Label: ETODOLAC tablet, coated

  • NDC Code(s): 0185-0675-01, 0185-0675-05, 0185-0675-10, 0185-0687-01, view more
    0185-0687-05, 0185-0687-10
  • Packager: Eon Labs, Inc.
  • Category: HUMAN PRESCRIPTION DRUG LABEL
  • DEA Schedule: None
  • Marketing Status: Abbreviated New Drug Application

Drug Label Information

Updated March 12, 2021

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  • Rx Only

  • BOXED WARNING (What is this?)

    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 tablets are contraindicated in the setting of coronary artery bypass graft (CABG) surgery (see CONTRAINDICATIONS and WARNINGS).

    Gastrointestinal Risk

    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 (GI) events (see WARNINGS).
  • DESCRIPTION

    Etodolac tablets, USP are a member of the pyranocarboxylic acid group of nonsteroidal anti-inflammatory drugs (NSAIDs). Each tablet contains etodolac, USP for oral administration. Etodolac, USP is a racemic mixture of [+]S and [-]R-enantiomers. Etodolac, USP 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 of the base is 287.37. It has a pKa of 4.65 and an n-octanol:water partition coefficient of 11.4 at pH 7.4. The molecular formula for etodolac is C17H21NO3 and it has the following structural formula:

    Chemical-Structure

    Each tablet, for oral administration contains 400 mg and 500 mg of etodolac, USP. In addition, each tablet contains the following inactive ingredients: lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, povidone, sodium starch glycolate (potato), talc and titanium dioxide.

  • CLINICAL PHARMACOLOGY

    Pharmacodynamics

    Etodolac is a nonsteroidal anti-inflammatory drug (NSAID) that exhibits anti-inflammatory, analgesic, and antipyretic activities in animal models. The mechanism of action of etodolac, like that of other NSAIDs, is not completely understood, but may be related to the prostaglandin synthetase inhibition.

    Etodolac is a racemic mixture of [-]R- and [+]S-etodolac. As with other NSAIDs, it has been demonstrated in animals that the [+]S-form is biologically active. Both enantiomers are stable and there is no [-]R to [+]S conversion in vivo.

    Pharmacokinetics

    Absorption

    The systemic bioavailability of etodolac from etodolac tablets is 100% as compared to solution and at least 80% as determined from mass balance studies. Etodolac is well absorbed and had a relative bioavailability of 100% when 200 mg capsules were compared with a solution of etodolac. Based on mass balance studies, the systemic availability of etodolac from the tablet is at least 80%. Etodolac does not undergo significant first-pass metabolism following oral administration. Mean (± 1 SD) peak plasma concentrations (Cmax) range from approximately 14 ± 4 mcg/mL to 37 ± 9 mcg/mL after 200 mg to 600 mg single doses and are reached in 80 ± 30 minutes (see Table 1 for summary of pharmacokinetic parameters). The dose-proportionality based on the area under the plasma concentration-time curve (AUC) is linear following doses up to 600 mg every 12 hours. Peak concentrations are dose proportional for both total and free etodolac following doses up to 400 mg every 12 hours, but following a 600 mg dose, the peak is about 20% higher than predicted on the basis of lower doses. The extent of absorption of etodolac is not affected when etodolac is administered after a meal. Food intake, however, reduces the peak concentration reached by approximately one-half and increases the time to peak concentration by 1.4 to 3.8 hours.

    Table 1: Mean (CV%)* Pharmacokinetic Parameters of Etodolac in Normal Healthy Adults and Various Special Populations
    *
    %Coefficient of variation
    Age Range (years)

    PK

    Parameters

    Normal

    Healthy

    Adults

    (18-65)

    (n=179)

    Healthy

    Males (18-65)

    (n=176)

    Healthy

    Females

    (27-65)

    (n=3)

    Elderly

    (>65)

    (70-84)

    Hemodialysis

    (24-65)

    (n=9)

    Dialysis Dialysis

    On Off

    Renal Impairment

    (46-73)

    (n=10)

    Hepatic

    Impairment

    (34-60)

    (n=9)

    Tmax, h

    1.4

    (61%)*

    1.4

    (60%)

    1.7

    (60%)

    1.2

    (43%)

    1.7

    (88%)

    0.9

    (67%)

    2.1

    (46%)

    1.1

    (15%)

    Oral

    Clearance,

    mL/h/kg

    (CL/F)

    49.1

    (33%)

    49.4

    (33%)

    35.7

    (28%)

    45.7

    (27%)

    NA

    NA

    58.3

    (19%)

    42.0

    (43%)

    Apparent

    Volume of

    Distribution,

    mL/kg (Vd/F)

    393

    (29%)

    394

    (29%)

    300

    (8%)

    414

    (38%)

    NA

    NA

    NA

    NA

    Terminal

    Half-Life, h

    6.4

    (22%)

    6.4

    (22%)

    7.9

    (35%)

    6.5

    (24%)

    5.1

    (22%)

    7.5

    (34%)

    NA

    5.7

    (24%)

    NA = not available

    Distribution

    The mean apparent volume of distribution (Vd/F) of etodolac is approximately 390 mL/kg. Etodolac is more than 99% bound to plasma proteins, primarily to albumin. The free fraction is less than 1% and is independent of etodolac total concentration over the dose range studied. It is not known whether etodolac is excreted in human milk; however, based on its physical-chemical properties, excretion into breast milk is expected. Data from in vitro studies, using peak serum concentrations at reported therapeutic doses in humans, show that the etodolac free fraction is not significantly altered by acetaminophen, ibuprofen, indomethacin, naproxen, piroxicam, chlorpropamide, glipizide, glyburide, phenytoin, and probenecid.

    Metabolism

    Etodolac is extensively metabolized in the liver. The role, if any, of a specific cytochrome P450 system in the metabolism of etodolac is unknown. Several etodolac metabolites have been identified in human plasma and urine. Other metabolites remain to be identified. The metabolites include 6-, 7-, and 8-hydroxylated-etodolac and etodolac glucuronide. After a single dose of 14C-etodolac, hydroxylated metabolites accounted for less than 10% of total drug in serum. On chronic dosing, hydroxylated-etodolac metabolite does not accumulate in the plasma of patients with normal renal function. The extent of accumulation of hydroxylated-etodolac metabolites in patients with renal dysfunction has not been studied. The hydroxylated-etodolac metabolites undergo further glucuronidation followed by renal excretion and partial elimination in the feces.

    Excretion

    The mean oral clearance of etodolac following oral dosing is 49 (± 16) mL/h/kg. Approximately 1% of an etodolac dose is excreted unchanged in the urine with 72% of the dose excreted into urine as parent drug plus metabolite:

    - etodolac, unchanged

    1%

    - etodolac glucuronide

    13%

    - hydroxylated metabolites (6-, 7- and 8-OH)

    5%

    - hydroxylated metabolite glucuronides

    20%

    - unidentified metabolites

    33%

    Although renal elimination is a significant pathway of excretion for etodolac metabolites, no dosing adjustment in patients with mild to moderate renal dysfunction is generally necessary. The terminal half-life (t1/2) of etodolac is 6.4 hours (22% CV). In patients with severe renal dysfunction or undergoing hemodialysis, dosing adjustment is not generally necessary.

    Fecal excretion accounted for 16% of the dose.

    Special Populations

    Geriatric

    In etodolac clinical studies, no overall differences in safety or effectiveness were observed between these patients and younger patients. In pharmacokinetic studies, age was shown not to have any effect on etodolac half-life or protein binding, and there was no change in expected drug accumulation. Therefore, no dosage adjustment is generally necessary in the elderly on the basis of pharmacokinetics (see PRECAUTIONS, Geriatric Use).

    Etodolac is eliminated primarily by the kidney. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function (see WARNINGS, Renal Effects).

    Pediatric

    Safety and effectiveness in pediatric patients below the age of 18 years have not been established.

    Race

    Pharmacokinetic differences due to race have not been identified. Clinical studies included patients of many races, all of whom responded in a similar fashion.

    Hepatic Insufficiency

    Etodolac is predominantly metabolized by the liver. In patients with compensated hepatic cirrhosis, the disposition of total and free etodolac is not altered. Patients with acute and chronic hepatic diseases do not generally require reduced doses of etodolac compared to patients with normal hepatic function. However, etodolac clearance is dependent on liver function and could be reduced in patients with severe hepatic failure. Etodolac plasma protein binding did not change in patients with compensated hepatic cirrhosis given etodolac.

    Renal Insufficiency

    Etodolac pharmacokinetics have been investigated in subjects with renal insufficiency. Etodolac renal clearance was unchanged in the presence of mild-to-moderate renal failure (creatinine clearance 37 mL/min to 88 mL/min). Furthermore, there were no significant differences in the disposition of total and free etodolac in these patients. However, etodolac should be used with caution in such patients because, as with other NSAIDs, it may further decrease renal function in some patients. In patients undergoing hemodialysis, there was a 50% greater apparent clearance of total etodolac, due to a 50% greater unbound fraction. Free etodolac clearance was not altered, indicating the importance of protein binding in etodolac’s disposition. Etodolac is not significantly removed from the blood in patients undergoing hemodialysis.

  • CLINICAL TRIALS

    Analgesia

    Controlled clinical trials in analgesia were single-dose, randomized, double-blind, parallel studies in three pain models, including dental extractions. The analgesic effective dose for etodolac established in these acute pain models was 200 mg to 400 mg. The onset of analgesia occurred approximately 30 minutes after oral administration. Etodolac 200 mg provided efficacy comparable to that obtained with aspirin (650 mg). Etodolac 400 mg provided efficacy comparable to that obtained with acetaminophen with codeine (600 mg + 60 mg). The peak analgesic effect was between 1 to 2 hours. Duration of relief averaged 4 to 5 hours for 200 mg of etodolac and 5 to 6 hours for 400 mg of etodolac as measured by when approximately half of the patients required remedication.

    Osteoarthritis

    The use of etodolac in managing the signs and symptoms of osteoarthritis of the hip or knee was assessed in double-blind, randomized, controlled clinical trials in 341 patients. In patients with osteoarthritis of the knee, etodolac, in doses of 600 mg/day to 1000 mg/day, was better than placebo in two studies. The clinical trials in osteoarthritis used b.i.d. dosage regimens.

    Rheumatoid Arthritis

    In a 3-month study with 426 patients, etodolac 300 mg b.i.d. was effective in management of rheumatoid arthritis and comparable in efficacy to piroxicam 20 mg/day. In a long-term study with 1,446 patients in which 60% of patients completed 6 months of therapy and 20% completed 3 years of therapy, etodolac in a dose of 500 mg b.i.d. provided efficacy comparable to that obtained with ibuprofen 600 mg q.i.d. In clinical trials of rheumatoid arthritis patients, etodolac has been used in combination with gold, d-penicillamine, chloroquine, corticosteroids and methotrexate.

  • INDICATIONS AND USAGE

    Carefully consider the potential benefits and risks of etodolac tablets and other treatment options before deciding to use etodolac tablets. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS).

    Etodolac tablets are indicated:

    For acute and long-term use in the management of signs and symptoms of the following:
    1.
    Osteoarthritis
    2.
    Rheumatoid arthritis
    For the management of acute pain
  • CONTRAINDICATIONS

    Etodolac is contraindicated in patients with known hypersensitivity to etodolac or other ingredients in etodolac.

    Etodolac 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, Pre-existing Asthma).

    Etodolac is contraindicated in the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS).

  • WARNINGS

    Cardiovascular Effects

    Cardiovascular Thrombotic Events

    Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction (MI) and stroke, which can be fatal. Based on available data, it is unclear that the risk for CV thrombotic events is similar for all NSAIDs. The relative increase in serious CV thrombotic events over baseline conferred by NSAID use appears to be similar in those with and without known CV disease or risk factors for CV disease. However, patients with known CV disease or risk factors had a higher absolute incidence of excess serious CV thrombotic events, due to their increased baseline rate. Some observational studies found that this increased risk of serious CV thrombotic events began as early as the first weeks of treatment. The increase in CV thrombotic risk has been observed most consistently at higher doses.

    To minimize the potential risk for an adverse CV event in NSAID-treated patients, use the lowest effective dose for the shortest duration possible. Physicians and patients should remain alert for the development of such events, throughout the entire treatment course, even in the absence of previous CV symptoms. Patients should be informed about the symptoms of serious CV events and the steps to take if they occur.

    There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID, such as etodolac, increases the risk of serious gastrointestinal (GI) events (see WARNINGS).

    Status Post Coronary Artery Bypass Graft (CABG) Surgery

    Two large, controlled clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10 to 14 days following CABG surgery found an increased incidence of myocardial infarction and stroke. NSAIDs are contraindicated in the setting of CABG (see CONTRAINDICATIONS).

    Post-MI Patients

    Observational studies conducted in the Danish National Registry have demonstrated that patients treated with NSAIDs in the post-MI period were at increased risk of reinfarction, CV-related death, and all-cause mortality beginning in the first week of treatment. In this same cohort, the incidence of death in the first year post MI was 20 per 100 person years in NSAID-treated patients compared to 12 per 100 person years in non-NSAID exposed patients. Although the absolute rate of death declined somewhat after the first year post-MI, the increased relative risk of death in NSAID users persisted over at least the next four years of follow-up.

    Avoid the use of etodolac tablets in patients with a recent MI unless the benefits are expected to outweigh the risk of recurrent CV thrombotic events. If etodolac tablets are used in patients with a recent MI, monitor patients for signs of cardiac ischemia.

    Hypertension

    NSAIDs, including etodolac, can lead to onset of new hypertension or worsening of pre-existing hypertension, either of which may contribute to the increased incidence of CV events. Patients taking thiazides or loop diuretics may have impaired response to these therapies when taking NSAIDs. NSAIDs, including etodolac, should be used with caution in patients with hypertension. Blood pressure (BP) should be monitored closely during the initiation of NSAID treatment and throughout the course of therapy.

    Heart Failure and Edema

    The Coxib and traditional NSAID Trialists’ Collaboration meta-analysis of randomized controlled trials demonstrated an approximately two-fold increase in hospitalizations for heart failure in COX-2 selective-treated patients and nonselective NSAID-treated patients compared to placebo-treated patients. In a Danish National Registry study of patients with heart failure, NSAID use increased the risk of MI, hospitalization for heart failure, and death.

    Additionally, fluid retention and edema have been observed in some patients treated with NSAIDs. Use of etodolac may blunt the CV effects of several therapeutic agents used to treat these medical conditions [e.g., diuretics, ACE inhibitors, or angiotensin receptor blockers (ARBs)] (see Drug Interactions).

    Avoid the use of etodolac tablets in patients with severe heart failure unless the benefits are expected to outweigh the risk of worsening heart failure. If etodolac tablets are used in patients with severe heart failure, monitor patients for signs of worsening heart failure.

    Gastrointestinal Effects - Risk of Ulceration, Bleeding, and Perforation

    NSAIDs, including etodolac, can cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of the stomach, small intestine or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Only one in five patients, who develop a serious upper GI adverse event on NSAID therapy, is symptomatic. Upper GI ulcers, gross bleeding, or perforation caused by NSAIDs occur in approximately 1% of patients treated for 3 to 6 months, and in about 2% to 4% of patients treated for one year. These trends continue with longer duration of use, increasing the likelihood of developing a serious GI event at some time during the course of therapy. However, even short-term therapy is not without risk. Physicians should inform patients about the signs and/or symptoms of serious GI toxicity and what steps to take if they occur.

    NSAIDs should be prescribed with extreme caution in those with a prior history of ulcer disease, or gastrointestinal bleeding. Patients with a prior history of peptic ulcer disease and/or gastrointestinal bleeding and who use NSAIDs have a greater than 10-fold increased risk for developing a GI bleed compared to patients with neither of these risk factors. Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include concomitant use of oral corticosteroids or anticoagulants, longer duration of NSAID therapy, smoking, use of alcohol, older age, and poor general health status. Most spontaneous reports of fatal GI events are in elderly or debilitated patients and therefore, special care should be taken in treating this population.

    To minimize the potential risk for an adverse GI event in patients treated with an NSAID, the lowest effective dose should be used for the shortest possible duration. Patients and physicians should remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy and promptly initiate additional evaluation and treatment if a serious GI adverse event is suspected. This should include discontinuation of the NSAID until a serious GI adverse event is ruled out. For high risk patients, alternate therapies that do not involve NSAIDs should be considered.

    Renal Effects

    Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of a nonsteroidal anti-inflammatory drug may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greater risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state.

    Renal pelvic transitional epithelial hyperplasia, a spontaneous change occurring with variable frequency, was observed with increased frequency in treated male rats in a 2-year chronic study.

    Caution is recommended in patients with pre-existing kidney disease.

    Advanced Renal Disease

    No information is available from controlled clinical studies regarding the use of etodolac in patients with advanced renal disease. Therefore, treatment with etodolac is not recommended in these patients with advanced renal disease. If etodolac therapy must be initiated, close monitoring of the patient’s renal function is advisable.

    Anaphylactoid Reactions

    As with other NSAIDs, anaphylactoid reactions may occur in patients without prior exposure to etodolac. Etodolac 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. Fatal reactions have been reported in such patients (see CONTRAINDICATIONS and PRECAUTIONS, General, Pre-existing Asthma). Emergency help should be sought in cases where an anaphylactoid reaction occurs.

    Skin Reactions

    NSAIDs, including etodolac, can cause serious skin adverse events such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. These serious events may occur without warning. Patients should be informed about the signs and symptoms of serious skin manifestations and use of the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity.

    Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)

    Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported in patients taking NSAIDs such as etodolac. Some of these events have been fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling. Other clinical manifestations may include hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis. Sometimes symptoms of DRESS may resemble an acute viral infection. Eosinophilia is often present. Because this disorder is variable in its presentation, other organ systems not noted here may be involved. It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. If such signs or symptoms are present, discontinue etodolac and evaluate the patient immediately.

    Pregnancy

    Fetal Toxicity

    Premature Closure of Fetal Ductus Arteriosus

    Avoid use of NSAIDs, including etodolac, in pregnant women at about 30 weeks gestation and later. NSAIDs including etodolac, increase the risk of premature closure of the fetal ductus arteriosus at approximately this gestational age.

    Oligohydramnios/Neonatal Renal Impairment

    Use of NSAIDs, including etodolac, at about 20 weeks gestation or later in pregnancy may cause fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. These adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after NSAID initiation.

    Oligohydramnios is often, but not always, reversible with treatment discontinuation. Complications of prolonged oligohydramnios may, for example, include limb contractures and delayed lung maturation. In some postmarketing cases of impaired neonatal renal function, invasive procedures such as exchange transfusion or dialysis were required.

    If NSAID treatment is necessary between about 20 weeks and 30 weeks gestation, limit etodolac use to the lowest effective dose and shortest duration possible. Consider ultrasound monitoring of amniotic fluid if etodolac treatment extends beyond 48 hours. Discontinue etodolac if oligohydramnios occurs and follow up according to clinical practice (see PRECAUTIONS, Pregnancy).

  • PRECAUTIONS

    General

    Etodolac 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 solely if a decision is made to discontinue corticosteroids.

    The pharmacological activity of etodolac in reducing fever and inflammation may diminish the utility of these diagnostic signs in detecting complications of presumed noninfectious, painful conditions.

    Hepatic Effects

    Borderline elevations of one or more liver tests may occur in up to 15% of patients taking NSAIDs including etodolac. These laboratory abnormalities may progress, may remain unchanged, or may be transient with continuing therapy. Notable elevations of ALT or AST (approximately three or more times the upper limit of normal) have been reported in approximately 1% of patients in clinical trials with NSAIDs. In addition, rare cases of severe hepatic reactions, including jaundice and fatal fulminant hepatitis, liver necrosis and hepatic failure, some of them with fatal outcomes, have been reported.

    A patient with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal liver test has occurred, should be evaluated for evidence of the development of a more severe hepatic reaction while on therapy with etodolac. If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), etodolac should be discontinued.

    Hematological Effects

    Anemia is sometimes seen in patients receiving NSAIDs including etodolac. This may be due to fluid retention, occult or gross GI blood loss, or an incompletely described effect upon erythropoiesis. Patients on long-term treatment with NSAIDs, including etodolac, should have their hemoglobin or hematocrit checked if they exhibit any signs or symptoms of anemia.

    NSAIDs inhibit platelet aggregation and have been shown to prolong bleeding time in some patients. Unlike aspirin, their effect on platelet function is quantitatively less, of shorter duration, and reversible. Patients receiving etodolac who may be adversely affected by alterations in platelet function, such as those with coagulation disorders or patients receiving anticoagulants, should be carefully monitored.

    Pre-existing Asthma

    Patients with asthma may have aspirin-sensitive asthma. The use of aspirin in patients with aspirin-sensitive asthmas 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 should not be administered to patients with this form of aspirin sensitivity and should be used with caution in all patients with pre-existing asthma.

    Information for Patients

    Patients should be informed of the following information before initiating therapy with an NSAID and periodically during the course of ongoing therapy. Patients should also be encouraged to read the NSAID Medication Guide that accompanies each prescription dispensed.

    1.
    Cardiovascular Thrombotic Events: Advise patients to be alert for the symptoms of cardiovascular thrombotic events, including chest pain, shortness of breath, weakness, or slurring of speech, and to report any of these symptoms to their health care provider immediately (see WARNINGS).
    2.
    Etodolac, like other NSAIDs, can cause GI discomfort and, rarely, serious GI side effects, such as ulcers and bleeding, which may result in hospitalization and even death. Although serious GI tract ulcerations and bleeding can occur without warning symptoms, patients should be alert for the signs and symptoms of ulcerations and bleeding, and should ask for medical advice when observing any indicative sign or symptoms including epigastric pain, dyspepsia, melena, and hematemesis. Patients should be apprised of the importance of this follow-up (see WARNINGS, Gastrointestinal Effects - Risk of Ulceration, Bleeding, and Perforation).
    3.
    Serious Skin Reactions, including DRESS: Advise patients to stop taking etodolac immediately if they develop any type of rash or fever and to contact their healthcare provider as soon as possible (see WARNINGS).
    4.
    Heart Failure And Edema: Advise patients to be alert for the symptoms of congestive heart failure including shortness of breath, unexplained weight gain, or edema and to contact their healthcare provider if such symptoms occur (see WARNINGS).
    5.
    Patients should be informed of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, pruritus, jaundice, right upper quadrant tenderness, and “flu-like” symptoms). If these occur, patients should be instructed to stop therapy and seek immediate medical therapy.
    6.
    Patients should be informed of the signs of an anaphylactoid reaction (e.g., difficulty breathing, swelling of the face or throat). If these occur, patients should be instructed to seek immediate emergency help (see WARNINGS).
    7.
    Fetal Toxicity: Inform pregnant women to avoid use of etodolac and other NSAIDs starting at 30 weeks gestation because of the risk of the premature closing of the fetal ductus arteriosus. If treatment with etodolac is needed for a pregnant woman between about 20 to 30 weeks gestation, advise her that she may need to be monitored for oligohydramnios, if treatment continues for longer than 48 hours (see WARNINGS, Fetal Toxicity; PRECAUTIONS, Pregnancy).

    Laboratory Tests

    Because serious GI tract ulcerations and bleeding can occur without warning symptoms, physicians should monitor for signs or symptoms of GI bleeding. Patients on long-term treatment with NSAIDs should have their CBC and a chemistry profile checked periodically for signs or symptoms of anemia. Appropriate measures should be taken in case such signs of anemia occur. If clinical signs and symptoms consistent with liver or renal disease develop, systemic manifestations occur (e.g., eosinophilia, rash, etc.) or if abnormal liver tests persist or worsen, etodolac should be discontinued.

    Drug Interactions

    ACE-Inhibitors

    Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE-inhibitors. This interaction should be given consideration in patients taking NSAIDs concomitantly with ACE-inhibitors (see WARNINGS).

    Antacids

    The concomitant administration of antacids has no apparent effect on the extent of absorption of etodolac. However, antacids can decrease the peak concentration reached by 15% to 20% but have no detectable effect on the time-to-peak.

    Aspirin

    When etodolac is administered with aspirin, its protein binding is reduced, although the clearance of free etodolac is not altered. The clinical significance of this interaction is not known; however, as with other NSAIDs, concomitant administration of etodolac and aspirin is not generally recommended because of the potential of increased adverse effects.

    Cyclosporine, Digoxin, Methotrexate

    Etodolac, like other NSAIDs, through effects on renal prostaglandins, may cause changes in the elimination of these drugs leading to elevated serum levels of cyclosporine, digoxin, methotrexate, and increased toxicity. Nephrotoxicity associated with cyclosporine may also be enhanced. Patients receiving these drugs who are given etodolac, or any other NSAID, and particularly those patients with altered renal function, should be observed for the development of the specific toxicities of these drugs. NSAIDs, such as etodolac, should not be administered prior to or concomitantly with high doses of methotrexate. NSAIDs have been reported to competitively inhibit methotrexate accumulation in rabbit kidney slices. This may indicate that they could enhance the toxicity of methotrexate. In general, caution should be used when NSAIDs are administered concomitantly with methotrexate.

    Diuretics

    Etodolac has no apparent pharmacokinetic interaction when administered with furosemide or hydrochlorothiazide. Nevertheless, clinical studies, as well as post-marketing observations have shown that etodolac can reduce the natriuretic effect of furosemide and thiazides in some patients with possible loss of blood pressure control. This response has been attributed to inhibition of renal prostaglandin synthesis. During concomitant therapy with NSAIDs, the patient should be observed closely for signs of renal insufficiency or failure (see WARNINGS, Renal Effects), as well as to assure diuretic efficacy.

    Glyburide

    Etodolac has no apparent pharmacokinetic interaction when administered with glyburide.

    Lithium

    NSAIDs have produced an elevation of plasma lithium levels and a reduction in renal lithium clearance. The mean minimum lithium concentration increased 15% and the renal clearance was decreased by approximately 20%. These effects have been attributed to inhibition of renal prostaglandin synthesis by the NSAID. Thus, when NSAIDs and lithium are administered concurrently, subjects should be observed carefully for signs of lithium toxicity. Careful monitoring of lithium levels is advised in the event NSAID dosage adjustments are required.

    Phenylbutazone

    Phenylbutazone causes increase (by about 80%) in the free fraction of etodolac. Although in vivo studies have not been done to see if etodolac clearance is changed by co-administration of phenylbutazone, it is not recommended that they be co-administered.

    Phenytoin

    Etodolac has no apparent pharmacokinetic interaction when administered with phenytoin.

    Warfarin

    The effects of warfarin and NSAIDs on GI bleeding are synergistic, such that users of both drugs together have a risk of serious GI bleeding higher than that of users of either drug alone. Short-term pharmacokinetic studies have demonstrated that concomitant administration of warfarin and etodolac results in reduced protein binding of warfarin, but there was no change in the clearance of free warfarin. There was no significant difference in the pharmacodynamic effect of warfarin administered alone and warfarin administered with etodolac as measured by prothrombin time. Thus, concomitant therapy with warfarin and etodolac should not require dosage adjustment of either drug. However, caution should be exercised because there have been a few spontaneous reports of prolonged prothrombin times, with or without bleeding, in etodolac-treated patients receiving concomitant warfarin therapy. Close monitoring of such patients is therefore recommended.

    Drug/Laboratory Test Interactions

    The urine of patients who take etodolac can give a false-positive reaction for urinary bilirubin (urobilin) due to the presence of phenolic metabolites of etodolac. Diagnostic dip-stick methodology, used to detect ketone bodies in urine, has resulted in false-positive findings in some patients treated with etodolac. Generally, this phenomenon has not been associated with other clinically significant events. No dose relationship has been observed.

    Etodolac treatment is associated with a small decrease in serum uric acid levels. In clinical trials, mean decreases of 1 mg/dL to 2 mg/dL were observed in arthritic patients receiving etodolac (600 mg/day to 1000 mg/day) after 4 weeks of therapy. These levels then remained stable for up to 1 year of therapy.

    Carcinogenesis, Mutagenesis, and Impairment of Fertility

    No carcinogenic effect of etodolac was observed in mice or rats receiving oral doses of 15 mg/kg/day (45 mg/m2 to 89 mg/m2, respectively) or less for periods of 2 years or 18 months, respectively. Etodolac was not mutagenic in in vitro tests performed with S. typhimurium and mouse lymphoma cells as well as in an in vivo mouse micronucleus test. However, data from the in vitro human peripheral lymphocyte test showed an increase in the number of gaps (3% to 5.3% unstained regions in the chromatid without dislocation) among the etodolac-treated cultures (50 mcg/mL to 200 mcg/mL) compared to negative controls (2%); no other difference was noted between the controls and drug-treated groups. Etodolac showed no impairment of fertility in male and female rats up to oral doses of 16 mg/kg (94 mg/m2). However, reduced implantation of fertilized eggs occurred in the 8 mg/kg group.

    Pregnancy

    Risk Summary

    Use of NSAIDs, including etodolac, can cause premature closure of the fetal ductus arteriosus and fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. Because of these risks, limit dose and duration of etodolac use between about 20 and 30 weeks of gestation, and avoid etodolac use at about 30 weeks of gestation and later in pregnancy (see WARNINGS, Fetal Toxicity).

    The estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

    Premature Closure of Fetal Ductus Arteriosus

    Use of NSAIDs, including etodolac, at about 30 weeks gestation or later in pregnancy increases the risk of premature closure of the fetal ductus arteriosus.

    Oligohydramnios/Neonatal Renal Impairment

    Use of NSAIDs at about 20 weeks gestation or later in pregnancy has been associated with cases of fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment.

    Data from observational studies regarding other potential embryofetal risks of NSAID use in women in the first or second trimesters of pregnancy are inconclusive. Animal reproduction studies are not always predictive of human response. There are no adequate and well-controlled studies in pregnant women. Etodolac should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus. Based on animal data, prostaglandins have been shown to have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization. In animal studies, administration of prostaglandin synthesis inhibitors such as etodolac, resulted in increased pre- and post-implantation loss. Prostaglandins also have been shown to have an important role in fetal kidney development. In published animal studies, prostaglandin synthesis inhibitors have been reported to impair kidney development when administered at clinically relevant doses.

    Clinical Considerations

    Fetal/Neonatal Adverse Reactions

    Premature Closure of Fetal Ductus Arteriosus

    Avoid use of NSAIDs in women at about 30 weeks gestation and later in pregnancy, because NSAIDs, including etodolac, can cause premature closure of the fetal ductus arteriosus (see WARNINGS, Fetal Toxicity).

    Oligohydramnios/Neonatal Renal Impairment

    If an NSAID is necessary at about 20 weeks gestation or later in pregnancy, limit the use to the lowest effective dose and shortest duration possible. If etodolac treatment extends beyond 48 hours, consider monitoring with ultrasound for oligohydramnios. If oligohydramnios occurs, discontinue etodolac and follow up according to clinical practice (see WARNINGS, Fetal Toxicity).

    Data

    Human Data

    Premature Closure of Fetal Ductus Arteriosus

    Published literature reports that the use of NSAIDs at about 30 weeks of gestation and later in pregnancy may cause premature closure of the fetal ductus arteriosus.

    Oligohydramnios/Neonatal Renal Impairment

    Published studies and postmarketing reports describe maternal NSAID use at about 20 weeks gestation or later in pregnancy associated with fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. These adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after NSAID initiation. In many cases, but not all, the decrease in amniotic fluid was transient and reversible with cessation of the drug. There have been a limited number ofcase reports of maternal NSAID use and neonatal renal dysfunction without oligohydramnios, some of which were irreversible. Some cases of neonatal renal dysfunction required treatment with invasive procedures, such as exchange transfusion or dialysis.

    Methodological limitations of these postmarketing studies and reports include lack of a control group; limited information regarding dose, duration, and timing of drug exposure; and concomitant use of other medications. These limitations preclude establishing a reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal NSAID use. Because the published safety data on neonatal outcomes involved mostly preterm infants, the generalizability of certain reported risks to the full-term infant exposed to NSAIDs through maternal use is uncertain.

    Labor and Delivery

    In rat studies with NSAIDs, as with other drugs known to inhibit prostaglandin synthesis, an increased incidence of dystocia, delayed parturition, and decreased pup survival occurred. The effects of etodolac on labor and delivery in pregnant women are unknown.

    Nursing Mothers

    Trace amounts of some NSAIDs have been reported in human milk. It is not known whether etodolac is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from etodolac, a decision should be made whether to discontinue nursing or to discontinue the drug taking into account the importance of the drug to the mother.

    Pediatric Use

    Safety and effectiveness in pediatric patients below the age of 18 years have not been established.

    Geriatric Use

    As with any NSAID, caution should be exercised in treating the elderly (65 years and older) and when increasing the dose (see WARNINGS).

    In etodolac clinical studies, no overall differences in safety or effectiveness were observed between these patients and younger patients. In pharmacokinetic studies, age was shown not to have any effect on etodolac half-life or protein binding, and there was no change in expected drug accumulation. Therefore, no dosage adjustment is generally necessary in the elderly on the basis of pharmacokinetics (see CLINICAL PHARMACOLOGY, Special Populations).

    Elderly patients may be more sensitive to the antiprostaglandin effects of NSAIDs (on the gastrointestinal tract and kidneys) than younger patients (see WARNINGS). In particular, elderly or debilitated patients who receive NSAID therapy seem to tolerate gastrointestinal ulceration or bleeding less well than other individuals, and most spontaneous reports of fatal GI events are in this population.

    Etodolac is eliminated primarily by the kidney. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function (see WARNINGS, Renal Effects).

  • ADVERSE REACTIONS

    In patients taking etodolac or other NSAIDs, the most frequently reported adverse experiences occurring in approximately 1% to 10% of patients are:

    Gastrointestinal experiences including

    Abdominal pain, constipation, diarrhea, dyspepsia, flatulence, gross bleeding/perforation, heartburn, nausea, GI ulcers (gastric/duodenal), vomiting.

    Other events including

    Abnormal renal function, anemia, dizziness, edema, elevated liver enzymes, headaches, increased bleeding time, pruritis, rashes, tinnitus.

    Adverse reaction information for etodolac was derived from 2,629 arthritic patients treated with etodolac in double-blind and open-label clinical trials of 4 to 320 weeks in duration and worldwide post-marketing surveillance studies. In clinical trials, most adverse reactions were mild and transient. The discontinuation rate in controlled clinical trials, because of adverse events, was up to 10% for patients treated with etodolac.

    New patient complaints (with an incidence greater than or equal to 1%) are listed below by body system. The incidences were determined from clinical trials involving 465 patients with osteoarthritis treated with 300 mg to 500 mg of etodolac b.i.d. (i.e., 600 mg/day to 1000 mg/day).

    Incidence Greater Than Or Equal To 1% - Probably Causally Related

    Body as a Whole

    Chills and fever.

    Digestive System

    Dyspepsia (10%), abdominal pain1, diarrhea2, flatulence3, nausea4, abdominal distension, epigastric pain, abnormal stools, constipation, gastritis, melena, vomiting.

    Nervous System

    Asthenia/malaise5, dizziness6, depression, nervousness, fatigue.

    Skin and Appendages

    Pruritus, rash.

    Special Senses

    Blurred vision, tinnitus.

    Urogenital System

    Dysuria, urinary frequency.

    Musculoskeletal

    Arthralgia

    1Drug-related patient complaints occurring in 3 to 9% of patients treated with etodolac.

    2Drug-related patient complaints occurring in 3 to 9% of patients treated with etodolac.

    3Drug-related patient complaints occurring in 3 to 9% of patients treated with etodolac.

    4Drug-related patient complaints occurring in 3 to 9% of patients treated with etodolac.

    5Drug-related patient complaints occurring in 3 to 9% of patients treated with etodolac.

    6Drug-related patient complaints occurring in 3 to 9% of patients treated with etodolac.

    Drug-related patient complaints occurring in fewer than 3%, but more than 1%, are unmarked.

    Incidence Less Than 1% - Probably Causally Related

    (Adverse reactions reported only in worldwide post-marketing experience, not seen in clinical trials, are considered rarer and are italicized.)

    Body as a Whole

    Allergic reaction, anaphylactic/anaphylactoid reactions (including shock).

    Cardiovascular System

    Hypertension, congestive heart failure, flushing, palpitations, syncope, vasculitis (including necrotizing and allergic).

    Digestive System

    Thirst, dry mouth, ulcerative stomatitis, anorexia, eructation, elevated liver enzymes, cholestatic hepatitis, hepatitis, cholestatic jaundice, duodenitis, jaundice, hepatic failure, liver necrosis, peptic ulcer with or without bleeding and/or perforation, intestinal ulceration, pancreatitis.

    Hemic and Lymphatic System

    Ecchymosis, anemia, thrombocytopenia, bleeding time increased, agranulocytosis, hemolytic anemia, aplastic anemia, leukopenia, neutropenia, pancytopenia.

    Metabolic and Nutritional

    Edema, serum creatinine increase, hyperglycemia in previously controlled diabetic patients.

    Nervous System

    Insomnia, somnolence.

    Respiratory System

    Asthma, pulmonary infiltration with eosinophilia.

    Skin and Appendages

    Angioedema, sweating, urticaria, exfoliative dermatitis, vesiculobullous rash, cutaneous vasculitis with purpura, Stevens-Johnson Syndrome, toxic epidermal necrolysis, leukocytoclastic vasculitis, hyperpigmentation, erythema multiforme.

    Special Senses

    Photophobia, transient visual disturbances.

    Urogenital System

    Elevated BUN, renal failure, renal insufficiency, renal papillary necrosis.

    Incidence Less Than 1% - Causal Relationship Unknown

    (Medical events occurring under circumstances where causal relationship to etodolac is uncertain. These reactions are listed as alerting information for physicians.)

    Body as a Whole

    Infection, headache.

    Cardiovascular System

    Arrhythmias, myocardial infarction, cerebrovascular accident.

    Digestive System

    Esophagitis with or without stricture or cardiospasm, colitis, GI discomfort, burning sensation, blood in stools, gastralgia, upper abdominal discomfort.

    Metabolic and Nutritional

    Change in weight.

    Nervous System

    Paresthesia, confusion, irritability.

    Respiratory System

    Bronchitis, bronchospasm, dyspnea, pharyngitis, rhinitis, sinusitis.

    Skin and Appendages

    Alopecia, maculopapular rash, photosensitivity, skin peeling.

    Special Senses

    Conjunctivitis, deafness, taste perversion, loss of taste.

    Urogenital System

    Cystitis, hematuria, leukorrhea, renal calculus, interstitial nephritis, uterine bleeding irregularities, renal impairment.

    Musculoskeletal

    Muscle pain.

    Additional Adverse Reactions Reported with NSAIDs

    Body as a Whole

    Sepsis, death

    Cardiovascular System

    Tachycardia

    Digestive System

    Gastric ulcers, gastritis, gastrointestinal bleeding, glossitis, hematemesis

    Hemic and Lymphatic System

    Lymphadenopathy

    Nervous System

    Anxiety, dream abnormalities, convulsions, coma, hallucinations, meningitis, tremors, vertigo

    Respiratory System

    Respiratory depression, pneumonia

    Urogenital System

    Oliguria/polyuria, proteinuria

  • OVERDOSAGE

    Symptoms following acute NSAID overdose are usually limited to lethargy, drowsiness, nausea, vomiting, and epigastric pain, which are generally reversible with supportive care. Gastrointestinal bleeding can occur and coma has occurred following massive ibuprofen or mefenamic-acid overdose. Hypertension, acute renal failure, and respiratory depression may occur but are rare. Anaphylactoid reactions have been reported with therapeutic ingestion of NSAIDs, and may occur following overdose.

    Patients should be managed by symptomatic and supportive care following an NSAID overdose. There are no specific antidotes. Emesis and/or activated charcoal (60 g to 100 g in adults, 1 g/kg to 2 g/kg in children) and/or osmotic cathartic may be indicated in patients seen within 4 hours of ingestion with symptoms or following a large overdose (5 to 10 times the usual dose). Forced diuresis, alkalinization of the urine, hemodialysis, or hemoperfusion would probably not be useful due to etodolac’s high protein binding.

  • DOSAGE AND ADMINISTRATION

    Carefully consider the potential benefits and risks of etodolac tablets and other treatment options before deciding to use etodolac tablets. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS).

    After observing the response to initial therapy with etodolac tablets, the dose and frequency should be adjusted to suit an individual patient’s needs.

    Dosage adjustment of etodolac tablets is generally not required in patients with mild to moderate renal impairment. Etodolac should be used with caution in such patients, because, as with other NSAIDs, it may further decrease renal function in some patients with impaired renal function (see WARNINGS, Renal Effects).

    Analgesia

    The recommended total daily dose of etodolac tablets for acute pain is up to 1000 mg, given as 200 mg to 400 mg every 6 to 8 hours. Doses of etodolac tablets greater than 1000 mg/day have not been adequately evaluated in well-controlled trials.

    Osteoarthritis and Rheumatoid Arthritis

    The recommended starting dose of etodolac for the management of the signs and symptoms of osteoarthritis or rheumatoid arthritis is: 300 mg b.i.d., t.i.d., or 400 mg b.i.d., or 500 mg b.i.d. A lower dose of 600 mg/day may suffice for long-term administration. Physicians should be aware that doses above 1000 mg/day have not been adequately evaluated in well-controlled clinical trials.

    In chronic conditions, a therapeutic response to therapy with etodolac tablets is sometimes seen within one week of therapy, but most often is observed by two weeks. After a satisfactory response has been achieved, the patient’s dose should be reviewed and adjusted as required.

  • HOW SUPPLIED

    Etodolac Tablets USP, for oral administration, are available as:

    400 mg: White, oval, unscored, film-coated tablets, debossed “E 140” on one side and plain on the other side and supplied as:

    NDC 0185-0675-01 bottles of 100

    NDC 0185-0675-05 bottles of 500

    NDC 0185-0675-10 bottles of 1000

    500 mg: White, oval, unscored, film-coated tablets, debossed “E 139” on one side and plain on the other side and supplied as:

    NDC 0185-0687-01 bottles of 100

    NDC 0185-0687-05 bottles of 500

    NDC 0185-0687-10 bottles of 1000

    Store at 20º to 25ºC (68º to 77ºF) [see USP Controlled Room Temperature].

    Store tablets in original container until ready to use.

    KEEP TIGHTLY CLOSED.

    Dispense contents in a tight, light-resistant container as defined in the USP with a child-resistant closure, as required.

    KEEP OUT OF THE REACH OF CHILDREN.

  • Medication Guide

    FOR NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS)

    ETODOLAC TABLETS, USP

    (ee-toe-DOE-lak)

    What is the most important information I should know about medicines called Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?

    NSAIDs can cause serious side effects, including:

    Increased risk of a heart attack or stroke that can lead to death. This risk may happen early in treatment and may increase:
    o
    with increasing doses of NSAIDs
    o
    with longer use of NSAIDs

    Do not take NSAIDs right before or after a heart surgery called a “coronary artery bypass graft (CABG).”

    Avoid taking NSAIDs after a recent heart attack, unless your healthcare provider tells you to. You may have an increased risk of another heart attack if you take NSAIDs after a recent heart attack.

    Increased risk of bleeding, ulcers, and tears (perforation) of the esophagus (tube leading from the mouth to the stomach), stomach and intestines:
    o
    anytime during use
    o
    without warning symptoms
    o
    that may cause death

    The risk of getting an ulcer or bleeding increases with:

    o
    past history of stomach ulcers, or stomach or intestinal bleeding with use of NSAIDs
    o
    taking medicines called “corticosteroids”, “anticoagulants”, “SSRIs”, or “SNRIs”
    o
    increasing doses of NSAIDs
    o
    older age
    o
    longer use of NSAIDs
    o
    poor health
    o
    smoking
    o
    advanced liver disease
    o
    drinking alcohol
    o
    bleeding problems

    NSAIDs should only be used:

    o
    exactly as prescribed
    o
    at the lowest dose possible for your treatment
    o
    for the shortest time needed

    What are NSAIDs?

    NSAIDs are used to treat pain and redness, swelling, and heat (inflammation) from medical conditions such as different types of arthritis, menstrual cramps, and other types of short-term pain.

    Who should not take NSAIDs?

    Do not take NSAIDs:

    if you have had an asthma attack, hives, or other allergic reaction with aspirin or any other NSAIDs.
    right before or after heart bypass surgery.

    Before taking NSAIDs, tell your healthcare provider about all of your medical conditions, including if you:

    have liver or kidney problems
    have high blood pressure
    have asthma
    are pregnant or plan to become pregnant. Taking NSAIDs at about 20 weeks of pregnancy or later may harm your unborn baby. If you need to take NSAIDs for more than 2 days when you are between 20 and 30 weeks of pregnancy, your healthcare provider may need to monitor the amount of fluid in your womb around your baby. You should not take NSAIDs after about 30 weeks of pregnancy.
    are breastfeeding or plan to breast feed.

    Tell your healthcare provider about all of the medicines you take, including prescription or over-the-counter medicines, vitamins or herbal supplements. NSAIDs and some other medicines can interact with each other and cause serious side effects. Do not start taking any new medicine without talking to your healthcare provider first.

    What are the possible side effects of NSAIDs?

    NSAIDs can cause serious side effects, including:

    See “What is the most important information I should know about medicines called Nonsteroidal Anti-inflammatory Drugs (NSAIDs)?”

    new or worse high blood pressure
    heart failure
    liver problems including liver failure
    kidney problems including kidney failure
    low red blood cells (anemia)
    life-threatening skin reactions
    life-threatening allergic reactions
    Other side effects of NSAIDs include: stomach pain, constipation, diarrhea, gas, heartburn, nausea, vomiting, and dizziness.

    Get emergency help right away if you get any of the following symptoms:

    shortness of breath or trouble breathing
    slurred speech
    weakness in one part or side of your body
    swelling of the face or throat
    chest pain

    Stop taking your NSAID and call your healthcare provider right away if you get any of the following symptoms:

    nausea
    there is blood in your bowel movement or it is black and sticky like tar
    more tired or weaker than usual
    diarrhea
    unusual weight gain
    itching
    your skin or eyes look yellow
    skin rash or blisters with fever
    indigestion or stomach pain
    swelling of the arms, legs, hands and feet
    flu-like symptoms
    vomit blood

    If you take too much of your NSAID, call your healthcare provider or get medical help right away.

    These are not all the possible side effects of NSAIDs. For more information, ask your healthcare provider or pharmacist about NSAIDs.

    Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

    Other information about NSAIDs

    Aspirin is an NSAID but it does not increase the chance of a heart attack. Aspirin can cause bleeding in the brain, stomach, and intestines. Aspirin can also cause ulcers in the stomach and intestines.
    Some NSAIDs are sold in lower doses without a prescription (over-the-counter). Talk to your healthcare provider before using over-the-counter NSAIDs for more than 10 days.

    General information about the safe and effective use of NSAIDs

    Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use NSAIDs for a condition for which it was not prescribed. Do not give NSAIDs to other people, even if they have the same symptoms that you have. It may harm them.

    If you would like more information about NSAIDs, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about NSAIDs that is written for health professionals.

    For more information, go to www.us.sandoz.com or call 1-800-525-8747.

    This Medication Guide has been approved by the U.S. Food and Drug Administration.

    Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

    Distributed by

    Sandoz Inc.,

    Princeton, NJ 08540

    46193277

    Rev 03/21

    MF0675REV03/21

  • Package/Label Display Panel

    NDC 0185-0675-01

    Etodolac Tablets USP

    400 mg

    PHARMACIST: Please dispense with Medication Guide provided separately.

    Rx only

    100 Tablets

    Sandoz

    400mg-100Tabs
  • Package/Label Display Panel

    NDC 0185-0687-01

    Etodolac Tablets USP

    500 mg

    PHARMACIST: Please dispense with Medication Guide provided separately.

    Rx only

    100 Tablets

    Sandoz

    500mg-100Tabs
  • INGREDIENTS AND APPEARANCE
    ETODOLAC 
    etodolac tablet, coated
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC:0185-0675
    Route of AdministrationORAL
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    ETODOLAC (UNII: 2M36281008) (ETODOLAC - UNII:2M36281008) ETODOLAC400 mg
    Inactive Ingredients
    Ingredient NameStrength
    LACTOSE MONOHYDRATE (UNII: EWQ57Q8I5X)  
    MAGNESIUM STEARATE (UNII: 70097M6I30)  
    MICROCRYSTALLINE CELLULOSE (UNII: OP1R32D61U)  
    POLYETHYLENE GLYCOL, UNSPECIFIED (UNII: 3WJQ0SDW1A)  
    POVIDONE, UNSPECIFIED (UNII: FZ989GH94E)  
    SODIUM STARCH GLYCOLATE TYPE A POTATO (UNII: 5856J3G2A2)  
    TITANIUM DIOXIDE (UNII: 15FIX9V2JP)  
    TALC (UNII: 7SEV7J4R1U)  
    Product Characteristics
    ColorWHITEScoreno score
    ShapeOVALSize19mm
    FlavorImprint Code E140
    Contains    
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC:0185-0675-01100 in 1 BOTTLE; Type 0: Not a Combination Product04/20/201507/31/2025
    2NDC:0185-0675-05500 in 1 BOTTLE; Type 0: Not a Combination Product04/20/201504/20/2015
    3NDC:0185-0675-101000 in 1 BOTTLE; Type 0: Not a Combination Product04/20/201503/31/2024
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    ANDAANDA07490304/20/201507/31/2025
    ETODOLAC 
    etodolac tablet, coated
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC:0185-0687
    Route of AdministrationORAL
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    ETODOLAC (UNII: 2M36281008) (ETODOLAC - UNII:2M36281008) ETODOLAC500 mg
    Inactive Ingredients
    Ingredient NameStrength
    LACTOSE MONOHYDRATE (UNII: EWQ57Q8I5X)  
    MAGNESIUM STEARATE (UNII: 70097M6I30)  
    MICROCRYSTALLINE CELLULOSE (UNII: OP1R32D61U)  
    POLYETHYLENE GLYCOL, UNSPECIFIED (UNII: 3WJQ0SDW1A)  
    POVIDONE, UNSPECIFIED (UNII: FZ989GH94E)  
    SODIUM STARCH GLYCOLATE TYPE A POTATO (UNII: 5856J3G2A2)  
    TITANIUM DIOXIDE (UNII: 15FIX9V2JP)  
    TALC (UNII: 7SEV7J4R1U)  
    Product Characteristics
    ColorWHITEScoreno score
    ShapeOVALSize19mm
    FlavorImprint Code E139
    Contains    
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC:0185-0687-01100 in 1 BOTTLE; Type 0: Not a Combination Product04/20/201512/31/2023
    2NDC:0185-0687-05500 in 1 BOTTLE; Type 0: Not a Combination Product04/20/201504/20/2015
    3NDC:0185-0687-101000 in 1 BOTTLE; Type 0: Not a Combination Product04/20/201504/20/2015
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    ANDAANDA07490304/20/201507/31/2025
    Labeler - Eon Labs, Inc. (012656273)