Etolex-P

Acetaminophen:

• Pharmacological action
• Why is Etolex-P (Acetaminophen) prescribed?
• Etolex-P dosage and administration
• Etolex-P side effects, adverse reactions
• Contraindications
• Using during pregnancy and breastfeeding
• Special Instructions
• Etolex-P (Acetaminophen) Drug Interactions
• Etolex-P in case of emergency / overdose
• Etolex-P (Acetaminophen) reviews

Pharmacological action

Etolex-P is an analgesic-antipyretic. It has analgesic, antipyretic and weak anti-inflammatory action. The mechanism of action is associated with inhibition of prostaglandin synthesis, the predominant influence on the thermoregulation center in the hypothalamus, enhances heat transfer.

Why is Etolex-P (Acetaminophen) prescribed?

Pain weak and moderate intensity of different genesis (including headache, migraine, toothache, neuralgia, myalgia, algomenorrhea; pain in trauma, burns). Fever in infectious and inflammatory diseases.

Etolex-P dosage and administration

Oral or rectally adults and adolescents with a body weight over 60 kg is used in a single dose of 500 mg, the multiplicity of admission - up to 4 times / Maximum duration of treatment - 5-7 days.

Maximum dose: single - 1 g, daily - 4 g.

Single dose for oral administration for children aged 6-12 years - 250-500 mg, 1-5 years - 120-250 mg, from 3 months to 1 year - 60-120 mg, up to 3 months - 10 mg / kg. Single dose rectal in children aged 6-12 years - 250-500 mg, 1-5 years - 125-250 mg.

Multiplicity - 4 at intervals of not less than 4 h. The maximum duration of treatment - 3 days.

Maximum dose: 4 single dose per day.

Etolex-P side effects, adverse reactions

Digestive system: rarely - dyspepsia; long-term use at high doses - hepatotoxic effects, methemoglobinemia, renal dysfunction and liver, hypochromic anemia. Hemopoietic system: rarely - thrombocytopenia, leukopenia, pancytopenia, neutropenia, agranulocytosis. Allergic reactions: rarely - skin rash, itching, hives.

Contraindications

Chronic active alcoholism, increased sensitivity to Etolex-P, marked disturbances of liver function and / or kidney disease, anemia, pregnancy (I term).

Using during pregnancy and breastfeeding

Etolex-P (Acetaminophen) crosses the placental barrier. So far, no observed adverse effects of Etolex-P (Acetaminophen) on the fetus in humans.

Etolex-P (Acetaminophen) is excreted in breast milk: the content in milk was 0.04-0.23% of the dose adopted mother.

If necessary, use of Etolex-P (Acetaminophen) during pregnancy and lactation (breastfeeding) should carefully weigh the potential benefits of therapy for the mother and the potential risk to the fetus or child.

In experimental studies found no embryotoxic, teratogenic and mutagenic action of Etolex-P (Acetaminophen).

Special Instructions

Etolex-P is used with caution in patients with disorders of the liver and kidneys, with benign hyperbilirubinemia, as well as in elderly patients.

With prolonged use of Etolex-P (Acetaminophen) is necessary to monitor patterns of peripheral blood and functional state of the liver.

Used for treatment of premenstrual tension syndrome in combination with pamabrom (diuretic, a derivative of xanthine) and mepyramine (Histamine H1-receptors blocker).

Etolex-P (Acetaminophen) Drug Interactions

With the simultaneous use with inducers of microsomal liver enzymes, means having hepatotoxic effect, increasing the risk of hepatotoxic action of Etolex-P (Acetaminophen).

With the simultaneous use of anticoagulants may be slight to moderate increase in prothrombin time.

With the simultaneous use of anticholinergics may decrease absorption of Etolex-P (Acetaminophen).

With the simultaneous use of oral contraceptives accelerated excretion of Etolex-P (Acetaminophen) from the body and may reduce its analgesic action.

With the simultaneous use with urological means reduced their effectiveness.

With the simultaneous use of activated charcoal reduced bioavailability of Etolex-P (Acetaminophen).

When Etolex-P (Acetaminophen) applied simultaneously with diazepam may decrease excretion of diazepam.

There have been reports about the possibility of enhancing mielodepression effect of zidovudine while applying with Etolex-P (Acetaminophen). A case of severe toxic liver injury.

Described cases of toxic effects of Etolex-P (Acetaminophen), while the use of isoniazid.

When applied simultaneously with carbamazepine, phenytoin, phenobarbital, primidonom decreases the effectiveness of Etolex-P (Acetaminophen), which is caused by an increase in its metabolism and excretion from the body. Cases of hepatotoxicity, while the use of Etolex-P (Acetaminophen) and phenobarbital.

In applying cholestyramine a period of less than 1 h after administration of Etolex-P (Acetaminophen) may decrease of its absorption.

At simultaneous application with lamotrigine moderately increased excretion of lamotrigine from the body.

With the simultaneous use of metoclopramide may increase absorption of Etolex-P (Acetaminophen) and its increased concentration in blood plasma.

When applied simultaneously with probenecid may decrease clearance of Etolex-P (Acetaminophen), with rifampicin, sulfinpyrazone - may increase clearance of Etolex-P (Acetaminophen) due to increasing its metabolism in the liver.

At simultaneous application of Etolex-P (Acetaminophen) with ethinylestradiol increases absorption of Etolex-P (Acetaminophen) from the gut.

Enhances the effect of indirect anticoagulants (coumarin derivatives and indandione). Antipyretic and analgesic activity of caffeine increases, reduce - rifampicin, phenobarbital and alcohol (accelerated biotransformation, inducing microsomal liver enzymes).

Etolex-P in case of emergency / overdose

At a reception in toxic doses (10-15 g in adults) may develop liver necrosis.

Symptoms of overdose may include: nausea, vomiting, loss of appetite, sweating, extreme tiredness, unusual bleeding or bruising, pain in the upper right part of the stomach, yellowing of the skin or eyes, flu-like symptoms

Etodolac:

• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Overdosage
• Dosage and administration
• How supplied
• Medication guide
• Etolex-P (Etodolac) reviews

INDICATIONS AND USAGE

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

Etolex-P (Etodolac) tablets USP are indicated:

• For acute and long-term use in the management of signs and symptoms of the following:

• Osteoarthritis
• Rheumatoid arthritis

• For the management of acute pain

CONTRAINDICATIONS

Etolex-P (Etodolac) is contraindicated in patients with known hypersensitivity to Etolex-P (Etodolac) or other ingredients in Etolex-P (Etodolac).

Etolex-P (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).

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 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 Etolex-P (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 CABR (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 Etolex-P (Etodolac) tablets in patients with a recent MI unless the benefits are expected to outweigh the risk of recurrent CV thrombotic events. If Etolex-P (Etodolac) tablets are used in patients with a recent MI, monitor patients for signs of cardiac ischemia.

Hypertension

NSAIDs, including Etolex-P (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 Etolex-P (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 Etolex-P 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 Etolex-P (Etodolac) tablets in patients with severe heart failure unless the benefits are expected to outweigh the risk of worsening heart failure. If Etolex-P (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 Etolex-P (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 Etolex-P in patients with advanced renal disease. Therefore, treatment with Etolex-P (Etodolac) is not recommended in these patients with advanced renal disease. If Etolex-P (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 Etolex-P (Etodolac). Etolex-P (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 Etolex-P, 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.

Pregnancy

In late pregnancy, the third trimester, as with other NSAIDs, Etolex-P (Etodolac) should be avoided because it may cause premature closure of the ductus arteriosus (see PRECAUTIONS, Pregnancy, Nonteratogenic Effects ).

PRECAUTIONS

General

Etolex-P 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 Etolex-P (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 Etolex-P (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 Etolex-P (Etodolac). If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), Etolex-P (Etodolac) should be discontinued.

Hematological Effects

Anemia is sometimes seen in patients receiving NSAIDs including Etolex-P. 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 Etolex-P (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 Etolex-P (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, Etolex-P (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.

• 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.
• Etolex-P (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 ).
• Etolex-P (Etodolac), like other NSAIDs, can cause serious skin side effects such as exfoliative dermatitis, SJS, and TEN, which may result in hospitalizations and even death. Although serious skin reactions may occur without warning, patients should be alert for the signs and symptoms of skin rash and blisters, fever, or other signs of hypersensitivity such as itching, and should ask for medical advice when observing any indicative signs or symptoms. Patients should be advised to stop the drug immediately if they develop any type of rash and contact their physicians as soon as possible.
• 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 ).
• 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.
• 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 ).
• In late pregnancy, the third trimester, as with other NSAIDs, Etolex-P (Etodolac) should be avoided because it may cause premature closure of the ductus arteriosus.

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, Etolex-P (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.

Antacids

The concomitant administration of antacids has no apparent effect on the extent of absorption of Etolex-P (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 Etolex-P is administered with aspirin, its protein binding is reduced, although the clearance of free Etolex-P (Etodolac) is not altered. The clinical significance of this interaction is not known; however, as with other NSAIDs, concomitant administration of Etolex-P (Etodolac) and aspirin is not generally recommended because of the potential of increased adverse effects.

Cyclosporine, Digoxin, Methotrexate

Etolex-P (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 Etolex-P (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 Etolex-P (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

Etolex-P has no apparent pharmacokinetic interaction when administered with furosemide or hydrochlorothiazide. Nevertheless, clinical studies, as well as post-marketing observations have shown that Etolex-P (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

Etolex-P (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 in the free fraction of Etolex-P (Etodolac). Although in vivo studies have not been done to see if Etolex-P (Etodolac) clearance is changed by co-administration of phenylbutazone, it is not recommended that they be co-administered.

Phenytoin

Etolex-P (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 Etolex-P 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 Etolex-P (Etodolac) as measured by prothrombin time. Thus, concomitant therapy with warfarin and Etolex-P (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 Etolex-P (Etodolac) can give a false-positive reaction for urinary bilirubin (urobilin) due to the presence of phenolic metabolites of Etolex-P (Etodolac). Diagnostic dip-stick methodology, used to detect ketone bodies in urine, has resulted in false-positive findings in some patients treated with Etolex-P (Etodolac). Generally, this phenomenon has not been associated with other clinically significant events. No dose relationship has been observed.

Etolex-P (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 Etolex-P (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 Etolex-P was observed in mice or rats receiving oral doses of 15 mg/kg/day (45 mg/m ² to 89 mg/m ², respectively) or less for periods of 2 years or 18 months, respectively. Etolex-P (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. Etolex-P (Etodolac) showed no impairment of fertility in male and female rats up to oral doses of 16 mg/kg (94 mg/m ²). However, reduced implantation of fertilized eggs occurred in the 8 mg/kg group.

Pregnancy

Teratogenic Effects

Pregnancy Category C

In teratology studies, isolated occurrences of alterations in limb development were found and included polydactyly, oligodactyly, syndactyly, and unossified phalanges in rats and oligodactyly and synostosis of metatarsals in rabbits. These were observed at dose levels close to human clinical doses. However, the frequency and the dosage group distribution of these findings in initial or repeated studies did not establish a clear drug or dose-response relationship. Animal reproduction studies are not always predictive of human response. There are no adequate and well-controlled studies in pregnant women. Etolex-P (Etodolac) should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nonteratogenic Effects

Etolex-P (Etodolac) should be used during pregnancy only if the potential benefits justify the potential risk to the fetus. Because of the known effects of nonsteroidal anti-inflammatory drugs on the fetal cardiovascular system (closure of ductus arteriosus), use during pregnancy (particularly during the third trimester) should be avoided.

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 Etolex-P 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 Etolex-P (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 Etolex-P (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 Etolex-P (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 Etolex-P (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.

Etolex-P (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 Etolex-P (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 Etolex-P (Etodolac) was derived from 2,629 arthritic patients treated with Etolex-P (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 Etolex-P (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 Etolex-P (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 pain ¹, diarrhea ², flatulence ³, nausea ⁴, abdominal distension, epigastric pain, abnormal stools, constipation, gastritis, melena, vomiting.

Nervous System: Asthenia/malaise ⁵, dizziness ⁶, 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 Etolex-P (Etodolac).

²Drug-related patient complaints occurring in 3 to 9% of patients treated with Etolex-P (Etodolac).

³Drug-related patient complaints occurring in 3 to 9% of patients treated with Etolex-P (Etodolac).

⁴Drug-related patient complaints occurring in 3 to 9% of patients treated with Etolex-P (Etodolac).

⁵Drug-related patient complaints occurring in 3 to 9% of patients treated with Etolex-P (Etodolac).

⁶Drug-related patient complaints occurring in 3 to 9% of patients treated with Etolex-P (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 Etolex-P (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 Etolex-P tablets and other treatment options before deciding to use Etolex-P (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 Etolex-P (Etodolac) tablets, the dose and frequency should be adjusted to suit an individual patient’s needs.

Dosage adjustment of Etolex-P (Etodolac) tablets is generally not required in patients with mild to moderate renal impairment. Etolex-P (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 Etolex-P (Etodolac) tablets for acute pain is up to 1000 mg, given as 200 mg to 400 mg every 6 to 8 hours. Doses of Etolex-P (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 Etolex-P (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 Etolex-P (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

Etolex-P (Etodolac) Tablets USP, for oral administration, are available as:

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

bottles of 14, 20 and 30.

Store at 20º to 25ºC (68º to 77ºF).

Store tablets in original container until ready to use.

Dispense in light-resistant container.

KEEP THIS AND ALL MEDICATION OUT OF REACH OF CHILDREN.

Medication Guide

For Non -Steroidal Anti-Inflammatory Drugs (NSAIDs)

What is the most important information I should know abo ut 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:
  • with increasing doses of NSAIDs
  • 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:
  • anytime during use
  • without warning symptoms
  • that may cause death

The risk of getting an ulcer or bleeding increases with:

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

NSAIDs should only be used:

• • exactly as prescribed
  • at the lowest dose possible for your treatment
  • 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. Talk to your healthcare provider if you are considering taking NSAIDs during pregnancy. You should not take NSAIDs after 29 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
• chest pain
• swelling of the face or throat
• weakness in one part or side of your body

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

• nausea
• vomit blood
• more tired or weaker than usual
• there is blood in your bowel movement or it is black and sticky like tar
• diarrhea
• itching
• unusual weight gain
• 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

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.

Sandoz Inc.

Princeton, NJ 08540

46139393

Rev 07/15

MF0675REV07/15

MG #35633

Etolex-P (Etodolac) Tablets USP

500 mg

PHARMACIST: Please dispense with Medication Guide provided separately.

Rx only