ARISTOROFEB 25MG TABLET

Indications

• Osteoarthritis
• Rheumatoid arthritis
• Acute pain
• Dysmenorrhea
• Postoperative pain

Dosage

Children: Refer to the BNF for Children for specific dosing recommendations for paediatric patients.

Adults: Refer to the BNF for specific dosing recommendations for adults based on the condition being treated.

Mechanism of action

Rofecoxib selectively inhibits the COX-2 isoenzyme, leading to decreased synthesis of prostaglandins from arachidonic acid precursors. This selective inhibition results in reduced inflammation and pain without significantly affecting platelet aggregation or the COX-1 pathway, which is responsible for maintaining gastrointestinal mucosal integrity.

Pharmacodynamics

As a selective COX-2 inhibitor, rofecoxib exhibits anti-inflammatory, analgesic, and antipyretic activities. It reduces the production of prostaglandins, mediating pain and inflammation. By inhibiting COX-2 specifically, rofecoxib aims to minimize gastrointestinal adverse effects compared to traditional NSAIDs that inhibit both COX-1 and COX-2.

Pharmacokinetics

Rofecoxib is absorbed well from the gastrointestinal tract, with peak plasma concentrations occurring within 1-2 hours after oral administration. It has a high volume of distribution and is metabolized primarily by the liver via oxidative pathways, not requiring CYP450 enzymes for its metabolism. The elimination half-life is approximately 17 hours, allowing for once-daily dosing in many cases. Renal excretion is a significant route for the elimination of its metabolites.

Contra-indications

• History of hypersensitivity to rofecoxib or any of its components
• Active or history of peptic ulcer disease or gastrointestinal bleeding
• Severe hepatic impairment
• Severe renal impairment
• Congestive heart failure
• Uncontrolled hypertension

Adverse effects

• Cardiovascular events (e.g., myocardial infarction, stroke)
• Gastrointestinal complications (e.g., ulceration, perforation, bleeding)
• Renal impairment
• Hepatic toxicity
• Skin reactions (e.g., rash, allergic reactions)
• Headache
• Dizziness
• Nausea
• Diarrhea

Interactions

• Increased risk of gastrointestinal toxicity when used with other NSAIDs
• May decrease the effectiveness of antihypertensive medications
• Potential interaction with anticoagulants, increasing the risk of bleeding
• Caution with diuretics due to potential renal impairment

Precautions

• Use with caution in patients with a history of cardiovascular disease
• Monitor renal function in patients with existing kidney impairment
• Consider the cardiovascular risks associated with long-term use
• Avoid use in patients with active gastrointestinal disease
• Assess patient history for any allergic reactions to NSAIDs

Pregnancy

Rofecoxib should be avoided during pregnancy, especially in the third trimester, due to potential risks to the fetus and complications during delivery.

Breast-feeding

It is not known if rofecoxib is excreted in human breast milk. Caution should be exercised when administering to nursing mothers.

Storage

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

Formulations

• Tablets: 12.5 mg, 25 mg, 50 mg

Mechanism of action

The anti-inflammatory, analgesic, and antipyretic effects of NSAIDs appear to result from the inhibition of prostaglandin synthesis. Although the exact mechanism of action has not been determined, these effects appear to be mediated through the inhibition of the COX-2 isoenzyme at the sites of inflammation with subsequent reduction in the synthesis of certain prostaglandins from their arachidonic acid precursors. Rofecoxib selectively inhibits the cyclooxygenase-2 (COX-2) enzyme, which is important for the mediation of inflammation and pain. Unlike non-selective NSAIDs, rofecoxib does not inhibit platelet aggregation. It also has little to no affinity for COX-1. Rofecoxib is a nonsteroidal anti-inflammatory drug (NSAID) with anti-inflammatory, analgesic, and antipyretic therapeutic effects. It has been proposed that rofecoxib inhibits the activity of the enzyme cyclooxygenase-2 (COX-2), resulting in a decreased formation of precursors of prostaglandins. Rofecoxib does not inhibit cyclooxygenase-1 (COX-1) isoenzyme in humans at therapeutic concentrations.

Pharmacodynamics

Rofecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is classified as a nonsteroidal anti-inflammatory drug (NSAID). Unlike celecoxib, rofecoxib lacks a sulfonamide chain and does not require CYP450 enzymes for metabolism. Like other NSAIDs, rofecoxib exhibits anti-inflammatory, analgesic, and antipyretic activity. NSAIDs appear to inhibit prostaglandin synthesis via the inhibition of cyclooxygenase (COX), which are responsible for catalyzing the formation of prostaglandins in the arachidonic acid pathyway. There are at least two isoenzymes, COX-1 and COX-2, that have been identified. Although the exact mechanisms have not been clearly established, NSAIDs exert their anti-inflammatory, analgesic, and antipyretic primarily through the inhibition of COX-2. The inhibition of COX-1 is principally responsible for the negative effects on the GI mucosa. As rofecoxib is selective for COX-2, it may be potentially associated with a decreased risk of certain adverse events, but more data is needed to fully evaulate the drug.