Celecoxib

Usage

Celecoxib is a nonsteroidal anti-inflammatory drug (NSAID) specifically classified as a COX-2 inhibitor. It is prescribed for the management of:

• Osteoarthritis
• Rheumatoid arthritis
• Ankylosing spondylitis
• Acute pain (short-term management)
• Primary dysmenorrhea
• Juvenile rheumatoid arthritis (JRA) in children 2 years and older
• Familial adenomatous polyposis (FAP) - as an adjunct to surgery and endoscopic surveillance

Celecoxib’s mechanism of action involves selective inhibition of cyclooxygenase-2 (COX-2), an enzyme responsible for prostaglandin synthesis, which plays a key role in inflammation and pain. By inhibiting COX-2, celecoxib reduces inflammation and pain with a lower risk of gastrointestinal side effects compared to non-selective NSAIDs.

Alternate Names

While “celecoxib” is the generic name, it is marketed under various brand names, most notably Celebrex. Onsenal and Elyxyb are also brand names used for celecoxib. Regional or international variations may exist.

How It Works

Pharmacodynamics: Celecoxib exerts its therapeutic effects by selectively inhibiting COX-2. This reduces the production of prostaglandins, which mediate inflammation, pain, and fever. The selectivity for COX-2 theoretically minimizes the inhibition of COX-1, an enzyme involved in protecting the gastric mucosa and promoting platelet aggregation. Consequently, celecoxib may have a lower incidence of gastrointestinal side effects and does not significantly affect platelet function.

Pharmacokinetics:

• Absorption: Celecoxib is well-absorbed orally, with peak plasma concentrations reached in approximately 2-3 hours. Food may slightly delay absorption, but it doesn’t significantly affect the overall extent of absorption.
• Metabolism: Primarily metabolized in the liver by CYP2C9 enzyme to inactive metabolites. Genetic polymorphisms in CYP2C9 can affect celecoxib metabolism, requiring dose adjustments.
• Elimination: Primarily eliminated via hepatic metabolism, with approximately 27% excreted in urine and 57% in feces. The elimination half-life is about 11 hours.

Mode of Action: Celecoxib binds reversibly to the active site of the COX-2 enzyme, inhibiting its activity. This reduces the synthesis of pro-inflammatory mediators, leading to decreased inflammation and pain.

Receptor Binding/Enzyme Inhibition: Celecoxib selectively targets COX-2 enzyme inhibition.

Elimination Pathways: Celecoxib is primarily eliminated by hepatic metabolism, involving CYP2C9 enzymes, with subsequent excretion in urine and feces.

Dosage

Standard Dosage

Adults:

• Osteoarthritis/Ankylosing Spondylitis: 200 mg orally once daily or 100 mg twice daily. May increase to 400 mg daily (as a single dose or divided into two doses) if needed.
• Rheumatoid Arthritis: 100-200 mg orally twice daily.
• Acute Pain/Primary Dysmenorrhea: Initial dose of 400 mg, followed by 200 mg if needed on the first day. Then, 200 mg twice daily as needed (maximum 7 days).
• Migraine: 120 mg single dose. Not to exceed 120 mg/24 hours. (Applies to certain formulations).
• FAP: 400 mg orally twice daily with food.

Children (JRA):

• 2 years and older (10-25 kg): 50 mg orally twice daily.
• 2 years and older (>25 kg): 100 mg orally twice daily.

Special Cases:

• Elderly Patients (>65 years): No dosage adjustment is generally necessary unless body weight is less than 50 kg, in which case initiate at the lowest recommended dose.
• Patients with Renal Impairment: Mild to moderate impairment: No dose adjustment. Severe impairment: Use with caution; avoid if creatinine clearance is less than 30 mL/min unless the benefits outweigh the risks.
• Patients with Hepatic Dysfunction: Mild impairment: No dose adjustment. Moderate impairment (Child-Pugh Class B): Reduce dose by 50%. Severe impairment (Child-Pugh Class C): Not recommended.
• CYP2C9 Poor Metabolizers: Consider starting at half the lowest recommended dose or consider alternative therapy.

Clinical Use Cases

Celecoxib is not typically used in clinical scenarios such as intubation, surgical procedures (except for postoperative pain management), mechanical ventilation, ICU use, or emergency situations like status epilepticus or cardiac arrest. It may be administered preoperatively for surgical procedures. In surgical settings, it is given primarily for postoperative pain management and not as part of the anesthetic protocol itself.

Dosage Adjustments

Dose modifications are necessary for patients with moderate hepatic impairment and those identified as CYP2C9 poor metabolizers. Renal impairment warrants careful consideration and potential dose adjustments. The lowest effective dose for the shortest duration should be used to minimize potential adverse effects.

Side Effects

Common Side Effects:

• Headache
• Dizziness
• Indigestion
• Abdominal pain
• Diarrhea
• Flatulence
• Rash
• Upper respiratory tract infections
• Peripheral edema

Rare but Serious Side Effects:

• Myocardial infarction
• Stroke
• Heart failure
• Gastrointestinal bleeding/perforation
• Hypertension
• Renal dysfunction
• Hepatotoxicity
• Hypersensitivity reactions (including Stevens-Johnson syndrome)
• Thrombotic events

Long-Term Effects:

Chronic use of celecoxib can increase the risk of cardiovascular events and gastrointestinal complications.

Adverse Drug Reactions (ADR):

Serious ADRs necessitate immediate intervention and include myocardial infarction, stroke, gastrointestinal bleeding, anaphylaxis, and severe skin reactions.

Contraindications

• Known hypersensitivity to celecoxib or sulfonamides.
• History of asthma, urticaria, or allergic-type reactions after aspirin or NSAID use.
• History of or recent myocardial infarction or stroke.
• Advanced renal disease.
• Severe hepatic impairment.
• Perioperative pain in coronary artery bypass graft surgery.

Drug Interactions

• Warfarin: Celecoxib can enhance the anticoagulant effect of warfarin.
• Lithium: May increase lithium levels.
• ACE inhibitors/Angiotensin Receptor Blockers: May decrease the antihypertensive effect of these drugs and increase the risk of renal impairment.
• Fluconazole: Can increase celecoxib concentrations.
• CYP2C9 Inhibitors/Inducers: Can alter celecoxib metabolism.

Pregnancy and Breastfeeding

• Pregnancy: Celecoxib is contraindicated during the third trimester of pregnancy due to potential premature closure of the ductus arteriosus. Use during the first and second trimesters should be avoided unless the potential benefit outweighs the potential risk to the fetus.
• Breastfeeding: Celecoxib is present in breast milk. Exercise caution when administering to breastfeeding mothers.

Drug Profile Summary

• Mechanism of Action: Selective COX-2 inhibitor.
• Side Effects: Headache, dizziness, GI upset, cardiovascular risks, renal dysfunction.
• Contraindications: Hypersensitivity, aspirin/NSAID-induced reactions, recent MI or stroke, severe renal/hepatic impairment.
• Drug Interactions: Warfarin, lithium, ACE inhibitors, fluconazole, CYP2C9 inhibitors/inducers.
• Pregnancy & Breastfeeding: Use with caution; contraindicated in the third trimester of pregnancy.
• Dosage: Refer to dosage section above.
• Monitoring Parameters: Blood pressure, renal function, liver function tests, signs of gastrointestinal bleeding.

Popular Combinations

Celecoxib may be used in combination with other analgesics like acetaminophen for enhanced pain relief. However, caution is needed to avoid exceeding maximum daily doses for individual medications.

Precautions

• Pre-existing cardiovascular or gastrointestinal conditions require careful monitoring.
• Assess renal and hepatic function before and during treatment.
• Monitor for signs and symptoms of cardiovascular, gastrointestinal, and dermatological adverse reactions.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Celecoxib?

A: The dosage depends on the indication and patient characteristics. Refer to the detailed dosage section above.

Q2: What are the most serious side effects of Celecoxib?

A: Cardiovascular events (MI, stroke, heart failure), gastrointestinal bleeding/perforation, and serious skin reactions.

Q3: Can Celecoxib be used during pregnancy?

A: It should be avoided during the first and second trimesters and is contraindicated in the third trimester.

Q4: How does Celecoxib differ from other NSAIDs?

A: It selectively inhibits COX-2, potentially reducing the risk of gastrointestinal side effects.

Q5: What are the common drug interactions with Celecoxib?

A: Warfarin, lithium, ACE inhibitors, and fluconazole.

Q6: What patient populations require dosage adjustments for Celecoxib?

A: Patients with moderate hepatic impairment, CYP2C9 poor metabolizers, elderly individuals with low body weight, and those with severe renal impairment.

Q7: Can Celecoxib be used for acute pain management?

A: Yes, for short-term management (up to 7 days) of moderate to severe acute pain.

Q8: What are the key contraindications for Celecoxib use?

A: Hypersensitivity to celecoxib or sulfonamides, history of aspirin/NSAID-induced reactions, recent MI or stroke, advanced renal/hepatic impairment, and perioperative pain in CABG surgery.

Q9: Can patients with a history of cardiovascular disease use Celecoxib?

A: Patients with significant cardiovascular risk factors should use celecoxib cautiously and at the lowest effective dose, as it can increase the risk of cardiovascular events. Alternative therapies should be considered first.