Risk also appears to be increased by traumatic or repeated epidural or spinal puncture.Patients should be frequently monitored for signs and symptoms of neurological impairment.Neurologicpromise 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 , and ).DESCRIPTION Lovenox Injection is a sterile aqueous solution containing enoxaparin sodium, a low molecular weight heparin.Injection is available in two concentrations: 1.MG PER ML -Prefilled Syringes 30 mg / 0.40 mg / 0.-Graduated Prefilled Syringes 60 mg / 0.80 mg / 0.100 mg / 1 mL -Multiple-Dose Vials 300 mg / 3 mL Lovenox Injection 100 mg/mL Concentration contains 10 mg enoxaparin sodium (approximate anti-Factor Xa activity of 1000 IU ) per 0.Water for Injection.2.MG PER ML -Graduated Prefilled Syringes 120 mg / 0.150 mg / 1 mL Lovenox Injection 150 mg/mL Concentration contains 15 mg enoxaparin sodium (approximate anti-Factor Xa activity of 1500 IU ) per 0.Water for Injection.The Lovenox prefilled syringes and graduated prefilled syringes are preservative-free and intended for use only as a single-dose injection.Multiple-dose vial contains 15 mg benzyl alcohol per 1 mL as a preservative.And for dosage unit descriptions.PH of the injection is 5.7.Enoxaparin sodium is obtained by alkaline depolymerization of heparin benzyl ester derived from porcine intestinal mucosa.Structure is characterized by a 2-O-sulfo-4-enepyranosuronic acid group at the non-reducing end and a 2-N,6-O-disulfo-D-glucosamine at the reducing end of the chain.(ranging between 15% and 25%) of the enoxaparin structure contains an 1,6 anhydro derivative on the reducing end of the polysaccharide chain.Drug substance is the sodium salt.Average molecular weight is about 4500 daltons.Molecular weight distribution is: 8000 daltons 18% STRUCTURAL FORMULA X = Percent of polysaccharide chain containing 1,6 anhydro derivative on the reducing end.R X= 15 to 25% n= 0 to 20 100 - X H n =1 to 21 CLINICAL PHARMACOLOGY Enoxaparin is a low molecular weight heparin which has antithrombotic properties.Humans, enoxaparin given at a dose of 1.(SC) is characterized by a higher ratio of anti-Factor Xa to anti-Factor IIa activity (meanSD, 14.(based on areas under anti-Factor activity versus time curves)pared to the ratios observed for heparin (meanSD, 1.Increases of up to 1.Control values were seen in the thrombin time (TT) and the activated partial thromboplastin time (aPTT).At a 1 mg/kg dose (100 mg / mL concentration), administered SC every 12 hours to patients in a large clinical trial resulted in aPTT values of 45 seconds or less in the majority of patients (n = 1607).PHARMACOKINETICS (CONDUCTED USING 100 MG / ML CONCENTRATION) ABSORPTION Maximum anti-Factor Xa and anti-thrombin (anti-Factor IIa) activities occur 3 to 5 hours after SC injection of enoxaparin.Peak anti-Factor Xa activity was 0.G/mL) and 0.(3.The 20 mg and the 40 mg clinically tested SC doses, respectively.(n = 46) peak anti-Factor Xa activity was 1.At steady state in patients with unstable angina receiving 1 mg/kg SC every 12 hours for 14 days.Absolute bioavailability of enoxaparin, after 1.Given SC, based on anti-Factor Xa activity is approximately 100% in healthy volunteers.Pharmacokinetics appear to be linear over the rmended dosage ranges (see ).Repeated subcutaneous administration of 40 mg once daily and 1.Once-daily regimens in healthy volunteers, the steady state is reached on day 2 with an average exposure ratio about 15% higher than after a single dose.Enoxaparin activity levels are well predicted by single-dose pharmacokinetics.Subcutaneous administration of the 1 mg/kg twice daily regimen, the steady state is reached from day 4 with mean exposure about 65% higher than after a single dose and mean peak and trough levels of about 1.0.Respectively.On enoxaparin sodium pharmacokinetics, this difference in steady state is expected and within the therapeutic range.Although not studied clinically, the 150 mg/mL concentration of enoxaparin sodium is projected to result in anticoagulant activities similar to those of 100 mg/mL and 200 mg/mL concentrations at the same enoxaparin dose.A daily 1.SC injection of enoxaparin sodium was given to 25 healthy male and female subjects using a 100 mg/mL or a 200 mg/mL concentration the following pharmacokinetic profiles were obtained (see table below): Pharmacokinetic Parameters After 5 Days of 1.SC Once Daily Doses of Enoxaparin Sodium Using 100 mg/mL or 200 mg/mL Concentrations CONCENTRATION ANTI-XA ANTI-IIA HEPTEST APTT Means SD at Day 5 and 90% Confidence Interval (CI) of the ratio Median (range) Amax (IU/mL or О" sec) 100 mg/mL 1.23 (0.(16.(4.1.26 (0.(17.CI 102-110% 102-111% tmax (h) 100 mg/mL 3 (2-6) 4 (2-5) 2.(2-4.(2-6) 4.3 (2-5) 3 (2-5) AUC (ss) (hIU/mL or hО" sec) 100 mg/mL 14.54 (0.200 mg/mL 15.77 (0.90% CI 105-112% 103-109% DISTRIBUTION The volume of distribution of anti-Factor Xa activity is about 4.ELIMINATION Following intravenous (i.Dosing, the total body clearance of enoxaparin is 26 mL/min.I.Dosing of enoxaparin labeled with the gamma-emitter, 99mTc, 40% of radioactivity and 8 to 20% of anti-Factor Xa activity were recovered in urine in 24 hours.Based on anti-Factor Xa activity was 4.After a single SC dose to about 7 hours after repeated dosing.40 mg SC once a day dose, significant anti-Factor Xa activity persists in plasma for about 12 hours.Following SC dosing, the apparent clearance (CL/F) of enoxaparin is approximately 15 mL/min.METABOLISM Enoxaparin sodium is primarily metabolized in the liver by desulfation and/or depolymerization to lower molecular weight species with much reduced biological potency.Clearance of active fragments represents about 10% of the administered dose and total renal excretion of active and non-active fragments 40% of the dose.SPECIAL POPULATIONS GENDER Apparent clearance and Amax derived from anti-Factor Xa values following single SC dosing (40 mg and 60 mg) were slightly higher in males than in females.Source of the gender difference in these parameters has not been conclusively identified, however, body weight may be a contributing factor.GERIATRIC Apparent clearance and Amax derived from anti-Factor Xa values following single and multiple SC dosing in elderly subjects were close to those observed in young subjects.Once a day SC dosing of 40 mg enoxaparin, the Day 10 mean area under anti-Factor Xa activity versus time curve (AUC) was approximately 15% greater than the mean Day 1 AUC value..Read more [cardiopulmonary support and physiology] atorvastatin impairs the myocardial angiogenic response to chronic ischemia in normocholesterolemic swine
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