Parix

Approved Indications:

• Short-term treatment of postoperative pain in adults, especially following orthopedic, abdominal, gynecological, and dental surgeries.
• Moderate to severe acute pain where parenteral NSAID administration is appropriate.

Clinically Accepted Off-label Uses:

• Multimodal analgesia in Enhanced Recovery After Surgery (ERAS) protocols.
• Cancer-related procedural pain, especially where opioids need to be minimized.
• Alternative to opioids in patients at risk for opioid-induced respiratory depression.

Adults:

• Initial dose: 40 mg IV or IM.
• Maintenance dose: 20 to 40 mg every 6–12 hours as needed.
• Maximum daily dose: 80 mg.
• Route of administration: Intravenous (IV) or Intramuscular (IM).

Elderly (≥65 years):

• Start with 20 mg; adjust based on clinical response.
• Monitor closely for renal, hepatic, and cardiovascular function.

Pediatric Use:

• Safety and efficacy not established; not recommended under 18 years of age.

Hepatic Impairment:

• Mild to moderate: Use the lowest effective dose; monitor liver enzymes.
• Severe impairment: Contraindicated.

Renal Impairment:

• Moderate (CrCl 30–59 mL/min): Use with caution; lower dosage may be required.
• Severe (CrCl <30 mL/min): Not recommended.

Duration of Use:

• For short-term use only, typically not exceeding 3–5 days.

Parecoxib is a water-soluble prodrug that is rapidly converted in vivo to valdecoxib, its active form. Valdecoxib is a selective cyclooxygenase-2 (COX-2) inhibitor that blocks the conversion of arachidonic acid to prostaglandins involved in pain and inflammation. By selectively inhibiting COX-2 rather than COX-1, parecoxib reduces inflammatory pain without significantly affecting platelet aggregation or causing gastrointestinal mucosal damage, making it favorable for short-term use in acute pain settings.

• Absorption: Rapid conversion to valdecoxib within ~30 minutes after IV/IM administration.
• Bioavailability: Not applicable (parenteral drug).
• Distribution: Volume of distribution ~55 L; highly protein-bound (~98%).
• Metabolism: Hepatic via CYP3A4 and CYP2C9 enzymes.
• Half-life: Parecoxib ~22 minutes; valdecoxib ~8 hours.
• Excretion: Mainly via urine (~70%) as inactive metabolites; ~20% in feces.

• Pregnancy: FDA Category C; not recommended during pregnancy, especially in the third trimester due to risk of premature closure of ductus arteriosus.
• Lactation: Valdecoxib is excreted in small amounts in breast milk. Use caution; avoid if possible during breastfeeding due to potential adverse effects in infants.
• Recommendation: Avoid during late pregnancy and use cautiously during lactation.

• Therapeutic Class: Nonsteroidal Anti-inflammatory Drug (NSAID)
• Subclass: Selective COX-2 Inhibitor
• Form: Injectable (parenteral) NSAID

• Known hypersensitivity to parecoxib, valdecoxib, sulfonamides, or any component of the formulation
• History of asthma, urticaria, or other allergic-type reactions to NSAIDs
• Active gastrointestinal bleeding or peptic ulcer disease
• Severe hepatic impairment
• Severe renal impairment (CrCl <30 mL/min)
• Coronary artery bypass graft (CABG) surgery (perioperative use)
• Pregnancy in the third trimester

• Cardiovascular Risk: May increase risk of serious events like myocardial infarction or stroke; especially with prolonged use or in patients with existing cardiovascular disease.
• Gastrointestinal Effects: Though lower than non-selective NSAIDs, there remains a risk of GI ulceration and bleeding.
• Renal Function: Monitor closely in elderly, dehydrated, or patients with renal compromise.
• Skin Reactions: Rare but serious conditions such as Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) may occur.
• Hypersensitivity: Potential cross-reactivity with sulfonamide-sensitive patients.
• Monitoring: Liver function tests, renal function, and signs of allergic reactions should be routinely monitored.

Common (≥1%):

• Nausea
• Headache
• Injection site pain or inflammation
• Constipation
• Dizziness

Less Common:

• Edema
• Flatulence
• Sweating
• Abnormal liver enzymes

Serious (Rare):

• Myocardial infarction
• Stroke
• Gastrointestinal hemorrhage or perforation
• Hypersensitivity reactions
• Anaphylaxis
• SJS/TEN
• Hepatotoxicity

• ACE inhibitors, ARBs, and diuretics: May potentiate nephrotoxic effects.
• Warfarin and anticoagulants: Increased risk of bleeding; monitor INR closely.
• Lithium: NSAIDs may elevate lithium plasma levels; monitor lithium concentrations.
• CYP2C9 inhibitors (e.g., fluconazole): May increase exposure to valdecoxib.
• Other NSAIDs or salicylates: Concomitant use increases the risk of GI and renal side effects and is not recommended.
• Alcohol: May enhance gastrointestinal toxicity.

• FDA and EMA safety communications reaffirm the cardiovascular and renal risks associated with COX-2 inhibitors.
• Enhanced Recovery After Surgery (ERAS) guidelines promote parecoxib as part of multimodal analgesia with opioid-sparing effects.
• New warning (EMA, 2023): Reaffirmed avoidance in patients with sulfonamide allergy and updated labeling to include specific renal dosing caution.

• Temperature: Store below 25°C.
• Humidity: Keep dry; avoid moisture exposure.
• Light Protection: Store in the original packaging to protect from light.
• Handling: Use aseptic technique during reconstitution.
• Reconstitution Instructions: Reconstitute powder for injection with sterile water as per manufacturer instructions; use immediately after reconstitution or within the advised time frame.
• Do not freeze.