ETOTAC SR 600

Indications

• Pain and inflammation in rheumatoid arthritis
• Pain and inflammation in osteoarthritis
• Control of acute pain

Dosage

Children: Refer to the BNF for Children for specific dosing information.

Adults: 600 mg once daily, administered orally

Mechanism of action

Etodolac inhibits cyclooxygenase (COX), a key enzyme in the conversion of arachidonic acid to prostaglandins. It preferentially binds to the COX-2 isoform, which is primarily involved in inflammation, thereby reducing the production of inflammatory mediators. This selective inhibition is responsible for its anti-inflammatory and analgesic effects.

Pharmacodynamics

As an anti-inflammatory agent, etodolac has analgesic and antipyretic properties. It is effective in treating osteoarthritis and rheumatoid arthritis by reducing pain, swelling, and fever through the inhibition of prostaglandin synthesis. The active S-enantiomer contributes to its therapeutic effects, while the R-enantiomer is inactive.

Pharmacokinetics

Etodolac is well-absorbed following oral administration, with peak plasma concentrations occurring within 1 to 2 hours. It has a half-life of approximately 6 to 8 hours and is extensively metabolized in the liver. Approximately 50% of the drug is excreted in urine as metabolites, with a small proportion excreted unchanged. Food does not significantly affect its absorption.

Contra-indications

• Active gastrointestinal bleeding
• History of gastrointestinal perforation related to previous NSAID use
• Severe renal impairment
• Hypersensitivity to etodolac or any other component of the formulation

Adverse effects

• Gastrointestinal discomfort
• Nausea
• Vomiting
• Dizziness
• Headache
• Rash
• Renal impairment
• Hepatic dysfunction
• Cardiovascular thrombotic events

Interactions

• Increased risk of bleeding with anticoagulants such as warfarin
• Potential increase in plasma concentrations of lithium
• May reduce the antihypertensive effect of ACE inhibitors and diuretics
• Concurrent use with other NSAIDs may increase the risk of gastrointestinal toxicity

Precautions

• Use with caution in patients with a history of peptic ulcer disease
• Monitor renal function in patients with renal impairment
• Assess cardiovascular risk in patients with cardiovascular diseases
• Consider potential gastrointestinal risks in elderly patients

Pregnancy

Etodolac should be avoided, especially during the third trimester, due to potential risks of fetal cardiovascular effects and inhibition of labor.

Breast-feeding

Caution is advised as etodolac is excreted in breast milk; consult a healthcare professional before use.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Tablets 400 mg
• Tablets 600 mg
• Capsules 300 mg
• Extended-release tablets 500 mg

Mechanism of action

Similar to other NSAIDs, the anti-inflammatory effects of etodolac result from inhibition of the enzyme cycooxygenase (COX). This decreases the synthesis of peripheral prostaglandins involved in mediating inflammation. Etodolac binds to the upper portion of the COX enzyme active site and prevents its substrate, arachidonic acid, from entering the active site. Etodolac was previously thought to be a non-selective COX inhibitor, but it is now known to be 5 – 50 times more selective for COX-2 than COX-1. Antipyresis may occur by central action on the hypothalamus, resulting in peripheral dilation, increased cutaneous blood flow, and subsequent heat loss.

Pharmacodynamics

Etodolac is an anti-inflammatory agent with analgesic and antipyretic properties. It is used to treat osteoarthritis, rheumatoid arthritis and control acute pain. The therapeutic effects of etodolac are achieved via inhibition of the synthesis of prostaglandins involved in fever, pain, swelling and inflammation. Etodolac is administered as a racemate. As with other NSAIDs, the S-form has been shown to be active while the R-form is inactive. Both enantiomers are stable and there is no evidence of R- to S- conversion _in vivo_.