Usage
Indomethacin + Paracetamol is prescribed for the relief of pain and inflammation associated with various conditions, including gout, osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, and other acute pain conditions.
It is classified pharmacologically as a Non-Steroidal Anti-Inflammatory Drug (NSAID) and analgesic combination.
The mechanism of action involves inhibiting cyclooxygenase (COX) enzymes, thereby reducing prostaglandin synthesis, which plays a key role in inflammation and pain. Paracetamol’s analgesic mechanism is not fully understood but is believed to involve central inhibition of COX and other pathways.
Alternate Names
There are no widely recognized alternate names for this combination. Brand names may vary regionally. One example from the sources is “Combiflam.”
How It Works
Pharmacodynamics: Indomethacin, an NSAID, primarily inhibits COX-1 and COX-2 enzymes, reducing prostaglandin production and mitigating inflammation and pain. Paracetamol has analgesic and antipyretic effects but minimal anti-inflammatory action. It likely acts centrally on COX-3 enzyme isoforms in the brain and spinal cord.
Pharmacokinetics: Both drugs are well-absorbed orally. Indomethacin peak plasma concentrations are reached in 1-2 hours. It is highly protein-bound and metabolized in the liver, primarily via CYP2C9. Paracetamol is also rapidly absorbed, metabolized in the liver primarily by glucuronidation and sulfation pathways, and excreted in the urine. A small fraction is metabolized by CYP2E1 to a potentially hepatotoxic metabolite, N-acetyl-p-benzoquinone imine (NAPQI).
Elimination: Indomethacin is primarily eliminated via renal excretion of metabolites, with some biliary excretion. Paracetamol is mainly eliminated in the urine as glucuronide and sulfate conjugates.
Dosage
Standard Dosage
Adults:
The dosage varies depending on the indication. A common regimen for gout is Indomethacin 25 mg + Paracetamol 500 mg three times daily, taken with meals. For other conditions, Indomethacin doses typically range from 25 mg two or three times a day up to a maximum of 200 mg per day, while Paracetamol is typically given up to 1000 mg every four to six hours, not exceeding 4000 mg per day.
Children:
Paracetamol dosing for children is weight-based (15 mg/kg every 4-6 hours, maximum 4 doses in 24 hours). Indomethacin use in children under 14 is not generally recommended for pain and inflammation, but pediatric dosages are determined by the physician for specific indications like the closure of ductus arteriosus.
Special Cases:
- Elderly Patients: Start with lower doses and monitor renal function.
- Patients with Renal Impairment: Dose reduction may be necessary.
- Patients with Hepatic Dysfunction: Dose reduction is recommended for both components, particularly Paracetamol.
- Patients with Comorbid Conditions: Exercise caution in patients with cardiovascular disease, peptic ulcer disease, or bleeding disorders.
Clinical Use Cases
Dosages for intubation, surgical procedures, mechanical ventilation, ICU use, and emergencies are determined by individual patient needs and are based on the specific condition being treated. This combination is not typically the primary analgesic in these settings.
Dosage Adjustments
Dose modifications are necessary based on individual patient factors, including renal or hepatic dysfunction, age, concomitant medications, and response to therapy.
Side Effects
Common Side Effects
Nausea, headache, dizziness, vomiting, constipation, itching, diarrhea, indigestion, lightheadedness, rash, upper abdominal pain, drowsiness.
Rare but Serious Side Effects
Gastrointestinal bleeding, heart attack, heart failure, stroke, kidney problems, liver damage, allergic reactions (rash, hives, swelling), changes in blood pressure.
Long-Term Effects
Chronic kidney disease, gastrointestinal ulcers, cardiovascular complications with prolonged NSAID use.
Adverse Drug Reactions (ADR)
Severe allergic reactions (anaphylaxis), Stevens-Johnson syndrome, toxic epidermal necrolysis, acute kidney injury, liver failure.
Contraindications
Hypersensitivity to indomethacin or paracetamol, active peptic ulcer disease, recent heart attack, history of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs, severe heart failure, severe renal impairment, severe hepatic impairment, third trimester of pregnancy, perioperative pain in CABG surgery.
Drug Interactions
Anticoagulants (warfarin, heparin), antiplatelet agents (aspirin, clopidogrel), other NSAIDs, corticosteroids, ACE inhibitors, diuretics, lithium, methotrexate, alcohol.
Pregnancy and Breastfeeding
Indomethacin should be avoided in the third trimester of pregnancy due to potential for premature closure of the ductus arteriosus. Its use in earlier pregnancy should be under close medical supervision. While small amounts of both drugs transfer into breast milk, they are generally considered compatible with breastfeeding in recommended dosages. However, using alternative analgesics may be considered, especially for newborns or preterm infants.
Drug Profile Summary
- Mechanism of Action: COX inhibition (Indomethacin), central analgesic action (Paracetamol)
- Side Effects: Nausea, GI upset, headache, dizziness, potentially serious GI bleeding, cardiovascular events, renal or hepatic damage.
- Contraindications: Hypersensitivity, active peptic ulcer, recent MI, severe renal/hepatic impairment, third-trimester pregnancy.
- Drug Interactions: Anticoagulants, antiplatelets, other NSAIDs, alcohol.
- Pregnancy & Breastfeeding: Avoid in third trimester; generally compatible with breastfeeding at recommended doses.
- Dosage: Varies by indication, generally Indomethacin 25-50mg TID, Paracetamol 500-1000mg q4-6h.
- Monitoring Parameters: Renal and hepatic function, blood pressure, signs of GI bleeding.
Popular Combinations
This combination is already a common pairing for synergistic pain relief.
Precautions
Standard precautions for NSAIDs and Paracetamol should be observed. Patients should be screened for allergies, renal/hepatic impairment, cardiovascular disease, and GI bleeding risk. Pregnant and breastfeeding women should consult with their doctors. Avoid alcohol while taking this medication. Caution patients regarding operating machinery or driving.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Indomethacin + Paracetamol?
A: Dosage varies based on indication and patient factors. For adults with gout, a common regimen is Indomethacin 25mg + Paracetamol 500mg three times daily, with meals. Other pain conditions may require different dosages. Always tailor the dosage to the individual.
Q2: What are the main contraindications?
A: Hypersensitivity to either drug, active peptic ulcer, recent MI, severe renal/hepatic impairment, third-trimester pregnancy.
Q3: Can this combination be used in children?
A: Paracetamol can be used with weight-based dosing. Indomethacin use in children under 14 is generally avoided except for specific conditions under specialist supervision.
Q4: What are the most serious potential side effects?
A: GI bleeding, cardiovascular events (heart attack, stroke), renal impairment, hepatic damage.
Q5: How should dosage be adjusted for elderly patients?
A: Start with lower doses and closely monitor renal function.
Q6: What are the important drug interactions to consider?
A: Anticoagulants/antiplatelets, other NSAIDs, alcohol, and certain antihypertensives.
Q7: Can I take Indomethacin + Paracetamol if I am pregnant or breastfeeding?
A: Avoid Indomethacin in the third trimester. Discuss any use during pregnancy with your doctor. Generally compatible with breastfeeding at recommended doses, but discuss alternatives with your physician.
Q8: What should I do if I miss a dose?
A: Take the missed dose as soon as you remember, unless it is close to the time of the next dose. Do not double the dose.
Q9: What are the long-term safety concerns?
A: Chronic NSAID use can lead to renal damage, GI ulceration, and cardiovascular complications. Long-term paracetamol use at high doses can impact liver function.
A: Signs of GI bleeding (black stools, vomiting blood), chest pain, shortness of breath, signs of allergic reaction (swelling, hives, difficulty breathing), signs of stroke (sudden weakness, confusion, difficulty speaking), signs of liver damage (yellowing of skin/eyes).
