Etoricoxib

Usage

Etoricoxib is prescribed for the symptomatic relief of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, acute gouty arthritis, acute pain (including primary dysmenorrhea), and short-term treatment of moderate pain associated with dental surgery. It is classified as a non-steroidal anti-inflammatory drug (NSAID) and, more specifically, a COX-2 inhibitor. Etoricoxib works by selectively inhibiting the cyclooxygenase-2 (COX-2) enzyme, which is responsible for producing prostaglandins that mediate inflammation and pain. By inhibiting COX-2, etoricoxib reduces pain and inflammation with minimal impact on COX-1, the enzyme responsible for protecting the stomach lining and promoting platelet function.

Alternate Names

While “etoricoxib” is the generic name, it’s marketed under various brand names, most notably Arcoxia. Regional or international variations of the generic name may exist, but Arcoxia remains a globally recognized brand.

How It Works

Pharmacodynamics: Etoricoxib exerts its therapeutic effect by selectively inhibiting COX-2, reducing prostaglandin synthesis, thereby decreasing inflammation and pain. It has minimal effect on COX-1, minimizing gastrointestinal side effects associated with non-selective NSAIDs.

Pharmacokinetics:

• Absorption: Etoricoxib is well-absorbed orally, with peak plasma concentrations reached within approximately one hour when taken without food. Food may slightly delay absorption, but it does not affect the extent of absorption.
• Metabolism: Etoricoxib is extensively metabolized in the liver, primarily by CYP enzymes (mainly CYP3A4), into inactive metabolites.
• Elimination: Etoricoxib and its metabolites are primarily eliminated via hepatic (biliary/fecal) excretion, with a small amount excreted in the urine. The elimination half-life is approximately 22 hours.

Mode of Action: Etoricoxib binds selectively to the COX-2 enzyme’s active site, preventing the conversion of arachidonic acid into prostaglandins, the key mediators of inflammation and pain. This selective inhibition minimizes interference with COX-1, the enzyme responsible for maintaining gastrointestinal integrity and platelet function.

Dosage

Standard Dosage

Adults:

• Osteoarthritis: 30 mg once daily, increased to 60 mg if needed.
• Rheumatoid Arthritis: 60 mg once daily, increased to 90 mg if needed.
• Ankylosing Spondylitis: 60 mg once daily, increased to 90 mg if needed.
• Acute Gouty Arthritis: 120 mg once daily for up to 8 days.
• Acute Pain: 90 mg or 120 mg once daily for up to 8 days.
• Postoperative Dental Pain: 90 mg once daily for up to 3 days.
• Primary Dysmenorrhea: 120 mg once daily.

Children:

Etoricoxib is contraindicated in children under 16 years of age.

Special Cases:

• Elderly Patients: No dose adjustment is typically necessary, but caution should be exercised due to potential increased susceptibility to renal, gastrointestinal, and cardiovascular side effects.
• Patients with Renal Impairment: Contraindicated if creatinine clearance is less than 30 mL/min. No dose adjustment is needed for creatinine clearance ≥30 mL/min.
• Patients with Hepatic Dysfunction: For mild hepatic impairment (Child-Pugh 5-6), do not exceed 60 mg daily. For moderate impairment (Child-Pugh 7-9), do not exceed 30 mg daily or 60 mg every other day. Contraindicated in severe hepatic impairment (Child-Pugh ≥10).
• Patients with Comorbid Conditions: Caution is advised for patients with cardiovascular risk factors (e.g., hypertension, hyperlipidemia, diabetes, smoking), as etoricoxib may increase cardiovascular risk.

Clinical Use Cases

Etoricoxib does not have established dosing recommendations for intubation, surgical procedures (other than dental surgery), mechanical ventilation, ICU use, or emergency situations like status epilepticus or cardiac arrest. Other analgesics are generally preferred in these settings.

Dosage Adjustments

Dosage adjustments are necessary in patients with renal or hepatic dysfunction as outlined above. Dose modifications may also be needed based on individual patient response and tolerance.

Side Effects

Common Side Effects:

Gastrointestinal upset (dyspepsia, abdominal pain, nausea, diarrhea, constipation), fluid retention (edema), dizziness, headache, and increased blood pressure.

Rare but Serious Side Effects:

Myocardial infarction, stroke, gastrointestinal bleeding/ulceration, severe skin reactions (Stevens-Johnson syndrome), and liver dysfunction.

Long-Term Effects:

Chronic use of etoricoxib may increase the risk of cardiovascular events, gastrointestinal complications, and renal impairment.

Adverse Drug Reactions (ADR):

Severe allergic reactions (anaphylaxis), angioedema, and exfoliative dermatitis.

Contraindications

Absolute contraindications include hypersensitivity to etoricoxib or other NSAIDs, active peptic ulcer/gastrointestinal bleeding, severe heart failure, severe hepatic impairment, severe renal impairment, history of myocardial infarction or stroke, peripheral arterial disease, inflammatory bowel disease and coronary artery bypass graft surgery.

Drug Interactions

Etoricoxib can interact with numerous drugs, including:

• Anticoagulants (e.g., warfarin): Increased bleeding risk.
• Antiplatelets (e.g., aspirin): Increased risk of gastrointestinal ulceration. However, low-dose aspirin for cardioprotection can be co-administered.
• Antihypertensives and diuretics: Reduced antihypertensive effect.
• Lithium: Increased lithium levels.
• Methotrexate: Increased methotrexate toxicity.
• Rifampicin: Decreased etoricoxib levels.
• CYP3A4 inhibitors/inducers: Altered etoricoxib metabolism.
• Oral contraceptives: Reduced contraceptive efficacy.

Alcohol should be used cautiously as it may increase the risk of gastrointestinal side effects.

Pregnancy and Breastfeeding

Etoricoxib is contraindicated during pregnancy and breastfeeding. It is classified as Pregnancy Category D/X.

Drug Profile Summary

• Mechanism of Action: Selective COX-2 inhibitor.
• Side Effects: GI upset, fluid retention, dizziness, headache, increased blood pressure. Serious side effects: cardiovascular events, GI bleeding, liver dysfunction.
• Contraindications: Hypersensitivity, active peptic ulcer, severe heart/liver/renal failure, history of MI or stroke, peripheral arterial disease, inflammatory bowel disease and CABG surgery.
• Drug Interactions: Anticoagulants, antiplatelets, antihypertensives, lithium, methotrexate, rifampicin, CYP3A4 inhibitors/inducers, oral contraceptives.
• Pregnancy & Breastfeeding: Contraindicated.
• Dosage: See detailed dosage guidelines above.
• Monitoring Parameters: Blood pressure, renal function, liver function, and signs of gastrointestinal bleeding.

Popular Combinations

Etoricoxib is sometimes used in combination with gastroprotective agents (e.g., proton pump inhibitors) to mitigate GI risks in high-risk patients. However, this combination is not routinely recommended.

Precautions

• Pre-existing cardiovascular disease, renal impairment, or hepatic impairment require careful monitoring.
• Baseline blood pressure, renal function, and liver function tests should be obtained.
• Patients should be advised to report any signs of gastrointestinal bleeding or cardiovascular events.
• Alcohol and smoking should be limited.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Etoricoxib?

A: The dosage depends on the indication and patient-specific factors. Refer to the detailed dosage guidelines provided above.

Q2: Can Etoricoxib be used in patients with asthma?

A: Caution is advised, as etoricoxib may exacerbate asthma symptoms in some individuals.

Q3: Is Etoricoxib safe for long-term use?

A: Long-term use of etoricoxib carries increased risks of cardiovascular and gastrointestinal side effects. The lowest effective dose for the shortest duration should be used. Regular monitoring is crucial.

Q4: What are the key drug interactions to consider with Etoricoxib?

A: Key drug interactions include anticoagulants (e.g. warfarin), antihypertensives, lithium, and methotrexate. Consult the drug interaction section above for more information.

Q5: Can Etoricoxib be used during pregnancy or breastfeeding?

A: No. Etoricoxib is contraindicated during pregnancy and breastfeeding.

Q6: How does Etoricoxib compare to other NSAIDs?

A: Etoricoxib is a selective COX-2 inhibitor, associated with a lower risk of gastrointestinal side effects compared to traditional NSAIDs. However, it may carry a slightly higher cardiovascular risk.

Q7: What should patients be monitored for while taking Etoricoxib?

A: Monitor for signs of cardiovascular events (chest pain, shortness of breath), GI bleeding (black stools, abdominal pain), fluid retention (edema), and changes in renal and liver function.

Q8: What should I do if a patient experiences side effects while taking Etoricoxib?

A: The decision depends on the nature and severity of the side effects. Mild side effects may be manageable, while serious side effects necessitate discontinuation and potential alternative therapies. Prompt medical evaluation is essential for severe reactions.

Q9: Can Etoricoxib be used for acute pain management?

A: Yes, etoricoxib can be used for acute pain, including postoperative pain and acute gout, but only for the acute symptomatic period (up to 8 days).

Q10: Are there any dietary restrictions while taking Etoricoxib?

A: While no specific dietary restrictions are mandatory, patients should be advised to limit alcohol intake due to the potential increased risk of gastrointestinal side effects.