Instructions for Naproff film-coated tablets 550 mg No. 10
Composition
active ingredient: naproxen;
1 film-coated tablet contains 275 mg or 550 mg of naproxen sodium;
excipients: microcrystalline cellulose, povidone, talc, magnesium stearate;
shell composition: Opadry white (hypromellose, titanium dioxide (E 171), macrogol).
Dosage form
Film-coated tablets.
Main physicochemical properties:
film-coated tablets, 275 mg: round, biconvex, film-coated tablets, white;
Film-coated tablets, 550 mg: oval, biconvex, film-coated tablets, white in color, with a breakline on both sides.
Pharmacotherapeutic group
Nonsteroidal anti-inflammatory and antirheumatic drugs. ATC code M01A E02.
Pharmacological properties
Pharmacodynamics.
Naproxen is a nonsteroidal anti-inflammatory drug (NSAID), a derivative of arylcarboxylic acid belonging to the propionic group. It has a pronounced anti-inflammatory, analgesic, antipyretic effect and inhibits platelet function. These properties of naproxen are associated with inhibition of prostaglandin synthesis.
Pharmacokinetics.
Absorption.
After oral administration, naproxen is rapidly and almost completely absorbed from the gastrointestinal tract. The maximum plasma concentration is reached in less than 1 hour and is 77.4 μg/ml after taking 1 tablet of 275 mg. When using doses greater than 500 mg, the increase in naproxen plasma levels is not proportional to the dose taken.
Distribution.
Approximately 99% of naproxen is bound to blood plasma proteins.
Metabolism.
Naproxen is metabolized in the liver to desmethylnaproxen.
Breeding.
Approximately 70% of naproxen is excreted in the urine as unchanged naproxen, approximately 28% as desmethylnaproxen. The clearance of naproxen is 0.13 ml/min/kg. The half-life of naproxen is 13 hours.
Indication
Adults and children over 15 years of age:
Symptomatic long-term treatment:
chronic inflammatory joint diseases (such as rheumatoid arthritis, ankylosing spondylitis, Fissenger-Leroy-Reiter syndrome, psoriatic arthritis);
severe disabling forms of arthrosis.
Symptomatic short-term treatment:
acute attacks of extra-articular rheumatism (such as shoulder scapular periarthritis, tendonitis, bursitis);
osteoarthritis;
lower back pain;
radiculalgia;
pain syndrome in injuries of the musculoskeletal system;
pain syndrome in inflammatory processes in dentistry (regarding this indication, the emerging risks should be taken into account, in particular the increase in the septic process caused by NSAIDs, and the expected benefit in the form of an analgesic effect).
Symptomatic treatment:
dysmenorrhea (after determining its cause).
For children weighing 25 kg or more (age 8 years and older):
juvenile rheumatoid arthritis.
Contraindication
Hypersensitivity to the active substance or to other components of the medicinal product.
History of hypersensitivity and asthma symptoms caused by the use of acetylsalicylic acid and other non-steroidal anti-inflammatory drugs (NSAIDs).
Active peptic ulcer, history of peptic ulcer or recurrent bleeding (2 or more severe episodes of ulceration or bleeding).
History of gastrointestinal bleeding or perforation related to previous NSAID therapy.
Severe heart failure.
Severe renal failure.
Severe liver failure.
Use from the beginning of the 6th month of pregnancy (over 24 weeks of gestation) (see section "Use during pregnancy or breastfeeding").
Use in children weighing up to 25 kg (up to 8 years of age).
Interaction with other medicinal products and other types of interactions
Risks due to hyperkalemia.
Certain drugs or therapeutic classes may contribute to the development of hyperkalemia: potassium salts, potassium-sparing diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists (ARBs), NSAIDs, heparins (low molecular weight or unfractionated), immunosuppressants (cyclosporine or tacrolimus), trimethoprim.
The risk of hyperkalemia increases with the concomitant use of naproxen with such agents. This risk is particularly high with potassium-sparing diuretics, especially when combined with each other or with calcium salts, while the combination of ACE inhibitors and NSAIDs, for example, is less dangerous, provided the recommended precautions are followed.
When assessing the risk and stress levels caused by taking potassium-sparing drugs, it is necessary to consider the specific drug interactions inherent in each drug.
Some drugs, such as trimethoprim, are not a risk factor for drug interactions. However, they may act as co-factors when used with other drugs, including those mentioned above.
Other NSAIDs, including acetylsalicylic acid in anti-inflammatory doses (≥ 1 g/dose and/or ≥ 3 g/day) and in analgesic and antipyretic doses (≥ 500 mg/dose and/or ≥ 3 g/day): the risk of gastrointestinal ulcers and bleeding increases when naproxen is used concomitantly with these drugs.
Oral anticoagulants: when used simultaneously with naproxen, the effect of anticoagulants (e.g. warfarin) is enhanced and the risk of bleeding (due to damage to the gastric and duodenal mucosa) increases (see section "Special instructions"). If concomitant use of these drugs is necessary, careful clinical and biological monitoring is necessary.
Unfractionated heparin, low molecular weight heparin and related compounds (in therapeutic doses and/or in elderly patients): Concomitant use of naproxen with these drugs increases the risk of bleeding (due to damage to the gastric and duodenal mucosa). If concomitant use of these drugs is necessary, careful clinical monitoring is necessary.
Acetylsalicylic acid: Clinical pharmacodynamic data suggest that concomitant use of naproxen for more than one day may inhibit the effect of low-dose acetylsalicylic acid on platelet activity. This effect may persist for several days after discontinuation of naproxen. The clinical significance of this interaction is unknown.
Lithium: when used simultaneously with naproxen, the level of lithium in the blood plasma increases, which can lead to intoxication (due to a decrease in its renal clearance). If it is necessary to use these drugs simultaneously, the level of lithium in the blood plasma should be monitored and its dose adjusted during treatment and after discontinuation of naproxen.
Methotrexate in high doses (more than 20 mg per week): when used simultaneously with naproxen, the hematological toxicity of methotrexate is increased (due to a decrease in its renal clearance).
Pemetrexed (in patients with mild to moderate renal impairment (creatinine clearance 45 to 80 mL/min)): Concomitant use with naproxen increases the toxicity of pemetrexed (due to decreased renal clearance).
Concomitant use of naproxen with such agents should be done with caution.
Cyclosporine, tacrolimus: when used simultaneously with naproxen, the nephrotoxicity of these drugs increases, especially in elderly patients, therefore, at the beginning of their simultaneous use, renal function should be monitored.
Diuretics, ACE inhibitors, ARA II: when used simultaneously with naproxen, the antihypertensive effect is weakened, and in patients at risk (elderly patients and/or dehydrated patients) the development of acute renal failure (due to reduced glomerular filtration) is possible. In the case of simultaneous use of these drugs, the patient should be hydrated, and renal function should be monitored at the beginning of treatment.
Methotrexate in low doses (less than 20 mg per week): when used simultaneously with naproxen, the hematological toxicity of methotrexate is increased (due to a decrease in its renal clearance). In the first weeks of concomitant use of these drugs, blood tests should be performed weekly. Patients with even minor renal impairment, as well as elderly patients, require careful monitoring of the condition.
Pemetrexed (in patients with normal renal function): Concomitant use with naproxen increases the toxicity of pemetrexed (due to decreased renal clearance). Renal function should be monitored when these drugs are used concomitantly.
When using naproxen simultaneously with such agents, possible interactions should be considered.
Acetylsalicylic acid in antiplatelet doses of 50–375 mg/day: the simultaneous use of naproxen with acetylsalicylic acid increases the risk of gastrointestinal ulcers and gastrointestinal bleeding.
Corticosteroids (except hydrocortisone replacement therapy): Concomitant use of naproxen with these drugs increases the risk of gastrointestinal ulcers or bleeding (see section "Special warnings and precautions for use").
Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs): Concomitant use of naproxen with these drugs increases the risk of gastrointestinal bleeding (see section "Special warnings and precautions for use").
Unfractionated heparin, low molecular weight heparin and related compounds (in prophylactic doses): Concomitant use of naproxen with these drugs increases the risk of bleeding.
Beta-blockers (except esmolol): when used simultaneously with naproxen, the antihypertensive effect of beta-blockers may be weakened (due to inhibition of vasodilator prostaglandins, water and sodium retention).
Deferasirox: Concomitant use of naproxen with deferasirox increases the risk of gastrointestinal bleeding.
Application features
Concomitant use of the drug with other NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided.
Adverse drug reactions can be minimized by using the lowest effective dose for the shortest time necessary to improve the condition (see section “Method of administration and dosage” and subsections “Effects on the digestive tract” and “Effects on the cardiovascular system and cerebral circulation” below).
Patients with asthma in combination with chronic rhinitis, chronic sinusitis and/or nasal polyps are at higher risk of allergy to acetylsalicylic acid and/or NSAIDs than other patients. The use of the drug may cause asthma attacks or bronchospasm, especially in patients with allergy to acetylsalicylic acid or NSAIDs (see section "Contraindications").
Use in elderly patients.
Elderly patients are particularly susceptible to the development of adverse reactions when using NSAIDs, especially gastrointestinal bleeding and perforation, which can be fatal (see section "Method of administration and dosage" and below).
Effect on the digestive tract.
Gastrointestinal bleeding, ulceration or perforation, in some cases fatal, have been observed with all NSAIDs at various stages of treatment, regardless of the presence of warning symptoms or a history of serious gastrointestinal disease.
The risk of gastrointestinal bleeding, ulceration or perforation increases with increasing NSAID dose in patients with a history of ulcer, especially if complicated by bleeding or perforation (see section 4.5), and in the elderly. Treatment of such patients should be started with the lowest possible dose. For such patients and patients taking low-dose acetylsalicylic acid or other agents that increase the risk of gastrointestinal adverse reactions, combination therapy with protective agents such as misoprostol or proton pump inhibitors should be considered (see section 4.5 and below).
Patients, especially the elderly, who have a history of adverse reactions from the digestive tract should inform their doctor about all unusual symptoms related to the digestive system, in particular gastrointestinal bleeding, especially in the initial stages of treatment.
The drug should be used with caution in patients who are concomitantly taking agents that may increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants (e.g. warfarin), SSRIs or antiplatelet agents such as acetylsalicylic acid (see section "Interaction with other medicinal products and other types of interactions").
If an ulcer or gastrointestinal bleeding develops, the drug should be discontinued.
The drug should be used with caution in patients with a history of gastrointestinal diseases (ulcerative colitis, Crohn's disease), as there is a risk of their exacerbation (see section "Adverse reactions").
Effects on the cardiovascular system and cerebral circulation.
Close monitoring is recommended in patients with hypertension and/or a history of mild to moderate congestive heart failure, as fluid retention and edema have been reported with NSAIDs.
Clinical trial data and epidemiological data suggest that the use of some NSAIDs (especially at high doses and in long-term treatment) may be associated with a small increased risk of vascular thrombotic events (such as myocardial infarction or stroke). According to available data, the risk is minimal with naproxen at a dose of 1000 mg per day, but it cannot be completely excluded.
Patients with uncontrolled hypertension, congestive heart failure, established ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease should only be treated with the drug after careful evaluation. Such evaluation is necessary before starting long-term treatment in patients with risk factors for cardiovascular disease (e.g. hypertension, hyperlipidemia, diabetes mellitus, smokers).
Dermatological reactions.
Very rare cases of serious skin reactions (some fatal), including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis (Lyell's syndrome), have been reported with the use of NSAIDs (see section 4.8). Patients appear to be at greatest risk at the start of treatment, with most patients experiencing these reactions within the first month of treatment. The drug should be discontinued if skin rash, signs of mucosal involvement or other signs of hypersensitivity occur.
NSAIDs, due to inhibition of the vasodilatory effect of renal prostaglandins, can induce functional renal failure by reducing glomerular filtration. This side effect is dose-dependent. At the beginning of treatment or after increasing the dose, careful monitoring of diuresis and renal function is recommended in patients with the following risk factors:
old age;
concomitant use with ACE inhibitors, angiotensin II antagonists, sartans, diuretics (see section "Interaction with other medicinal products and other types of interactions");
hypovolemia (of any origin);
congestive heart failure;
chronic renal failure;
nephrotic syndrome;
lupus nephropathy;
decompensated cirrhosis of the liver.
Since the main part of naproxen and its metabolites (95%) is excreted by the kidneys by glomerular filtration, the drug should be used with caution in patients with impaired renal function. It is recommended to constantly monitor creatinine clearance. In such patients, the minimum effective dose should be used.
Effect on water-salt metabolism.
During the use of naproxen, fluid retention is possible, leading to edema, hypertension or worsening of existing hypertension, exacerbation of heart failure. During the use of the drug, clinical monitoring of the condition of patients with hypertension or heart failure is necessary. It is also possible to reduce the effectiveness of antihypertensive drugs (see section "Interaction with other drugs and other types of interactions").
Risk of hyperkalemia.
Hyperkalemia may develop when naproxen is used in patients with diabetes mellitus or in patients who are concomitantly taking drugs that increase potassium levels (see section "Interaction with other medicinal products and other forms of interaction"). Regular monitoring of plasma potassium levels is recommended in such patients.
Use in infectious lesions.
The drug should be used with caution in cases of infectious lesions or at risk of infection, since naproxen reduces the body's resistance to infectious agents and can mask the symptoms of infections.
Hematological reactions.
Naproxen inhibits platelet aggregation and may prolong bleeding time, which should be taken into account when determining bleeding time. Patients with bleeding disorders or those taking medications that affect hemostasis should be monitored during use of the drug.
Effect on the organs of vision.
Ocular disorders have been reported rarely with NSAIDs, including naproxen. Consultation with an ophthalmologist is recommended in patients who develop visual disturbances while taking the drug.
Long-term use.
In case of prolonged use of the drug, regular blood tests and monitoring of kidney and liver function should be performed.
Impact on fertility.
Naproxen, like other drugs that inhibit cyclooxygenase/prostaglandin synthesis, may adversely affect reproductive function and is not recommended for women attempting to conceive.
Precautions are related to excipients.
The 275 mg dose contains approximately 25 mg of sodium, the 550 mg dose contains approximately 50 mg of sodium, which should be taken into account by patients on a controlled sodium diet.
Use during pregnancy or breastfeeding
Pregnancy.
Inhibition of prostaglandin synthesis by NSAIDs may adversely affect pregnancy and/or embryo/fetal development.
Epidemiological studies have shown that the use of drugs that inhibit prostaglandin synthesis in early pregnancy increases the risk of miscarriage, fetal heart defects, and anterior abdominal wall nonunion. Thus, the absolute risk of developing cardiovascular anomalies increased from <1% to approximately 1.5%. It is believed that the risk of such phenomena increases with increasing dose and duration of therapy. The use of prostaglandin synthesis inhibitors in animals caused an increase in pre- and post-implantation losses and increased embryo-fetal mortality.
From the 20th week of pregnancy, use of naproxen may cause oligohydramnios due to fetal renal dysfunction. This may occur shortly after initiation of treatment and is usually reversible upon discontinuation of treatment. In addition, there have been reports of ductus arteriosus narrowing following treatment in the second trimester of pregnancy, most of which resolved after discontinuation of treatment.
Risks associated with use from the 12th week of gestation until birth.
Starting from the 12th week of gestation until delivery, NSAIDs, by inhibiting prostaglandin synthesis, can lead to impaired renal function in the fetus:
development of renal failure after birth (reversible or irreversible), especially in case of prolonged use in late pregnancy (with the risk of developing severe hyperkalemia).
Risks associated with use after the 24th week of gestation until birth.
After 24 weeks of gestation, NSAIDs can cause cardiopulmonary toxicity in the fetus (premature narrowing/closure of the ductus arteriosus and pulmonary hypertension) and lead to fetal or neonatal heart failure or even intrauterine fetal death. This risk is increased when naproxen is taken late in pregnancy (reversibility is low). This undesirable effect is possible even with a single dose.
At the end of pregnancy, NSAIDs in the mother and newborn can cause:
increased bleeding duration in mother and child, decreased platelet aggregation ability, even when using very low doses of naproxen;
suppression of uterine contractile function, which can lead to a delay or increase in the duration of labor.
The drug should not be used in women planning pregnancy and during the first 5 months of pregnancy (first 24 weeks of gestation), unless absolutely necessary. In this case, the lowest possible dose and duration of treatment should be observed. Long-term use is strictly not recommended.
Antenatal monitoring for oligohydramnios and ductus arteriosus should be considered after exposure to naproxen for several days, starting at 20 weeks of gestation. The drug should be discontinued if oligohydramnios or ductus arteriosus is detected.
From the beginning of the 6th month (over 24 weeks of gestation), the use of the drug (even short-term) is contraindicated. In case of unintentional (accidental) administration after 24 weeks of gestation, careful monitoring of cardiac activity and renal function is recommended, as well as monitoring of the condition of the fetus and/or newborn, taking into account the duration of administration. The duration of observation depends on the half-life.
Breastfeeding period.
NSAIDs can pass into breast milk. The drug is not recommended for use during breastfeeding.
Impact on fertility.
Naproxen, like other drugs that inhibit cyclooxygenase/prostaglandin synthesis, may impair reproductive function and is not recommended in women attempting to conceive. For women who have difficulty conceiving or are undergoing investigation of infertility, discontinuation of the drug should be considered.
Ability to influence reaction speed when driving vehicles or other mechanisms
When using the drug, the patient should be warned about the possibility of drowsiness, dizziness, and visual disturbances.
Method of administration and doses
The medicine is intended for oral use.
The tablets should be taken whole during meals, with sufficient water. The daily dose should be divided into 1–2 doses.
Adverse reactions can be minimized by using the lowest effective dose for the shortest period of time necessary to relieve symptoms.
According to research results, the fraction of unbound naproxen in blood plasma increases in elderly patients, although the total concentration of naproxen in blood plasma remains unchanged.
Clinical and biological monitoring is recommended when high doses of the drug are administered to such patients.
In case of decreased renal excretion, a reduction in the dose of the drug is recommended.
Adults and children aged 15 and over.
Rheumatology, gynecology.
Short-term treatment: the recommended dose is 1100 mg per day (4 tablets of 275 mg or 2 tablets of 550 mg).
Long-term treatment: the recommended dose is 550 mg per day (2 tablets of 275 mg or 1 tablet of 550 mg).
Dentistry.
The recommended dose is 275–1100 mg per day (1–4 tablets of 275 mg or ½–2 tablets of 550 mg).
Children weighing 25 kg or more (age 8 years and older).
Juvenile rheumatoid arthritis.
The recommended dose is 10 mg/kg per day.
Children.
The medicine should be used in children over 15 years of age.
For juvenile rheumatoid arthritis, the drug can be used in children weighing 25 kg or more (age 8 years and older).
Overdose
Symptoms.
Clinical signs of overdose include drowsiness, dizziness, disorientation, heartburn, indigestion, nausea or vomiting, and apnea.
Biological signs of overdose include impaired liver and kidney function, hypoprothrombinemia, and metabolic acidosis.
Treatment.
In case of overdose, the patient should be hospitalized, the stomach should be washed, adsorbents should be used, and symptomatic and supportive treatment should be provided.
Side effects
The most common adverse reactions are from the digestive tract. Erosions, ulcers or gastrointestinal bleeding may develop, sometimes with fatal outcome, especially in elderly patients (see section "Special warnings and precautions for use").
Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, ulcerative stomatitis, abdominal pain, melena, haematemesis, exacerbation of inflammatory bowel diseases (ulcerative colitis, Crohn's disease) with NSAIDs have been reported. Rare cases of gastritis have been reported.
Cases of edema, hypertension, and heart failure have also been reported with the use of NSAIDs.
From the blood and lymphatic system:
hemolytic anemia, leukopenia (mainly granulocytopenia), thrombocytopenia, bone marrow aplasia.
On the part of the immune system:
Hypersensitivity reactions, including skin rashes, urticaria, exacerbation of chronic urticaria, pruritus, angioedema, vasculitis, anaphylactoid reactions, asthma.
Asthma symptoms in some patients may be caused by allergy to acetylsalicylic acid or other NSAIDs (see section "Contraindications").
From the nervous system:
headache, dizziness, drowsiness.
Insomnia, impaired concentration, cognitive impairment, and aseptic meningitis have been reported.
On the part of the organs of vision:
visual impairment, papillitis, retrobulbar optic neuritis, papillary edema.
From the side of the organs of hearing and labyrinth:
hearing impairment, including tinnitus.
From the cardiovascular system:
peripheral edema in patients with impaired cardiac function, worsening of congestive heart failure, arterial hypertension.
Respiratory, thoracic and mediastinal disorders:
eosinophilic pneumonia.
From the digestive tract:
Epigastric pain (often mild to moderate), nausea, vomiting, flatulence, dyspepsia, diarrhea, constipation, ulcerative stomatitis.
In rare cases, ulcers, gastrointestinal bleeding and/or perforations have been observed (the frequency of gastrointestinal bleeding increases with increasing dose), and isolated cases of esophagitis, colitis, and pancreatitis have also been reported.
From the liver and biliary tract:
Cases of transient and reversible changes in liver function, jaundice, and isolated cases of severe hepatitis (one of which was fatal) have been reported.
From the skin and subcutaneous tissue:
Pruritus, alopecia, photosensitivity reactions, including rare cases of pseudoporphyria, purpura, erythema multiforme, erythema fixed, erythema nodosum, lichen planus have been reported rarely.
Bullous reactions, including Stevens-Johnson syndrome, drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), and Lyell's syndrome, have been reported very rarely.
From the kidneys and urinary tract:
fluid retention, hyperkalemia (see sections "Interaction with other medicinal products and other types of interactions" and "Special instructions for use"), acute renal failure in patients at risk (see section "Special instructions for use"), acute kidney injury, which may lead to acute renal failure: isolated cases of interstitial nephritis, acute tubular necrosis, nephrotic syndrome, papillary necrosis.
Reporting of suspected adverse reactions.
Reporting suspected adverse reactions that occur after the marketing authorisation of a medicinal product is very important. This allows the benefit/risk balance of the medicinal product to be continuously monitored. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system.
Expiration date
3 years.
Storage conditions
Store at a temperature not exceeding 25 °C in a dry place out of the reach of children.
Packaging
10 tablets in a blister; 1 or 2 blisters in a cardboard box.
Vacation category
According to the recipe.
Producer
WORLD MEDICINE ILACH SAN. VE TIJ. A.Sh., Turkey/
WORLD MEDICINE ILAC SAN. VE TIC. AS, Turkey.
Location of the manufacturer and address of its place of business.
15 Temmuz Mahalleshi Cami Yolu Caddesi No. 50 Guneshli Bagcilar/Istanbul, Turkey/
15 Temmuz Mahallesi Cami Yolu Caddesi No:50 Gunesli Bagcilar/Istanbul, Turkey.
Applicant.
LLC "WORLD MEDICINE", Ukraine/
WORLD MEDICINE, LLC, Ukraine.
