ETODOLAC- etodolac tablet, extended release
NORTHSTAR RX LLC
Cardiovascular Thrombotic Events
- Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use (see WARNINGS and PRECAUTIONS).
- Etodolac extended-release tablets, 400 mg, 500 mg and 600 mg are contraindicated in the setting of coronary artery bypass graft (CABG) surgery (see CONTRAINDICATIONS and WARNINGS).
- NSAIDs cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients are at greater risk for serious gastrointestinal events. (See WARNINGS).
Etodolac Extended-Release Tablets contain etodolac, which is a member of the pyranocarboxylic acid group of nonsteroidal anti-inflammatory drugs (NSAIDs). Each tablet contains etodolac for oral administration. Etodolac is a racemic mixture of [+]S and [-]R-enantiomers. It is a white crystalline compound, insoluble in water, but soluble in alcohols, chloroform, dimethyl sulfoxide, and aqueous polyethylene glycol.
The chemical name is (±) 1,8-diethyl-1,3,4,9-tetrahydropyrano-[3,4-b]indole-1-acetic acid. The molecular weight is 287.37. Its molecular formula is C17 H21 NO3 and it has the following structural formula:
The inactive ingredients in etodolac extended-release tablets include: HPMC 2910, hydroxypropyl methylcellulose, lactose anhydrous, magnesium stearate, microcrystalline cellulose, PEG 8000, polydextrose FCC, povidone, titanium dioxide and triacetin. In addition, the 500 mg and 600 mg tablets contain Indigo Carmine Lake and the 400 mg and 600 mg tablets contain Allura Red AC Lake and Sunset Yellow F.C.F. Lake. In addition, the 500 mg tablets contain yellow iron oxide. Meets USP Dissolution Test 4.
Etodolac extended-release tablets are a nonsteroidal anti-inflammatory drug (NSAID) that exhibits anti-inflammatory, analgesic, and antipyretic activities in animal models. The mechanism of action of etodolac extended-release tablets, like that of other NSAIDs, is not completely understood, but may be related to prostaglandin synthetase inhibition.
Etodolac extended-release tablets and etodolac tablets both contain etodolac, but differ in their release characteristics. The systemic availability of etodolac from etodolac extended-release tablets is generally greater than 80%. Etodolac does not undergo significant first-pass metabolism following oral administration. After oral administration of etodolac extended-release tablets in doses up to 800 mg once daily, peak concentrations occur approximately 6 hours after dosing and are dose proportional for both total and free etodolac.
Table 1 shows the comparison of etodolac pharmacokinetic parameters after the administration of etodolac tablets and etodolac extended-release tablets.
Table 2 shows the etodolac pharmacokinetic parameters in various populations. The data from patients with renal and hepatic impairment were obtained following administration of (immediate-release) etodolac tablets.
|Pharmacokinetic Parameters||Etodolac Tablets||Etodolac Extended-Release Tablets|
|Extent of Oral Absorption (Bioavailability) [F]||≥ 80%||≥ 80%|
|Time to Peak Concentration (Tmax ), h||1.4 (61%)||6.7 (47%)|
|Oral Clearance (CL/F), mL/h/kg||49.1 (33%)||46.8 (37%)|
|Apparent Volume of Distribution (Vd/F), mL/kg||393 (29%)||566 (26%)|
|Terminal Half-Life (t½), h||6.4 (22%)||8.4 (30%)|
|Etodolac Extended-Release Tablets||Etodolac Tablets|
|PK Parameters||Normal Healthy Adults||Healthy Males||Healthy Females||Elderly (> 65 yr)||Hemodialysis †(24 to 65) (n=9)||Renal Impairment †||Hepatic Impairment †|
|(18 to 44)‡(n=116)||(18 to 43) (n=102)||(25 to 44) (n=14)||(66 to 88) (n=24||Dialysis On||Dialysis Off||(46 to 73) (n=10)||(34 to 60) (n=9)|
|NA = not available|
|Tmax , h||6.7(47%)*||6.8(45%)||4.5(56%)||6.2(51%)||1.7(88%)||0.9(67%)||2.1(46%)||1.1(15%)|
|Oral Clearance, mL/h/kg (CL/F)||46.8(37%)||46.8(37%)||47.2(38%)||51.6(40%)||NA||NA||58.3(19%)||42.0(43%)|
|Apparent Volume of Distribution, mL/kg (Vd/F)||566(26%)||580(26%)||459(28%)||552(34%)||NA||NA||NA||NA|
|Terminal Half-Life, h||8.4(30%)||8.4(29%)||7.6(45%)||7.8(26%)||5.1(22%)||7.5(34%)||NA||5.7(24%)|
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