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Lodine® (etodolac capsules and tablets) is a pyranocarboxylic acid chemically designated as (±) 1,8-diethyl-1,3,4,9-tetrahydropyrano-[3,4-b]indole-1-acetic acid. The structural formula for etodolac is shown below:
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The empirical formula for etodolac is C 17 H 21 NO 3 . 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. Etodolac is a white crystalline compound, insoluble in water but soluble in alcohols, chloroform, dimethyl sulfoxide, and aqueous polyethylene glycol.
Inactive ingredients are:
Lodine is available in 200 and 300 mg capsules, and 400 and 500 mg tablets, for oral administration.
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 known but is believed to be associated with the inhibition of prostaglandin biosynthesis.
Lodine 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 .
Analgesia was demonstrable 1 / 2 hour following single doses of 200 to 400 mg Lodine, with the peak effect occurring in 1 to 2 hours. The analgesic effect generally lasted for 4 to 6 hours (see Clinical Trials ).
The pharmacokinetics of etodolac have been evaluated in 267 normal subjects, 44 elderly patients (>65 years old), 19 patients with renal failure (creatinine clearance 37 to 88 mL/min), 9 patients on hemodialysis, and 10 patients with compensated hepatic cirrhosis.
Etodolac, when administered orally, exhibits kinetics that are well described by a two-compartment model with first-order absorption.
Lodine has no apparent pharmacokinetic interaction when administered with phenytoin, glyburide, furosemide or hydrochlorothiazide.
ABSORPTION
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 either the tablet or capsule formulation, is at least 80%. Etodolac does not undergo significant first-pass metabolism following oral administration. Mean (± 1 SD) peak plasma concentrations range from approximately 14 ± 4 to 37 ± 9 µg/mL after 200 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 AUC (the area under the plasma concentration-time curve) 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.
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Antacid Effects
The extent of absorption of etodolac is not affected when Lodine is administered with an antacid. Coadministration with an antacid decreases the peak concentration reached by about 15 to 20%, with no measurable effect on time-to-peak.
Food Effects
The extent of absorption of etodolac is not affected when Lodine 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.
Etodolac has an apparent steady-state volume of distribution about 0.362 L/kg. Within the therapeutic dose range, etodolac is more than 99% bound to plasma proteins. The free fraction is less than 1% and is independent of etodolac total concentration over the dose range studied.
Etodolac is extensively metabolized in the liver, with renal elimination of etodolac and its metabolites being the primary route of excretion. The intersubject variability of etodolac plasma levels, achieved after recommended doses, is substantial.
Protein Binding
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.
Elimination
The mean plasma clearance of etodolac, following oral dosing is 47 (± 16) mL/h/kg, and terminal disposition half-life is 7.3 (± 4.0) hours. Approximately 72% of the administered dose is recovered in the urine as the following, indicated as % of the administered dose:
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Fecal excretion accounted for 16% of the dose.
SPECIAL POPULATIONS
Elderly Patients
In clinical studies, etodolac clearance was reduced by about 15% in older patients (>65 years of age). In these 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. No dosage adjustment is generally necessary in the elderly on the basis of pharmacokinetics. The elderly may need dosage adjustment, however, on the basis of body size (see Precautions -- GERIATRIC POPULATION ), as they may be more sensitive to antiprostaglandin effects than younger patients (see Precautions -- GERIATRIC POPULATION ).
Studies in patients with mild-to-moderate renal impairment (creatinine clearance 37 to 88 mL/min) showed no significant differences in the disposition of total and free etodolac. 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. Nevertheless, etodolac is not dialyzable.
In patients with compensated hepatic cirrhosis, the disposition of total and free etodolac is not altered. Although no dosage adjustment is generally required in this patient population, etodolac clearance is dependent on hepatic function and could be reduced in patients with severe hepatic failure.
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 Lodine established in these acute pain models was 200 to 400 mg. The onset of analgesia occurred approximately 30 minutes after oral administration. Lodine 200 mg provided efficacy comparable to that obtained with aspirin (650 mg). Lodine 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 Lodine and 5 to 6 hours for 400 mg of Lodine as measured by when approximately half of the patients required remedication.
The use of Lodine 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, Lodine, in doses of 600 to 1000 mg/day, was better than placebo in two studies. The clinical trials in osteoarthritis used b.i.d. dosage regimens.
In a 3-month study with 426 patients, Lodine 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, Lodine 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, Lodine has been used in combination with gold, d-penicillamine, chloroquine, corticosteroids, and methotrexate.
Lodine is indicated for acute and long-term use in the management of signs and symptoms of osteoarthritis and rheumatoid arthritis. Lodine is also indicated for the management of pain.
Lodine is contraindicated in patients with known hypersensitivity to etodolac. Lodine 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 Lodine have been reported in such patients (see -- ANAPHYLACTOID REACTIONS ).
RISK OF GASTROINTESTINAL (GI) ULCERATION, BLEEDING, AND PERFORATION WITH NONSTEROIDAL, ANTI-INFLAMMATORY DRUG (NSAID) THERAPY
Serious GI toxicity, such as bleeding, ulceration, and perforation, can occur at any time, with or without warning symptoms, in patients treated chronically with NSAIDs. Although minor upper GI problems, such as dyspepsia, are common, usually developing early in therapy, physicians should remain alert for ulceration and bleeding in patients treated chronically with NSAIDs, even in the absence of previous GI-tract symptoms. In patients observed in clinical trials of such agents for several months' to 2 years' duration, symptomatic upper GI ulcers, gross bleeding, or perforation appears to occur in approximately 1% of patients treated for 3 to 6 months and in about 2% to 4% of patients treated for 1 year. Physicians should inform patients about the signs and/or symptoms of serious GI toxicity and what steps to take if they occur.
Studies to date have not identified any subset of patients not at risk of developing peptic ulceration and bleeding. Except for a prior history of serious GI events and other risk factors known to be associated with peptic ulcer disease, such as alcoholism, smoking, etc., no risk factors (e.g., age, sex) have been associated with increased risk. Elderly or debilitated patients seem to tolerate ulceration or bleeding less well than other individuals, and most spontaneous reports of fatal GI events are in this population. Studies to date are inconclusive concerning the relative risk of various NSAIDs in causing such reactions. High doses of any NSAID probably carry a greater risk of these reactions, although controlled clinical trials showing this do not exist in most cases. In considering the use of relatively large doses (within the recommended dosage range), sufficient benefit should be anticipated to offset the potential increased risk of GI toxicity.
ANAPHYLACTOID REACTIONS
Anaphylactoid reactions may occur in patients without prior exposure to etodolac. Lodine should not be given to patients with the aspirin triad. The triad 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 nonsteroidal anti-inflammatory drugs. Fatal reactions have been reported in such patients (see Contraindications and Precautions -- Pre-existing Asthma ). Emergency help should be sought in cases where an anaphylactoid reaction occurs.
In cases with advanced kidney disease, as with other NSAIDs, treatment with Lodine should only be initiated with close monitoring of the patient' kidney function (see Precautions -- Renal Effects ).
In late pregnancy, as with other NSAIDs, Lodine should be avoided because it may cause premature closure of the ductus arteriosus (see Precautions -- Teratogenic Effects--Pregnancy Category C ).
GENERAL PRECAUTIONS
Renal Effects
As with other NSAIDs, long-term administration of etodolac to rats has resulted in renal papillary necrosis and other renal medullary changes. 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.
A second form of renal toxicity encountered with Lodine, as with other NSAIDs, is seen in patients with conditions in which renal prostaglandins have a supportive 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 greatest risk of this reaction are those with impaired renal function, heart failure, or liver dysfunction; those taking diuretics; and the elderly. Discontinuation of nonsteroidal anti-inflammatory drug therapy is usually followed by recovery to the pretreatment state.
Etodolac metabolites are eliminated primarily by the kidneys. The extent to which the inactive glucuronide metabolites may accumulate in patients with renal failure has not been studied. As with other drugs whose metabolites are excreted by the kidney, the possibility that adverse reactions (not listed in Adverse Reactions ) may be attributable to these metabolites should be considered.
Hepatic Effects
Borderline elevations of one or more liver tests may occur in up to 15% of patients taking NSAIDs, including Lodine. These abnormalities may disappear, remain essentially unchanged, or progress with continued therapy. Meaningful 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 Lodine. 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 Lodine. Rare cases of liver necrosis and hepatic failure, some of them with fatal outcomes have been reported. If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g. eosinophilia, rash, etc.), Lodine should be discontinued.
Hematological Effects
Anemia is sometimes seen in patients receiving NSAIDs including Lodine. This may be due to fluid retention, GI blood loss, or an incompletely described effect upon erythropoiesis. Patients on long-term treatment with NSAIDs, including Lodine, should have their hemoglobin or hematocrit checked if they exhibit any signs or symptoms of anemia.
All drugs which inhibit the biosynthesis of prostaglandins may interfere to some extent with platelet function and vascular responses to bleeding.
Fluid retention and edema have been observed in some patients taking NSAIDs, including Lodine. Therefore, Lodine should be used with caution in patients with fluid retention, hypertension, or heart failure.
Pre-existing Asthma
About 10% of 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
Lodine, like other drugs of its class, can cause discomfort and, rarely, more serious side effects, such as gastrointestinal bleeding, which may result in hospitalization and even fatal outcomes.
Physicians may wish to discuss with their patients the potential risks (see , Precautions , Adverse Reactions ) and likely benefits of nonsteroidal anti-inflammatory drug treatment.
Patients on Lodine should report to their physicians signs or symptoms of gastrointestinal ulceration or bleeding, blurred vision or other eye symptoms, skin rash, weight gain, or edema.
Because serious gastrointestinal tract ulcerations and bleeding can occur without warning symptoms, physicians should follow chronically treated patients for the signs and symptoms of ulcerations and bleeding and should inform them of the importance of this follow-up (see --RISK OF GI ULCERATION, BLEEDING AND PERFORATION WITH NONSTEROIDAL ANTI-INFLAMMATORY THERAPY).
Patients should also be instructed to seek medical emergency help in case of an occurrence of anaphylactoid reactions (see ).
LABORATORY TESTS
Patients on long-term treatment with Lodine, as with other NSAIDs, should have their hemoglobin or hematocrit 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 disease develop or if systematic manifestations occur (e.g., eosinophilia, rash, etc.) and if abnormal liver tests are detected, persist or worsen, Lodine should be discontinued.
Antacids
The concomitant administration of antacids has no apparent effect on the extent of absorption of Lodine. However, antacids can decrease the peak concentration reached by 15% to 20% but have no detectable effect on the time-to-peak.
Aspirin
When Lodine 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 Lodine and aspirin is not generally recommended because of the potential of increased adverse effects.
Warfarin
Short-term pharmacokinetic studies have demonstrated that concomitant administration of warfarin and Lodine 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 Lodine as measured by prothrombin time. Thus, concomitant therapy with warfarin and Lodine should not require dosage adjustment of either drug. However, there have been a few spontaneous reports of prolonged prothrombin times in Lodine-treated patients receiving concomitant warfarin therapy. Caution should be exercised because interactions have been seen with other NSAIDs.
Cyclosporin, Digoxin, Lithium, Methotrexate
Lodine, like other NSAIDs, through effects on renal prostaglandins, may cause changes in the elimination of these drugs leading to elevated serum levels of digoxin, lithium, and methotrexate and increased toxicity. Nephrotoxicity associated with cyclosporine may also be enhanced. Patients receiving these drugs who are given Lodine, 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.
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 coadministration of phenylbutazone, it is not recommended that they be coadministered.
DRUG/LABORATORY TEST INTERACTIONS
The urine of patients who take Lodine 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 Lodine. Generally, this phenomenon has not been associated with other clinically significant events. No dose relationship has been observed.
Lodine treatment is associated with a small decrease in serum uric acid levels. In clinical trials, mean decreases of 1 to 2 mg/dL were observed in arthritic patients receiving etodolac (600 mg 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 to 89 mg/m 2 , 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 (3.0 to 5.3% unstained regions in the chromatid without dislocation) among the Lodine-treated cultures (50 to 200 µg/mL) compared to negative controls (2.0%); 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/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 (2 to 14 mg/kg/day) 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.
There are no adequate or well-controlled studies in pregnant women. Lodine should be used during pregnancy only if the potential benefits justify the potential risk to the fetus. Because of the known effects of NSAIDs on parturition and on the human fetal cardiovascular system with respect to closure of the ductus arteriosus, use during late pregnancy should be avoided.
In rat studies with etodolac, as with other drugs known to inhibit prostaglandin synthesis, an increased incidence of dystocia, delayed parturition, and decreased pup survival occurred. The effects of Lodine on labor and delivery in pregnant women are unknown.
NURSING MOTHERS
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 have not been established.
As with any NSAID, however, caution should be exercised in treating the elderly, and when individualizing their dosage, extra care should be taken when increasing the dose because the elderly seem to tolerate NSAID side effects less well than younger patients. In patients 65 years and older, no substantial differences in the side effect profile of Lodine were seen compared with the general population (see Clinical Pharmacology -- PHARMACOKINETICS .)
Adverse-reaction information for Lodine was derived from 2,629 arthritic patients treated with Lodine in double-blind and open-label clinical trials of 4 to 320 weeks in duration and worldwide postmarketing 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 Lodine.
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 to 500 mg of Lodine b.i.d. (i.e., 600 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*, diarrhea*, flatulence*, nausea*, constipation, gastritis, melena, vomiting.
Nervous system--Asthenia/malaise*, dizziness*, depression, nervousness.
Skin and appendages--Pruritus, rash.
Special senses--Blurred vision, tinnitus.
Urogenital system--Dysuria, urinary frequency.
*Drug-related patient complaints occurring in 3 to 9% of patients treated with Lodine.
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 postmarketing experience, not seen in clinical trials, are considered rarer and are italicized)
Body as a whole-- Allergic reaction, anaphylactoid reaction.
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, leukopenia, neutropenia, pancytopenia.
Metabolic and nutritional--Edema, serum creatinine increase, hyperglycemia in previously controlled diabetic patients.
Nervous system--Insomnia, somnolence.
Skin and appendages--Angioedema, sweating, urticaria, vesiculobullous rash, cutaneous vasculitis with purpura, Stevens-Johnson Syndrome, 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 Lodine 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.
Metabolic and nutritional--Change in weight.
Nervous system--Paresthesia, confusion.
Respiratory system--Bronchitis, dyspnea, pharyngitis, rhinitis, sinusitis.
Skin and appendages--Alopecia, maculopapular rash, photosensitivity, skin peeling.
Special senses--Conjunctivitis, deafness, taste perversion.
Urogenital system--Cystitis, hematuria, leukorrhea, renal calculus, interstitial nephritis, uterine bleeding irregularities.
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. Gut decontamination 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). This should be accomplished via emesis and/or activated charcoal (60 to 100 g in adults, 1 to 2 g/kg in children) with an osmotic cathartic. Forced diuresis, alkalinization of the urine, hemodialysis, or hemoperfusion would probably not be useful due to etodolac's high protein binding.
As with other NSAIDs, the lowest dose and longest dosing interval should be sought for each patient. Therefore, after observing the response to initial therapy with Lodine, the dose and frequency should be adjusted to suit an individual patient' needs.
Dosage adjustment of Lodine 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 Precautions -- GENERAL PRECAUTIONS , Renal Effects ).
The recommended total daily dose of Lodine for acute pain is up to 1000 mg, given as 200-400 mg every 6 to 8 hours. In some patients, if the potential benefits outweigh the risks; the dose may be increased to 1200 mg/day in order to achieve a therapeutic benefit that might not have been achieved with 1000 mg/day. Doses of etodolac greater than 1000 mg/day have not been adequately evaluated in well-controlled clinical trials.
OSTEOARTHRITIS AND RHEUMATOID ARTHRITIS
The recommended starting dose of Lodine 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. During long-term administration, the dose of Lodine may be adjusted up or down depending on the clinical response of the patient. A lower dose of 600 mg/day may suffice for long-term administration. In patients who tolerate 1000 mg/day, the dose may be increased to 1200 mg/day when a higher level of therapeutic activity is required. When treating patients with higher doses, the physician should observe sufficient increased clinical benefit to justify the higher dose. 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 Lodine 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' dose should be reviewed and adjusted as required.
Lodine (etodolac capsules and tablets) is available as:
Lodine® (etodolac capsules) Capsules
200 mg capsules (light gray with one wide red band with LODINE 200/white with two narrow red bands)
300 mg capsules (light gray with one red band with LODINE 300/light gray with two narrow red bands)
Store at controlled room temperature 20°-25°C (68°-77°F), protected from moisture.
Lodine® (etodolac tablets) Tablets
400 mg tablets (yellow-orange, oval, film-coated tablet, debossed LODINE 400 on one side)
Store at controlled room temperature 20°-25°C (68°-77°F).
Store tablets in original container until ready to use. Dispense in light-resistant container.
500 mg tablets (blue, oval, film-coated tablet, branded LODINE 500 on one side)
Store at controlled room temperature 20°-25°C (68°-77°F).
Store tablets in original container until ready to use. Dispense in light-resistant container.
The appearance of these capsules is a registered trademark of Wyeth-Ayerst Laboratories and the appearance of these tablets is a trademark of Wyeth-Ayerst Laboratories.
Caution: Federal law prohibits dispensing without prescription.
Manufactured by:
Ayerst Laboratories
A Wyeth-Ayerst Company
Philadelphia, PA 19101
CI 4861-1 Issued June 14, 1996
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