Naproxen
Naproxen
Generic Name
Naproxen
Drug Class
NSAID (non‑selective COX inhibitor)
Mechanism
Naproxen is a non‑steroidal anti‑inflammatory drug (NSAID) that exerts its effects by competitively inhibiting cellular cyclo‑oxygenase (COX) enzymes.
• COX‑1 inhibition → ↓ prostaglandin synthesis → reduced gastric mucosal protection and platelet aggregation.
• COX‑2 inhibition → ↓ inflammatory prostaglandins → analgesic, antipyretic, and anti‑arthritic benefits.
• The drug exhibits a balanced COX‑1/COX‑2 inhibition profile, giving it a moderate gastrointestinal safety margin compared to earlier NSAIDs.
Pharmacokinetics
| Parameter | Typical values | Notes |
| Absorption | Rapid; peak plasma concentration (Tmax) 1–2 h after oral dosing | Food slows absorption slightly but improves tolerance |
| Bioavailability | ~60–80 % | High hepatic first‑pass metabolism |
| Distribution | Protein‑bound ~93 % (mainly albumin) | Large volume of distribution (~2.8 L/kg) |
| Metabolism | Hepatic oxidation (mainly via CYP4A, CYP1A2) → carboxylate conjugation | Mostly non‑renal route |
| Half‑life | 12–17 h (steady‑state) | Supports once‑daily dosing |
| Excretion | Primarily renal (15 % unchanged), rest as metabolites in urine & bile | Caution in renal impairment |
Indications
- Musculoskeletal: osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, acute non‑traumatic pain.
- Gynecological: primary dysmenorrhea, pelvic inflammatory disease.
- Gout: acute flares.
- Other: low‑dose prophylaxis of cardiovascular events in selected patients.
Contraindications
- Absolute contraindications: History of peptic ulcer disease or gastrointestinal bleeding, known hypersensitivity to naproxen or any NSAID.
- Relative contraindications: Severe hepatic or renal disease, cardiovascular disease (unstable angina, recent MI), pregnancy (especially third trimester), lactation.
- Warnings:
- ↑ risk for GI ulceration, perforation, and hemorrhage.
- Renal impairment or dehydration can precipitate acute kidney injury.
- Cardiovascular safety concerns: increased risk for MI and stroke in long‑term therapy; use lowest effective dose.
- Possible drug‑drug interactions with anticoagulants, antihypertensives, and oral contraceptives.
Dosing
| Population | Typical Regimen | Notes |
| Adults | 220 mg (or 250 mg) PO once daily; can be titrated to 220 mg twice daily for severe pain | Start with lowest effective dose. Discuss with patient about meal timing. |
| Elderly | Same as adults; monitor renal function closely. | Reduced clearance may necessitate lower dosing. |
| Children (≥ 12 yrs) | 1 eucorpora (≈ 6.5 mg/kg) PO two‑weekly intervals | Use cautiously; limited data in younger ages. |
| Renal impairment | 220 mg PO once daily with dose adjustments per creatinine clearance | Avoid if CrCl < 30 mL/min unless essential. |
Administration Tips:
• Take with food or milk to minimize gastric irritation.
• Do not crush or chew tablets; they are formulated for osmotic release.
• Avoid prolonged high‑dose therapy; max 2 weeks for acute pain unless clinically justified.
Adverse Effects
- Common
- Gastrointestinal upset (nausea, dyspepsia, abdominal pain)
- Headache, dizziness
- Somnolence, rash
- Mild renal effect (creatinine rise)
- Serious
- Peptic ulcer disease and GI hemorrhage
- Acute kidney injury or chronic kidney disease progression
- Cardiovascular events (myocardial infarction, stroke)
- Hypersensitivity reactions (anaphylaxis, Stevens‑Johnson syndrome)
- Drug interactions leading to increased INR or blood pressure changes
Monitoring
| Parameter | Frequency | Rationale |
| Renal function (serum creatinine, eGFR) | Baseline, then every 3–6 months (or sooner if indicated) | Prevention of nephrotoxicity |
| Blood pressure | Every visit if hypertensive | NSAIDs can raise BP |
| Complete blood count (CBC) | Baseline, then annually | Identify bone‑marrow suppression |
| Liver function tests | Baseline; repeat if abnormal symptoms | Detect hepatotoxicity |
| Monitor INR | In patients on warfarin | Prolonged therapeutic effect |
Clinical Pearls
- Timing with Anticoagulants: Naproxen can potentiate warfarin or dabigatran effects; consider adding gastro‑protection and schedule INR checks within 48 h of initiation.
- High‑Risk RA Patients: For patients with prior GI ulcers, baseline endoscopy may be warranted; consider alternate NSAIDs or celecoxib with PPI.
- Agryr: If the patient has a mild renal impairment, reduce dose but maintain at least the minimal 220 mg once daily to preserve anti‑inflammatory activity.
- Pregnancy & Lactation: Naproxen is best avoided in the third trimester; after childbirth, it is excreted into breastmilk and should be avoided for the first few weeks.
- Drug‑Drug Interaction: Avoid concomitant intake of tamsulosin and naproxen together due to shared CYP1A2 metabolism—may increase tamsulosin levels.
- Persistent GI Symptoms: If dyspepsia persists, consider switching to ibuprofen or diclofenac as these may induce less gastric irritation in particular patient populations.
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• Quick Reference
• Drug Class: NSAID (non‑selective COX inhibitor)
• Half‑Life: 12–17 h (steady‑state)
• Key APO5: Protein‑bound (93 %), hepatic metabolism, renal excretion.
• Start Dose: 220 mg PO once daily; titrate to 220 mg twice daily if required.
These concise points equip medical students and clinicians with a clear, evidence‑based summary of Naproxen for everyday practice.