Xefokam pills p/o 8mg №10×1

Product DescriptionXefocam. Release form Coated tablets. Dosage 8 mg. Pack quantity: 10 pcs. Produced by Takeda GmbH. INNLornoxicam. FTGNpvp. Qualitative and quantitative composition One film-coated tablet contains 4.00 mg or 8.00 mg of lornoxicam. Excipients with known effect: Each 4 mg tablet contains 94.00 mg of lactose monohydrate. Each 8 mg tablet contains 90.00 mg of lactose monohydrate. For a complete list of excipients, see the “List of excipients” section. DescriptionFrom white to white with a yellowish tint, oblong film-coated tablets, debossed with “L04” (4 mg dosage) and “L08” (8 mg dosage). Indications for use – Short-term symptomatic therapy of acute pain syndrome of mild to moderate intensity in adults. – Symptomatic therapy of pain and inflammation in osteoarthritis in adults. – Symptomatic therapy of pain and inflammation in rheumatoid arthritis in adults. Route of administration and doses Dosing regimen For all patients, the appropriate dosing regimen should be based on the individual response to treatment. The risk of adverse effects can be minimized by using the lowest effective dose for the shortest possible course needed to control symptoms (see Precautions section). Pain syndrome The daily dose of lornoxicam is 8-16 mg, divided into 2-3 doses. The maximum recommended daily dose is 16 mg. Osteoarthritis and rheumatoid arthritis The recommended starting daily dose is 12 mg of lornoxicam divided into 2-3 doses. The maintenance dose should not exceed 16 mg of lornoxicam per day. Special Patient Populations Pediatric Patients Lornoxicam is not recommended for use in children and adolescents under 18 years of age due to a lack of safety and efficacy data. Elderly patients For elderly patients over 65 years of age, no special dose adjustment is required, except in cases of existing impaired renal or hepatic function. Lornoxicam should be administered with caution, since this group of patients is more difficult to tolerate adverse reactions from the gastrointestinal tract (see section “Precautions”). Renal impairment In patients with mild to moderate renal impairment, the maximum recommended daily dose is 12 mg divided into 2 or 3 divided doses (see Precautions section). Lornoxicam is contraindicated in patients with severe renal impairment (see section “Contraindications”). Hepatic impairment In patients with moderate hepatic impairment, the maximum recommended daily dose is 12 mg divided into 2 or 3 divided doses (see Precautions section). Lornoxicam is contraindicated in patients with severe hepatic impairment (see section “Contraindications”). Directions for use Xefocam film-coated tablets are intended for oral administration and should be taken with a sufficient amount of liquid. Contraindications – hypersensitivity to the active substance or to any of the excipients listed in the “List of excipients” section; – thrombocytopenia; – hypersensitivity (symptoms such as asthma, rhinitis, angioedema or urticaria) to other non-steroidal anti-inflammatory drugs (NSAIDs), including acetylsalicylic acid; – severe heart failure; – gastrointestinal bleeding, cerebrovascular bleeding or other bleeding; – history of gastrointestinal bleeding or perforation associated with previous NSAID therapy; – history of acute peptic ulcer/bleeding or recurrent peptic ulcer/bleeding (2 or more overt episodes of confirmed ulceration or bleeding); – severe liver failure; – severe renal insufficiency (serum creatinine >700 µmol/l); third trimester of pregnancy (see section “Period of pregnancy and breastfeeding”). Precautions Lornoxicam reduces platelet aggregation and prolongs bleeding time, so caution should be exercised when prescribing to patients with a tendency to bleed. For the following disorders, lornoxicam should be prescribed only after a careful assessment of the benefit-risk ratio: – Renal insufficiency: lornoxicam should be used with caution in patients with mild (serum creatinine 150-300 µmol/l) and moderate (serum creatinine 300-700 µmol/l) renal impairment. insufficiency due to the dependence of the maintenance of renal blood flow on the level of renal prostaglandins (see section “Method of application and dosage”). If renal function worsens during treatment, treatment with lornoxicam should be discontinued. – Monitoring of kidney function is necessary in patients: undergoing major surgery, with heart failure, during concomitant treatment with diuretics or drugs with a known or suspected nephrotoxic effect (see section “Interaction with other drugs and other forms of interaction”). – Patients with bleeding disorders: careful clinical observation and laboratory monitoring (eg, APTT) is recommended. – Hepatic insufficiency (for example, with cirrhosis of the liver): in patients with impaired liver function, careful clinical observation and laboratory monitoring should be considered, since after the use of daily doses of 12-16 mg, accumulation of lornoxicam (increased AUC) may occur (see section ” Pharmacokinetics). In other cases, impaired liver function is unlikely to affect the pharmacokinetics of lornoxicam compared to healthy individuals. – Patients receiving long-term treatment (more than 3 months): when taking NSAIDs, it is recommended to regularly evaluate the function of the kidneys and liver, as well as hematological parameters. – Elderly patients over 65 years of age: monitoring of kidney and liver function is recommended. It is recommended to use with caution in elderly patients after surgery. Simultaneous use with other NSAIDs Simultaneous use of lornoxicam with NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided (see section “Interaction with other medicinal products and other forms of interaction”). Minimizing the risk of adverse effects The risk of adverse effects can be minimized by using the lowest effective dose for the shortest possible course necessary to control symptoms (see the “Dosage and Administration” section, and also taking into account the gastrointestinal and cardiovascular risks listed below). Gastrointestinal bleeding, ulceration, and perforation Gastrointestinal bleeding, ulceration, and perforation: Gastrointestinal bleeding, ulceration, or perforation, which can be fatal, has been reported with all NSAIDs. They have occurred with or without warning symptoms or a history of serious gastrointestinal complications at any time during therapy. The risk of gastrointestinal bleeding, ulcers or perforation is higher with increasing dose of NSAIDs, in patients with a history of ulcers, especially if it was complicated by bleeding or perforation (see section “Contraindications”), and in elderly patients. In these patients, treatment should begin with the lowest possible dose (see section “Method of application and dosage”). For these patients, and for patients requiring concomitant treatment with low doses of acetylsalicylic acid or other medicinal products that may increase the risk of gastrointestinal adverse reactions, combination therapy with gastroprotective agents (eg, misoprostol or proton pump inhibitors) should be considered (see . information below, as well as the section “Interaction with other medicinal products and other forms of interaction”). Regular medical supervision is recommended. Patients with a history of gastrointestinal toxicity, especially the elderly, should be instructed to report all unusual abdominal symptoms (especially signs of gastrointestinal bleeding); especially at the beginning of treatment. Caution should be exercised in patients concomitantly taking drugs that increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants (such as warfarin), selective serotonin reuptake inhibitors or antiplatelet agents (such as acetylsalicylic acid) (see section “Interaction with other medicines and other forms of interaction). If gastrointestinal bleeding or ulceration occurs in patients taking lornoxicam, treatment should be interrupted. NSAIDs should be used with caution in patients with a history of gastrointestinal diseases (ulcerative colitis, Crohn’s disease), as their use may exacerbate the disease (see section “Side Effects”). Elderly patients In elderly patients, there is an increased incidence of adverse reactions to NSAIDs, primarily gastrointestinal bleeding and perforation, which can be fatal (see section “Method of application and dosage”). Cardiovascular and cerebrovascular effects Adequate monitoring and instruction of patients with arterial hypertension and / or heart failure in history or active state is necessary, since fluid retention and edema have been described in connection with NSAID therapy. Clinical studies and epidemiological data indicate that the use of some NSAIDs, particularly at high doses and as part of long-term treatment, may be associated with an increased risk of arterial thrombotic complications (eg, myocardial infarction and stroke). The available data are insufficient to rule out such a risk for lornoxicam. The use of lornoxicam in patients with uncontrolled hypertension, congestive heart failure, established coronary artery disease, peripheral arterial disease and/or cerebrovascular disease should be undertaken only after a careful assessment of the benefits and risks. Such an assessment should be made before initiating long-term treatment in patients with cardiovascular risk factors (eg, hypertension, hyperlipidemia, diabetes mellitus, smoking). Simultaneous treatment of NSAIDs and heparin in connection with spinal or epidural anesthesia increases the risk of spinal / epidural hematomas (see section “Interaction with other drugs and other forms of interaction”). Skin and subcutaneous tissue disorders Severe, sometimes fatal skin reactions, including exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, have very rarely been described in connection with the use of NSAIDs (see section “Side Effects”). The highest risk for such reactions exists at the beginning of therapy, in most cases in the first month of treatment. At the first appearance of a skin rash, mucosal lesions or other signs of increased individual sensitivity, lornoxicam should be discontinued. Respiratory system disorders Caution should be used in patients with or with a history of asthma, as NSAIDs have been reported to cause bronchospasm in such patients. Systemic lupus erythematosus and mixed connective tissue disease In patients with systemic lupus erythematosus (SLE) and mixed connective tissue disease, caution should be exercised due to an increased risk of aseptic meningitis. Nephrotoxicity Co-administration of NSAIDs and tacrolimus may increase the risk of nephrotoxicity due to reduced renal synthesis of prostacyclin. In patients receiving such combination therapy, renal function should be carefully monitored (see section “Interaction with other medicinal products and other forms of interaction”). Laboratory Abnormalities As with most other NSAIDs, increases in serum transaminases, bilirubin, or other liver function tests, as well as increases in creatinine and blood urea nitrogen, and other laboratory changes have been reported. If these abnormalities become significant or persist, the use of lornoxicam should be discontinued and an appropriate evaluation should be carried out. Lactose This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, the lactase deficiency and glucose-galactose malabsorption should not take this medicinal product. Fertility The use of lornoxicam, as with any drug known to inhibit cyclooxygenase/prostaglandin synthesis, may adversely affect fertility and is therefore not recommended for use in women planning pregnancy. For women who have difficulty becoming pregnant or who are undergoing investigations for infertility, discontinuation of lornoxicam should be considered (see the Pregnancy and Breastfeeding Period section). Chickenpox In exceptional cases, chickenpox can lead to serious infectious complications of the skin and soft tissues. So far, it cannot be ruled out that NSAIDs may contribute to the worsening of these infections. Therefore, it is advisable to avoid the use of lornoxicam in varicella. Interaction with other medicinal products and other forms of interaction Simultaneous use of lornoxicam with: – cimetidine: leads to increased plasma levels of lornoxicam, which may increase the risk of side effects of lornoxicam (no interactions between lornoxicam and ranitidine or between lornoxicam and antacids were found). – anticoagulants: NSAIDs may increase the effect of anticoagulants such as warfarin (see section “Precautions”). INR control is shown. – phenprocoumon: decreased effectiveness of treatment with phenprocoumon. – heparin: NSAIDs when used simultaneously with heparin in connection with spinal or epidural anesthesia increase the risk of bleeding, as well as spinal or epidural hematomas (see section “Precautions”). – ACE inhibitors: the antihypertensive effect of ACE inhibitors may be reduced. – diuretics: a decrease in the diuretic and antihypertensive effect of loop, thiazide and potassium-sparing diuretics (increased risk of hyperkalemia and nephrotoxicity). – beta-blockers: reduced antihypertensive effect. – angiotensin II receptor blockers: decreased antihypertensive effect; – digoxin: decreased renal clearance of digoxin, which increases the risk of digoxin toxicity. – corticosteroids: increased risk of gastrointestinal ulceration or bleeding (see section “Precautions”). – quinolone antibiotics (eg levofloxacin, ofloxacin): increased risk of seizures. – antiplatelet agents (eg clopidogrel): increased risk of bleeding (see section “Precautions”). – other NSAIDs: increased risk of gastrointestinal bleeding and ulceration. – methotrexate: elevated serum methotrexate. This can lead to increased toxicity. If joint therapy is necessary, attention should be paid to careful monitoring. – selective serotonin reuptake inhibitors: increased risk of bleeding (see section “Precautions”). – Lithium: NSAIDs inhibit the renal clearance of lithium and thus can increase the concentration of lithium in the blood serum beyond the limits of toxicity. Therefore, it is necessary to monitor the level of lithium in serum, especially during the initiation of treatment, when adjusting the dose or stopping treatment. – cyclosporine: an increase in the concentration of cyclosporine in the blood serum. Renal toxicity of ciclosporin may be enhanced by effects that are mediated by renal prostaglandins. With joint therapy, it is necessary to monitor renal function. – Sulfonylureas (eg glibenclamide): increased risk of hypoglycemia. – known inducers and inhibitors of CYP2C9 isoenzymes: lornoxicam (like other NSAIDs dependent on cytochrome P450 2C9 (CYP2C9 isoenzyme) interacts with known inducers and inhibitors of CYP2C9 isoenzymes (see the section “Pharmacokinetics” Biotransformation). – tacrolimus: increases the risk of renal toxicity in due to a decrease in the synthesis of prostacyclin in the kidneys.When used together, it is necessary to monitor renal function (see section “Precautions”) – pemetrexedom: NSAIDs can reduce the renal clearance of pemetrexed and thus increase renal and gastrointestinal toxicity and lead to myelosuppression. When Xefocam is taken with food, the absorption of lornoxicam slows down.As a result, Xefocam should not be taken with food if a rapid onset of an analgesic effect is required. Food can reduce drug absorption by approximately 20% and increase Tmax (see Pharmacokinetics, Biotransformation) Pregnancy and lactation Pregnancy Lornoxicam is contraindicated in the third trimester of pregnancy (see Contraindications), it should also not be used in the first and second trimester of pregnancy and during childbirth, since there are no clinical data on treatment during pregnancy. Sufficient data on the use of lornoxicam in pregnant women are not available. Experimental studies in animals have demonstrated the reproductive toxicity of the drug (see section “Preclinical safety data”). Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonic/fetal development. Data from epidemiological studies indicate an increased risk of miscarriage and cardiac malformations after the use of prostaglandin synthesis inhibitors in early pregnancy. The risk is expected to increase with increasing dose and duration of treatment. In animals, administration of a prostaglandin synthesis inhibitor resulted in increased pre- and post-implantation loss and increased embryofetal mortality. Prostaglandin synthesis inhibitors should not be used during the first and second trimesters of pregnancy unless clearly needed. During the third trimester of pregnancy, prostaglandin synthesis inhibitors can lead to fetal cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension) and cause renal impairment that may progress to renal failure with oligohydramnios. In late maternal and neonatal pregnancy, prostaglandin synthesis inhibitors may prolong bleeding time and suppress uterine contractions, which may delay or prolong labor. Therefore, the use of lornoxicam is contraindicated in the third trimester of pregnancy (see section “Contraindications”). Breast-feeding There are no data on the excretion of lornoxicam into breast milk. In lactating rats, relatively high concentrations of lornoxicam pass into the mother’s milk. Lornoxicam should not be used in breastfeeding women. Fertility The use of lornoxicam, as with any drug known to inhibit cyclooxygenase/prostaglandin synthesis, may adversely affect fertility and is therefore not recommended for use in women planning pregnancy. For women who have difficulty becoming pregnant or who are undergoing investigation for infertility, discontinuation of lornoxicam should be considered. Influence on the ability to drive vehicles or other mechanisms Patients who experience dizziness and / or drowsiness during treatment with lornoxicam should refrain from driving and operating other mechanisms. Side effects The most common adverse reactions of NSAIDs are reactions from the gastrointestinal tract. It is possible to develop peptic ulcers, perforation or gastrointestinal bleeding, in some cases life-threatening, especially in elderly patients (see section “Precautions”). After the use of NSAIDs, nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena, vomiting of blood, ulcerative stomatitis, exacerbation of colitis and Crohn’s disease were noted (see section “Precautions”). In more rare cases, gastritis developed. About 20% of patients taking lornoxicam may experience adverse reactions. When taking lornoxicam, the most common adverse reactions were nausea, dyspepsia, indigestion, abdominal pain, vomiting and diarrhea. In general, the available results of clinical studies indicate the development of these symptoms in less than 10% of patients. In the treatment of NSAIDs, cases of edema, arterial hypertension, and heart failure have been reported. Clinical studies and epidemiological data suggest that the use of certain NSAIDs (especially at high doses and in long-term treatment) may increase the risk of arterial thrombosis (eg, myocardial infarction or stroke) (see section “Precautions”). Extremely rarely, severe infectious complications of the skin and soft tissues can occur against the background of chicken pox. The following are data on adverse reactions that were detected in more than 0.05% of 6417 patients after the use of the drug lornoxicam during phase II, III and IV clinical trials. Adverse reactions are classified according to the frequency of occurrence: very often (≥1/10); often (≥1/100, <1/10); infrequently (≥1/1000, <1/100), rarely (≥1/10000, <1/1000), very rarely (<1/10000), the frequency is unknown (cannot be estimated from the available data). Table 1: Adverse effects System organ class Frequency Adverse reactions Infectious and parasitic diseases Rare Pharyngitis Blood and lymphatic system disorders Rare Anemia, thrombocytopenia, leukopenia, prolonged bleeding time Very rare Ecchymosis. NSAIDs have been reported to cause potentially severe hematopoietic disorders such as neutropenia, agranulocytosis, aplastic anemia and hemolytic anemia (class effects) Immune system disorders Rare Hypersensitivity, including anaphylactoid and anaphylactic reactions Metabolic and nutritional disorders Uncommon Anorexia , weight change Mental disorders Uncommon Insomnia, depression Rare Confusion, irritability, agitation Nervous system disorders Often Mild and transient headache, dizziness Rare Drowsiness, paresthesia, dysgeusia, tremor, migraine Very rare Aseptic meningitis in patients with SLE and mixed connective tissue disorders (see Precautions section) Eye disorders Common Conjunctivitis Rare Visual disturbances Hearing and labyrinth disorders Uncommon Dizziness, tinnitus Heart disorders Uncommon Heart palpitations, tachycardia, edema, heart failure (see Vascular disorders Uncommon Hyperemia, edema Rare Hypertension, hot flushes, bleeding, hematoma Respiratory, thoracic and mediastinal disorders Uncommon Rhinitis Rare Dyspnea, cough, bronchospasm Gastrointestinal disturbances Common Nausea, chest pain stomach, dyspepsia, diarrhea, vomiting Uncommon Constipation, flatulence, belching, dry mouth, gastritis, gastric ulcer, upper abdominal pain, duodenal ulcer, ulcerative stomatitis Rare Melena, hematemesis, stomatitis, esophagitis, gastroesophageal reflux, dysphagia, aphthous stomatitis, glossitis, peptic ulcer with perforation, gastrointestinal bleeding Liver and biliary tract disorders Uncommon Increased liver biochemical parameters (ALT or ACT) Very rare Hepatotoxicity, which can manifest as liver failure, hepatitis, jaundice and cholestasis Abnormalities from the skin and subcutaneous tissues Infrequently Rash, itching, hyperhidrosis, Rash erythematous, urticaria, angioedema, alopecia Rare Dermatitis, eczema, purpura Very rare Edema and bullous reactions, Stevens-Johnson syndrome, toxic epidermal necrolysis Muscular, skeletal and connective tissue disorders Uncommon Arthralgia Rare Bone pain, muscle spasm, myalgia Renal and urinary disorders Rare Nocturia, micturition disorders, elevated blood urea nitrogen and creatinine Very rare Lornoxicam may precipitate acute renal failure in patients with a history of renal impairment, as maintenance of renal blood flow is dependent on renal prostaglandin levels ( cm. section "Precautions"). The development of nephrotoxicity in various forms (including nephritis and nephrotic syndrome) is associated with the use of NSAIDs (class-specific effect) General disorders and reactions at the injection site Uncommon Malaise, swelling of the face Rare Asthenia Reporting suspected adverse reactions It is important to report suspected adverse reactions after drug registration means in order to ensure continuous monitoring of the benefit-risk ratio of the medicinal product. Medical professionals are encouraged to report any suspected adverse drug reactions to the Republican Unitary Enterprise "Center for Expertise and Testing in Health Care" (see section "Send information about adverse reactions to the address"). Overdose There are currently no data on acute overdose of lornoxicam to describe the consequences of overdose or to recommend specific therapies. However, in case of an overdose of lornoxicam, the following symptoms may occur: nausea, vomiting, cerebral symptoms (dizziness, blurred vision). Serious symptoms may also occur, such as ataxia up to coma and seizures, liver and kidney damage, and possibly coagulation disorders. In case of actual or suspected overdose, the drug should be discontinued. Lornoxicam is rapidly eliminated from the body due to its short half-life. Lornoxicam is not removed by dialysis. The specific antidote is still unknown. Routine emergency procedures, including gastric lavage, should be considered. Based on general principles, the use of activated charcoal only if it is taken immediately after taking lornoxicam may lead to a decrease in the absorption of the drug. Gastrointestinal disorders, for example, can be treated with prostaglandin analogs or ranitidine. Pharmacotherapeutic groupNon-steroidal anti-inflammatory and antirheumatic drugs, oxicams. ATC code: M01AC05 Pharmacological properties Pharmacodynamics Mechanism of action Lornoxicam belongs to NSAIDs of the oxicam class with analgesic properties. The mechanism of action of lornoxicam is based on the suppression of prostaglandin synthesis (inhibition of the activity of cyclooxygenase isoenzymes), which leads to desensitization of peripheral pain receptors and, accordingly, to inhibition of inflammation. It also suggests a central effect on pain perception independent of anti-inflammatory effects. Pharmacodynamic properties Lornoxicam does not affect the vital signs of the body (for example, body temperature, respiratory rate, heart rate, blood pressure, ECG, spirometry). Clinical efficacy and safety The analgesic effects of lornoxicam have been successfully demonstrated in several clinical trials during drug development. In the treatment with lornoxicam, as with other NSAIDs, common adverse effects are gastrointestinal complications due to local irritation of the gastrointestinal tract and systemic ulcerogenic effects, which are mediated by inhibition of prostaglandin synthesis. Pharmacokinetics Absorption Lornoxicam is rapidly and almost completely absorbed from the gastrointestinal tract. Peak plasma concentrations are reached in about 1-2 hours. The absolute bioavailability of lornoxicam is 90-100%. The effect of the first passage of the drug through the liver is not observed. Simultaneous intake of lornoxicam with food reduces Cmax by approximately 30% and increases Tmax from 1.5 h to 2.3 h. Absorption of lornoxicam (calculated by AUC) may be reduced by 20%. Distribution Lornoxicam is present in plasma unchanged, as well as in the form of a hydroxylated metabolite. The degree of binding of lornoxicam to plasma proteins is 99% and does not depend on concentration. After a repeated dose, it is also found in the synovial fluid. Biotransformation Lornoxicam undergoes extensive hepatic metabolism, primarily through hydroxylation to the inactive metabolite 5-hydroxylornoxicam. The CYP2C9 isoenzyme is involved in the biotransformation of lornoxicam. Due to genetic polymorphism for this enzyme, there are slow and fast metabolizers, therefore, slow metabolizers can experience significantly increased plasma levels of lornoxicam. The hydroxylated metabolite does not show pharmacological activity. Lornoxicam is completely metabolized, with approximately 2/3 being excreted by the liver and approximately 1/3 by the kidneys in the form of an inactive substance. In animal studies, lornoxicam did not induce liver enzymes. In clinical studies, no accumulation of lornoxicam was observed after repeated use at recommended doses. This result is supported by drug monitoring data from one-year studies. Withdrawal The average half-life of the parent substance is 3-4 hours. After oral administration, approximately 50% is excreted in the feces and 42% by the kidneys, mainly in the form of 5-hydroxylornoxicam. The elimination half-life of 5-hydroxylornoxicam after a single or double daily parenteral dose is approximately 9 hours. There is no evidence of a change in the rate of excretion with repeated use. In elderly patients over 65 years of age, clearance is reduced by 30-40%. Other than a reduction in clearance, there were no significant changes in the kinetic profile of lornoxicam in elderly patients. There are no significant changes in the kinetic profile of lornoxicam in patients with renal or hepatic insufficiency, except for cumulation in patients with chronic liver disease after 7 days of treatment with a daily dose of 12 mg and 16 mg. Preclinical Safety Data Preclinical data based on conventional safety pharmacology studies, repeated dose toxicity, genotoxicity, and carcinogenic potential have shown no particular hazards to humans. Lornoxicam caused renal toxicity and gastrointestinal ulceration in single and multiple dose toxicity studies in several species. In rats, lornoxicam reduces fertility (affects ovulation and implantation) and affects pregnancy and childbirth. In rabbits and rats, lornoxicam causes premature closure of the ductus arteriosus due to cyclooxygenase inhibition. In animals, the administration of prostaglandin synthesis inhibitors has been shown to increase pre- and post-implantation loss and fetal death. In addition, in animals treated with a prostaglandin synthesis inhibitor during the organogenetic period, an increase in the incidence of various malformations, including cardiovascular ones, was reported. List of excipients Core: Magnesium stearate Povidone (K 25) Croscarmellose sodium Cellulose Lactose monohydrate Shell: Macrogol (6000) Titanium dioxide E171 Talc Hypromellose Incompatibility Not applicable. Shelf life 3 years. Storage conditionsStore at a temperature not exceeding 30°C. Keep out of the reach of children. Release form Film-coated tablets 4 mg and 8 mg. 10 tablets in a blister of aluminum foil and PVC film. 1 blister with instructions for use is placed in a cardboard box. Disposal Precautions No special requirements. Conditions for dispensing from pharmacies According to a doctor's prescription.