The Study – Bioequivalence was determined through randomized, two-period, crossover single dose of Taro’s Etodolac Extended-Release Tablets 400 mg, 500 mg, and 600 mg and Lodine® XL 400 mg, 500 mg, and 600 mg, and multiple dose of Taro’s Etodolac Extended-Release Tablets 600 mg and Lodine® XL 600 mg.

Methods and Materials – Subjects (see sample sizes in corresponding tables) completed crossover studies after administration of single oral 1 x 400 mg, 1 x 500 mg, 1 x 600 mg Tablet doses and multiple dose 1 x 600 mg tablet for 7 days. Serial blood samples were collected pre-doses and at various intervals over 48 hours.

Conclusions – Taro’s Etodolac-Extended Release Tablets 400 mg, 500 mg, 600 mg are bioequivalent to Wyeth’s Lodine® XL 400 mg, 500 mg, and 600 mg.

CONTRAINDICATIONS
Etodolac extended-release tablets are contraindicated in patients with known hypersensitivity to etodolac. Etodolac extended-release tablets should not be given to patients who have experienced asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactic-like reactions to NSAIDs have been reported in such patients (see WARNINGS - ANAPHYLACTOID REACTIONS, and PRECAUTIONS - Preexisting Asthma). Please see full prescribing information for additional CONTRAINDICATIONS information.

WARNINGS
Gastrointestinal (GI) Effects - Risk of GI Ulceration, Bleeding, and Perforation:
Serious gastrointestinal toxicity, such as inflammation, bleeding, ulceration, and perforation of the stomach, small intestine or large intestine, can occur at any time, with or without warning symptoms, in patients treated with nonsteroidal anti-inflammatory drugs (NSAIDs). Minor upper gastrointestinal problems, such as dyspepsia, are common and may also occur at any time during NSAID therapy. Therefore, physicians and patients should remain alert for ulceration and bleeding, even in the absence of previous GI-tract symptoms. Patients should be informed about the signsand/or symptoms of serious GI toxicity and the steps to take if they occur. Please see full prescribing information for additional WARNINGS information.

ANAPHYLACTOID REACTIONS
As with other NSAIDs, anaphylactoid reactions may occur in patients without known prior exposure to etodolac extended-release tablets. Etodolac extended-release tablets should not be given to patients with the aspirin triad. This symptom complex typically occurs in asthmatic patients who experience rhinitis with or without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs (see CONTRAINDICATIONS and PRECAUTIONS - Pre-existing Asthma). Emergency help should be sought in cases where an anaphylactoid reaction occurs.

PRECAUTIONS
GENERAL
Etodolac extended-release tablets cannot be expected to substitute for corticosteroids or to treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to disease exacerbation. Patients on prolonged corticosteroid therapy should have their therapy tapered slowly if a decision is made to discontinue corticosteroids. Please see full prescribing information for additional PRECAUTIONS information.

Pre-existing Asthma
Patients with asthma may have aspirin-sensitive asthma. The use of aspirin in patients with aspirin-sensitive asthma has been associated with severe bronchospasm which can be fatal. Since cross reactivity, including bronchospasm, between aspirin and other nonsteroidal anti-inflammatory drugs has been reported in such aspirin-sensitive patients, etodolac extended-release tablets should not be administered to patients with
this form of aspirin sensitivity and should be used with caution in patients with pre-existing asthma.

ADVERSE REACTIONS
A total of 1552 patients were exposed to etodolac extended-release tablets in controlled clinical studies of at least 4 weeks in length and using daily doses in the range of 400 to 1200 mg. In the tabulations below, adverse event rates are generally categorized based on the incidence of events in the first 30 days of treatment with etodolac extended-release tablets. As with other NSAIDs, the cumulative adverse event rates may increase significantly over time with extended therapy.

In patients taking NSAIDs, including etodolac extended-release tablets, the most frequently reported adverse experiences occurring in approximately 1-10% of patients are:

Please see full prescribing information for additional ADVERSE REACTIONS information.