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ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Medication Safety Issues
Sound-alike/look-alike issues:
Lodine® may be confused with codeine, iodine, Iopidine®, Lopid®
Pronunciation
(ee toe DOE lak)
Index Terms
Generic Available
Yes
Canadian Brand Names
Pharmacologic Category
Use: Labeled Indications
Acute and long-term use in the management of signs and symptoms of osteoarthritis; rheumatoid arthritis and juvenile rheumatoid arthritis; management of acute pain
Use: Dental
Management of postoperative pain
Pregnancy Risk Factor
C
Pregnancy Considerations
Adverse events were not observed in the initial animal reproduction studies; therefore, the manufacturer classifies etodolac as pregnancy category C. NSAID exposure during the first trimester is not strongly associated with congenital malformations; however, cardiovascular anomalies and cleft palate have been observed following NSAID exposure in some studies. The use of an NSAID close to conception may be associated with an increased risk of miscarriage. Nonteratogenic effects have been observed following NSAID administration during the third trimester including: Myocardial degenerative changes, prenatal constriction of the ductus arteriosus, fetal tricuspid regurgitation, failure of the ductus arteriosus to close postnatally; renal dysfunction or failure, oligohydramnios; gastrointestinal bleeding or perforation, increased risk of necrotizing enterocolitis; intracranial bleeding (including intraventricular hemorrhage), platelet dysfunction with resultant bleeding; pulmonary hypertension. Because they may cause premature closure of the ductus arteriosus, use of NSAIDs late in pregnancy should be avoided (use after 31 or 32 weeks gestation is not recommended by some clinicians). The chronic use of NSAIDs in women of reproductive age may be associated with infertility that is reversible upon discontinuation of the medication.
Lactation
Excretion in breast milk unknown/not recommended
Breast-Feeding Considerations
It is not known if etodolac is excreted into breast milk. Use of etodolac while breast-feeding is not recommended by the manufacturer .
Contraindications
Hypersensitivity to etodolac, aspirin, other NSAIDs, or any component of the formulation; perioperative pain in the setting of coronary artery bypass graft (CABG) surgery
Warnings/Precautions
Boxed warnings:
• Cardiovascular events: See “Concerns related to adverse effects” below.
• Coronary artery bypass graft surgery: See “Disease-related concerns” below.
• Gastrointestinal events: See “Concerns related to adverse effects” below.
Concerns related to adverse effects:
• Anaphylactoid reactions: Even in patients without prior exposure anaphylactoid reactions may occur; patients with "aspirin triad" (bronchial asthma, aspirin intolerance, rhinitis) may be at increased risk. Do not use in patients who experience bronchospasm, asthma, rhinitis, or urticaria with NSAID or aspirin therapy.
• Cardiovascular events: [U.S. Boxed Warning]: NSAIDs are associated with an increased risk of adverse cardiovascular thrombotic events, including MI and stroke. Risk may be increased with duration of use or pre-existing cardiovascular risk factors or disease. Carefully evaluate individual cardiovascular risk profiles prior to prescribing. Use caution with fluid retention. Avoid use in heart failure. Concurrent administration of ibuprofen, and potentially other nonselective NSAIDs, may interfere with aspirin's cardioprotective effect. Use the lowest effective dose for the shortest duration of time, consistent with individual patient goals, to reduce risk of cardiovascular events; alternate therapies should be considered for patients at high risk.
• CNS effects: May cause drowsiness, dizziness, blurred vision, and other neurologic effects which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Discontinue use with blurred or diminished vision and perform ophthalmologic exam. Periodically evaluate vision in all patients receiving long term therapy.
• Gastrointestinal events: [U.S. Boxed Warning]: NSAIDs may increase risk of gastrointestinal irritation, inflammation, ulceration, bleeding, and perforation. These events may occur at any time during therapy and without warning. Use caution with a history of GI disease (bleeding or ulcers), concurrent therapy with aspirin, anticoagulants and/or corticosteroids, smoking, use of alcohol, the elderly or debilitated patients. Use the lowest effective dose for the shortest duration of time, consistent with individual patient goals, to reduce risk of GI adverse events; alternate therapies should be considered for patients at high risk. When used concomitantly with ?325 mg of aspirin, a substantial increase in the risk of gastrointestinal complications (eg, ulcer) occurs; concomitant gastroprotective therapy (eg, proton pump inhibitors) is recommended (Bhatt, 2008).
• Hematologic effects: Platelet adhesion and aggregation may be decreased; may prolong bleeding time; patients with coagulation disorders or who are receiving anticoagulants should be monitored closely. Anemia may occur; patients on long-term NSAID therapy should be monitored for anemia. Rarely, NSAID use has been associated with potentially severe blood dyscrasias (eg, agranulocytosis, thrombocytopenia, aplastic anemia).
• Hyperkalemia: NSAID use may increase the risk of hyperkalemia, particularly in the elderly, diabetics, renal disease, and with concomitant use of other agents capable of inducing hyperkalemia (eg, ACE-inhibitors). Monitor potassium closely.
• Skin reactions: NSAIDs may cause serious skin adverse events including exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN); discontinue use at first sign of skin rash or hypersensitivity.
Disease-related concerns:
• Asthma: Do not administer to patients with aspirin-sensitive asthma; severe bronchospasm may occur. Use caution in patients with other forms of asthma.
• Coronary artery bypass graft surgery: [U.S. Boxed Warning]: Use is contraindicated for treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery. Risk of MI and stroke may be increased with use following CABG surgery.
• Hepatic impairment: Use with caution in patients with decreased hepatic function. Closely monitor patients with any abnormal LFT. Severe hepatic reactions (eg, fulminant hepatitis, liver failure) have occurred with NSAID use, rarely; discontinue if signs or symptoms of liver disease develop, or if systemic manifestations occur.
• Hypertension: Use with caution; may cause new-onset hypertension or worsening of existing hypertension.
• Renal impairment: NSAID use may compromise existing renal function; dose-dependent decreases in prostaglandin synthesis may result from NSAID use, reducing renal blood flow which may cause renal decompensation. Patients with impaired renal function, dehydration, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly are at greater risk for renal toxicity. Rehydrate patient before starting therapy; monitor renal function closely. Not recommended for use in patients with advanced renal disease. Long-term NSAID use may result in renal papillary necrosis.
Special populations:
• Elderly: The elderly are at increased risk for adverse effects (especially peptic ulceration, CNS effects, renal toxicity) from NSAIDs even at low doses.
• Pediatrics: Safety and efficacy have not been established in children.
Dosage form specific issues:
• Extended release formulation: Use of extended release product consisting of a nondeformable matrix should be avoided in patients with stricture/narrowing of the GI tract; symptoms of obstruction have been associated with nondeformable products.
Other warnings/precautions:
• Surgical/dental procedures: Withhold for at least 4-6 half-lives prior to surgical or dental procedures.
Adverse Reactions
1% to 10%:
Central nervous system: Dizziness (3% to 9 %), chills/fever (1% to 3%), depression (1% to 3%), nervousness (1% to 3%)
Dermatologic: Rash (1% to 3%), pruritus (1% to 3%)
Gastrointestinal: Dyspepsia (10%), abdominal cramps (3% to 9%), diarrhea (3% to 9%), flatulence (3% to 9%), nausea (3% to 9%), vomiting (1% to 3%), constipation (1% to 3%), melena (1% to 3%), gastritis (1% to 3%)
Genitourinary: Dysuria (1% to 3%)
Neuromuscular & skeletal: Weakness (3% to 9%)
Ocular: Blurred vision (1% to 3%)
Otic: Tinnitus (1% to 3%)
Renal: Polyuria (1% to 3%)
<1%: Agranulocytosis, allergic reaction, allergic/necrotizing vasculitis, alopecia, anaphylactic/anaphylactoid reactions, anemia, angioedema, anorexia, arrhythmia, aseptic meningitis, asthma, bleeding time increased, CHF, confusion, conjunctivitis, CVA, cystitis, duodenitis, dyspnea, ecchymosis, edema, erythema multiforme, esophagitis (+/- stricture or cardiospasm), exfoliative dermatitis, GI ulceration, hallucination, headache, hearing decreased, hematemesis, hematuria, hepatic failure, hepatitis, hyperglycemia (in controlled patients with diabetes), hyperpigmentation, hypertension, infection, insomnia, interstitial nephritis, irregular uterine bleeding, jaundice, LFTs increased, leukopenia, MI, palpitation, pancreatitis, pancytopenia, paresthesia, peptic ulcer (+/- bleeding/perforation), peripheral neuropathy, photophobia, photosensitivity, pulmonary infiltration (eosinophilia), rectal bleeding, renal calculus, renal failure, renal insufficiency, shock, Stevens-Johnson syndrome, syncope, thrombocytopenia, toxic epidermal necrolysis, ulcerative stomatitis, urticaria, vesiculobullous rash, renal papillary necrosis, visual disturbances
Drug Interactions
ACE Inhibitors: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of ACE Inhibitors. Risk C: Monitor therapy
Aminoglycosides: Nonsteroidal Anti-Inflammatory Agents may decrease the excretion of Aminoglycosides. Data only in premature infants. Risk C: Monitor therapy
Angiotensin II Receptor Blockers: Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Angiotensin II Receptor Blockers. The combination of these two agents may also significantly decrease glomerular filtration and renal function. Risk C: Monitor therapy
Anticoagulants: Antiplatelet Agents may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Anticoagulants: Nonsteroidal Anti-Inflammatory Agents may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Antidepressants (Tricyclic, Tertiary Amine): May enhance the antiplatelet effect of NSAID (Nonselective). Risk C: Monitor therapy
Antiplatelet Agents: May enhance the anticoagulant effect of other Antiplatelet Agents. Risk C: Monitor therapy
Antiplatelet Agents: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Antiplatelet Agents. An increased risk of bleeding may occur. Nonsteroidal Anti-Inflammatory Agents may diminish the cardioprotective effect of Antiplatelet Agents. This interaction is likely specific to aspirin, and not to other antiplatelet agents. Risk C: Monitor therapy
Beta-Blockers: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Beta-Blockers. Exceptions: Levobunolol; Metipranolol. Risk C: Monitor therapy
Bile Acid Sequestrants: May decrease the absorption of Nonsteroidal Anti-Inflammatory Agents. Risk D: Consider therapy modification
Bisphosphonate Derivatives: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Bisphosphonate Derivatives. Both an increased risk of gastrointestinal ulceration and an increased risk of nephrotoxicity are of concern. Risk C: Monitor therapy
Corticosteroids (Systemic): May enhance the adverse/toxic effect of NSAID (Nonselective). Risk C: Monitor therapy
CycloSPORINE: Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of CycloSPORINE. Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of CycloSPORINE. Risk D: Consider therapy modification
Dasatinib: May enhance the anticoagulant effect of Antiplatelet Agents. Risk C: Monitor therapy
Desmopressin: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Desmopressin. Risk C: Monitor therapy
Drotrecogin Alfa: Antiplatelet Agents may enhance the adverse/toxic effect of Drotrecogin Alfa. Bleeding may occur. Risk D: Consider therapy modification
Eplerenone: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Eplerenone. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Eplerenone. Risk C: Monitor therapy
Glucosamine: May enhance the antiplatelet effect of Antiplatelet Agents. Risk C: Monitor therapy
Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Antiplatelet Agents. Bleeding may occur. Risk D: Consider therapy modification
Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Bleeding may occur. Risk D: Consider therapy modification
HydrALAZINE: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of HydrALAZINE. Risk C: Monitor therapy
Ibritumomab: Antiplatelet Agents may enhance the adverse/toxic effect of Ibritumomab. Both agents may contribute to impaired platelet function and an increased risk of bleeding. Risk C: Monitor therapy
Ketorolac: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination
Lithium: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Lithium. Risk D: Consider therapy modification
Loop Diuretics: Nonsteroidal Anti-Inflammatory Agents may diminish the diuretic effect of Loop Diuretics. Risk C: Monitor therapy
Methotrexate: Nonsteroidal Anti-Inflammatory Agents may decrease the excretion of Methotrexate. Risk D: Consider therapy modification
Nonsteroidal Anti-Inflammatory Agents: May enhance the adverse/toxic effect of Antiplatelet Agents. An increased risk of bleeding may occur. Nonsteroidal Anti-Inflammatory Agents may diminish the cardioprotective effect of Antiplatelet Agents. This interaction is likely specific to aspirin, and not to other antiplatelet agents. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May enhance the adverse/toxic effect of other Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy
Omega-3-Acid Ethyl Esters: May enhance the antiplatelet effect of Antiplatelet Agents. Risk C: Monitor therapy
Pemetrexed: NSAID (Nonselective) may increase the serum concentration of Pemetrexed. Management: Patients with mild-to-moderate renal insufficiency (CrCl 45-79 mL/minute) may use ibuprofen with caution, but should avoid other NSAIDs for 2-5 days prior to, the day of, and 2 days after pemetrexed. Risk D: Consider therapy modification
Pentosan Polysulfate Sodium: May enhance the adverse/toxic effect of Antiplatelet Agents. Specifically, the risk of bleeding may be increased by concurrent use of these agents. Risk C: Monitor therapy
Pentoxifylline: May enhance the antiplatelet effect of Antiplatelet Agents. Risk C: Monitor therapy
Potassium-Sparing Diuretics: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Potassium-Sparing Diuretics. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Pralatrexate: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Pralatrexate. More specifically, NSAIDS may decrease the renal excretion of pralatrexate. Management: Closely monitor for increased pralatrexate serum levels and/or toxicity if used concomitantly with an NSAID. Monitor for decreased pralatrexate serum levels with NSAID discontinuation. Risk C: Monitor therapy
Probenecid: May increase the serum concentration of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the antiplatelet effect of Antiplatelet Agents. Risk C: Monitor therapy
Quinolone Antibiotics: Nonsteroidal Anti-Inflammatory Agents may enhance the neuroexcitatory and/or seizure-potentiating effect of Quinolone Antibiotics. Risk C: Monitor therapy
Salicylates: NSAID (Nonselective) may enhance the adverse/toxic effect of Salicylates. An increased risk of bleeding may be associated with use of this combination. NSAID (Nonselective) may diminish the cardioprotective effect of Salicylates. Salicylates may decrease the serum concentration of NSAID (Nonselective). Exceptions: Choline Magnesium Trisalicylate. Risk D: Consider therapy modification
Salicylates: Antiplatelet Agents may enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result. Risk C: Monitor therapy
Selective Serotonin Reuptake Inhibitors: May enhance the antiplatelet effect of NSAID (Nonselective). Risk D: Consider therapy modification
Serotonin/Norepinephrine Reuptake Inhibitors: May enhance the antiplatelet effect of NSAID (Nonselective). Risk C: Monitor therapy
Thiazide Diuretics: Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Thiazide Diuretics. Risk C: Monitor therapy
Thrombolytic Agents: Antiplatelet Agents may enhance the anticoagulant effect of Thrombolytic Agents. Risk C: Monitor therapy
Thrombolytic Agents: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Thrombolytic Agents. An increased risk of bleeding may occur. Risk C: Monitor therapy
Tositumomab and Iodine I 131 Tositumomab: Antiplatelet Agents may enhance the adverse/toxic effect of Tositumomab and Iodine I 131 Tositumomab. Specifically, the risk of bleeding-related adverse events may be increased. Risk C: Monitor therapy
Treprostinil: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Bleeding may occur. Risk C: Monitor therapy
Vancomycin: Nonsteroidal Anti-Inflammatory Agents may decrease the excretion of Vancomycin. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): NSAID (Nonselective) may enhance the anticoagulant effect of Vitamin K Antagonists. Risk D: Consider therapy modification
Ethanol/Nutrition/Herb Interactions
Ethanol: Avoid ethanol (may enhance gastric mucosal irritation).
Food: Etodolac peak serum levels may be decreased if taken with food.
Herb/Nutraceutical: Avoid alfalfa, anise, bilberry, bladderwrack, bromelain, cat's claw, celery, chamomile, coleus, cordyceps, dong quai, evening primrose, fenugreek, feverfew, garlic, ginger, ginkgo biloba, ginseng (American, Panax, Siberian), grapeseed, green tea, guggul, horse chestnut seed, horseradish, licorice, prickly ash, red clover, reishi, SAMe (S-adenosylmethionine), sweet clover, turmeric, white willow (all have additional antiplatelet activity).
Storage
Store at 20°C to 25°C (68°F to 77°F). Protect from moisture.
Mechanism of Action
Reversibly inhibits cyclooxygenase-1 and 2 (COX-1 and 2) enzymes, which results in decreased formation of prostaglandin precursors; has antipyretic, analgesic, and anti-inflammatory properties
Other proposed mechanisms not fully elucidated (and possibly contributing to the anti-inflammatory effect to varying degrees), include inhibiting chemotaxis, altering lymphocyte activity, inhibiting neutrophil aggregation/activation, and decreasing proinflammatory cytokine levels.
Pharmacodynamics/Kinetics
Onset of action: Analgesic: 2-4 hours; Maximum anti-inflammatory effect: A few days
Absorption: ?80%
Distribution: Vd:
Immediate release: Adults:0.4 L/kg
Extended release: Adults: 0.57 L/kg; Children (6-16 years): 0 .08 L/kg
Protein binding: ?99%, primarily albumin
Metabolism: Hepatic
Bioavailability: 100%
Half-life elimination: Terminal: Adults: 5-8 hours
Extended release: Children (6-16 years): 12 hours
Time to peak, serum:
Immediate release: Adults: 1-2 hours
Extended release: Extended release: 5-7 hours, increased 1.4-3.8 hours with food
Excretion: Urine 73% (1% unchanged); feces 16%
Dosage
Note: For chronic conditions, response is usually observed within 2 weeks.
Children 6-16 years: Oral: Juvenile rheumatoid arthritis: Extended release formulation:
20-30 kg: 400 mg once daily
31-45 kg: 600 mg once daily
46-60 kg: 800 mg once daily
>60 kg: 1000 mg once daily
Adults: Oral:
Acute pain: Immediate release formulation: 200-400 mg every 6-8 hours, as needed, not to exceed total daily doses of 1000 mg
Rheumatoid arthritis, osteoarthritis:
Immediate release formulation: 400 mg 2 times/day or 300 mg 2-3 times/day or 500 mg 2 times/day (doses >1000 mg/day have not been evaluated)
Extended release formulation: 400-1000 mg once daily
Elderly: Refer to adult dosing; in patients ?65 years, no dosage adjustment required based on pharmacokinetics. The elderly are more sensitive to antiprostaglandin effects and may need dosage adjustments.
Dosage adjustment in renal impairment:
Mild-to-moderate: No adjustment required
Severe: Use not recommended; use with caution
Hemodialysis: Not removed
Dosage adjustment in hepatic impairment: No adjustment required.
Dental Usual Dosing
Acute pain: Adults: Oral: Immediate release formulation: 200-400 mg every 6-8 hours, as needed, not to exceed total daily doses of 1000 mg
Administration: Oral
May be administered with food to decrease GI upset.
Monitoring Parameters
Monitor CBC and chemistry profile, liver enzymes; in patients with an increased risk for renal failure (CHF or decreased renal function, taking ACE inhibitors or diuretics, elderly), monitor urine output and BUN/serum creatinine
Test Interactions
False-positive for urinary bilirubin and ketone
Dietary Considerations
May be taken with food to decrease GI upset.
Patient Education
Take this medication exactly as directed; do not increase dose without consulting prescriber. Do not crush tablets or break capsules. Take with food or milk to reduce GI distress. Maintain adequate hydration unless instructed to restrict fluid intake. Do not use alcohol, aspirin or aspirin-containing medication, or any other anti-inflammatory medications without consulting prescriber. You may experience anorexia, nausea, vomiting, or heartburn (small frequent meals, frequent mouth care, sucking lozenges, or chewing gum may help); drowsiness, dizziness, nervousness, or headache (use caution when driving or engaging in tasks requiring alertness until response to drug is known); or fluid retention (weigh yourself weekly and report unusual [3-5 lb/week] weight gain). GI bleeding, ulceration, or perforation can occur with or without pain; discontinue medication and contact prescriber if persistent abdominal pain or cramping, or blood in stool occurs. Report breathlessness, respiratory difficulty, or unusual cough; chest pain, rapid heartbeat, palpitations; unusual bruising/bleeding; blood in urine, stool, mouth, or vomitus; swollen extremities; skin rash, blisters, or itching; acute fatigue; fever; jaundice; abdominal tenderness; flu-like symptoms; or hearing changes (ringing in ears). Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. This drug should not be used in the 3rd trimester of pregnancy. Do not breast-feed.
Geriatric Considerations
The elderly are a high-risk population for adverse effects from nonsteroidal anti-inflammatory agents. As much as 60% of older adults who experience GI side effects can develop peptic ulceration and/or hemorrhage asymptomatically. The concomitant use of H2 blockers and sucralfate is not effective as prophylaxis with the exception of NSAID-induced duodenal ulcers which may be prevented by the use of ranitidine. Misoprostol and proton pump inhibitors are the only agents proven to help prevent the development of NSAID-induced ulcers. Also, concomitant disease and drug use contribute to the risk for GI adverse effects. Use lowest effective dose for shortest period possible. Consider renal function decline with age. Use of NSAIDs can compromise existing renal function especially when Clcr is ?30 mL/minute.
Tinnitus may be a difficult and unreliable indication of toxicity due to age-related hearing loss or eighth cranial nerve damage. CNS adverse effects such as confusion, agitation, and hallucination are generally seen in overdose or high dose situations, but older adults may demonstrate these adverse effects at lower doses than younger adults. In patients ?65 years, no substantial differences in the pharmacokinetics or side-effects profile were seen compared with the general population. Studies with etodolac in elderly demonstrated no difference in safety or efficacy compared to younger adults. No dosing adjustment necessary in elderly.
Anesthesia and Critical Care Concerns/Other Considerations
The 2002 ACCM/SCCM guidelines for analgesia (critically-ill adult) suggest that NSAIDs may be used in combination with opioids in select patients for pain management. Concern about adverse events (increased risk of renal dysfunction, altered platelet function and gastrointestinal irritation) limits its use in patients who have other underlying risks for these events.
In short-term use, NSAIDs vary considerably in their effect on blood pressure. When NSAIDs are used in patients with hypertension, appropriate monitoring of blood pressure responses should be completed and the duration of therapy, when possible, kept short. The use of NSAIDs in the treatment of patients with congestive heart failure may be associated with an increased risk for fluid accumulation and edema. May precipitate renal failure in dehydrated patients.
Cardiovascular Considerations
Blood Pressure: In short-term use, NSAIDs vary considerably in their effect on blood pressure. A recent meta-analysis (see References) showed that indomethacin and naproxen had the largest effect on blood pressure. Other NSAIDs, including piroxicam, ibuprofen, and sulindac had less of an effect. Ibuprofen combined with captopril or losartan may attenuate the antihypertensive effects of ACE inhibition or receptor blockade on sitting or 24-hour ambulatory diastolic blood pressure. When NSAIDs are used in patients with hypertension, appropriate monitoring of blood pressure responses should be completed and the duration of therapy, when possible, kept short.
Heart Failure: The use of NSAIDs in the treatment of patients with heart failure may be associated with an increased risk for fluid accumulation and edema. One study showed that NSAID use in elderly patients had an increased risk of hospitalization for heart failure. This study gives compelling reasons to avoid or limit the use of NSAIDs in patients with heart failure, particularly in the elderly population. The ACC/AHA 2009 heart failure guidelines suggest that NSAIDs be avoided or withdrawn whenever possible in patients with current or prior symptoms of heart failure and reduced LVEF.
Risk of Cardiovascular Events: Patients at increased risk of cardiovascular adverse events include patients immediately postoperative from CABG surgery, and those with existing CAD, CVD, or history of TIA. Prescribers are encouraged to use the lowest effective dose for the shortest duration of time based on individual patient treatment goals. Available evidence reviewed by the FDA does not suggest an increased risk of serious CV events when NSAIDs are given short term and in the lower doses used OTC.
Drug Interactions: Nonsteroidal anti-inflammatory agents, including ibuprofen and naproxen, may diminish the cardioprotective effect of aspirin (Catella-Lawson F, 2001; Capone ML, 2005). It is surmised that ibuprofen may exhibit greater affinity than aspirin for the COX-1 site or if dosed regularly (or prior to aspirin), it would gain access to the active site first. In either case, aspirin's inhibition of COX (irreversible) would be limited in favor of ibuprofen inhibition (reversible). Avoid regular use of NSAIDs (nonselective) if possible. If used occasionally, take after aspirin (immediate release) ingestion.
Dental Health: Effects on Dental Treatment
The dentist should be aware of the potential of abnormal coagulation. Caution should also be exercised in the use of NSAIDs in patients already on anticoagulant therapy with drugs such as warfarin (Coumadin®). See Effects on Bleeding.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
Dizziness is common; may cause nervousness; rarely produces confusion, depression, insomnia, or hallucinations
Mental Health: Effects on Psychiatric Treatment
May rarely cause agranulocytosis; use caution with clozapine and carbamazepine; may decrease the clearance of lithium resulting in elevated serum levels and potential toxicity; monitor serum lithium levels
Nursing: Physical Assessment/Monitoring
Evaluate cardiac risk and potential for GI bleeding prior to prescribing this medication. Assess effectiveness and interactions of other medications patient may be taking. Monitor blood pressure at the beginning of therapy and periodically during use. Assess results of laboratory tests and therapeutic and adverse reactions at beginning of therapy and periodically throughout therapy. Assess knowledge/teach patient appropriate use, interventions to reduce side effects, and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule: 200 mg, 300 mg
Tablet: 400 mg, 500 mg
Tablet, extended release: 400 mg, 500 mg, 600 mg
Pricing: U.S. (www.drugstore.com)
Capsules (Etodolac)
300 mg (60): $31.99
Tablet, 24-hour (Etodolac CR)
400 mg (30): $32.99
500 mg (30): $34.99
600 mg (30): $64.99
Tablets (Etodolac)
400 mg (60): $38.99
500 mg (60): $65.99
References
Bhatt DL, Scheiman J, Abraham NS, et al, “ACCF/ACG/AHA 2008 Expert Consensus Document on Reducing the Gastrointestinal Risk of Antiplatelet Therapy and NSAID Use. A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents,” J Am Coll Cardiol, 2008, 52(18):1502-17.
Boldy DA, Hale KA, and Vale JA, “Etodolac Overdose,” Hum Toxicol, 1988, 7(2):203-4.
Brooks PM and Day RO, “Nonsteroidal Anti-inflammatory Drugs - Differences and Similarities,” N Engl J Med, 1991, 324(24):1716-25.
Capone ML, Sciulli MG, Tacconelli S, et al, “Pharmacodynamic Interaction of Naproxen With Low-Dose Aspirin in Healthy Subjects,” J Am Coll Cardiol, 2005, 45(8):1295-1301.
Catella-Lawson F, Reilly MP, Kapoor SC, et al, “Cyclooxygenase Inhibitors and the Antiplatelet Effects of Aspirin,” N Engl J Med, 2001, 345(25):1809-17.
Clinch D, Banerjee AK, and Ostick G, “Absence of Abdominal Pain in Elderly Patients With Peptic Ulcer,” Age Ageing, 1984, 13(2):120-3.
Clive DM and Stoff JS, “Renal Syndromes Associated With Nonsteroidal Anti-inflammatory Drugs,” N Engl J Med, 1984, 310(9):563-72.
Conlin P, Moore T, Swartz S, et al, “Effect of Indomethacin on Blood Pressure Lowering by Captopril and Losartan in Hypertensive Patients,” Hypertension, 2000, 36(3):461-5.
Court H and Volans GN, “Poisoning After Overdose With Nonsteroidal Anti-inflammatory Drugs,” Adverse Drug React Acute Poisoning Rev, 1984, 3(1):1-21.
“Drugs for Pain,” Med Lett Drugs Ther, 2000, 42(1085):73-8.
Graham DY, “Prevention of Gastroduodenal Injury Induced by Chronic Nonsteroidal Anti-inflammatory Drug Therapy,” Gastroenterology, 1989, 96(2 Pt 2 Suppl):675-81.
Gurwitz JH, Avorn J, Ross-Degnan D, et al, “Nonsteroidal Anti-inflammatory Drug-Associated Azotemia in the Very Old,” JAMA, 1990, 264(4):471-5.
Hawkey CJ, Karrasch JA, Szczepañski L, et al, “Omeprazole Compared With Misoprostol for Ulcers Associated With Nonsteroidal Anti-inflammatory Drugs,” N Engl J Med, 1998, 338(11):727-34.
Heerdink ER, Leufkens HG, Herings RM, et al, “NSAIDs Associated With Increased Risk of Congestive Heart Failure in Elderly Patients Taking Diuretics,” Arch Intern Med, 1998, 158(10):1108-12.
Hoppmann RA, Peden JG, and Ober SK, “Central Nervous System Side Effects of Nonsteroidal Anti-inflammatory Drugs. Aseptic Meningitis, Psychosis, and Cognitive Dysfunction,” Arch Intern Med, 1991, 151(7):1309-13.
Hunt SA, Abraham WT, Chin MH, et al, “2009 Focused Update Incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the International Society for Heart and Lung Transplantation,” J Am Coll Cardiol, 2009, 53(15):e1-e90.
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International Brand Names
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Last full review/revision November 2009
Content last modified November 2009
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