Niaproff^® (Tablets) Instructions for Use

Marketing Authorization Holder

World Medicine İlaç San. ve Tic. A.Ş. (Turkey)

ATC Code

M01AE02 (Naproxen)

Active Substance

Naproxen (Rec.INN registered by WHO)

Dosage Form

Niaproff®

Film-coated tablets, 550 mg: 10 or 20 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets white or almost white, oblong, biconvex, with a score line on both sides.

Excipients: microcrystalline cellulose (type 101) – 107.5 mg, povidone (K30) – 27.5 mg, talc – 31.5 mg, magnesium stearate – 3.5 mg.

Shell composition Opadry^® white Y-1-7000 – 25 mg (hypromellose – 62.5%, titanium dioxide – 31.25%, macrogol 400 – 6.25%).

10 pcs. – blisters (1) – cardboard packs.
10 pcs. – blisters (2) – cardboard packs.

Clinical-Pharmacological Group

NSAID

Pharmacotherapeutic Group

NSAID

Pharmacological Action

NSAID, a derivative of naphthylpropionic acid. It has anti-inflammatory, analgesic, and antipyretic effects.

The mechanism of action is associated with inhibition of the COX enzyme, which leads to suppression of prostaglandin synthesis from arachidonic acid.

It is used for symptomatic therapy (to reduce pain, inflammation, and lower elevated body temperature) and does not affect the progression of the underlying disease.

Pharmacokinetics

After oral administration, Naproxen is rapidly and completely absorbed from the gastrointestinal tract. Bioavailability is 95% (food intake has practically no effect on either the completeness or the rate of absorption). C_max in plasma is reached in 1-2 hours.

At therapeutic concentrations, Naproxen binds to plasma proteins by more than 99%. The equilibrium concentration in blood plasma is determined after taking 4-5 doses of the drug (2-3 days). The plasma concentration of naproxen increases proportionally at doses up to 500 mg; at higher doses, an increase in clearance is observed due to saturation of plasma proteins. Naproxen diffuses into the synovial fluid.

Metabolism occurs in the liver to dimethylnaproxen with the participation of the CYP2C9 isoenzyme. Clearance is 0.13 ml/min/kg. T_1/2 is 12-15 hours. Approximately 98% of the dose is excreted in the urine as unchanged substance (10%) and 6-O-desmethylnaproxen and its conjugates. 0.5-2.5% is excreted in the bile.

In renal failure, accumulation of metabolites is possible.

Indications

Diseases of the musculoskeletal system (rheumatic soft tissue lesions, osteoarthritis of peripheral joints and spine, including with radicular syndrome, tenosynovitis, bursitis); mild or moderate pain syndrome: neuralgia, bone pain, myalgia, lumbosacral radiculopathy, post-traumatic pain syndrome (sprains and bruises) accompanied by inflammation, headache, migraine, dysmenorrhea, toothache; as part of complex therapy for infectious and inflammatory diseases of the ear, throat, nose with severe pain syndrome (pharyngitis, tonsillitis, otitis); febrile syndrome in “cold” and infectious diseases.

ICD codes

Dosage Regimen

Determine the dosage individually, based on the indication and severity of symptoms.

Administer orally to adults and adolescents over 15 years of age.

For pain and inflammation, the typical initial dose is 275 mg or 550 mg twice daily.

Alternatively, administer a total daily dose of 550 mg to 825 mg, divided into two or three doses.

Do not exceed the maximum daily dose of 825 mg.

For mild to moderate pain and dysmenorrhea, use the lowest effective dose for the shortest duration necessary.

Limit use for self-medication of pain or fever to no more than 5 days.

For chronic conditions like arthritis, the maintenance dose is typically 275 mg to 550 mg twice daily.

For acute gout, initiate with a 750 mg loading dose, followed by 275 mg every 8 hours until the attack subsides.

Swallow tablets whole with a sufficient amount of water.

Take with food or milk to minimize the risk of gastrointestinal irritation.

In elderly patients and those with hepatic cirrhosis, initiate therapy at the lower end of the dosage range.

Adjust dosage carefully and monitor patients with impaired renal function (creatinine clearance 30-60 ml/min).

Contraindicated in patients with severe renal impairment (creatinine clearance less than 30 ml/min).

Adverse Reactions

From the digestive system nausea, vomiting, epigastric discomfort, impaired liver function; possible development of peptic ulcer, perforation or gastrointestinal bleeding, sometimes fatal, especially in elderly patients.

From the hematopoietic system infrequently – eosinophilia, granulocytopenia, leukopenia, thrombocytopenia, aplastic anemia, hemolytic anemia.

From the nervous system often – headache, vertigo, dizziness, drowsiness, visual impairment, tinnitus, hearing impairment; infrequently – depression, sleep disorders, inability to concentrate, insomnia, malaise.

From the heart: often – swelling, palpitations; infrequently – congestive heart failure.

From the respiratory system rarely – eosinophilic pneumonia.

From the skin and subcutaneous tissues often – skin itching, skin rash, ecchymosis, purpura; infrequently – alopecia, photodermatoses; very rarely – bullous reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis; frequency unknown – DRESS syndrome.

From the urinary system infrequently – glomerulonephritis, hematuria, interstitial nephritis, nephrotic syndrome, renal failure, renal papillary necrosis.

Contraindications

Hypersensitivity to naproxen or naproxen sodium; complete or incomplete combination of bronchial asthma, recurrent nasal polyposis or sinusitis and intolerance to acetylsalicylic acid and other NSAIDs (including in history); period after coronary artery bypass surgery; erosive and ulcerative changes in the gastric or duodenal mucosa, active gastrointestinal bleeding; inflammatory bowel diseases (ulcerative colitis, Crohn’s disease) in the acute phase; hemophilia and other bleeding disorders and hemostasis disorders; cerebrovascular hemorrhage or other bleeding; decompensated heart failure; severe hepatic failure or active liver disease; severe renal failure (creatinine clearance less than 30 ml/min), progressive kidney disease, confirmed hyperkalemia; pregnancy, breastfeeding period; children under 15 years of age.

Use in Pregnancy and Lactation

Contraindicated during pregnancy and breastfeeding.

The use of naproxen, like other drugs that block prostaglandin synthesis, may affect fertility, so it is not recommended for women planning pregnancy.

Use in Hepatic Impairment

Should be prescribed with caution to patients with liver diseases. In liver cirrhosis, the concentration of unbound naproxen increases, so the use of lower doses is recommended. Use is contraindicated in severe hepatic failure or active liver disease.

Use in Renal Impairment

Should be prescribed with caution to patients with renal failure. In patients with renal failure, creatinine clearance should be monitored. Use of Naproxen is contraindicated if creatinine clearance is less than 30 ml/min.

Pediatric Use

Contraindicated in children under 15 years of age.

Geriatric Use

Elderly patients are recommended to take naproxen in lower doses.

Special Precautions

Should be used with caution in coronary artery disease, cerebrovascular diseases, congestive heart failure, diabetes mellitus, peripheral arterial diseases, smoking, impaired renal function (creatinine clearance 30-60 ml/min), history of ulcerative gastrointestinal lesions, in elderly patients, in systemic connective tissue diseases.

Do not exceed the recommended doses. To reduce the risk of adverse gastrointestinal events, the minimum effective dose should be used for the shortest possible course.

Patients with bronchial asthma, bleeding disorders, as well as patients with hypersensitivity to other analgesics should consult a doctor before taking naproxen.

Should be prescribed with caution to patients with liver diseases and renal failure. In patients with renal failure, creatinine clearance should be monitored. Use of Naproxen is not recommended if creatinine clearance is less than 30 ml/min. In chronic alcoholic and other forms of liver cirrhosis, the concentration of unbound naproxen increases, so such patients are recommended lower doses. After two weeks of using the drug, liver function tests should be monitored.

Naproxen should not be taken simultaneously with other anti-inflammatory and analgesic drugs, except as prescribed by a doctor.

Elderly patients are recommended to take naproxen in lower doses.

Avoid taking naproxen for 48 hours before surgery.

If it is necessary to determine 17-ketosteroids, the drug should be discontinued 48 hours before the study. Similarly, Naproxen may affect the determination of 5-hydroxyindoleacetic acid in urine.

Drug Interactions

When used concomitantly with anticoagulants, it should be borne in mind that Naproxen may increase bleeding time. Should not be used simultaneously with acetylsalicylic acid, other NSAIDs, including selective COX-2 inhibitors (increased risk of side effects).

According to clinical pharmacodynamics, simultaneous use of naproxen and acetylsalicylic acid for more than one day may inhibit the effect of low-dose acetylsalicylic acid on platelet activity; inhibition may persist for several days after discontinuation of naproxen therapy. The clinical significance of this interaction is unknown.

Naproxen may reduce the antihypertensive effect of propranolol and other beta-blockers, and may also increase the risk of renal failure associated with the use of ACE inhibitors.

NSAIDs may reduce the diuretic effect of diuretics. Under the influence of naproxen, the natriuretic effect of furosemide is inhibited. Diuretics may increase the risk of nephrotoxicity of NSAIDs.

When used concomitantly with antacids containing magnesium and aluminum, sodium bicarbonate, the absorption of naproxen is reduced.

When used concomitantly, a change in the pharmacokinetic parameters of diazepam is possible; with caffeine – the effect of naproxen is enhanced; with lithium carbonate – an increase in the plasma concentration of lithium is possible; with methotrexate – an increase in the toxicity of methotrexate is possible.

When used concomitantly with prednisolone, a significant increase in the plasma concentration of prednisolone is possible; with probenecid – a decrease in the plasma concentration of naproxen; with salicylamide – the effect of salicylamide is enhanced.

According to in vitro studies, simultaneous use of naproxen and zidovudine increases the plasma concentration of zidovudine.

Simultaneous use of naproxen with tacrolimus or cyclosporine increases the risk of nephrotoxicity.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.