Nalgezin® forte

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Nalgesin® forte (Nalgesin® forte)

Composition:

Active substance: sodium naproxen;

One film-coated tablet contains 550 mg of sodium naproxen;

Excipients: povidone, microcrystalline cellulose, talc, magnesium stearate, hypromellose, titanium dioxide (E 171), macrogol, indigocarmine (E 132), purified water.

Pharmaceutical form. Film-coated tablets.

Main physicochemical characteristics: oval, slightly biconvex, film-coated tablets of blue color with a groove on one side.

Pharmacotherapeutic group. Non-steroidal anti-inflammatory and anti-rheumatic drugs. Propionic acid derivatives. Naproxen. ATC code M01AE02.

Pharmacological properties.

Pharmacodynamics.

Sodium naproxen is a nonsteroidal anti-inflammatory drug (NSAID). It exerts analgesic, anti-inflammatory, and antipyretic effects. The mechanism of action is based on inhibition of cyclooxygenase, an enzyme involved in prostaglandin synthesis. As a result, levels of prostaglandins in various body fluids and tissues are reduced.

Pharmacokinetics.

After oral administration, sodium naproxen is hydrolyzed in the acidic gastric juice. Maximum plasma concentration is observed within 1–2 hours after drug administration. Naproxen plasma concentration increases proportionally with increasing dose. Approximately 99.5% of naproxen is bound to plasma albumin at drug concentrations up to 50 mcg/mL. About 70% of naproxen is excreted unchanged and about 30% as the inactive metabolite 6-desmethylnaproxen. Approximately 95% of the drug is excreted in urine and 5% in feces. The biological half-life of naproxen does not depend on plasma concentration or dose and is 12–15 hours.

Clinical characteristics.

Indications.

• Migraine;
• Dental pain;
• Menstrual pain;
• Pain following injuries (ligament sprains, contusions, overexertion);
• Pain after surgical procedures (in traumatology, orthopedics, gynecology, dentistry);
• Rheumatic diseases (rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, and gout).

Contraindications.

Hypersensitivity to naproxen or to any excipient.

Hypersensitivity to salicylates and to other NSAIDs, manifested as bronchial asthma, urticaria, rhinitis, or nasal polyps.

Acute phase or recurrence of gastric or duodenal ulcer, gastrointestinal bleeding.

Severe impairment of liver or kidney function (creatinine clearance less than 30 mL/min).

Heart failure.

Pregnancy or breastfeeding (see section "Use in pregnancy or breastfeeding").

Interaction with other medicinal products and other forms of interaction.

Concomitant use of acetylsalicylic acid and other nonsteroidal anti-inflammatory drugs is not recommended due to the high risk of adverse reactions.

Pharmacodynamic data indicate that concomitant use of naproxen for more than one consecutive day may inhibit the effect of low-dose acetylsalicylic acid on platelet activity, and this inhibition may persist for several days after discontinuation of naproxen therapy. The clinical significance of this interaction is unknown.

Concomitant administration with antacids or cholestyramine, as well as with food, may slow the absorption of naproxen, but does not affect the total amount of absorbed active substance.

Concomitant use with cardiac glycosides may lead to exacerbation of heart failure, decreased glomerular filtration rate, and increased blood levels of cardiac glycosides.

Naproxen should not be used within 8–12 days after mifepristone administration due to its ability to reduce the effects of the latter.

Concomitant use of naproxen with corticosteroids should be done with caution due to an increased risk of gastrointestinal ulcers and bleeding.

Sodium naproxen may reduce platelet aggregation and prolong bleeding time; this should be considered when determining bleeding time and during concomitant anticoagulant therapy.

Concomitant use of naproxin is not recommended due to its content of the same active substance, namely naproxen.

Patients taking quinolones have an increased risk of seizures.

Since naproxen is almost completely protein-bound, it should be used with caution when administered concomitantly with hydantoin derivatives and sulfonylurea derivatives.

Naproxen may reduce the natriuretic effect of furosemide.

Naproxen may reduce the efficacy of antihypertensive agents.

Concomitant use of lithium and sodium naproxen increases lithium plasma concentration.

Naproxen, like other NSAIDs, may reduce the antihypertensive effect of propranolol and other beta-blockers and may increase the risk of renal failure in patients concurrently receiving ACE inhibitors.

Naproxen reduces tubular secretion of methotrexate; therefore, methotrexate toxicity may increase during concomitant use.

Concomitant use of probenecid prolongs the biological half-life of naproxen and increases its plasma concentrations.

Concomitant use of cyclosporine may increase the risk of renal function impairment.

In vitro studies have shown that concomitant use of sodium naproxen and zidovudine increases the latter's plasma concentration.

Special precautions for use.

The incidence of adverse reactions can be minimized by using the lowest effective doses and reducing the duration of treatment.

Continuous monitoring is required during prolonged use of NSAIDs to detect adverse reactions. Gastrointestinal bleeding has been observed with naproxen use; therefore, it should be administered with particular caution to patients with a history of gastrointestinal disorders. Serious gastrointestinal adverse reactions have been reported with NSAID use. The risk of developing such reactions is independent of treatment duration. Elderly and debilitated patients are more prone to developing gastrointestinal ulcers, bleeding, and serious adverse reactions. Bronchospasm may occur in individuals with a history of bronchial asthma, allergic conditions, or previous episodes of bronchospasm. Abnormalities in liver function laboratory tests may occur. Naproxen reduces platelet aggregation and prolongs bleeding time. This should be taken into account when assessing bleeding time. Peripheral edema of minor degree may occur during naproxen therapy, with a higher risk in patients with impaired cardiac function. Patients with coagulation disorders and those receiving drugs affecting hemostasis require closer monitoring. Concomitant use of anticoagulants increases the risk of bleeding. When infection is present, the anti-inflammatory and antipyretic effects of naproxen should be considered, as they may mask signs of infection.

Naproxen should be used with extreme caution in patients with impaired renal function. Patients with renal insufficiency should undergo creatinine clearance assessment, and this parameter should be monitored throughout treatment. Naproxen is not recommended if creatinine clearance is less than 30 mL/min.

Cases of Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported, which may be life-threatening or fatal, associated with naproxen treatment. If signs or symptoms suggestive of these reactions occur, Nalgezin should be discontinued immediately. If a patient develops SJS, TEN, or DRESS during Nalgezin therapy, re-administration of Nalgezin is contraindicated and treatment must be permanently discontinued.

Anaphylactoid (anaphylactic) reactions may occur in individuals both with and without a history of hypersensitivity reactions to aspirin, other NSAIDs, or products containing naproxen. Anaphylactoid reactions may also develop in patients with a history of angioedema, bronchospasm, asthma, rhinitis, or nasal polyps. Some of these reactions, such as anaphylactic shock, may be fatal.

When reducing or discontinuing corticosteroid therapy during naproxen treatment, the corticosteroid dose should be tapered gradually and under close medical supervision to detect any adverse reactions, including adrenal insufficiency and exacerbation of arthritis symptoms.

Before initiating naproxen therapy, it is necessary to determine (by consulting a physician) whether the patient has a history of hypertension and/or heart failure with fluid retention and edema associated with NSAID use. Based on clinical trial results and epidemiological data, increased risk of arterial thrombosis may be associated with the use of certain NSAIDs (particularly at high doses and for prolonged periods). According to these data, naproxen use (1000 mg daily) is associated with lower risks; however, some risk cannot be entirely excluded.

Naproxen use should be carefully considered in patients with uncontrolled hypertension, congestive heart failure, ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease. For individuals with risk factors for cardiovascular events (e.g., hypertension, hyperlipidemia, diabetes, smoking), the necessity of naproxen use should also be carefully evaluated before initiating long-term therapy.

Like other inhibitors of cyclooxygenase synthesis, naproxen may affect fertility. Women attempting to conceive and/or experiencing fertility problems should discontinue naproxen use.

Naproxen should be administered with caution in patients with impaired liver function. In chronic alcoholic cirrhosis and other forms of cirrhosis, total plasma concentration of naproxen is decreased, while the concentration of unbound naproxen in plasma is increased.

Physicians should closely monitor patients with epilepsy or porphyria who are taking naproxen.

Concomitant use with acetylsalicylic acid and other nonsteroidal anti-inflammatory drugs is not recommended due to increased risk of adverse effects.

Elderly patients should take naproxen at the lowest effective doses.

Rare ocular disorders, including papillitis, retrobulbar neuritis, and optic disc swelling, have been observed during treatment with NSAIDs, including naproxen, although a causal relationship has not been established. Therefore, patients who develop visual disturbances during naproxen therapy should undergo ophthalmological examination.

Important information about some ingredients of Nalgezin® forte

The medicinal product contains 2.18 mmol (50.16 mg) of sodium per dose. This should be considered by patients on a sodium-restricted diet.

Use during pregnancy or breastfeeding.

Use of Nalgezin® forte during pregnancy is contraindicated. From the 20th week of pregnancy, use of Nalgezin® forte may cause oligohydramnios due to fetal renal dysfunction. This disorder may occur soon after initiation of treatment and is usually reversible upon discontinuation of treatment. Prenatal monitoring for oligohydramnios and constriction of the arterial duct may be appropriate after exposure to Nalgezin® forte for several days, starting from the 20th gestational week. Treatment with Nalgezin® forte should be discontinued if oligohydramnios or arterial duct constriction is detected.

If use of Nalgezin® forte is necessary during lactation, breastfeeding must be discontinued.

Ability to influence reaction rate while driving or operating machinery.

During treatment with Nalgezin® forte, some patients may experience somnolence, dizziness, vertigo, visual disturbances, insomnia, or depression, which may affect reaction speed while driving or operating machinery.

Method of Administration and Dosage.

Adults

The tablet should be swallowed with a glass of water during or after a meal. It is recommended to use the lowest effective dose for the shortest possible duration of treatment. Dose adjustment should be made based on observation of clinical effects and adverse reactions.

The usual daily dose for pain relief is 550–1100 mg of naproxen. The initial dose is 550 mg (1 tablet). This may later be increased, if necessary, to 1100 mg per day. In subsequent days, the usual dose is 275 mg (half a tablet) 3–4 times daily, every 6–8 hours.

For patients who tolerate lower doses well and have no history of gastrointestinal disorders, the daily dose may be increased up to 1375 mg in cases of exceptionally severe pain (migraine, musculoskeletal disorders, dysmenorrhea, acute gout attack).

At the first signs of migraine, a dose of 825 mg (1.5 tablets) should be administered, and if necessary, an additional dose of 275 mg (half a tablet) to 550 mg (1 tablet) may be taken after 30 minutes.

For relief of pain and cramps during menstruation, the recommended initial dose is 550 mg (1 tablet), followed by 275 mg as needed. The daily dose should not exceed 1375 mg.

In the case of an acute gout attack, the initial dose is 825 mg (1.5 tablets), followed by 275 mg (half a tablet) every 8 hours until the attack subsides and provided the daily dose does not exceed 1375 mg.

The initial dose for rheumatic diseases (rheumatoid arthritis, osteoarthritis, ankylosing spondylitis) ranges from 550 mg to 1100 mg, divided into morning and evening doses. For patients with severe nighttime pain or morning stiffness, for patients switching from high doses of other anti-inflammatory drugs to naproxen, and for patients with osteoarthritis where pain is the predominant symptom, the initial daily dose should be 825–1375 mg. Treatment should continue with daily doses of 550–1100 mg, divided into two doses. The morning and evening doses should not be equal; they should be adjusted according to predominant symptoms, i.e., nighttime pain or morning stiffness. Some patients may require only a single daily dose in the morning or evening.

Dosing in patients with impaired renal or hepatic function.

Lower doses should be prescribed for patients with impaired renal or hepatic function.

The drug is contraindicated if creatinine clearance is less than 30 ml/min due to accumulation of naproxen metabolites in patients with severe renal impairment or those undergoing dialysis.

The treatment course should be reviewed at regular intervals. If no positive effect is observed, therapy should be discontinued.

Children.

Nalgesin® Forte is not recommended for use in children.

The medicinal product should not be prescribed to children due to the high amount of active substance available.

Overdose.

Following accidental or intentional ingestion of a large amount of naproxen, symptoms may include abdominal pain, nausea, vomiting, dizziness, tinnitus, irritability, and in more severe cases, vomiting with blood, melena, impaired consciousness, respiratory disturbances, seizures, and renal failure. Recommended treatment includes gastric lavage, activated charcoal, antacids, H2-receptor antagonists, proton pump inhibitors, misoprostol, and other forms of symptomatic treatment.

Adverse Reactions

Adverse effects are most commonly associated with the use of high doses.

Blood and lymphatic system disorders: eosinophilia, granulocytopenia, leukopenia, thrombocytopenia, aplastic anemia, hemolytic anemia.

Immune system disorders: hypersensitivity reactions, anaphylactic reactions.

Nervous system disorders: headache, vertigo, dizziness, somnolence, depression, sleep disturbances, inability to concentrate, insomnia, weakness, aseptic meningitis, cognitive disorders.

Psychiatric disorders: convulsions, abnormal dreams.

Ear and labyrinth disorders: tinnitus, hearing disturbances, hearing impairment.

Eye disorders: visual disturbances, corneal clouding, papillitis, retrobulbar neuritis, optic disc edema.

Cardiac disorders: edema, palpitations, congestive heart failure.

Vascular disorders: vasculitis.

Respiratory, thoracic and mediastinal disorders: dyspnea, eosinophilic pneumonia, agranulocytosis, asthma, pulmonary edema.

Metabolism and nutrition disorders: hyperglycemia, hypoglycemia.

Gastrointestinal disorders: constipation, abdominal pain, nausea, dyspepsia, diarrhea, stomatitis, ulcerative stomatitis, gastrointestinal ulceration, gastrointestinal bleeding and/or gastrointestinal perforation, vomiting, vomiting of blood, melena, esophagitis, pancreatitis, colitis.

Hepatobiliary disorders: elevated liver enzymes, jaundice, hepatitis.

Skin and subcutaneous tissue disorders: pruritus, skin rash, bruising, purpura, alopecia, photosensitive dermatitis, nodular erythema, discoid lupus erythematosus, pustules, systemic lupus erythematosus, epidermal necrolysis, polymorphic erythema, photosensitivity reactions resembling chronic hematoporphyria and bullous epidermolysis, Stevens–Johnson syndrome, urticaria, drug reaction with eosinophilia and systemic symptoms (DRESS) (see "Special precautions"), fixed drug eruption.

Musculoskeletal and connective tissue disorders: muscle pain, muscle weakness.

Renal and urinary disorders: glomerulonephritis, hematuria, interstitial nephritis, nephrotic syndrome, renal dysfunction, renal failure, renal papillary necrosis.

Reproductive system and breast disorders: infertility in women.

General disorders: thirst, sweating, menstrual disorders, hyperthermia (chills and fever), angioneurotic edema.

Laboratory and diagnostic test findings: hyperkalemia, increased creatinine levels.

Edema, hypertension, and heart failure have been reported with the use of NSAIDs.

Based on clinical trials and epidemiological data, an increased risk of arterial thrombosis (e.g., myocardial infarction or stroke) may be associated with the use of certain NSAIDs, particularly at high doses and during prolonged treatment.

Treatment should be discontinued if severe adverse reactions occur.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after marketing authorization is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals, pharmacists, patients, and their legal representatives are encouraged to report any suspected adverse reactions and lack of efficacy of the medicinal product via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life.

5 years.

Storage conditions.

No special storage conditions are required for this medicinal product. Keep the blister in the outer packaging to protect from light. Store in a place inaccessible to children.

Packaging.

10 film-coated tablets in a blister; 1 or 2 blisters per cardboard box.

Prescription status.

Prescription only.

Manufacturer.

KRKA, d.d., Novo mesto / KRKA, d.d., Novo mesto.

Manufacturer's address and place of business.

Smarjeska cesta 6, 8501 Novo mesto, Slovenia / Smarjeska cesta 6, 8501 Novo mesto, Slovenia.