Etodolac (Page 6 of 8)

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 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 1,000 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, fatal fulminant hepatitis, 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 To report SUSPECTED ADVERSE REACTIONS contact AvKARE, Inc. at 1-855-361-3993; email drugsafety@avkare.com; or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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/hypotension, 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 to 100 g in adults, 1 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.