PROXYM-300 300MG TABLET

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

Dosage

Children: Refer to specific product information for paediatric dosage guidelines based on the active ingredient and clinical condition.

Adults: Refer to specific product information for dosage instructions, as extended-release formulations vary by active ingredient and condition treated.

Mechanism of action

Extended-release formulations typically work by utilizing a matrix or coating that delays the release of the active ingredient. The release mechanism may involve diffusion, erosion, or osmotic processes, which allow the drug to be released slowly into the systemic circulation. This controlled release helps achieve stable plasma drug concentrations and minimizes peaks and troughs associated with immediate-release formulations.

Pharmacodynamics

The pharmacodynamics of extended-release medications depend on the specific active ingredient used. Generally, these medications aim to provide a steady-state concentration of the drug, leading to more consistent therapeutic effects. The prolonged exposure to the drug can enhance its efficacy and reduce side effects associated with rapid absorption, such as peak-related toxicity or adverse reactions.

Pharmacokinetics

Pharmacokinetics of extended-release formulations involves absorption, distribution, metabolism, and elimination phases that differ from immediate-release forms. The extended-release form is designed to slow the absorption rate, resulting in a longer half-life and sustained therapeutic effect. The drug may be absorbed over several hours to days, depending on the formulation. Metabolism and elimination pathways remain similar to those of the immediate-release counterparts, but the sustained exposure may necessitate careful monitoring for potential accumulation and side effects.

Indications

• Bacterial infections
• Infections caused by susceptible organisms
• Prophylaxis in certain surgical procedures

Dosage

Children: Refer to the BNF for Children for specific dosing recommendations based on age, weight, and condition.

Adults: Refer to the BNF for specific dosages based on the condition being treated, severity of infection, and patient factors.

Mechanism of action

Release exerts its effects by inhibiting bacterial cell wall synthesis, leading to cell lysis and death. This mechanism is primarily mediated through the disruption of peptidoglycan cross-linking, which is essential for maintaining the structural integrity of bacterial cell walls.

Pharmacodynamics

The pharmacodynamics of Release involves its bactericidal action against a wide range of gram-positive and some gram-negative bacteria. The drug displays a time-dependent killing effect, meaning that its efficacy is related to the duration of exposure rather than the peak concentration achieved. Resistance to Release can develop through various mechanisms, including alterations in target sites or enzymatic degradation.

Pharmacokinetics

Release is absorbed and distributed throughout the body following administration. Peak plasma concentrations are typically achieved within a few hours. The drug is metabolized primarily in the liver, with metabolites excreted via the kidneys. The half-life of Release can vary depending on individual patient factors, including age, liver function, and concurrent medications.

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_.