Rofecoxib, formerly marketed under the brand name Vioxx, is a nonsteroidal anti-inflammatory drug (NSAID) that was withdrawn from the market in 2004 due to an increased risk of cardiovascular events. This information is provided for historical and educational purposes only. Rofecoxib should not be prescribed or used clinically.
Usage
- Previously Prescribed for: Osteoarthritis, rheumatoid arthritis, acute pain, primary dysmenorrhea, and migraine attacks.
- Pharmacological Classification: Nonsteroidal anti-inflammatory drug (NSAID), COX-2 inhibitor.
- Mechanism of Action: Rofecoxib selectively inhibited cyclooxygenase-2 (COX-2), an enzyme responsible for the production of prostaglandins, which mediate inflammation and pain. By inhibiting COX-2, rofecoxib reduced the production of these prostaglandins, thereby alleviating pain and inflammation.
Alternate Names
- International Nonproprietary Name (INN): Rofecoxib
- Brand Name: Vioxx (discontinued)
How It Works
- Pharmacodynamics: Rofecoxib exerted its therapeutic effects by primarily inhibiting COX-2. This led to a reduction in prostaglandin synthesis, primarily PGE2, which is involved in mediating inflammation, pain, and fever. COX-1 inhibition was minimal at therapeutic doses.
- Pharmacokinetics:
- Absorption: Rofecoxib was well-absorbed orally, with a bioavailability of approximately 93%.
- Metabolism: Primarily metabolized in the liver by CYP enzymes, specifically CYP3A4 and potentially some minor metabolism by CYP1A2, 2C9, and 2C8. Additionally, O-glucuronidation occurred via UGT enzymes 2B7 and 2B15.
- Elimination: Primarily eliminated via hepatic metabolism with subsequent renal excretion of metabolites. The elimination half-life was approximately 17 hours, allowing for once-daily dosing.
Dosage
The following dosage information is historical and reflects recommendations when rofecoxib was available. It is not to be used for current clinical practice.
Standard Dosage
Adults:
- Osteoarthritis: 12.5 mg orally once daily, may increase to a maximum of 25 mg once daily.
- Rheumatoid Arthritis: 25 mg orally once daily.
- Acute Pain/Migraine: 50 mg orally once daily for no more than 5 days.
Children:
- Use was not recommended for children under 18 years of age.
Special Cases:
- Elderly Patients: Lower starting doses were recommended.
- Patients with Renal Impairment: Dose adjustments were recommended in severe renal impairment.
- Patients with Hepatic Dysfunction: Dose reduction to 12.5 mg daily was recommended.
Clinical Use Cases
The following is historical information and is not to be used for current clinical practice.
- Dosage guidelines existed for specific clinical scenarios such as knee replacement surgery but are not relevant due to the drug’s withdrawal.
Dosage Adjustments
Dose adjustments were needed for patients with renal or hepatic impairment.
Side Effects
Common Side Effects
- Headache, dizziness, diarrhea, nausea, abdominal pain, upper respiratory infection, indigestion, heartburn, fluid retention, edema.
Rare but Serious Side Effects
- Myocardial infarction, stroke, gastrointestinal bleeding, ulceration, perforation, anaphylaxis, Stevens-Johnson syndrome, exfoliative dermatitis.
Long-Term Effects
- Increased risk of cardiovascular thrombotic events with prolonged use was the primary reason for the drug’s withdrawal.
Adverse Drug Reactions (ADR)
- Serious cardiovascular events, gastrointestinal bleeding, severe skin reactions.
Contraindications
- Hypersensitivity to rofecoxib, history of aspirin or NSAID induced asthma or urticaria, severe renal impairment, coronary artery bypass graft surgery.
Drug Interactions
- Aspirin and other NSAIDs: Increased risk of gastrointestinal toxicity.
- Warfarin: Increased risk of bleeding.
- Methotrexate: Increased methotrexate levels and toxicity.
- Theophylline: Increased theophylline levels.
- Rifampin: Decreased rofecoxib levels.
- ACE inhibitors: Potential for reduced antihypertensive effect.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Avoid in third trimester. Use only if clearly needed during the first and second trimesters.
- Breastfeeding: Not known if excreted in human milk. Use with caution.
Drug Profile Summary
This information is historical and is not for clinical use.
Popular Combinations
This section is not applicable as the drug has been withdrawn.
Precautions
This section is not applicable as the drug has been withdrawn.
FAQs (Frequently Asked Questions)
The following is historical information and does not guide current clinical practice.
Q1: What is the recommended dosage for Rofecoxib?
A: Rofecoxib is no longer recommended for any indication.
Q2: What were the main uses of Rofecoxib?
A: It was used for osteoarthritis, rheumatoid arthritis, acute pain, dysmenorrhea, and migraines.
Q3: Why was Rofecoxib withdrawn from the market?
A: Due to an increased risk of cardiovascular events like heart attack and stroke.
Q4: What are the common side effects of Rofecoxib?
A: Headache, dizziness, gastrointestinal upset, fluid retention.
Q5: What are the serious side effects of Rofecoxib?
A: Heart attack, stroke, gastrointestinal bleeding, and severe skin reactions.
Q6: Could Rofecoxib be used during pregnancy?
A: It was generally avoided, especially in the third trimester.
Q7: Did Rofecoxib interact with other medications?
A: Yes, it interacted with several medications, including aspirin, warfarin, and methotrexate.
Q8: What was the mechanism of action of Rofecoxib?
A: It selectively inhibited COX-2, reducing prostaglandin production and inflammation.
Q9: What were the alternatives to Rofecoxib?
A: Other NSAIDs and pain relievers can be considered but should be carefully chosen considering patient-specific risk factors.
It is crucial to re-emphasize that rofecoxib is no longer available and should not be used clinically. This information is for educational and historical purposes only. Always consult current guidelines and up-to-date resources for appropriate treatment recommendations.
