Celecoxib
1. Drug Name
Generic Name: Celecoxib
Brand Names: Celebrex
2. Drug Classification
Class: Nonsteroidal anti-inflammatory drug (NSAID)
Subclass: COX-2 selective inhibitor
3. Mechanism of Action
Primary Action: Celecoxib is a selective inhibitor of cyclooxygenase-2 (COX-2), an enzyme involved in the synthesis of prostaglandins, which are mediators of pain, inflammation, and fever. By selectively inhibiting COX-2, celecoxib reduces the production of prostaglandins at sites of inflammation, leading to its analgesic, anti-inflammatory, and antipyretic effects. Unlike non-selective NSAIDs, which inhibit both COX-1 and COX-2, celecoxib predominantly spares COX-1, helping to reduce gastrointestinal side effects such as ulcers and bleeding.
Additional Effects: Celecoxib’s selective COX-2 inhibition makes it effective for treating pain and inflammation while minimizing the gastrointestinal risks commonly associated with traditional NSAIDs.
4. Pharmacokinetics
Absorption: Well absorbed orally, with a bioavailability of approximately 40%. Food decreases the rate of absorption but not the extent. Maximum plasma concentrations are typically reached within 3 hours.
Distribution: Volume of distribution (Vd) is 500-700 L, with about 97% protein binding, primarily to albumin.
Metabolism: Celecoxib is extensively metabolized in the liver by the cytochrome P450 enzymes, primarily CYP2C9. It is converted into inactive metabolites.
Excretion: The elimination half-life (t½) of celecoxib is about 11 hours. Excretion occurs primarily through feces (approximately 57%) and, to a lesser extent, in the urine (approximately 27%).
Special Considerations: Celecoxib’s pharmacokinetics may be altered in individuals with hepatic impairment or in the elderly, requiring dose adjustments.
5. Indications
Primary Indications:
Osteoarthritis
Rheumatoid arthritis
Acute pain (e.g., post-operative or menstrual pain)
Primary dysmenorrhea
Off-label Uses:
Juvenile rheumatoid arthritis
Ankylosing spondylitis
Chronic low back pain
Specific Populations: Celecoxib is particularly beneficial in patients with osteoarthritis and rheumatoid arthritis who require long-term NSAID treatment but are at increased risk for gastrointestinal complications.
6. Dosage and Administration
Adult Dosing:
Osteoarthritis and Rheumatoid Arthritis: 200 mg once daily or 100 mg twice daily.
Acute Pain and Primary Dysmenorrhea: 400 mg on the first day, followed by 200 mg twice daily as needed.
Maximal Dose: 400 mg/day for pain or 200 mg/day for chronic conditions.
Pediatric Dosing: Celecoxib is approved for use in children aged 2 years and older for juvenile rheumatoid arthritis, with dosing based on body weight.
Renal/Hepatic Adjustments: Caution in patients with renal or hepatic impairment. Lower doses may be required in the elderly and those with moderate liver dysfunction.
Routes: Oral capsules (50 mg, 100 mg, 200 mg, and 400 mg).
7. Contraindications
Absolute Contraindications:
Known hypersensitivity to celecoxib or any of its components.
History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs.
Active gastrointestinal bleeding or peptic ulcer disease.
Relative Contraindications:
Severe liver or renal impairment.
Use during the third trimester of pregnancy.
8. Warnings and Precautions
Black Box Warnings:
Cardiovascular Risk: Use of celecoxib may increase the risk of serious cardiovascular events, such as heart attack and stroke, especially with long-term use, in high-risk patients, or in those with pre-existing cardiovascular conditions.
Gastrointestinal Risk: As with other NSAIDs, celecoxib increases the risk of gastrointestinal bleeding, ulceration, and perforation, which can be fatal.
Pregnancy and Lactation: Celecoxib should be avoided during the third trimester of pregnancy due to the risk of premature closure of the ductus arteriosus and fetal renal impairment. It is excreted in breast milk, so caution is advised when used by nursing mothers.
Monitoring Parameters: Blood pressure (for cardiovascular risks), renal function (serum creatinine, glomerular filtration rate), liver function tests, and signs of gastrointestinal bleeding.
9. Adverse Effects
Common Adverse Effects (≥10%):
Headache
Diarrhea
Hypertension
Abdominal pain
Indigestion (dyspepsia)
Less Common but Clinically Significant:
Peripheral edema
Dizziness
Skin rash
Nausea and vomiting
Serious Adverse Reactions:
Gastrointestinal bleeding or ulcers
Heart attack, stroke, or other serious cardiovascular events
Hepatic injury (e.g., elevated liver enzymes, jaundice)
Severe allergic reactions (e.g., anaphylaxis, angioedema)
10. Drug Interactions
Major Drug Interactions:
Anticoagulants (e.g., warfarin): Increased risk of bleeding.
CYP2C9 Inhibitors (e.g., fluconazole): Increased levels of celecoxib, requiring dose adjustment.
Lithium: Celecoxib may increase lithium levels, increasing the risk of lithium toxicity.
ACE inhibitors, Angiotensin II Receptor Blockers (ARBs), and Diuretics: Risk of renal impairment due to the inhibition of COX-2 in the kidneys.
Methotrexate: Celecoxib can increase methotrexate toxicity.
Food-Drug Interactions: No significant interactions, though food may delay the absorption of celecoxib.
Lab Test Interference: May alter renal function tests (e.g., serum creatinine), and liver enzyme tests.
11. Clinical Pharmacology
Pharmacodynamic Profile: Celecoxib provides pain relief through COX-2 inhibition, reducing inflammation without significantly inhibiting COX-1, thus preserving gastrointestinal mucosal integrity. This selective inhibition makes it more favorable for long-term therapy compared to non-selective NSAIDs.
Additional Effects: Celecoxib may also reduce the production of prostacyclin, which can lead to an increase in blood pressure and a potential increase in cardiovascular risk, especially in long-term use.
12. Special Populations
Pregnancy: Category C in the first and second trimesters; avoid use during the third trimester due to the risk of fetal harm.
Lactation: Use with caution; limited data on excretion in breast milk.
Geriatric Use: Increased risk of adverse cardiovascular and gastrointestinal effects in the elderly. Dose adjustments may be necessary, particularly in those with renal impairment.
Renal/Hepatic Impairment: Celecoxib should be used cautiously in patients with mild to moderate renal or hepatic impairment. Severe impairment may require dose reduction or alternative treatments.
13. Therapeutic Uses
First-Line Use: Celecoxib is often considered the drug of choice for managing chronic inflammatory conditions like osteoarthritis and rheumatoid arthritis in patients at risk of gastrointestinal complications.
Combination Therapy: Can be combined with acetaminophen or other analgesics for better pain control, especially in cases of moderate-to-severe pain.
Clinical Trials and Efficacy: Studies show that celecoxib is as effective as traditional NSAIDs in managing pain and inflammation, with a more favorable gastrointestinal side effect profile.
14. Monitoring and Follow-Up
Recommended Lab Tests: Routine monitoring of renal and hepatic function, blood pressure, and gastrointestinal symptoms during long-term treatment.
Patient Symptom Checklists: Monitoring for signs of cardiovascular events (e.g., chest pain, shortness of breath) and gastrointestinal issues (e.g., blood in stool, black or tarry stools).
Therapeutic and Toxic Levels: Monitoring for signs of overdose or toxicity, particularly with long-term use.
15. Overdose Management
Symptoms of Overdose: Drowsiness, nausea, vomiting, abdominal pain, and in severe cases, renal failure.
Treatment Protocols: There is no specific antidote for celecoxib overdose. Treatment is symptomatic and supportive, including activated charcoal if the overdose is recent.
Monitoring in Overdose: Continuous monitoring of vital signs, renal function, and any signs of acute toxicity.
16. Patient Counseling Information
Key Counseling Points:
Take the medication with food to reduce gastrointestinal irritation.
Avoid use with other NSAIDs or alcohol.
Report any signs of gastrointestinal bleeding (e.g., black stools, vomiting blood) or cardiovascular symptoms (e.g., chest pain, shortness of breath).
Signs Requiring Immediate Attention: Sudden severe headache, blurred vision, swelling of the face or throat, or difficulty breathing, which may indicate serious side effects.