Etodolac is a non-specific prostaglandin synthesis inhibitor which produces ant-inflammatory, antipyretic (anti-fever), and analgesic pharmacologic effects in approximately 30 minutes after an oral doses of 200-400mg for a duration of 4-6 hours. The drug’s absorption is not affected when administered with an antacid or food, however food will reduce its peak concentration blood levels.
Etodolac is metabolized in the liver and primarily excreted via the kidneys. The drug’s dosage however does not need to be reduced in those patients who are elderly, or have mild to moderate renal insufficiency or liver impairment, unless those with severe liver failure as documented by hepatic enzyme blood tests.
The analgesia produced by 200mg is equivalent to aspirin, and at higher doses of 400mg provides the therapeutic benefit of acetaminophen (600mg)/codeine (60mg) apap#4. For the analgesia needed post dental extraction, a study revealed only half of the patients required to have a second dose given 5-6 hours later. In osteoarthritic patients with knee and hip pathology, Etodolac dosed at 600-1000mg per day provided management. Rheumatoid patients receiving 300mg twice daily exhibited therapeutic efficiency to 20mg of piroxicam (Feldene) daily. At 500mg orally twice daily, Etodolac was comparable to ibuprofen (Motrin) 600mg 4 times daily. It may be co administered with gold salts, corticosteroids, Methotrexate, and chloroquine.
Etodolac is indicated for the treatment of acute and long-term manifestations of osteoarthritis and rheumatoid arthritis and for relief of pain. The drug should be avoided in patients with a known reaction to aspirin or any of the non-steroidal anti-inflammatory medications, have asthma, or nasal polyps. The drug should not be used in pregnant or lactating women due to the effect of prostaglandin inhibition on the developing fetal cardiovascular system and of the newborn, and is not indicated in the patient less than 18 years of age.
Adverse effects may manifest in the gastrointestinal system such as gastritis, peptic ulcerations, bleeding and perforation. Long term usage may cause renal (kidney) changes such as papillary necrosis, medullary alterations, epithelia hyperplasia, and reduced renal perfusion flow due to the reduction of prostaglandins which serve an important role in renal blood flow maintenance, especially those patients on diuretics (water pills), the elderly, and those with heart failure. This may be reversed by discontinuing the medication. Liver enzymes may be elevated in 15% of the patients. Though liver necrosis is rare, significantly elevated enzymes (up to three fold) which do not reverse by discontinuance of the drug, should be evaluated. Those patients with unexplained rash and/or other blood cell changes should also be further evaluated. The prescribing physician should be made aware of other systemic changes such as significant unexplained constant weight gain, blurred vision or other eye problems, and edema.
Patients on long term therapy which exhibit reduction in pain or arthritic symptoms and will continue with Etodolac, should have periodical blood tests including hemoglobin and hematocrit along with previously mentioned labs.
Drug interactions are due to the highly protein bound characteristic of the drug. These include aspirin which will be in competition for the binding sites and thus have a reduction in therapeutic effect, elevated serum levels of digoxin (which may be cardio toxic), lithium and methotrexate both of which may lead to toxic blood levels. Etodolac in short term usage does not interfere or require dosage adjustment with warfarin (coumadin), antacids, phenytoin (for epileptic seizures), and glyburide (an oral hypoglycemic for type 2 diabetes).
The dosage of Etodolac, as with all medications, should be the lowest for the indication (analgesia, osteoarthritis, rheumatoid arthritis) which provides the desired response. The usual dose for the relief of pain is 200-400mg orally every 6-8 hours up to 1000mg (one gram) daily. Higher blood levels are required for the relief of the osteoarthritis and rheumatoid arthritis and is dosed at 300 or 400mg orally increased up to 1200mg daily. The drug is available as 200mg, 300mg capsules and 400mg and 500mg film-coated tablets. A time released or extended release tablets are available in 400XL, 500XL, and 600XL mg.
REFERENCES
PDR, PHYSICIANS’ DESK REFERENCE, 59th edition
MPR, MONTHLY PRESCRIBING REFERENCE, PODIATRY EDITION 2009.
My personal experience with Etodolac has been with the extended release formulations of Lodine for those active patients with busy schedules which were in need of pain relief following repeated injury to an arthritic foot or ankle to ascertain patient compliance. I have also found the benefits of Lodine in those patients which would normally require a codeine derivative with documented allergy.
ADDITIONAL REFERENCES
See our other pain medication discussions.
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