Usage
Naproxen is prescribed for various medical conditions, primarily to alleviate pain and reduce inflammation. These include:
- Osteoarthritis
- Rheumatoid arthritis
- Ankylosing spondylitis
- Acute gout
- Bursitis
- Tendonitis
- Dysmenorrhea (painful menstruation)
- Acute musculoskeletal disorders
- Fever
- Headache, including migraine (off-label use)
- Postoperative pain
Pharmacological Classification: Non-steroidal anti-inflammatory drug (NSAID).
Mechanism of Action: Naproxen inhibits cyclooxygenase (COX), an enzyme responsible for producing prostaglandins, which mediate inflammation and pain. By reducing prostaglandin synthesis, naproxen diminishes pain signals and inflammatory responses.
Alternate Names
Naproxen sodium (the sodium salt of naproxen)
Brand Names: Naprosyn, Anaprox, Aleve, Naprelan, and others.
How It Works
Pharmacodynamics: Naproxen’s primary therapeutic effects are analgesic (pain-relieving) and anti-inflammatory. It achieves this by inhibiting prostaglandin synthesis via COX inhibition. It may also have antipyretic (fever-reducing) effects.
Pharmacokinetics: Naproxen is well-absorbed orally. The sodium salt (naproxen sodium) is absorbed more rapidly than naproxen base. Naproxen is highly protein-bound in plasma. It is metabolized in the liver, primarily by CYP1A2 and CYP2C9 enzymes, and eliminated via renal excretion. Naproxen has a relatively long half-life (around 12-15 hours), allowing for once or twice-daily dosing.
Mode of Action: Naproxen reversibly inhibits both COX-1 and COX-2 isoforms. COX-1 is constitutively expressed and involved in physiological functions like protecting the gastric mucosa, while COX-2 is induced during inflammation. Inhibiting both contributes to naproxen’s therapeutic and adverse effects.
Elimination Pathways: Naproxen is primarily eliminated by hepatic metabolism followed by renal excretion of the metabolites.
Dosage
Standard Dosage
Adults:
- Osteoarthritis, Rheumatoid Arthritis, Ankylosing Spondylitis: 250-500 mg twice daily or 375-500 mg (delayed-release) twice daily. May increase to 1500 mg/day for limited periods, if tolerated. Extended-release formulations: 750-1000 mg once daily; may increase to 1500 mg/day for limited periods.
- Acute Musculoskeletal Disorders, Dysmenorrhea, Pain: 500 mg initially, then 250 mg every 6-8 hours or 500 mg every 12 hours as needed. Maximum: 1250 mg on day 1, then 1000 mg/day. Extended-release: 750-1000 mg once daily, may increase to 1500 mg/day for a limited duration.
- Acute Gout: 750 mg initially, then 250 mg every 8 hours until the attack subsides. Or, 825 mg naproxen sodium initially followed by 275 mg every 8 hours.
Children:
- Juvenile Rheumatoid Arthritis (over 5 years): 10 mg/kg/day divided twice daily.
- Use and dosage for other indications in children must be determined by a doctor.
Special Cases:
- Elderly Patients: Start with lower doses due to increased risk of adverse effects and age-related decline in renal and hepatic function.
- Patients with Renal Impairment: Lower doses are advised. Contraindicated in severe renal impairment (creatinine clearance < 30 mL/min).
- Patients with Hepatic Dysfunction: Lower doses are recommended.
- Patients with Comorbid Conditions: Exercise caution in patients with cardiovascular disease, history of gastrointestinal bleeding, or other relevant comorbidities. Dose adjustments might be necessary.
Clinical Use Cases
The use of naproxen in clinical scenarios like intubation, surgical procedures, mechanical ventilation, and ICU settings varies based on the patient’s specific needs for pain and inflammation management, while considering the potential risks of NSAIDs in critically ill patients. Dosage should be determined based on the patient’s condition. For specific dosage recommendations, consultation with resources like EMCrit (emcrit.org) is helpful. The information on EMCrit can be particularly relevant to Indian doctors who want to stay updated on the best practices in critical care management.
Dosage Adjustments
Dose adjustments are required for patients with renal or hepatic impairment, elderly patients, and those with certain comorbid conditions. Consider genetic polymorphisms affecting drug metabolism, especially CYP2C9. Always start with the lowest effective dose and titrate up based on patient response and tolerance.
Side Effects
Common Side Effects
- Gastrointestinal upset (dyspepsia, heartburn, nausea, constipation)
- Headache
- Dizziness
- Drowsiness
- Fluid retention
Rare but Serious Side Effects
- Gastrointestinal bleeding or ulcers
- Myocardial infarction
- Stroke
- Heart failure
- Stevens-Johnson syndrome
- Severe allergic reactions
Long-Term Effects
- Chronic kidney disease
- Gastrointestinal problems
Adverse Drug Reactions (ADR)
- Anaphylaxis
- Angioedema
- Severe skin reactions
Contraindications
- Hypersensitivity to naproxen or other NSAIDs
- History of aspirin-exacerbated respiratory disease (AERD)
- Active peptic ulcer disease
- Severe renal impairment
- Severe heart failure
- Peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery
- Third trimester of pregnancy
Drug Interactions
- Anticoagulants (warfarin): Increased risk of bleeding.
- Antihypertensives: May decrease efficacy of antihypertensives.
- Lithium: May increase lithium levels.
- Methotrexate: May increase methotrexate toxicity.
- Other NSAIDs and aspirin: Increased risk of gastrointestinal adverse effects.
- CYP450 inhibitors and inducers can affect naproxen metabolism.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C (first and second trimester), D (third trimester)
- Fetal Risks: Premature closure of ductus arteriosus, prolonged labor, increased risk of bleeding.
- Breastfeeding: Naproxen is excreted in breast milk. Use with caution.
Drug Profile Summary
- Mechanism of Action: COX inhibitor, reduces prostaglandin synthesis.
- Side Effects: GI upset, headache, dizziness, serious cardiovascular and GI risks.
- Contraindications: Hypersensitivity, AERD, active peptic ulcer, severe renal/heart failure, third-trimester pregnancy.
- Drug Interactions: Anticoagulants, antihypertensives, lithium, methotrexate, other NSAIDs.
- Pregnancy & Breastfeeding: Avoid in third trimester. Use cautiously during breastfeeding.
- Dosage: Varies depending on indication and patient factors. See detailed dosage section.
- Monitoring Parameters: Renal function, liver function, blood pressure, signs of GI bleeding.
Popular Combinations
- Naproxen + esomeprazole (Vimovo): Combines naproxen with a proton pump inhibitor to reduce the risk of GI side effects.
Precautions
- Use the lowest effective dose for the shortest duration.
- Monitor for signs of GI bleeding, renal or hepatic dysfunction.
- Patients with cardiovascular risk factors require careful monitoring.
- Caution advised in elderly patients.
- Alcohol consumption can increase the risk of GI bleeding.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Naproxen?
A: The dosage varies depending on the indication and patient factors. See the detailed dosage section above.
Q2: What are the serious side effects of Naproxen?
A: Serious side effects include gastrointestinal bleeding, ulcers, myocardial infarction, stroke, and heart failure.
Q3: Can Naproxen be used during pregnancy?
A: Naproxen should be avoided during the third trimester. Use with caution during the first and second trimesters.
Q4: How does Naproxen interact with other medications?
A: Naproxen can interact with anticoagulants, antihypertensives, lithium, methotrexate, and other NSAIDs. See the drug interactions section for details.
Q5: What are the contraindications to Naproxen use?
A: Contraindications include hypersensitivity to naproxen or other NSAIDs, history of AERD, active peptic ulcer disease, severe renal impairment, and severe heart failure.
Q6: What are the long-term effects of Naproxen use?
A: Long-term use can increase the risk of chronic kidney disease and gastrointestinal problems.
Q7: How should Naproxen be administered?
A: Naproxen can be administered orally as tablets, capsules, or a suspension. It’s usually taken with food to minimize GI upset.
Q8: How does Naproxen work at the molecular level?
A: Naproxen reversibly inhibits COX-1 and COX-2, thereby reducing prostaglandin production.
Q9: Are there any special precautions for elderly patients taking Naproxen?
A: Elderly patients should start with lower doses due to an increased risk of adverse effects and reduced renal and hepatic function.
Q10: What should I do if a patient experiences a suspected Naproxen overdose?
A: Contact a poison control center or seek immediate medical attention. Treatment may involve supportive care and measures to enhance elimination.
