Etodolac Capsules

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 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 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.

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 Capsules 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 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 to 500 mg of etodolac 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*, abdominal distension, epigastric pain, abnormal stools, constipation, gastritis, melena, vomiting.

Nervous system - Asthenia/malaise*, dizziness*, depression, nervousness, fatigue.

Skin and appendages - Pruritus, rash.

Special senses - Blurred vision, tinnitus.

Urogenital system - Dysuria, urinary frequency.

Musculoskeletal - Arthralgia.

* Drug-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 postmarketing 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.