Paracetamol + Rofecoxib

Usage

This drug combination is primarily indicated for the relief of mild to moderate pain and fever. It combines the analgesic and antipyretic effects of paracetamol with the anti-inflammatory action of rofecoxib. It may be particularly useful in situations where pain has an inflammatory component, such as osteoarthritis or other musculoskeletal conditions. However, due to the potential cardiovascular risks associated with rofecoxib, its use is restricted and carefully considered. It belongs to the pharmacological classifications of analgesics and NSAIDs (specifically a COX-2 inhibitor).

Alternate Names

There are no officially recognized alternate names for the combination product itself. However, the individual components have other names:

• Paracetamol: Acetaminophen (primarily used in the United States and some other countries)
• Rofecoxib: Vioxx (brand name, now withdrawn from the market due to cardiovascular safety concerns).

How It Works

Paracetamol:

• Pharmacodynamics: Paracetamol’s exact mechanism of action is not fully understood, but it is believed to primarily inhibit COX enzymes in the central nervous system, reducing prostaglandin synthesis and thereby affecting pain and temperature regulation. It also has weak effects on peripheral COX enzymes.
• Pharmacokinetics: Paracetamol is rapidly absorbed from the gastrointestinal tract, reaching peak plasma concentrations within 30-60 minutes. It is metabolized primarily in the liver via glucuronidation and sulfation pathways, with a small fraction undergoing oxidation via the cytochrome P450 system to form a potentially hepatotoxic metabolite (NAPQI), which is usually detoxified by glutathione. It is excreted primarily in the urine.

Rofecoxib:

• Pharmacodynamics: Rofecoxib is a selective COX-2 inhibitor. COX-2 is an enzyme involved in the production of prostaglandins that mediate inflammation and pain. By selectively inhibiting COX-2, rofecoxib reduces inflammation and pain with theoretically less impact on gastrointestinal side effects compared to non-selective NSAIDs.
• Pharmacokinetics: Rofecoxib is well absorbed orally, with a bioavailability of approximately 93%. Peak plasma levels are achieved in about 2-3 hours. It is metabolized primarily in the liver, with about 72% of the dose excreted in the urine and 16% in the feces.

Dosage

Since Rofecoxib was withdrawn from the market, prescribing this combination is not current practice. Therefore, no standard dosage guidelines exist. Doctors should not prescribe this combination.

Side Effects

Common Side Effects

Paracetamol: Generally well-tolerated at therapeutic doses, but possible side effects include nausea, vomiting, and allergic reactions (rash, itching).

Rofecoxib: Potential side effects include gastrointestinal upset (dyspepsia, abdominal pain, diarrhea), fluid retention, and increased blood pressure.

Rare but Serious Side Effects

Paracetamol: Rare but serious side effects include severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), liver failure (with overdose or in patients with pre-existing liver disease).

Rofecoxib: Serious but rare side effects include myocardial infarction, stroke, and other cardiovascular events. This is the main reason for its withdrawal from the market.

Contraindications

Paracetamol: Contraindicated in patients with severe hepatic impairment.

Rofecoxib: Contraindicated in individuals with known hypersensitivity, history of myocardial infarction, stroke, or other cardiovascular events.

Drug Interactions

Paracetamol: Interacts with alcohol (increased risk of hepatotoxicity), warfarin (increased risk of bleeding).

Rofecoxib: Interacts with ACE inhibitors, angiotensin receptor blockers, and diuretics (decreased antihypertensive effect), lithium (increased lithium levels), warfarin (increased risk of bleeding).

Pregnancy and Breastfeeding

Paracetamol: Generally considered safe for use during pregnancy and breastfeeding at recommended doses.

Rofecoxib: Contraindicated during pregnancy and breastfeeding.

Drug Profile Summary

This combination is no longer used due to rofecoxib’s risks. If pain relief is needed, doctors can offer other options.

Popular Combinations

This specific combination isn’t currently relevant.

Precautions

This combination should not be used.

FAQs (Frequently Asked Questions)

This combination isn’t relevant now because of rofecoxib’s safety issues. If you’re dealing with a patient in pain, you should consider and discuss other suitable medications based on the individual’s condition and medical history. You can consider paracetamol alone or other safer alternatives. Always exercise caution when prescribing medications and factor in the patient’s overall health status.