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Registry Hub
Peer-Reviewed Evidence
HomeDrug RegistryCompareNAPROSYN vs INDOCIN
Comparative Pharmacology

NAPROSYN vs INDOCIN Comparison

Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.

Clinical EssentialsPharmacokineticsSpecial PopulationsSafety & MonitoringPregnancy & Lactation
Differential Analysis

NAPROSYN vs INDOCIN

Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.

View NAPROSYN Monograph View INDOCIN Monograph
Clinical Insights
NAPROSYN
NSAID
Category C
INDOCIN
NSAID
Category C
TL;DR — Key Differences
  • Half-life: NAPROSYN has a half-life of Terminal elimination half-life is 12-17 hours. This long half-life allows twice-daily dosing, but may lead to drug accumulation in elderly or renally impaired patients.; INDOCIN has Terminal elimination half-life approximately 4.5 hours (range 2.6–11.2 hours); prolonged in elderly and patients with hepatic impairment..
  • No direct drug-drug interaction has been documented between NAPROSYN and INDOCIN.
  • Pregnancy: NAPROSYN is rated Category C; INDOCIN is rated Category C.

Last clinically reviewed: June 2026 · OpiCalc Medical Review Team

Clinical Essentials

NAPROSYN
INDOCIN
Mechanism of Action
NAPROSYN

Nonsteroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase (COX-1 and COX-2) enzymes, thereby reducing prostaglandin synthesis. This results in decreased inflammation, pain, and fever.

INDOCIN

Indomethacin is a nonsteroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase (COX-1 and COX-2) enzymes, thereby reducing prostaglandin synthesis, which mediates inflammation, pain, and fever. It also decreases renal blood flow and may cause ductus arteriosus closure.

Indications
NAPROSYN

Rheumatoid arthritis,Osteoarthritis,Ankylosing spondylitis,Juvenile arthritis,Tendonitis,Bursitis,Acute gout,Primary dysmenorrhea,Mild to moderate pain

INDOCIN

Moderate to severe rheumatoid arthritis,Ankylosing spondylitis,Osteoarthritis,Acute gouty arthritis,Acute painful shoulder (bursitis/tendinitis),Patent ductus arteriosus in neonates (off-label)

Standard Dosing
NAPROSYN

250-500 mg orally twice daily; maximum 1500 mg/day. For extended-release: 750-1000 mg orally once daily.

INDOCIN

25 mg orally 2-3 times daily; maximum 200 mg/day. Intravenous: 0.5-1 mg/kg as single dose for ductus arteriosus closure.

Direct Interaction
NAPROSYN
No Direct Interaction
INDOCIN
No Direct Interaction

Pharmacokinetics

NAPROSYN
INDOCIN
Half-Life
NAPROSYN

Terminal elimination half-life is 12-17 hours. This long half-life allows twice-daily dosing, but may lead to drug accumulation in elderly or renally impaired patients.

INDOCIN

Terminal elimination half-life approximately 4.5 hours (range 2.6–11.2 hours); prolonged in elderly and patients with hepatic impairment.

Metabolism
NAPROSYN

Extensively metabolized in the liver via glucuronidation and oxidation; CYP450 involvement is minor. Major metabolite is 6-desmethylnaproxen.

Special Populations

NAPROSYN
INDOCIN
Renal Adjustments
NAPROSYN

GFR 30-59 m L/min: decrease dose by 50% or use alternative; GFR <30 m L/min: contraindicated.

INDOCIN

Cr Cl 10-50 m L/min: dose reduction 50%; Cr Cl <10 m L/min: avoid use or reduce to 25% of usual dose.

Hepatic Adjustments
NAPROSYN

Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: avoid use.

Safety & Monitoring

NAPROSYN
INDOCIN
Black Box Warnings
NAPROSYN
FDA Black Box Warning

Increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. Increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation, which can be fatal.

Pregnancy & Lactation

NAPROSYN
INDOCIN
Teratogenic Risk
NAPROSYN

First trimester: Case-control studies suggest a small increased risk of cardiac defects and oral clefts; absolute risk remains low. Second/third trimester: Exposure may cause premature constriction of the ductus arteriosus, oligohydramnios due to fetal renal effects, and risk of necrotizing enterocolitis, intracranial hemorrhage, and renal dysfunction in the neonate; avoid after 30 weeks gestation.

INDOCIN

First trimester: Avoid because of risk of spontaneous abortion and congenital malformations (cardiac, orofacial clefts) based on epidemiologic studies. Second/third trimester: Contraindicated due to risk of premature closure of ductus arteriosus, oligohydramnios, and neonatal renal impairment.

Clinical Insights

NAPROSYN
INDOCIN
Clinical Pearls
NAPROSYN

Naprosyn (naproxen) is a nonsteroidal anti-inflammatory drug (NSAID) with a long half-life (~12-17 hours), allowing twice-daily dosing. Use with caution in patients with cardiovascular disease, renal impairment, or history of GI bleeding. It can mask signs of infection. Monitor renal function and blood pressure regularly. Avoid concurrent use with other NSAIDs or anticoagulants due to increased bleeding risk. Naprosyn may cause photosensitivity; advise sun protection.

INDOCIN

Indomethacin (Indocin) is a potent NSAID with significant anti-inflammatory, analgesic, and antipyretic effects. It is particularly effective for acute gout flares and closure of patent ductus arteriosus (PDA) in neonates. Due to high risk of gastrointestinal bleeding, renal impairment, and cardiovascular events, use the lowest effective dose for the shortest duration. Contraindicated in patients with history of aspirin or NSAID-induced asthma, urticaria, or allergic reactions. Monitor renal function, blood pressure, and signs of GI bleeding. Avoid concurrent use with other NSAIDs, anticoagulants, and corticosteroids.

Safety Verification

Known Interactions

NAPROSYN Risks

No interactions on record

INDOCIN Risks

No interactions on record

Clinical Q&A

Frequently Asked Questions

Common clinical questions about NAPROSYN vs INDOCIN, answered by our medical review team.

1. What is the main difference between NAPROSYN and INDOCIN?

NAPROSYN is a NSAID that works by Nonsteroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase (COX-1 and COX-2) enzymes, thereby reducing prostaglandin synthesis. This results in decreased inflammation, pain, and fever.. INDOCIN is a NSAID that works by Indomethacin is a nonsteroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase (COX-1 and COX-2) enzymes, thereby reducing prostaglandin synthesis, which mediates inflammation, pain, and fever. It also decreases renal blood flow and may cause ductus arteriosus closure.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.

2. Which is stronger: NAPROSYN or INDOCIN?

Potency comparisons between NAPROSYN and INDOCIN depend on the specific clinical indication. These are both NSAID agents and are not directly interchangeable by dose. A physician or clinical pharmacist should guide any therapeutic switching decisions.

3. What is the standard dosing for NAPROSYN vs INDOCIN?

The standard adult dose of NAPROSYN is: 250-500 mg orally twice daily; maximum 1500 mg/day. For extended-release: 750-1000 mg orally once daily.. The standard adult dose of INDOCIN is: 25 mg orally 2-3 times daily; maximum 200 mg/day. Intravenous: 0.5-1 mg/kg as single dose for ductus arteriosus closure.. Dosing should always be individualized based on indication, renal and hepatic function, age, and other patient factors.

4. Can you take NAPROSYN and INDOCIN together?

No direct drug-drug interaction has been formally documented between NAPROSYN and INDOCIN in current clinical databases. However, individual patient risk factors including other medications, organ function, and comorbidities should always be evaluated by a qualified healthcare provider.

5. Are NAPROSYN and INDOCIN safe during pregnancy?

The maternal-fetal safety profiles differ. NAPROSYN is classified as Category C. First trimester: Case-control studies suggest a small increased risk of cardiac defects and oral clefts; absolute risk remains low. Second/third trimester: Exposure may cause prema. INDOCIN is classified as Category C. First trimester: Avoid because of risk of spontaneous abortion and congenital malformations (cardiac, orofacial clefts) based on epidemiologic studies. Second/third trimester: Cont. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.

INDOCIN

Primarily hepatic metabolism via O-demethylation and N-deacylation; minor pathways include glucuronidation. Involved enzymes include CYP2C9 and possibly CYP3A4.

Excretion
NAPROSYN

Renal excretion of conjugated metabolites accounts for approximately 95% of a dose, with 1-2% as unchanged naproxen. Fecal excretion is minimal (<5%).

INDOCIN

Renal (60% as unchanged drug and glucuronide conjugates), biliary/fecal (33% via enterohepatic circulation).

Protein Binding
NAPROSYN

>99% bound to albumin.

INDOCIN

Approximately 90% bound to albumin (saturable binding at high concentrations).

VD (L/kg)
NAPROSYN

0.16 L/kg (approximately 10-12 L in a 70 kg adult). Low Vd indicates distribution primarily in plasma and extracellular fluid.

INDOCIN

0.1–0.2 L/kg (indicating low tissue penetration; primarily in plasma and interstitial fluid).

Bioavailability
NAPROSYN

Oral: 95% (completely absorbed). Rectal: approximately 80% of oral bioavailability.

INDOCIN

Oral: 100% (immediate release); Rectal: 80–90%; IV: 100%.

INDOCIN

Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: contraindicated.

Pediatric Dosing
NAPROSYN

For juvenile arthritis: 10-15 mg/kg/day divided twice daily; maximum 1000 mg/day. For other indications: 5-10 mg/kg/dose every 8-12 hours.

INDOCIN

For inflammatory conditions: 1-2 mg/kg/day in 3-4 divided doses; maximum 4 mg/kg/day or 200 mg/day. For patent ductus arteriosus: IV 0.2-0.25 mg/kg/dose every 12-24 hours for 3 doses.

Geriatric Dosing
NAPROSYN

Start at lowest effective dose (250 mg twice daily); monitor renal function and gastrointestinal bleeding risk.

INDOCIN

Initiate at 25 mg twice daily; maximum 100 mg/day; monitor renal function and GI bleeding risk.

INDOCIN
FDA Black Box Warning

Cardiovascular Risk: NSAIDs increase the risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk increases with duration of use and in patients with cardiovascular disease or risk factors. Indomethacin is contraindicated for treatment of perioperative pain in coronary artery bypass graft (CABG) surgery. Gastrointestinal Risk: NSAIDs increase the risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time without warning symptoms, and elderly patients and those with prior history of peptic ulcer disease or GI bleeding are at greater risk.

Warnings/Precautions
NAPROSYN
  • Cardiovascular risk: Use lowest effective dose for shortest duration; avoid in coronary artery bypass graft surgery.
  • Gastrointestinal risk: History of peptic ulcer disease or GI bleeding increases risk.
  • Renal effects: May cause renal toxicity, especially in patients with impaired renal function, heart failure, or on diuretics.
  • Hepatic effects: Elevation of liver enzymes may occur; discontinue if signs of hepatic toxicity.
  • Anaphylactoid reactions: May occur in patients with aspirin sensitivity.
  • Hypertension: May worsen blood pressure control.
  • Fluid retention: Use with caution in patients with heart failure or hypertension.
  • Hematologic effects: May inhibit platelet aggregation; monitor for bleeding.
INDOCIN

Cardiovascular thrombotic events; GI bleeding, ulceration, and perforation; renal toxicity including renal papillary necrosis; anemia; hepatic effects; hypertension; exacerbation of asthma; fluid retention; skin reactions including Stevens-Johnson syndrome; central nervous system effects including dizziness and headache; use in pregnancy (avoid in third trimester).

Contraindications
NAPROSYN
  • Hypersensitivity to naproxen or any component of the formulation
  • History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs
  • Perioperative pain in coronary artery bypass graft surgery
  • Advanced renal disease
  • Active peptic ulcer disease or GI bleeding
INDOCIN

History of allergic reaction to indomethacin or aspirin; history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs; perioperative pain in CABG surgery; severe renal impairment; active GI bleeding or peptic ulcer disease.

Adverse Reactions
NAPROSYN
Data Pending
INDOCIN
Data Pending
Food Interactions
NAPROSYN

Naproxen may be taken with food or milk to minimize gastrointestinal irritation. Avoid alcohol, as it increases the risk of stomach bleeding. No specific food restrictions beyond general NSAID precautions.

INDOCIN

Avoid alcohol, as it increases the risk of gastrointestinal bleeding and liver toxicity. Take with food or milk to minimize gastrointestinal irritation. Limit salt intake to reduce fluid retention and hypertension risk. Avoid high-potassium foods if renal impairment is present, as indomethacin can increase potassium levels.

Lactation Summary
NAPROSYN

Naproxen is excreted into breast milk in small amounts (M/P ratio approximately 0.01). The relative infant dose is about 1% of the maternal weight-adjusted dose. Use with caution in breastfeeding; monitor infant for gastrointestinal effects, rash, or bleeding.

INDOCIN

Indomethacin is excreted into breast milk in low concentrations (M/P ratio approximately 0.1-0.4). Use with caution, especially in infants with known cardiovascular or renal compromise. Consider alternatives if possible.

Pregnancy Dosing
NAPROSYN

Due to increased renal clearance and volume of distribution in pregnancy, standard doses may be subtherapeutic; however, increased doses are not recommended due to fetal risks. Use lowest effective dose for shortest duration; avoid in third trimester.

INDOCIN

Due to increased volume of distribution and clearance, dose adjustments are not routinely recommended. However, use lowest effective dose for shortest duration; avoid use after 30 weeks gestation.

Maternal Safety Status
NAPROSYN
Category C
INDOCIN
Category C
Patient Counseling
NAPROSYN

Take with food or milk to reduce stomach upset.,Do not take more than the recommended dose; overdose can cause serious side effects.,Avoid alcohol while taking this medication to lower the risk of stomach bleeding.,Tell your doctor if you have a history of stomach ulcers, high blood pressure, or kidney disease.,Watch for signs of stomach bleeding: black/tarry stools, vomit that looks like coffee grounds.,Stop taking and seek medical help if you experience chest pain, weakness, slurred speech, or shortness of breath.,Store at room temperature away from moisture and heat.,Do not combine with other products containing naproxen or other NSAIDs.

INDOCIN

Take with food, milk, or an antacid to reduce stomach upset.,Report any black/bloody stools, coffee-ground vomit, chest pain, shortness of breath, or signs of bleeding immediately.,Avoid alcohol, aspirin, and other NSAIDs (e.g., ibuprofen, naproxen) while taking this medication.,Do not take if you are allergic to aspirin or any NSAID, or if you have a history of asthma attacks after taking these drugs.,Notify your healthcare provider if you have kidney disease, high blood pressure, heart disease, or are pregnant or breastfeeding.