Anaflex 500 mg Tablet (Naproxen Sodium) – ACI Limited

1. About Anaflex 500 mg (Naproxen Sodium)

Anaflex 500 mg Tablet contains Naproxen Sodium 500 mg, a long-acting Non-Steroidal Anti-Inflammatory Drug (NSAID) of the propionic acid class, manufactured by ACI Limited, Bangladesh. Naproxen sodium is the water-soluble salt of naproxen with faster absorption compared to naproxen base, providing more rapid onset of analgesia and anti-inflammatory effect.

A key clinical advantage of naproxen over shorter-acting NSAIDs (e.g., ibuprofen, diclofenac) is its long plasma half-life of 12–17 hours, enabling twice-daily dosing — improving patient compliance and providing more sustained pain and inflammation control. ACI Limited's Anaflex range offers naproxen in multiple strengths and formulations including the 500 mg standard tablet, 250 mg tablet, SR 500 mg sustained-release form, topical 10% gel, and gastroprotective combination (Anaflex Max — with esomeprazole) for comprehensive pain management across clinical settings.

2. Mechanism of Action

Naproxen sodium exerts its analgesic, anti-inflammatory, and antipyretic effects through cyclooxygenase inhibition:

• COX-1 and COX-2 inhibition: Naproxen non-selectively inhibits both cyclooxygenase isoforms (COX-1 and COX-2), blocking the conversion of arachidonic acid to prostaglandins and thromboxanes. Reduced prostaglandin synthesis at the site of inflammation results in decreased pain, swelling, heat, and redness.
• Central and peripheral analgesia: Reduced prostaglandin synthesis in the CNS (spinal cord sensitisation) and periphery (sensory nerve sensitisation) decreases pain signalling at multiple levels.
• Anti-inflammatory effect: Decreased prostaglandin E2 (PGE2) and prostacyclin (PGI2) reduces vascular permeability, vasodilation, and neutrophil recruitment at inflammatory foci — reducing joint swelling in arthritis and tissue inflammation.
• Antipyretic effect: Inhibition of hypothalamic PGE2 synthesis resets the thermoregulatory set point during fever.
• Naproxen sodium vs naproxen acid: The sodium salt dissolves more rapidly in GI fluid, reaching peak plasma concentration ~1 hour faster than naproxen acid, making it preferable for acute pain states (e.g., dysmenorrhoea, dental pain) where rapid onset is desired.

3. Indications

Anaflex 500 mg Tablet (Naproxen Sodium) is indicated for:

• Rheumatoid Arthritis (RA): Long-term management of joint pain, stiffness, and swelling — twice-daily dosing provides sustained anti-inflammatory effect throughout the day including overnight
• Osteoarthritis (OA): Pain relief and functional improvement in degenerative joint disease of the knee, hip, hands, and spine — highly prevalent in Bangladesh's elderly population
• Ankylosing Spondylitis: Reduces pain and improves spinal mobility in seronegative spondyloarthropathy
• Acute Gout: Effective NSAID for acute gouty arthritis — reduces joint pain and swelling during attacks
• Primary Dysmenorrhoea: Menstrual pain — naproxen sodium is one of the most effective NSAIDs for dysmenorrhoea due to its rapid onset and long duration
• Acute Musculoskeletal Conditions: Sprains, strains, tendinitis, bursitis, periarthritis, and sports injuries
• Post-Operative and Post-Traumatic Pain: As part of multimodal analgesia after surgery or trauma
• Dental Pain: Acute toothache and post-extraction pain management
• Migraine: Treatment of acute migraine attacks
• Juvenile Idiopathic Arthritis (JIA): Naproxen is one of the NSAIDs used in paediatric inflammatory arthritis

4. Dosage and Administration

Rheumatoid Arthritis / Osteoarthritis / Ankylosing Spondylitis (long-term):

• Adults: 500 mg twice daily (morning and evening) — maximum 1,000 mg/day for long-term use
• Initial dose may be 750 mg–1,000 mg/day in divided doses; reduce to lowest effective dose after response achieved

Acute Gout:

• Initial dose: 750 mg (1½ tablets of 500 mg), then 250 mg every 8 hours until attack resolves

Acute Musculoskeletal Pain / Post-Operative Pain:

• 500–550 mg initially, then 250–275 mg every 6–8 hours; maximum 1,375 mg on day 1, then 1,100 mg/day

Primary Dysmenorrhoea:

• 500 mg initially, then 250 mg every 6–8 hours; start at onset of pain

Elderly: Use the lowest effective dose for the shortest duration. Start with 250 mg twice daily. Elderly are at higher risk of GI, renal, and cardiovascular NSAID complications.

Renal/Hepatic impairment: Use with caution; avoid in severe impairment.

Administration: Take with food, milk, or antacids to reduce GI irritation. Swallow tablet whole with a full glass of water. Do not lie down for 10 minutes after taking.

5. Contraindications

• Active peptic ulcer disease or a history of GI bleeding related to NSAID use
• Hypersensitivity to naproxen, aspirin, or any other NSAID (cross-sensitivity)
• Aspirin-exacerbated respiratory disease (NSAID-/aspirin-sensitive asthma, rhinosinusitis, nasal polyps)
• Severe renal impairment (CrCl <30 ml/min)
• Severe hepatic impairment
• Severe heart failure
• Third trimester of pregnancy — NSAIDs cause premature closure of ductus arteriosus and neonatal renal impairment
• Coronary artery bypass graft (CABG) surgery — all NSAIDs contraindicated perioperatively

6. Warnings and Precautions

GI Risk: NSAIDs including naproxen carry a risk of serious GI adverse events — peptic ulceration, perforation, and bleeding — at any point during treatment and without warning symptoms. Risk is higher with: higher doses, longer duration, history of peptic ulcer disease, concomitant steroids or anticoagulants, heavy alcohol use, or elderly patients. Consider co-prescribing a proton pump inhibitor (PPI) or consider Anaflex Max (naproxen + esomeprazole) in high-GI-risk patients.

Cardiovascular Risk: Like all NSAIDs, naproxen may increase the risk of serious cardiovascular thrombotic events (myocardial infarction, stroke) — particularly with prolonged use or in patients with pre-existing cardiovascular disease or risk factors. Use the lowest effective dose for the shortest duration. Among NSAIDs, naproxen may have a relatively lower CV risk profile compared to selective COX-2 inhibitors.

Renal Effects: NSAIDs reduce renal prostaglandin synthesis which is important for maintaining renal blood flow under conditions of reduced perfusion (dehydration, heart failure, diuretic use). Acute renal failure can occur. Monitor renal function in elderly patients, those with diabetes, hypertension, or pre-existing renal impairment.

Diabetic patients — specific caution:

• Diabetic nephropathy: NSAID use — including naproxen — can precipitate acute deterioration in already compromised renal function. Baseline eGFR and regular monitoring is important. Use only when clearly necessary and for shortest possible duration.
• Blood pressure: NSAIDs can elevate blood pressure and oppose the effects of antihypertensives (ACE inhibitors, ARBs, diuretics) — of critical importance in diabetic patients who rely on these agents for both BP control and renal protection. Monitor BP closely during naproxen use.
• Fluid retention and oedema: Can worsen heart failure and peripheral oedema
• Hypoglycaemia: Naproxen may rarely potentiate the hypoglycaemic effect of sulphonylureas — monitor blood glucose if on these agents

Pregnancy: Avoid in first trimester if possible; do not use in third trimester. Naproxen crosses the placenta.

7. Side Effects

Common (≥1–10%):

• GI: nausea, dyspepsia, heartburn, abdominal pain, constipation
• Headache, dizziness
• Oedema (ankle swelling)
• Tinnitus (particularly at higher doses or prolonged use)

Uncommon:

• GI: peptic ulcer, GI bleeding (black stools, haematemesis)
• Elevated liver enzymes, hepatitis (rare)
• Skin: rash, urticaria, photosensitivity
• Elevated blood pressure, fluid retention
• Renal: increased creatinine, acute kidney injury (especially in dehydrated/at-risk patients)

Rare/Serious:

• GI perforation — surgical emergency
• Severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis)
• Anaphylaxis
• Myocardial infarction, stroke (with prolonged use in high-CV-risk patients)

8. Drug Interactions

• Other NSAIDs/Aspirin: Increased GI and renal side effects — avoid combination
• Anticoagulants (warfarin, heparin): Additive bleeding risk — monitor INR closely
• ACE inhibitors/ARBs: Reduced antihypertensive and renoprotective effect; increased risk of acute kidney injury — particularly important in diabetic patients on ACE inhibitors/ARBs for nephroprotection
• Diuretics: Reduced diuretic efficacy; increased renal failure risk
• Sulphonylureas: Possible enhanced hypoglycaemic effect (protein-binding displacement) — monitor blood glucose
• Methotrexate: Naproxen reduces methotrexate clearance — increased methotrexate toxicity
• Lithium: Reduced renal lithium clearance — increased lithium levels and toxicity
• Antihypertensives generally: NSAIDs oppose blood pressure lowering effects
• SSRIs: Additive GI bleeding risk
• Corticosteroids: Significantly increased GI ulceration risk — consider PPI co-prescription

9. Pharmacokinetics

Absorption: Naproxen sodium is rapidly absorbed — oral bioavailability ~95%. Tmax ~1–2 hours for naproxen sodium (faster than naproxen acid due to better GI solubility). Food slightly delays but does not reduce absorption.

Distribution: Highly protein-bound (~99% to albumin). This high protein binding means naproxen displaces other protein-bound drugs (warfarin, sulphonylureas). Vd ~0.16 L/kg (limited tissue distribution due to high protein binding).

Metabolism: Extensively metabolised in the liver by CYP2C9 to 6-desmethylnaproxen and other inactive metabolites.

Elimination: Excreted primarily in urine (95% as conjugated metabolites). Terminal half-life 12–17 hours — the basis for twice-daily dosing. In elderly patients, half-life may be prolonged.

10. Naproxen Sodium vs. Other NSAIDs

Clinically important differences that make naproxen a preferred NSAID in certain situations:

• vs. Ibuprofen: Naproxen has a longer half-life (twice daily vs. 3–4 times daily), providing more sustained effect and better overnight pain control in arthritis — particularly valuable for patients with morning stiffness in RA.
• vs. Diclofenac: Similar anti-inflammatory potency; naproxen may have a lower cardiovascular risk profile based on meta-analyses. Diclofenac has more hepatotoxic potential.
• vs. COX-2 inhibitors (celecoxib): Naproxen has lower GI bleeding risk than non-selective NSAIDs at standard doses; COX-2 inhibitors have better GI safety but higher CV risk. In patients with arthritis and high GI risk, naproxen + PPI (Anaflex Max) is a safe and effective alternative to COX-2 inhibitors.
• Sodium vs. Acid formulation: The sodium salt (Anaflex 500 mg) has faster onset — preferred for acute pain. Naproxen base (acid) tablets have identical long-term efficacy.

11. NSAID Use in Diabetic Patients

NSAIDs including naproxen require careful consideration in patients with diabetes:

• Renal protection first: Diabetic nephropathy affects ~30–40% of diabetic patients — NSAID use can accelerate renal decline. Use only when genuinely needed; prefer paracetamol (acetaminophen) for mild pain in diabetic patients with renal impairment.
• Blood pressure impact: NSAIDs may raise BP by 3–5 mmHg on average — significant for diabetics where every mmHg of BP control matters for preventing nephropathy and retinopathy progression.
• Short-term use principles: For diabetic patients with painful arthritis requiring NSAIDs, use the lowest effective dose for the shortest duration. Monitor renal function (serum creatinine, eGFR) before and after treatment. Ensure adequate hydration.
• Arthritis management in diabetes: Physiotherapy, weight management, and paracetamol should be first-line; NSAIDs reserved for inadequate response.

12. ACI Limited — Anaflex Range

ACI Limited's Anaflex brand offers a comprehensive naproxen portfolio covering all clinical pain management scenarios:

• Anaflex 250 mg Tablet — lower-dose for mild pain, elderly dosing, initial therapy
• Anaflex 500 mg Tablet (Naproxen Sodium) — standard adult dose, fast onset
• Anaflex SR 500 mg — sustained-release for overnight symptom control
• Anaflex Max 375/500 mg — combined with esomeprazole 20 mg for gastroprotection in GI-risk patients
• Anaflex 10% Topical Gel — topical application for localised musculoskeletal pain without systemic GI/CV risk

13. Storage

• Store below 30°C in a cool, dry place
• Protect from sunlight and moisture
• Keep in original strip/box
• Keep out of reach of children
• Do not use after expiry date

Frequently Asked Questions (FAQ)

Q1: What is Anaflex 500 mg (Naproxen Sodium) used for?

Anaflex 500 mg (Naproxen Sodium) is a long-acting NSAID used for: arthritis (rheumatoid arthritis, osteoarthritis, ankylosing spondylitis) — the most common long-term use; acute gout attacks; primary dysmenorrhoea (period pain) — one of the most effective NSAIDs for menstrual pain; musculoskeletal pain (sprains, sports injuries, tendinitis, bursitis); post-operative and dental pain; and migraine attacks. Its long half-life means it works effectively with just twice-daily dosing, providing day-and-night symptom control.

Q2: Can diabetic patients take Anaflex (Naproxen)?

Diabetic patients can take naproxen but require extra precautions: (1) Renal risk — naproxen (like all NSAIDs) can worsen kidney function, particularly in diabetic nephropathy. Check kidney function before starting and during treatment. Use the lowest dose for the shortest time. (2) Blood pressure — NSAIDs can raise BP and oppose ACE inhibitors/ARBs that diabetic patients take for kidney protection. Monitor BP carefully. (3) Sulphonylurea interaction — may enhance hypoglycaemia; monitor blood glucose. For mild arthritis pain, paracetamol is generally safer than NSAIDs in diabetic patients with renal impairment. Always discuss with your physician before starting naproxen if you have diabetes.

Q3: Why is Anaflex 500 mg taken twice a day instead of 3–4 times like some other pain tablets?

Naproxen has a long half-life of 12–17 hours — meaning it stays active in your body much longer than ibuprofen (half-life 2 hours) or diclofenac (half-life 1–2 hours). This long duration allows effective pain and inflammation control with just twice-daily dosing — once in the morning and once in the evening. This is particularly beneficial for arthritis patients who experience pain overnight and early morning stiffness — naproxen's overnight concentration remains therapeutic, reducing morning symptoms. Better twice-daily compliance also improves long-term adherence compared to 3–4 times daily NSAIDs.

Q4: Do I need to take Anaflex with food?

Yes — always take Anaflex 500 mg with food, milk, or an antacid. NSAIDs including naproxen can irritate the stomach lining directly, causing nausea, dyspepsia, and in susceptible patients, peptic ulcers or gastric bleeding. Taking with food or milk significantly reduces this risk. Drink a full glass of water with each dose. If you experience persistent stomach pain, nausea, vomiting, black stools, or blood in stools during naproxen treatment — stop the medication and see a doctor immediately. Patients with a history of peptic ulcer or on warfarin should consider Anaflex Max (naproxen + esomeprazole) for added stomach protection.