (n = 3,616), and an extended prophylaxis trial (n = 327), an active-controlled trial with dalteparin sodium (n = 1,425), a dose-response trial in DVT treatment (n = 111), an active-controlled trial with enoxaparin sodium in DVT treatment (n = 1,091), and an active-controlled trial with heparin in PE treatment (n = 1,092) (see CLINICAL STUDIES).<br/>Hemorrhage: During administration of ARIXTRA, the most common adverse reactions were bleeding complications (see WARNINGS).<br/>Hip Fracture, Hip Replacement and Knee Replacement Surgery: The rates of major bleeding events reported during the hip fracture, hip replacement, or knee replacement surgery clinical trials with ARIXTRA 2.5 mg Injection are provided in Tables 8 and 9 below. A separate analysis of major bleeding across all randomized, controlled, peri-operative, prophylaxis clinical studies of hip fracture, hip replacement, or knee replacement surgery according to the time of the first injection of ARIXTRA after surgical closure was performed in patients who received ARIXTRA only post-operatively. In this analysis, the incidences of major bleeding were as follows:<4 hours was 4.8% (5/104), 4-6 hours was 2.3% (28/1196), 6-8 hours was 1.9% (38/1965). In all studies, the majority (���75%) of the major bleeding events occurred during the first 4 days after surgery.<br/>Abdominal Surgery: The rates of major bleeding reported during the abdominal surgery clinical trial with ARIXTRA 2.5 mg are provided in Table 10 below. A separate analysis of major bleeding according to the time of the first injection of ARIXTRA after surgical closure was performed. In this analysis the incidences of major bleeding were as follows:<6 hours was 3.4% (9/263) and 6-8 hours was 2.9% (32/1112).<br/>Treatment of Deep Vein Thrombosis and Pulmonary Embolism: The rates of bleeding events reported during the DVT and PE clinical trials with the ARIXTRA injection treatment regimen are provided in Table 11 below.<br/>Thrombocytopenia: See WARNINGS: Thrombocytopenia.<br/>Local Reactions: Mild local irritation (injection site bleeding, rash, and pruritus) may occur following subcutaneous injection of ARIXTRA.<br/>Elevations of Serum Aminotransferases: In the peri-operative prophylaxis randomized clinical trials of 7��2 days asymptomatic increases in aspartate (AST [SGOT]) and alanine (ALT [SGPT]) aminotransferase levels greater than 3 times the upper limit of normal of the laboratory reference range have been reported in 1.7% and 2.6% of patients, respectively, during treatment with ARIXTRA 2.5 mg Injection versus 3.2% and 3.9%, of patients, respectively, during treatment with enoxaparin sodium 30 mg every 12 hours or 40 mg once daily enoxaparin sodium. Such elevations are fully reversible and are rarely associated with increases in bilirubin. In the extended prophylaxis clinical trial no significant differences in aspartate (AST [SGOT]) and alanine (ALT [SGPT]) aminotransferase levels between ARIXTRA 2.5 mg Injection and placebo treated patients were observed. In the DVT and PE treatment clinical trials asymptomatic increases in aspartate (AST [SGOT]) and alanine (ALT [SGPT]) aminotransferase levels greater than 3 times the upper limit of normal of the laboratory reference range have been reported in 0.7% and 1.3% of patients, respectively, during treatment with the ARIXTRA injection treatment regimen. In comparison, these increases have been reported in 4.8% and 12.3%, of patients, respectively, in the DVT treatment trial during treatment with enoxaparin sodium 1 mg/kg every 12 hours, and in 2.9% and 8.7%, of patients, respectively, in the PE treatment trial during treatment with aPTT adjusted heparin. Since aminotransferase determinations are important in the differential diagnosis of myocardial infarction, liver disease, and pulmonary emboli, elevations that might be caused by drugs like ARIXTRA should be interpreted with caution.<br/>Other Adverse Events: Other adverse events that occurred during treatment with ARIXTRA, or enoxaparin sodium in clinical trials with patients undergoing hip fracture surgery, hip replacement surgery, or knee replacement surgery and that occurred at a rate of at least 2% in either treatment group, are provided in Table 12 below. Other adverse events that occurred during treatment with ARIXTRA or dalteparin sodium in clinical trials with patients undergoing abdominal surgery and that occurred at a rate of at least 2% in either treatment group are provided in Table 13 below. Other adverse events that occurred during treatment with ARIXTRA, enoxaparin sodium, or heparin in the DVT and PE treatment clinical trials and that occurred at a rate of at least 2% in any treatment group are provided in Table 14 below.<br/>Postmarketing Experience: The following adverse reactions have been identified during post-approval use of ARIXTRA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Rare cases of elevated aPTT and heparin-induced thrombocytopenia have been reported. A causal relationship of these events to fondaparinux has not been established. | lld:dailymed |
| dailymed-drugs:94 | dailymed-instance:warning | ARIXTRA Injection is not intended for intramuscular administration. ARIXTRA cannot be used interchangeably (unit for unit) with heparin, low molecular weight heparins or heparinoids, as they differ in manufacturing process, anti-Xa and anti-IIa activity, units, and dosage. Each of these medicines has its own instructions for use.<br/>Renal Impairment (See also CONTRAINDICATIONS):<br/>Hip Fracture, Hip Replacement and Knee Replacement Surgeries: Major bleeding in patients receiving prophylactic therapy in hip fracture, hip replacement, or knee replacement surgery occurred in 1.6% (25/1,565) of patients with normal renal function, in 2.4% (31/1,288) with mild renal impairment, in 3.8% (19/504) with moderate renal impairment, and in 4.8% (4/83) with severe renal impairment. When ARIXTRA was used according to the recommended timing of the first injection (6 to 8 hours after surgery), major bleeding occurred in 1.8% (16/905) of patients with normal renal function, in 2.2% (15/675)with mild renal impairment, in 2.3% (6/265) with moderate renal impairment, and in 0% (0/40) with severe renal impairment.<br/>Abdominal Surgery: Major bleeding in patients receiving prophylactic therapy in abdominal surgery occurred in 2.1% (13/606) of patients with normal renal function, in 3.6% (22/613) with mild renal impairment, in 6.7% (12/179) with moderate renal impairment, and in 7.1% (1/14) with severe renal impairment. When ARIXTRA was used according to the recommended timing of the first injection (6 to 8 hours after surgery), major bleeding occurred in 2.1% (10/467) of patients with normal renal function, in 3.3% (16/481) with mild renal impairment, in 5.8% (8/137) with moderate renal impairment, and in 7.7%(1/13) with severe renal impairment.<br/>Treatment of Deep Vein Thrombosis and Pulmonary Embolism: Major bleeding in patients receiving treatment for DVT and PE occurred in 0.4% (4/1,132) of patients with normal renal function, in 1.6% (12/733) with mild renal impairment, in 2.2% (7/318) with moderate renal impairment, and in 7.3% (4/55) with severe renal impairment. ARIXTRA should be used with caution in patients with moderate renal impairment (creatinine clearance 30-50 mL/min). (See CLINICAL PHARMACOLOGY: Special Populations, Renal Impairment.) Renal function should be assessed periodically in patients receiving ARIXTRA. The drug should be discontinued immediately in patients who develop severe renal impairment while on therapy. After discontinuation of ARIXTRA, its anticoagulant effects may persist for 2-4 days in patients with normal renal function (i.e., at least 3-5 half-lives). The anticoagulant effects of ARIXTRA may persist even longer in patients with renal impairment (see CLINICAL PHARMACOLOGY).<br/>Hemorrhage: ARIXTRA Injection, like other anticoagulants, should be used with extreme caution in conditions with increased risk of hemorrhage, such as congenital or acquired bleeding disorders, active ulcerative and angiodysplastic gastrointestinal disease, hemorrhagic stroke, or shortly after brain, spinal, or ophthalmological surgery, or in patients treated concomitantly with platelet inhibitors.<br/>Laboratory Testing: Because routine coagulation tests such as Prothrombin Time (PT) and Activated Partial Thromboplastin Time (aPTT) are relatively insensitive measures of the activity of ARIXTRA and international standards of heparin or LMWH are not calibrators to measure anti-Factor Xa activity of ARIXTRA, if during therapy with ARIXTRA, unexpected changes in coagulation parameters or major bleeding occurs, ARIXTRA should be discontinued (see PRECAUTIONS: Laboratory Tests).<br/>Neuraxial Anesthesia and Post-operative Indwelling Epidural Catheter Use: Spinal or epidural hematomas, which may result in long-term or permanent paralysis, can occur with the use of anticoagulants and neuraxial (spinal/epidural) anesthesia or spinal puncture. The risk of these events may be higher with post-operative use of indwelling epidural catheters or concomitant use of other drugs affecting hemostasis such as NSAIDs (see Boxed Warning for Spinal/Epidural Hematomas). In spontaneous post-marketing reports, there have been several cases of epidural or spinal hematoma that have occurred in association with the use of ARIXTRA by SC injection.<br/>Thrombocytopenia: Thrombocytopenia can occur with the administration of ARIXTRA. Moderate thrombocytopenia (platelet counts between 100,000/mmand 50,000/mm) occurred at a rate of 3.0% in patients given ARIXTRA 2.5 mg in the peri-operative hip fracture, hip replacement or knee replacement surgery, and abdominal surgery clinical trials. Severe thrombocytopenia (platelet counts less than 50,000/mm) occurred at a rate of 0.2% in patients given ARIXTRA 2.5 mg in these clinical trials. During extended prophylaxis, no cases of moderate or severe thrombocytopenia were reported. Moderate thrombocytopenia occurred at a rate of 0.5% in patients given the ARIXTRA treatment regimen in the DVT and PE treatment clinical trials. Severe thrombocytopenia occurred at a rate of 0.04% in patients given the ARIXTRA treatment regimen in the DVT and PE treatment clinical trials. Thrombocytopenia of any degree should be monitored closely. If the platelet count falls below 100,000/mm, ARIXTRA should be discontinued. | lld:dailymed |
| dailymed-drugs:94 | dailymed-instance:indicatio... | ARIXTRA Injection is indicated for the prophylaxis of deep vein thrombosis, which may lead to pulmonary embolism: ARIXTRA Injection is indicated for: (See DOSAGE AND ADMINISTRATION section for appropriate dosage regimen.) | lld:dailymed |
| dailymed-drugs:94 | dailymed-instance:represent... | http://www4.wiwiss.fu-berli... | lld:dailymed |
| dailymed-drugs:94 | dailymed-instance:routeOfAd... | http://www4.wiwiss.fu-berli... | lld:dailymed |
| dailymed-drugs:94 | dailymed-instance:name | ARIXTRA | lld:dailymed |
| http://www4.wiwiss.fu-berli... | dailymed-instance:producesD... | dailymed-drugs:94 | lld:dailymed |
| diseasome-diseases:96 | diseasome-instance:possible... | dailymed-drugs:94 | lld:diseasome |