Allopathy
Prescription Required
DCGI (Drugs Controller General of India)
Schedule H
India, Germany, Canada, France, USA
Naproxen is a propionic acid derivative belonging to Non-Steroidal anti-inflammatory Drug
Naproxen is used in the treatment as an Anti-inflammatory, Dysmenorrhea, pain and fever. It is also used to treat Abnormal uterine bleeding, nonacute; Migraine, acute treatment.
Naproxen is Readily and completely absorbed from the gastrointestinal tract. Naproxen Na is more rapidly absorbed as compared to naproxen. Decreased rate but not the extent of absorption with food. Bioavailability: 95%. Time to peak plasma concentrations: Conventional tab: 2-4 hours (naproxen); 1-2 hours (naproxen Na). Delayed-release tab: Approx 4-6 hours (fasted state); approx 12 hours (with food). Oral suspension: 1-4 hours and Crosses the placenta; enters breast milk (small amounts). Volume of distribution: 0.16 L/kg. Plasma protein binding: >99%, mainly to albumin and get extensively metabolised in the liver by CYP1A2 and CYP2C9 isoenzymes to 6-O-desmethylnaproxen. Both naproxen and the desmethyl metabolite undergo further metabolism to their respective acylglucuronide conjugated metabolites and get excreted Via urine (approx 95%, mainly as metabolites); faeces (≤3%). Elimination half-life: 12-17 hours.
The onset of action of Naproxen was about 0.5-1 hours.
The Duration of action of Naproxen was about 12 hours.
Naproxen shows common side effects like Acute interstitial nephritis, nephrotic syndrome, renal papillary necrosis, haematuria, proteinuria, renal failure; elevated transaminases, hyperkalaemia, fluid retention, oedema, new-onset or exacerbation of hypertension, decreased platelet aggregation.
Naproxen is available in tablets, capsules and suspension
Naproxen is available in India, Germany, Canada, France, USA
Reversibly inhibits cyclooxygenase-1 and 2 (COX-1 and 2) enzymes, which results in decreased formation of prostaglandin precursors; has antipyretic, analgesic, and anti-inflammatory properties
Naproxen is available in the form of tablets, capsules and suspension
Naproxen is used in the treatment as an Anti-inflammatory, Dysmenorrhea, pain and fever. It is also used to treat Abnormal uterine bleeding, nonacute; Migraine, acute treatment.
Naproxen is approved for use in the following clinical indications
Anti-inflammatory: Relief of the signs and symptoms of gout, ankylosing spondylitis, bursitis, polyarticular juvenile idiopathic arthritis (excluding ER tablets), osteoarthritis, rheumatoid arthritis, and tendinopathy. Delayed-release naproxen is not recommended for initial treatment of acute pain.
Dysmenorrhea, primary: Treatment of primary dysmenorrhea. Delayed-release naproxen is not recommended for initial treatment of acute pain.
Pain and/or fever: Relief of mild to moderate pain and/or fever. Delayed-release naproxen is not recommended for initial treatment of acute pain.
Although not approved there have been certain off labelled uses documented for Naproxen which includes:
Abnormal uterine bleeding, nonacute; Migraine, acute treatment
Abnormal uterine bleeding, nonacute (alternative agent) (off-label use): Note: Not indicated for management of acute abnormal bleeding (ie, excessively heavy or prolonged bleeding that requires urgent evaluation). Alternative agent for patients who cannot or choose not to use hormonal therapies .
Oral: Immediate release: 500 mg at the first sign of menses; may repeat 500 mg 3 to 5 hours later, followed by 250 to 500 mg twice daily for 2 to 3 days or until cessation of bleeding; maximum dose: 1 g/day.
Anti-inflammatory (eg, for arthritis associated with rheumatic disease):
Oral:
Immediate release: 250 to 500 mg every 12 hours; maximum dose: 1.5 g/day.
Extended release: 750 mg to 1 g once daily; maximum dose: 1.5 g/day.
Note: Some experts generally recommend a maximum dose of 1 g/day for chronic use, except during a disease flare when 1.25 to 1.5 g/day may be considered for several weeks until flare resolves.
Dysmenorrhea, primary:
Oral:
Immediate release: Initial: 500 mg once, begin at menses onset or 1 to 2 days prior to onset of menses for severe symptoms; then 500 mg every 12 hours as needed or 250 mg every 6 to 8 hours as needed; maximum dose: 1.25 g/day on day 1, then 1 g/day thereafter; usual duration: 1 to 5 days.
Extended release: Initial: 1 g once daily as needed; begin at menses onset or 1 to 2 days prior to onset of menses for severe symptoms; may increase to a maximum of 1.5 g once daily if needed; usual duration: 1 to 5 days.
Fever (alternative agent):
Oral: OTC labeling (patient-guided therapy): Immediate release: Initial: 200 to 400 mg once, followed by 200 mg every 8 to 12 hours as needed; maximum dose: 400 mg in any 8- to 12-hour period or 600 mg in a 24-hour period.
Gout, prophylaxis during initiation of urate-lowering therapy (alternative agent):
Note: For use in patients not able to tolerate or with contraindications to colchicine (ACR Oral: Immediate release: 250 mg twice daily.
Duration of prophylaxis:
Patients without tophi: ≥3 to 6 months after initiating urate-lowering therapy. Patients with ≥1 tophi: Optimal duration is uncertain; some experts continue prophylaxis ≥6 months; some patients with severe disease may require >12 months prophylaxis.
Gout, treatment (acute flares):
Note: Some experts reserve use for patients who are not candidates for intra-articular glucocorticoids or when intra-articular glucocorticoid administration is not feasible.
Oral:
Immediate release: Initial: 500 mg twice daily within 24 to 48 hours of flare onset; reduce dose as symptoms improve; discontinue 2 to 3 days after resolution of clinical signs. Usual duration: 5 to 7 days.
Extended release: Initial: 1 to 1.5 g once, followed by 1 g once daily; initiate within 24 to 48 hours of flare onset; reduce dose as symptoms improve; discontinue 2 to 3 days after resolution of clinical signs. Usual duration: 5 to 7 days.
Migraine, acute treatment (off-label use):
Note: For use as monotherapy in mild to moderate attacks not associated with vomiting or severe nausea; may be used in combination with triptans for severe migraine.
Oral: Immediate release: 500 to 750 mg once.
Pain (monotherapy or as adjunctive agent):
Oral:
Immediate release: Initial: 500 mg once, followed by 250 to 500 mg every 12 hours as needed or 250 mg every 6 to 8 hours as needed; maximum dose: 1.25 g on day 1, then 1 g/day thereafter. For postoperative pain, doses may be scheduled initially (Schwenk 2020, manufacturer’s labeling).
Extended release: 1 g once daily; may increase to 1.5 g once daily for acute pain, then reduce to a usual maximum dose of 1 g/day.
OTC labeling (patient-guided therapy): Immediate release: Initial: 200 to 400 mg once, followed by 200 mg every 8 to 12 hours as needed; maximum dose: 400 mg in any 8- to 12-hour period or 600 mg in a 24-hour period.
Naproxen is available in the dosage strength of 220mg, 250mg, 275mg, 375mg, 500mg, 550mg, 750 mg, 25mg/mL
Naproxen is available in the form of tablets, capsules and suspension
Dosage Adjustment in Kidney Patient
CrCl ≥60 mL/minute: No dosage adjustment necessary (<1% of unchanged drug excreted in the urine
CrCl >30 to <60 mL/minute: No dosage adjustment necessary (<1% of unchanged drug excreted in the urine). However, use the lowest effective dose for the shortest duration possible. Use of analgesics other than nonsteroidal anti-inflammatory drugs (NSAIDs) or topical NSAIDs may be preferred. Avoid use in patients at high risk for acute kidney injury (ie, volume depleted, hypotensive, elderly, or taking concurrent nephrotoxic medications)
CrCl ≤30 mL/minute: Avoid use due to increased risk of acute kidney injury, use of analgesics other than NSAIDs or topical NSAIDs are preferred. However, in select patients where alternatives are not effective, after careful assessment of risks versus benefits, use of naproxen may be considered; use the lowest effective dose for the shortest duration possible with close monitoring of kidney function (expert opinion).
Hemodialysis, intermittent (thrice weekly): Not significantly dialyzable. Avoid use, as patients with end-stage kidney disease may be at increased risk for bleeding (eg, GI), cardiovascular adverse effects, and loss of residual kidney function However, in select patients after careful assessment of risks versus benefits, use of naproxen may be considered; use the lowest effective dose for the shortest duration possible.
Peritoneal dialysis: Unlikely to be significantly dialyzable (high protein binding): Avoid use, as patients with end-stage kidney disease may be at increased risk for bleeding (eg, GI), cardiovascular adverse effects, and loss of residual kidney. However, in select patients after careful assessment of risks versus benefits, use of naproxen may be considered; use the lowest effective dose for the shortest duration possible.
CRRT: Avoid use (expert opinion).
PIRRT (eg, sustained, low-efficiency diafiltration): Avoid use (expert opinion).
Acute kidney injury while on naproxen therapy: Discontinue use (expert opinion)
Dosage Adjustment for Pediatric Patients:
Analgesia/pain, mild to moderate:
Children and Adolescents <60 kg: Limited data available: Oral: 5 to 7 mg/kg/dose every 8 to 12 hours; maximum daily dose: 1,000 mg/day (Berde 2002; Zeltzer 2020).
Children and Adolescents ≥60 kg: Limited data available: Oral: 5 to 7 mg/kg/dose every 8 to 12 hours; maximum daily dose: 1,000 mg/day (Berde 2002; Zeltzer 2020). Note: Usual adult dose is 500 mg once, followed by 250 to 500 mg every 12 hours as needed or 250 mg every 6 to 8 hours as needed (manufacturer's labeling).
OTC labeling: Children ≥12 years and Adolescents: Immediate release (eg, Aleve): Oral: 200 mg every 8 to 12 hours; if needed may use 400 mg for the initial dose; maximum daily dose: 600 mg/day.
Ankylosing spondylitis: Limited data available: Children and Adolescents: Immediate release, controlled/delayed release: Oral: 15 to 20 mg/kg/day in 2 divided doses; maximum daily dose: 1,500 mg/day; adult dosing suggests limiting this maximum daily dose to <6 months of therapy.
Fever: OTC labeling: Children ≥12 years and Adolescents: Immediate release (eg, Aleve): Oral: 200 mg every 8 to 12 hours; if needed may use 400 mg for the initial dose; maximum daily dose: 600 mg/day.
Juvenile idiopathic arthritis (JIA):
Note: Scheduled nonsteroidal anti-inflammatory drug (NSAID) therapy may be an appropriate first-line treatment option with or without intraarticular glucocorticoids for certain types of JIA; however, due to adverse effect risks with NSAIDs, therapy should be discontinued if not found beneficial after an adequate trial. An adequate NSAID trial duration has not been defined in expert recommendations ; in clinical trials of NSAIDs for JIA, initial beneficial effects were generally observed within 2 weeks . As initial therapy for polyarticular JIA, NSAID monotherapy should be not initiated over a disease-modifying anti-rheumatic drug .
Children and Adolescents: Immediate release, controlled/delayed release: Oral: 10 to 15 mg/kg/day in 2 divided doses; maximum daily dose: 1,000 mg/day.
Migraine, treatment: Limited data available: Children >6 years and Adolescents: Immediate release, controlled/delayed release: Oral: 5 to 7 mg/kg/dose every 8 to 12 hours; maximum daily dose: 1,000 mg/day.
Take after eating and with a full glass of water to decrease gastric upset
Naproxen is contraindicated in patients with:
Hypersensitivity to naproxen. History of asthma, nasal polyps, rhinitis, angioedema, urticaria or other allergic-type reactions after taking aspirin, ibuprofen, or other NSAIDs; active peptic ulcer or gastrointestinal bleeding, history of recurrent gastrointestinal ulceration or bleeding (≥2 distinct episodes of proven ulceration or bleeding), chronic dyspepsia, history of gastrointestinal bleeding or perforation related to previous NSAID use; severe heart failure, treatment of perioperative pain in the setting of CABG surgery. Severe renal (CrCl <30 mL/min) and hepatic impairment. Pregnancy (3rd trimester).
Concerns related to adverse effects:
• CNS effects: May cause drowsiness, dizziness, blurred vision, and other neurologic effects that may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving). Discontinue use with blurred or diminished vision and perform ophthalmologic exam. Periodically evaluate vision in all patients receiving long-term therapy.
• Hyperkalemia: NSAID use may increase the risk of hyperkalemia, particularly in patients ≥65 years of age, in patients with diabetes or renal disease, and with concomitant use of other agents capable of inducing hyperkalemia (eg, ACE-inhibitors). Monitor potassium closely.
Disease-related concerns:
• Aseptic meningitis: May increase the risk of aseptic meningitis, especially in patients with systemic lupus erythematosus (SLE) and mixed connective tissue disorders.
• Asthma: Contraindicated in patients with aspirin-sensitive asthma; severe and potentially fatal bronchospasm may occur. Use caution in patients with other forms of asthma.
• Bariatric surgery: Gastric ulceration: Avoid chronic use of oral nonselective NSAIDs after bariatric surgery; development of anastomotic ulcerations/perforations may occur. Short-term use of celecoxib or IV ketorolac are recommended as part of a multimodal pain management strategy for postoperative pain
Alcohol Warning
Naproxen may cause liver problems, and using it with substantial quantities of ethanol may increase that risk.
Food Warning
Food may decrease the rate but not the extent of absorption. Naproxen peak serum levels may be delayed if taken with food. Management: Administer with food or milk to minimize GI upset
- Common Adverse effects:
Acute interstitial nephritis, nephrotic syndrome, renal papillary necrosis, haematuria, proteinuria, renal failure; elevated transaminases, hyperkalaemia, fluid retention, oedema, new-onset or exacerbation of hypertension, decreased platelet aggregation
- Less Common Adverse effects:
- Nausea, vomiting, dyspepsia, constipation, diarrhoea, flatulence, abdominal pain or discomfort, epigastric distress, heartburn.
- Rare Adverse effects
Dizziness, headache, drowsiness, paraesthesia, convulsions, cognitive dysfunction.
- May reduce the therapeutic efficacy of antihypertensive agents (e.g. ACE inhibitors, β-blockers, angiotensin II receptor blockers) and diuretics (e.g. furosemide, thiazide diuretics).
- May increase the risk of renal impairment with ACE inhibitors or angiotensin II receptor blockers. Increased plasma levels and prolonged half-life with probenecid.
- May increase the plasma levels of lithium, methotrexate, and digoxin. May increase the nephrotoxic effects of ciclosporin and tacrolimus.
- May reduce the effect of mifepristone.
- May increase the risk of haematological toxicity with zidovudine. Concomitant use of antacids, colestyramine, and sucralfate may delay the absorption of naproxen.
- Potentially Fatal: Increased risk of gastrointestinal toxicity or bleeding when used concomitantly with other NSAIDs, corticosteroids, anticoagulants (e.g. warfarin), SSRIs, or antiplatelet agents (e.g. aspirin).
The common side effects of Naproxen include the following :
Acute interstitial nephritis, nephrotic syndrome, renal papillary necrosis, haematuria, proteinuria, renal failure; elevated transaminases, hyperkalaemia, fluid retention, oedema, new-onset or exacerbation of hypertension, decreased platelet aggregation
Symptoms: Nausea, vomiting, indigestion, epigastric pain, headache, drowsiness, dizziness, gastrointestinal bleeding, liver damage, transient prolongation of prothrombin time. Rarely, diarrhoea, heartburn, tinnitus, disorientation, excitation, fainting, hypertension, acute renal failure, convulsions, respiratory depression, and coma.
Management: Symptomatic and supportive treatment. Consider administration of activated charcoal or performing gastric lavage (in adults) within 1 hour of ingestion, or inducing emesis and/or use of osmotic cathartic (in symptomatic patients seen within 4 hours of ingestion). Ensure good urine output. Monitor liver and renal function. Observe the patient for at least 4 hours following ingestion. Administer IV diazepam for frequent or prolonged convulsions
- Pharmacodynamics
Naproxen, a propionic acid derivative, is an NSAID that has analgesic, anti-inflammatory and antipyretic properties. Its mechanism of action is not fully understood but may involve the reversible inhibition of cyclooxygenase-1 and 2 (COX-1 and 2) enzymes, which leads to decreased formation of prostaglandin precursors..
- Pharmacokinetics
Absorption: Readily and completely absorbed from the gastrointestinal tract. Naproxen Na is more rapidly absorbed as compared to naproxen. Decreased rate but not the extent of absorption with food. Bioavailability: 95%. Time to peak plasma concentrations: Conventional tab: 2-4 hours (naproxen); 1-2 hours (naproxen Na). Delayed-release tab: Approx 4-6 hours (fasted state); approx 12 hours (with food). Oral suspension: 1-4 hours.
Distribution: Crosses the placenta; enters breast milk (small amounts). Volume of distribution: 0.16 L/kg. Plasma protein binding: >99%, mainly to albumin.
Metabolism: Extensively metabolised in the liver by CYP1A2 and CYP2C9 isoenzymes to 6-O-desmethylnaproxen. Both naproxen and the desmethyl metabolite undergo further metabolism to their respective acylglucuronide conjugated metabolites.
Excretion: Via urine (approx 95%, mainly as metabolites); faeces (≤3%). Elimination half-life: 12-17 hours.
1. https://pubmed.ncbi.nlm.nih.gov/1091001/
2. https://clinicaltrials.gov/ct2/show/NCT01422915
3. https://clinicaltrials.gov/ct2/show/NCT02263547
4. https://www.medicines.org.uk/emc/product/128/smpc.
1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1364710/
2. https://reference.medscape.com/drug/colestid-Naproxen -342452
3. https://go.drugbank.com/drugs/DB00375
4. https://www.sciencedirect.com/topics/medicine-and-dentistry/Naproxen
5. https://europepmc.org/article/med/6988203
