Instructions for Teraliv film-coated tablets 220 mg No. 12
Composition
active ingredient: naproxen sodium;
1 tablet contains 220 mg of naproxen sodium;
excipients: microcrystalline cellulose, povidone K30, talc, magnesium stearate;
tablet shell: Opadry blue YS-1-4215 (hydroxypropylmethylcellulose, titanium dioxide (E 171), macrogol 8000, FD&C Blue No 2 (indigo carmine (E 132)) aluminum lacquer.
Dosage form
Film-coated tablets.
Main physicochemical properties: oval biconvex tablets, film-coated, light blue, embossed with “BAYER” on one side.
Pharmacotherapeutic group
Nonsteroidal anti-inflammatory and antirheumatic drugs. Propionic acid derivatives. Naproxen. ATC code M01A E02.
Pharmacological properties
Pharmacodynamics.
It has analgesic, antipyretic and anti-inflammatory effects. The duration of action is up to 12 hours.
Naproxen is a non-selective COX inhibitor, the mechanism of action of which is the inhibition of the enzymes COX-1 and COX-2. Naproxen inhibits the formation of COX-1-dependent thromboxane synthase A2 (TXA2), which leads to a decrease in platelet aggregation and COX-2-dependent prostacyclin (PGI2), the main mediator of vasodilation. Naproxen inhibits prostaglandin synthesis, which explains its analgesic and antipyretic effects.
Pharmacokinetics.
Absorption. Naproxen sodium is rapidly and almost completely absorbed from the gastrointestinal tract. After oral administration, peak plasma concentrations are reached within one hour. Concomitant food intake may delay the absorption of naproxen sodium, but does not affect the extent of absorption.
Distribution. The volume of distribution of naproxen is 0.16 l/kg. More than 99% of the active substance is bound to serum albumin. At doses above 500 mg/day, the increase in plasma levels is no longer proportional, since due to saturation of protein binding at higher doses, clearance increases. Despite this, the increase in unbound naproxen levels remains proportional to the dose administered.
Naproxen enters synovial fluid, crosses the placental barrier, and is found in the breast milk of lactating women at concentrations approximately 1% of plasma concentrations.
Metabolism: Naproxen is metabolized in the liver, mainly to 6-O-desmethyl-naproxen.
Excretion: Approximately 95% of the drug dose is excreted in the urine (as unchanged naproxen, inactive 6-O-desmethyl-naproxen, or conjugates). A small amount (≤ 3%) is excreted in the feces.
The clearance of naproxen is 0.13 ml/min/kg. The biological half-life from blood plasma is approximately 14 hours.
Pharmacokinetics in special patient groups
Hepatic impairment: In patients with significantly impaired hepatic function, plasma concentrations of unbound naproxen may be increased.
Renal impairment: In renal failure, there is a potential for accumulation of naproxen and its metabolites, as they are excreted primarily by the kidneys. The elimination of naproxen is reduced in patients with significantly reduced renal function.
Indication
Short-term symptomatic treatment of pain:
in the back;
in joints and muscles;
post-traumatic;
menstrual;
dental;
main.
And also to reduce fever during flu and colds.
Contraindication
Hypersensitivity to the active substance or to any of the excipients included in the medicinal product.
History of bronchospasm, urticaria, or allergy-like symptoms after taking acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs (NSAIDs).
Third trimester of pregnancy (see section "Use during pregnancy or breastfeeding").
Active gastric and/or duodenal ulcer or gastrointestinal bleeding.
Inflammatory bowel diseases (e.g. Crohn's disease, ulcerative colitis).
Severe liver dysfunction (cirrhosis and ascites).
Severe renal impairment (creatinine clearance < 30 ml/min).
Severe heart failure (NYHA class III−IV).
Treatment of postoperative pain after coronary artery bypass grafting (or use of a cardiopulmonary bypass machine).
Interaction with other medicinal products and other types of interactions
Concomitant administration with antacids or cholestyramine, as well as with food, may slow the absorption of naproxen and does not affect the extent of absorption.
Clinical studies have not shown any interaction between naproxen and anticoagulants or sulfonylureas. However, caution should be exercised when co-administering, as interactions have been observed with other drugs in this class.
Naproxen may slow the irreversible inhibition of ADP-induced platelet aggregation. Pharmacodynamic data indicate that the effect of low-dose acetylsalicylic acid on platelet activity is inhibited when naproxen is taken concomitantly with low-dose acetylsalicylic acid for more than one day. This effect may persist for several days after discontinuation of naproxen. The clinical significance of this interaction is unknown. Treatment with naproxen may limit the cardiovascular protection of acetylsalicylic acid in patients at risk of cardiovascular disease.
Concomitant administration with probenecid increases the blood level and prolongs the biological half-life of naproxen.
Naproxen and methotrexate should be prescribed with caution, as naproxen and some other NSAIDs have been shown to reduce the tubular secretion of methotrexate in animal models, which likely increases its toxicity.
In addition, naproxen may reduce the hypotensive effect of beta-blockers.
There is evidence that some drugs in this class inhibit the natriuretic effect of furosemide.
Inhibition of renal clearance of lithium, leading to increased plasma lithium concentrations, has also been reported.
Impact on laboratory test results
Since naproxen may interfere with certain tests for the determination of 17-ketosteroids, treatment should be discontinued 48 hours before adrenal function tests. Naproxen may also interfere with the determination of urinary 5-hydroxyindoleacetic acid.
Naproxen causes reversible inhibition of platelet aggregation and prolongs bleeding time. This effect should be taken into account when determining bleeding time.
Application features
General precautions for the use of systemic nonsteroidal anti-inflammatory drugs
Gastrointestinal ulcers, bleeding or perforation may occur at any time during treatment with NSAIDs, regardless of COX-2 selectivity, even in the absence of previous symptoms or history. To minimise this risk, treatment should be initiated at the lowest effective dose for the shortest duration.
Placebo-controlled studies have shown that there is an increased risk of thrombotic cardiovascular and cerebrovascular events with certain selective COX-2 inhibitors. It is not yet known whether this risk is directly related to the COX-1/COX-2 selectivity of the individual NSAIDs. There are currently no data from comparative clinical trials comparing maximum doses and long-term treatment with naproxen, and the possibility of a similar increased risk cannot be excluded. Until such data become available, the risk-benefit ratio of naproxen should be carefully assessed in patients with clinically proven coronary heart disease, cerebrovascular disorders, peripheral arterial occlusive disease, or significant risk factors (e.g., hypertension, hyperlipidemia, diabetes mellitus, smoking). Therefore, the lowest effective dose should be used for the shortest duration possible.
Renal effects of NSAIDs include fluid retention with edema and/or hypertension. Therefore, naproxen should be used with caution in patients with heart failure and other conditions that cause fluid retention. Caution is also required in patients receiving concomitant diuretics or ACE inhibitors and in patients at increased risk of hypovolemia.
Naproxen should be taken with caution or only as prescribed and under the supervision of a doctor in the following cases:
Elderly patients should be cautious for general medical reasons. In elderly patients, plasma concentrations of non-protein-bound naproxen are increased, while total concentrations remain unchanged; it is recommended to use the lowest effective dose in frail elderly patients or those with low body weight;
in patients who have or have previously had bronchial asthma, the use of naproxen may lead to the development of bronchospasm;
in case of renal failure;
in case of heart failure;
with impaired liver function or liver failure.
Hematological effects
Like other NSAIDs, naproxen may reduce platelet aggregation and prolong bleeding time.
This effect should be taken into account when determining the duration of bleeding. Patients with coagulation disorders or taking medications that negatively affect hemostasis should be closely monitored during treatment with naproxen-containing drugs. In patients at high risk of bleeding and in patients who are fully anticoagulated (e.g., with dicumarol derivatives), the tendency to bleed may be increased when naproxen-containing drugs are used concomitantly.
Caution should be exercised in patients with diseases that result in decreased blood volume and/or renal blood flow and in whom renal prostaglandins play a supporting role in maintaining renal perfusion. In such patients, the use of naproxen-containing products and other NSAIDs may result in a dose-dependent decrease in renal prostaglandin formation and may lead to renal decompensation or renal failure. The highest risk of this reaction is in patients with impaired renal function, hypovolemia, heart failure, impaired liver function or salt depletion syndrome, in patients receiving diuretics or ACE inhibitors, and in elderly patients. Naproxen-containing products should be used with greater caution in such patients, and monitoring of serum creatinine and/or creatinine clearance is recommended. To prevent excessive accumulation of naproxen metabolites in such patients, a reduction in the daily dose should be considered.
Naproxen is not recommended for patients with baseline creatinine clearance less than 20 mL/min, as accumulation of naproxen metabolites has been observed in such cases.
Due to the significant level of protein binding of naproxen, its plasma concentration is not reduced by hemodialysis.
Dermatological effects
Photosensitivity reactions may rarely occur. Therefore, exposure to sunlight (UV rays) should be reduced during treatment with naproxen.
Use during pregnancy or breastfeeding
Pregnancy.
Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonal/fetal development. Epidemiological data suggest an increased risk of miscarriage and of cardiac malformations and gastroschisis following the use of prostaglandin synthesis inhibitors in early pregnancy. This risk is believed to be dose- and duration-dependent.
In animal studies, the use of prostaglandin synthesis inhibitors has been shown to increase pre- and post-implantation losses and embryo/fetal death. An increased incidence of various malformations has been reported in animals treated with prostaglandin synthesis inhibitors during organogenesis, including cardiovascular abnormalities.
When administered orally at a dose of 20 mg/kg/day during organogenesis in rats and rabbits, naproxen was not teratogenic (did not cause fetal malformations).
From the 20th week of pregnancy onwards, the use of the medicinal product may cause oligohydramnios (low water in the blood) due to fetal renal dysfunction. This may occur shortly after initiation of treatment and is usually reversible after discontinuation of treatment. In addition, cases of ductus arteriosus narrowing have been reported following administration of the medicinal product in the second trimester, most of which resolved after discontinuation of treatment. Therefore, during the first and second trimesters of pregnancy, naproxen should be used only when clearly needed. When naproxen is used by women attempting to conceive or during the first or second trimester of pregnancy, the dose should be kept as low as possible and the duration of treatment as short as possible. Antenatal monitoring for oligohydramnios and ductus arteriosus should be considered after exposure for several days from the 20th week of pregnancy onwards. Treatment should be discontinued if oligohydramnios or ductus arteriosus is detected.
Naproxen is contraindicated during the third trimester of pregnancy. All prostaglandin synthesis inhibitors may affect the fetus, resulting in:
cardiopulmonary toxicity (with premature narrowing/closure of the ductus arteriosus and pulmonary hypertension);
renal dysfunction, including renal failure with oligohydramnios (low water).
In the mother and newborn, it can lead to prolonged bleeding time (an effect of inhibiting platelet aggregation, which can occur even at very low doses); suppression of uterine contractions, which can lead to delayed or prolonged labor.
Breast-feeding.
NSAIDs are excreted in breast milk. Therefore, as a precautionary measure, naproxen should not be used in nursing women. If treatment is necessary, the infant should be transferred to formula feeding.
Fertility.
Oral administration of naproxen at a dose of 30 mg/kg/day to male rats and at a dose of 20 mg/kg/day to female rats did not show any adverse effects on fertility. Naproxen may affect female fertility and is therefore not recommended for women attempting to conceive. Discontinuation of naproxen should be considered in women who have difficulty conceiving or who are undergoing investigation of infertility.
Ability to influence reaction speed when driving vehicles or other mechanisms
Naproxen may affect the speed of reaction. This should be taken into account when driving vehicles and operating other mechanisms (see section "Adverse reactions").
Method of administration and doses
Film-coated tablets should be taken without chewing, with sufficient water.
If necessary, the initial dose may be 2 film-coated tablets, followed by 1 more film-coated tablet after 12 hours if necessary.
Do not exceed the recommended dose: 3 tablets of naproxen sodium (660 mg) per day. Duration of use - 3 days. If necessary, use for more than 3 days, consult a doctor.
Elderly patients (over 65 years of age).
Unless otherwise prescribed by a doctor, no more than 2 film-coated tablets per day.
Children
Naproxen is not intended for use in children and adolescents under 16 years of age.
Overdose
Overdose with naproxen may cause dizziness, drowsiness, abdominal pain, stomach pain, indigestion, nausea, temporary liver dysfunction, hypoprothrombinemia, renal dysfunction, metabolic acidosis, apnea, disorientation, or vomiting. Since naproxen is sometimes rapidly absorbed, high levels of the active substance in the blood should be expected shortly after administration. Some patients have experienced seizures, but it is not known whether they are related to naproxen.
If a patient accidentally or intentionally takes a large amount of a drug containing naproxen, gastric lavage and other supportive measures should be considered. Animal studies indicate that ingestion (over 15 minutes) of 50-100 g of activated charcoal as a liquid mass within 2 hours of overdose can significantly reduce the absorption of the drug.
Due to the significant level of protein binding of naproxen, its plasma concentration is not reduced by hemodialysis.
Side effects
The following adverse reactions have been observed with the use of naproxen.
Frequency of adverse reactions: very common (>1/10), common (>1/100, <1/10), uncommon (>1/1000, <1/100), rare (>1/10000, <1/1000), very rare (<1/10000).
| Organ classes/systems | Frequency | Adverse reactions |
| Blood system and lymphatic system | Very rare | Leukopenia, thrombocytopenia, agranulocytosis, aplastic anemia, eosinophilia, hemolytic anemia |
| Immune system | Very rare | Anaphylaxis, anaphylactoid reactions, angioedema |
| Mental disorders | Very rare | Psychotic symptoms, depression, sleep disturbances |
| Nervous system | Often Very rare | Headache, dizziness, drowsiness, fatigue. Aseptic meningitis, cognitive impairment, seizures |
| Organs of vision | Very rare | Visual impairment, corneal opacity, papillitis, retrobulbar neuritis, optic disc edema |
| Hearing organs | Infrequently Very rare | Vertigo Hearing disorders, ringing in the ears |
| Cardiovascular system | Very rare | Heart failure, hypertension, pulmonary edema, vasculitis |
| Respiratory system | Infrequently Very rare | Shortness of breath, asthma Eosinophilic pneumonia |
| Gastrointestinal disorders | Often Infrequently Rarely Very rare | Dyspepsia, nausea, heartburn, abdominal pain Diarrhea, constipation, vomiting Peptic ulcers with or without bleeding/perforation, gastrointestinal bleeding, haematemesis, melena Pancreatitis, colitis, aphthae, stomatitis, esophagitis, intestinal ulcer |
| Liver and gallbladder | Very rare | Hepatitis, jaundice |
| Skin and subcutaneous tissue disorders | Infrequently Very rare | Exanthema (rash), itching, urticaria Hair loss (in most cases reversible), porphyria, erythema multiforme exudative, epidermal necrolysis, erythema nodosum, drug eruption, lichen planus, pustular reactions, systemic lupus erythematosus, photosensitivity reactions including cases resembling porphyria cutanea tarda ("pseudoporphyria") or epidermolysis bullosa |
| Kidneys and urinary tract | Infrequently Very rare | Renal impairment, edema Interstitial nephritis, papillonecrosis, nephrotic syndrome, acute renal failure |
| General violations | Rarely | Temperature increase |
Expiration date
3 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 °C.
Keep out of reach of children.
Packaging
12 tablets in a blister; 1 blister in a cardboard box.
Vacation category
Without a prescription.
Producer
Bayer Bitterfeld GmbH.
Location of the manufacturer and its business address.
Ortsteil Greppin, Salegaster Chaussee 1, 06803 Bitterfeld-Wolfen, Germany.
