Etoricoxib + Paracetamol

Usage

• Etoricoxib + Paracetamol is prescribed for the short-term relief of pain and inflammation in conditions affecting joints and muscles, such as osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, acute gouty arthritis, and post-operative pain (especially after dental surgery). It is also used to manage other acute pain conditions, such as pain due to injuries.
• Pharmacological Classification: Non-Steroidal Anti-Inflammatory Drug (NSAID) and Analgesic.
• Mechanism of Action: Etoricoxib selectively inhibits cyclooxygenase-2 (COX-2) enzyme, reducing prostaglandin production, which mediates pain and inflammation. Paracetamol has central analgesic and antipyretic effects, possibly by inhibiting prostaglandin synthesis in the central nervous system and raising the pain threshold.

Alternate Names

• No widely recognized alternate names exist for this specific combination.
• Brand Names: Some examples of Brand Names are Nucoxia P, Newcox-P. Brand names can vary significantly by region.

How It Works

• Pharmacodynamics: Etoricoxib primarily targets peripheral inflammation by inhibiting COX-2, reducing pain and inflammation at the injury site. Paracetamol acts centrally to reduce pain and fever.
• Pharmacokinetics:
  • Absorption: Both drugs are well-absorbed orally.
  • Metabolism: Etoricoxib is primarily metabolized in the liver by CYP enzymes, with some contribution from intestinal CYP3A4. Paracetamol is mainly metabolized in the liver through glucuronidation and sulfation pathways, with a minor pathway involving CYP2E1, leading to the formation of a potentially hepatotoxic metabolite.
  • Elimination: Etoricoxib is primarily excreted in the urine and feces as metabolites, with minor amounts eliminated unchanged. Paracetamol is mainly excreted in the urine as glucuronide and sulfate conjugates.
• Mode of Action: Etoricoxib binds to and inhibits COX-2 enzyme. Paracetamol’s precise mechanism is not fully understood, but it may involve inhibiting central prostaglandin synthesis, altering serotonin pathways, or interacting with pain/inflammation-related receptors.
• Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Etoricoxib directly inhibits COX-2. Paracetamol’s mechanism likely involves multiple pathways, including central COX inhibition and potential interaction with serotonin and cannabinoid receptors.
• Elimination Pathways: Etoricoxib is primarily eliminated by hepatic metabolism followed by renal and fecal excretion. Paracetamol undergoes hepatic conjugation (glucuronidation and sulfation) followed by renal excretion.

Dosage

Standard Dosage

Adults:

• Osteoarthritis: Etoricoxib 60 mg + Paracetamol 325 mg once daily. In some cases, Etoricoxib 90 mg or 120 mg + Paracetamol 325 mg once daily.
• Rheumatoid Arthritis/Ankylosing Spondylitis: Etoricoxib 90 mg + Paracetamol 325 mg once daily.
• Acute Gouty Arthritis: Etoricoxib 120 mg + Paracetamol 325 mg once daily for up to 8 days.
• Post-operative Dental Pain: Etoricoxib 90 mg + Paracetamol 325 mg once daily for up to 3 days.
• General Acute Pain: Etoricoxib 60 or 120 mg + Paracetamol 325 mg once daily for a short period, not exceeding 8 days, depending on individual needs and pain severity.

Children:

• Not recommended for children under 16 years of age. Safety and efficacy have not been established.

Special Cases:

• Elderly Patients: Use with caution; dose adjustments may be needed.
• Patients with Renal Impairment: Use with caution in patients with creatinine clearance <30 mL/min; consider dose adjustment.
• Patients with Hepatic Dysfunction: Consider dose reduction in patients with mild to moderate hepatic impairment. Contraindicated in severe hepatic impairment.
• Patients with Comorbid Conditions: Use with caution in patients with heart disease, hypertension, and history of gastrointestinal ulcers.

Clinical Use Cases

• Use in clinical settings such as intubation, surgical procedures, mechanical ventilation, and ICU is determined based on individual patient needs and pain assessment. Dosages would generally align with those mentioned for specific conditions like post-operative pain or acute pain management. Etoricoxib + Paracetamol is not typically used for emergency situations like status epilepticus or cardiac arrest.

Dosage Adjustments

• Adjust dosage based on individual patient response, tolerability, renal function, and hepatic function.

Side Effects

Common Side Effects:

• Nausea, diarrhea, constipation, indigestion, abdominal pain, flatulence, swelling of hands and feet, dizziness, headache, skin rash, elevated liver enzymes (especially with prolonged use or overdose of paracetamol).

Rare but Serious Side Effects:

• Gastrointestinal bleeding, peptic ulcers, allergic reactions, liver damage, heart attack, stroke, high blood pressure, kidney damage (with prolonged usage).

Long-Term Effects:

• Potential for liver and kidney damage with prolonged usage.

Adverse Drug Reactions (ADR):

• Stevens-Johnson syndrome, toxic epidermal necrolysis, hypersensitivity reactions, severe hepatic injury.

Contraindications

• Hypersensitivity to etoricoxib, paracetamol, or any component of the formulation.
• Active peptic ulceration or gastrointestinal bleeding.
• Severe hepatic impairment.
• Severe renal impairment (creatinine clearance <30 mL/min).
• Inflammatory bowel disease.
• History of asthma, urticaria, or allergic-type reaction after taking aspirin or other NSAIDs.

Drug Interactions

• Anticoagulants (e.g., warfarin): Increased risk of bleeding.
• Antiplatelet agents (e.g., aspirin, clopidogrel): Increased risk of bleeding.
• Diuretics, ACE inhibitors, angiotensin receptor blockers: May reduce the antihypertensive effect and increase the risk of renal impairment.
• Lithium: May increase lithium levels.
• Methotrexate: May enhance methotrexate toxicity.
• Oral hypoglycemic agents: May alter blood glucose control.
• Rifampicin: May decrease etoricoxib levels.
• Alcohol: Increases the risk of gastrointestinal bleeding and paracetamol-induced hepatotoxicity.

Pregnancy and Breastfeeding

• Pregnancy: Should be avoided during the third trimester due to potential fetal risks (premature closure of ductus arteriosus). Use in earlier trimesters should be under strict medical supervision only if the potential benefit justifies the potential risk to the fetus.
• Breastfeeding: Etoricoxib is excreted in breast milk. Paracetamol is generally considered compatible with breastfeeding. However, due to the etoricoxib component and the potential risk for neonatal side effects, alternative pain management options are generally preferred if possible. Consult with a doctor before use during breastfeeding.

Drug Profile Summary

• Mechanism of Action: Etoricoxib: Selective COX-2 inhibitor; Paracetamol: Central analgesic and antipyretic.
• Side Effects: Nausea, diarrhea, gastrointestinal issues, dizziness, skin rash, liver enzyme elevation, potentially serious cardiovascular and gastrointestinal events.
• Contraindications: Hypersensitivity, active peptic ulcers, severe hepatic/renal impairment, pregnancy (third trimester).
• Drug Interactions: Anticoagulants, antiplatelets, diuretics, lithium, methotrexate.
• Pregnancy & Breastfeeding: Use with extreme caution; avoid in the third trimester and consult physician during lactation.
• Dosage: Adults: Varies by condition; Children: Not recommended under 16 years.
• Monitoring Parameters: Liver function tests, blood pressure, signs of gastrointestinal bleeding.

Popular Combinations

• While Etoricoxib and Paracetamol are already combined in a single formulation, some clinicians may add opioids or other analgesics for short-term management of severe pain.

Precautions

• Use cautiously in patients with cardiovascular risk factors, renal or hepatic impairment, history of gastrointestinal ulcers, or asthma/allergy to NSAIDs. Monitor for liver function, blood pressure, and gastrointestinal side effects. Avoid alcohol. Exercise caution while driving or operating machinery.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Etoricoxib + Paracetamol?

A: The dosage varies depending on the indication and can range from Etoricoxib 60 mg + Paracetamol 325 mg to Etoricoxib 120 mg + Paracetamol 325 mg once daily.

Q2: Can this combination be used long-term?

A: It is generally recommended for short-term use due to the potential for adverse effects, particularly with the etoricoxib component. Long-term use should be carefully evaluated and managed by a physician, if deemed absolutely necessary.

Q3: What are the serious side effects I should be aware of?

A: Serious side effects include cardiovascular events (heart attack, stroke), gastrointestinal bleeding, ulcers, and severe liver or kidney damage.

Q4: Can I take this while pregnant or breastfeeding?

A: It’s generally contraindicated in the third trimester of pregnancy. Consult a physician before use during pregnancy or breastfeeding.

Q5: Can it be used in children?

A: Not recommended for children under 16 years old.

Q6: Does this combination interact with other medications?

A: Yes, it can interact with numerous drugs, including anticoagulants, antiplatelets, diuretics, and lithium. Always inform your doctor about all medications you are currently taking.

Q7: What should I do if I experience side effects?

A: Contact your physician if you experience any bothersome or severe side effects.

Q8: Can this medication cause drowsiness?

A: It can cause dizziness and drowsiness in some patients. Avoid driving or operating machinery if affected.

Q9: Are there any dietary restrictions while taking this medication?

A: Avoid excessive alcohol consumption, as it can increase the risk of stomach bleeding and liver damage.

Q10: Can I stop taking this medicine abruptly?

A: If taken for short-term pain relief, it can generally be stopped abruptly. If used long-term, consult your physician before discontinuing. They may recommend gradually tapering off the medication to avoid potential withdrawal symptoms.