Parecoxib

Usage

Parecoxib is prescribed for the short-term treatment of postoperative pain in adults. It is also indicated for a single perioperative dose for the management of postoperative pain. Its pharmacological classification is a non-narcotic analgesic, specifically a selective cyclooxygenase-2 (COX-2) inhibitor. Parecoxib works by selectively inhibiting COX-2, an enzyme responsible for producing prostaglandins, which mediate inflammation and pain. By inhibiting COX-2, parecoxib reduces the production of these prostaglandins, thus alleviating pain and inflammation.

Alternate Names

The active metabolite of Parecoxib is valdecoxib. Parecoxib sodium is another name used. A common brand name under which it is marketed is Dynastat®. Rayzon is another trade name for parecoxib.

How It Works

Pharmacodynamics: Parecoxib, a prodrug, is rapidly hydrolyzed in the liver to its active metabolite, valdecoxib. Valdecoxib exerts its analgesic and anti-inflammatory effects through the selective inhibition of COX-2. This leads to a decrease in prostaglandin synthesis, reducing pain and inflammation.

Pharmacokinetics: Following intravenous (IV) or intramuscular (IM) administration, parecoxib is rapidly and extensively converted to valdecoxib. Peak plasma concentrations of valdecoxib are generally reached within approximately 30 minutes after IV administration and 1 hour after IM administration. Valdecoxib is primarily metabolized in the liver by cytochrome P450 (CYP) enzymes, mainly CYP3A4 and CYP2C9, with glucuronidation as a minor pathway. The elimination half-life of parecoxib is about 22 minutes, while the half-life of valdecoxib is around 8 hours. Excretion of valdecoxib and its metabolites occurs mainly through the kidneys.

Mode of Action: Valdecoxib binds selectively to the COX-2 enzyme, preventing the conversion of arachidonic acid to prostaglandin H2, a precursor to other pro-inflammatory prostaglandins. This selective inhibition of COX-2 reduces pain and inflammation with a potentially lower risk of gastrointestinal side effects compared to non-selective NSAIDs. Elimination is primarily through hepatic metabolism by CYP3A4 and CYP2C9.

Dosage

Standard Dosage

Adults:

The recommended initial dose is 40 mg administered IV or IM. This can be followed by 20 mg or 40 mg every 6 to 12 hours as needed, not exceeding a maximum daily dose of 80 mg. For postoperative pain, a single 40 mg dose is often used.

Children:

Safety and efficacy have not been established in children under 18 years old. However, some research suggests weight-based dosing for children over 2 years old, ranging from 0.65 mg/kg to 1 mg/kg, with a maximum of 40mg.

Special Cases:

• Elderly Patients (≥ 65 years): No dose adjustment is generally needed. However, elderly patients weighing less than 50 kg should start with half the usual recommended dose (20 mg), with a maximum daily dose of 40 mg.

• Patients with Renal Impairment: For patients with severe renal impairment (creatinine clearance <30 mL/minute), or those predisposed to fluid retention, parecoxib should be started at the lowest recommended dose (20 mg), and kidney function closely monitored.

• Patients with Hepatic Dysfunction: No dosage adjustment is required for mild hepatic impairment (Child-Pugh Class A). For moderate impairment (Child-Pugh Class B), start at the lowest recommended dose (20 mg) and reduce the maximum daily dose to 40 mg. Parecoxib is contraindicated in patients with severe hepatic impairment (Child-Pugh Class C).

• Patients with Comorbid Conditions: Use with caution in patients with cardiovascular disease, hypertension, or fluid retention.

Clinical Use Cases:

Dosage is consistent across various clinical use cases, such as intubation, surgical procedures, mechanical ventilation, intensive care unit (ICU) use, and emergency situations. However, the lowest effective dose for the shortest duration should be used, especially in patients with comorbidities.

Dosage Adjustments:

Dose modifications should be considered for renal or hepatic dysfunction as described above.

Side Effects

Common Side Effects:

Nausea, vomiting, constipation, dizziness, headache, insomnia, dyspepsia, abdominal pain, and increased blood pressure.

Rare but Serious Side Effects:

Allergic reactions (including anaphylaxis and angioedema), myocardial infarction, stroke, heart failure, gastrointestinal bleeding and perforation, renal failure, Stevens-Johnson syndrome, and toxic epidermal necrolysis.

Long-Term Effects:

Long-term use of COX-2 inhibitors can increase the risk of cardiovascular events. Parecoxib is only indicated for short-term use, therefore minimizing this risk.

Adverse Drug Reactions (ADR):

Any signs of allergic reaction, chest pain, shortness of breath, weakness on one side of the body, slurred speech, and signs of gastrointestinal bleeding require immediate medical attention.

Contraindications

• Hypersensitivity to parecoxib, valdecoxib, or other COX-2 inhibitors.
• History of aspirin- or NSAID-induced asthma, urticaria, or allergic-type reactions.
• Active peptic ulcer or gastrointestinal bleeding.
• Severe hepatic impairment (Child-Pugh Class C).
• Third trimester of pregnancy and breastfeeding.
• Inflammatory bowel disease.
• Congestive heart failure (NYHA II-IV).
• Post-operative pain following coronary artery bypass graft (CABG) surgery.

Drug Interactions

• Warfarin: Parecoxib can enhance the anticoagulant effect of warfarin. Careful monitoring of INR is essential.
• Fluconazole: Concomitant use with fluconazole (a CYP2C9 inhibitor) can increase parecoxib exposure. The lowest recommended dose of parecoxib should be used.
• Ketoconazole: Co-administration with ketoconazole (a CYP3A4 inhibitor) may moderately increase parecoxib exposure.
• ACE inhibitors, Angiotensin II receptor blockers, Beta-blockers, and Diuretics: Parecoxib can reduce the effectiveness of these medications and may increase the risk of renal dysfunction, particularly in elderly or volume-depleted patients.
• Other NSAIDs: Concurrent use should be avoided due to the potential for additive adverse effects.
• Lithium: Parecoxib can increase lithium levels.

Pregnancy and Breastfeeding

Parecoxib is contraindicated during the third trimester of pregnancy and breastfeeding. It should be avoided in the first two trimesters unless the potential benefits outweigh the risks. Parecoxib may make it more difficult to become pregnant.

Drug Profile Summary

• Mechanism of Action: Selective COX-2 inhibition, reducing prostaglandin synthesis.
• Side Effects: Nausea, vomiting, constipation, dizziness, headache; rarely: serious cardiovascular events, GI bleeding.
• Contraindications: Hypersensitivity, severe hepatic impairment, third-trimester pregnancy.
• Drug Interactions: Warfarin, fluconazole, antihypertensives.
• Pregnancy & Breastfeeding: Contraindicated in the third trimester and during breastfeeding. Avoid during the first two trimesters.
• Dosage: 40 mg IV/IM initially, followed by 20-40 mg every 6-12 hours; max 80 mg/day.
• Monitoring Parameters: Blood pressure, kidney function, signs of GI bleeding or allergic reaction, liver function tests (LFTs) if used beyond three days.

Popular Combinations

Parecoxib is often used in combination with opioid analgesics. This combination can reduce opioid requirements and enhance pain relief.

Precautions

• Assess cardiovascular risk factors before administering.
• Pre-existing hepatic or renal insufficiency may necessitate dose adjustments.
• Monitor for signs of GI bleeding or allergic reaction.
• Avoid long-term use.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Parecoxib?

A: The standard adult dose is 40 mg IV/IM initially, which can be followed by 20-40 mg every 6-12 hours, not to exceed 80 mg/day. Adjustments are needed for elderly patients weighing under 50kg, and for those with moderate to severe hepatic or renal impairment. It is not recommended for children under 18.

Q2: How does Parecoxib differ from traditional NSAIDs?

A: Parecoxib selectively inhibits COX-2, while traditional NSAIDs inhibit both COX-1 and COX-2. This selectivity may reduce the risk of GI side effects.

Q3: Can Parecoxib be used during pregnancy?

A: Parecoxib is contraindicated during the third trimester of pregnancy. It should be avoided during the first two trimesters unless benefits outweigh the risks to the fetus.

Q4: What are the major drug interactions with Parecoxib?

A: Significant interactions occur with warfarin, fluconazole, and antihypertensives such as ACE inhibitors, ARBs, beta-blockers and diuretics.

Q5: How long does Parecoxib provide pain relief?

A: Analgesia typically starts within 7-14 minutes after administration and can last for 6-24 hours after a single dose.

Q6: What are the most common side effects?

A: Common side effects include nausea, vomiting, constipation, dizziness, and headache.

Q7: Can Parecoxib be used for chronic pain?

A: No, Parecoxib is only indicated for short-term use (usually up to 3 days) for acute postoperative pain.

Q8: How is Parecoxib administered?

A: Parecoxib is administered intravenously or intramuscularly.

Q9: What should I do if a patient experiences an allergic reaction to Parecoxib?

A: Discontinue Parecoxib immediately and provide supportive care as needed. Severe reactions, such as anaphylaxis, require immediate medical intervention.

Q10: Can Parecoxib be used in patients with a history of peptic ulcers?

A: Parecoxib should be used with caution in patients with a history of peptic ulcers due to a potential risk of gastrointestinal bleeding and perforation.