Instructions for Nayzilat film-coated tablets 600 mg blister No. 10
Composition
active ingredient: amtolmetin guacil;
1 tablet contains: amtolmetin guacil 600 mg;
Excipients: lactose monohydrate; hypromellose; colloidal anhydrous silica; sodium starch glycolate (type A); magnesium stearate; titanium dioxide (E 171); macrogol.
Dosage form
Film-coated tablets.
Main physicochemical properties: white or almost white capsule-shaped, film-coated tablets, with a smooth surface on both sides.
Pharmacotherapeutic group
Nonsteroidal anti-inflammatory and antirheumatic drugs. ATC code M01A.
Pharmacological properties
Pharmacodynamics.
Amtolmetin guacil is a nonsteroidal anti-inflammatory drug (NSAID) with anti-inflammatory, analgesic, and antipyretic effects, which are due to the inhibition of prostaglandin synthesis through non-selective inhibition of cyclooxygenase (COX) enzymes, but, unlike traditional NSAIDs, due to its structure, it provides gastroprotective, antisecretory, and antioxidant effects.
The protective effects are due to at least two ways. Due to the structure of amtolmetin guacil, when it is used internally, the level of antioxidant enzymes in the gastric mucosa increases - superoxide dismutase (SOD), catalase, glutathione - at the same time the level of superoxide anions, peroxynitrite or peroxychloride and malondialdehyde decreases, which is observed mainly in conditions of lipid peroxidation. One of the metabolites of amtolmetin guacil - guaiacol (2-methoxyphenol) - increases the level of gastric nitric oxide synthase (NO). It is known that nitric oxide plays a significant role in the mechanisms of protection of the gastroduodenal mucosa, which is important during the period when prostaglandin synthesis is suppressed. Amtolmetin guacil acts on peripheral capsaicin receptors, thereby providing a local analgesic effect.
Pharmacokinetics.
Absorption of amtolmetin guacil after oral administration is rapid and complete. It is mainly deposited on the walls of the gastrointestinal tract, where the highest concentration is maintained for 2 hours after administration. Its transformation into active metabolites begins after the drug enters the blood plasma, so amtolmetin guacil itself is difficult to determine in plasma and tissues. Amtolmetin guacil is hydrolyzed by plasma esterase into the following metabolites: tolmetin-glycinamide (MED5), which predominates in blood plasma, tolmetin and guaiacol (2-methoxyphenol). Tolmetin-glycinamide (MED5) is directly further metabolized to tolmetin. Active metabolites reach high concentrations in tissues. The drug is excreted almost completely within 24 hours in the urine (77% of the administered dose) in the form of glucuronides, and in somewhat smaller amounts in the bile (9.4%) and feces (7.5%).
Indication
Pain and inflammatory syndrome in diseases of the musculoskeletal system: osteoarthritis, rheumatoid arthritis; post-traumatic pain.
Contraindication
Hypersensitivity to amtolmetin, tolmetin; complete or incomplete combination of bronchial asthma, recurrent nasal polyposis or paranasal sinuses and intolerance to acetylsalicylic acid and other nonsteroidal anti-inflammatory drugs (including a history);
erosive-ulcerative changes in the mucous membrane of the stomach and duodenum, active gastrointestinal bleeding; cerebrovascular or other bleeding; inflammatory bowel diseases (Crohn's disease, ulcerative colitis) in the acute phase;
severe renal failure (creatinine clearance less than 30 ml/min), progressive kidney disease;
confirmed hyperkalemia;
decompensated heart failure;
liver failure or active liver disease; hemophilia and other blood clotting disorders;
the period after coronary artery bypass grafting; arterial hypertension;
congenital lactase deficiency, lactose intolerance, glucose-galactose malabsorption; glucose-6-phosphate dehydrogenase deficiency;
pregnancy, lactation period;
childhood
Interaction with other medicinal products and other types of interactions
Diuretics and antihypertensives. Amtolmetin guacil, like other NSAIDs, when used concomitantly with diuretics or antihypertensive drugs (e.g., beta-blockers of calcium channels, inhibitors of angiotensin converting enzyme (ACE)) may reduce their antihypertensive effect. Therefore, the combination of such drugs should be prescribed with caution, and patients (especially the elderly) should periodically monitor blood pressure. It is necessary to maintain adequate water content in the body and monitor renal function at the beginning and during the combined treatment. The simultaneous use of potassium-sparing diuretics may lead to an increase in serum potassium levels, in the case of such a combination of drugs this indicator should be kept under control.
Therefore, in the case of this combination of drugs, close and regular monitoring of patients is recommended.
Other NSAIDs and corticosteroids. Concomitant use of amtolmetin guacil and other systemic NSAIDs may increase the incidence of gastrointestinal adverse reactions. Concomitant use with systemic NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided. Amtolmetin guacil enhances the effects of corticosteroids, glucocorticosteroids, and mineralocorticoids.
In some patients with impaired renal function, the concomitant use of NSAIDs and angiotensin-converting enzyme (ACE) inhibitors may lead to further deterioration of renal function.
Selective serotonin reuptake inhibitors (SSRIs): Concomitant use of systemic NSAIDs and SSRIs may increase the risk of gastrointestinal bleeding.
Amtolmetin guacyl enhances the hypoglycemic effect of sulfonylurea derivatives, the effect of fibrinolytics, and the side effects of estrogens.
Myelotoxic drugs increase the manifestations of hematotoxicity of the drug. Antacids and cholestyramine reduce the absorption of amtolmetin guacil.
Concomitant administration of amtolmetin guacil with lithium preparations and methotrexate increases their concentration in the blood.
Application features
Amtolmetin guacil should be used under the supervision of a physician in patients with liver and kidney disease, with periodic laboratory tests of renal and hepatic function and monitoring of peripheral blood counts. If, during prolonged therapy, renal and hepatic function tests are impaired and blood counts deteriorate, treatment should be discontinued. It should be borne in mind that hepatitis may occur without prodromal symptoms when taking NSAIDs.
Patients with impaired blood clotting function or patients who have undergone anticoagulant therapy should use the drug under the supervision of a physician.
NSAIDs may temporarily inhibit platelet aggregation. Therefore, patients with impaired hemostasis require careful monitoring of relevant laboratory parameters.
If visual impairment occurs due to the use of amtolmetin guacil, treatment should be discontinued and an ophthalmological examination should be performed.
Elderly patients (over 65 years of age), who usually have impaired renal and/or hepatic function, should be used with caution at lower daily doses to prevent the occurrence of adverse events.
Although amtolmetin guacyl has gastroprotective safety, it should be borne in mind that this drug belongs to NSAIDs (active metabolite – tolmetin), that is, there is a possibility of gastrointestinal bleeding, ulcers, perforation, which are characteristic of all NSAIDs, which may be accompanied by warning symptoms, or in their absence. Such phenomena are most dangerous for elderly patients. If they are detected, the drug should be discontinued.
In the above patients and in patients requiring concomitant use of medicinal products containing low doses of acetylsalicylic acid (aspirin) or other medicinal products that may increase the risk of adverse gastrointestinal reactions, the feasibility of combination therapy in combination with protective medicinal products (e.g. proton pump inhibitors) should be considered.
NSAIDs may increase the risk of serious cardiovascular thrombotic events, myocardial infarction and stroke, which can be fatal.
Severe skin reactions, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs. The risk of these reactions is highest at the beginning of therapy, and the development of these reactions is noted in most cases within the first month of treatment.
Patients with asthma, seasonal allergic rhinitis, nasal congestion, chronic obstructive pulmonary disease, or chronic respiratory tract infections are more likely to experience allergic reactions to NSAIDs than other patients. Therefore, special caution is required when treating such patients.
Since prostaglandins play an important role in maintaining renal blood flow, special caution is required when treating patients with impaired cardiac or renal function, patients with a history of hypertension, elderly patients, patients taking diuretics, and patients who have a significant decrease in circulating plasma volume of any etiology, for example, in the period before and after surgical interventions.
NSAIDs may temporarily inhibit platelet aggregation. Therefore, patients with impaired hemostasis require careful monitoring of relevant laboratory parameters.
Particular attention should be paid to patients taking other medications that may increase the risk of ulceration or bleeding, including oral medications (corticosteroids, anticoagulants, selective serotonin reuptake inhibitors, antiplatelet agents). If any adverse reactions occur, the drug should be discontinued.
Due to their pharmacodynamic properties, NSAIDs can mask symptoms characteristic of infectious and inflammatory diseases.
Treatment should be discontinued in case of any allergic reactions and/or symptoms of adverse reactions. Treatment should be discontinued 48 hours before the determination of 17-ketosteroids. During treatment, one should refrain from engaging in potentially hazardous activities that require increased attention and speed of mental and motor reactions.
Use during pregnancy or breastfeeding
The safety of amtolmetin in pregnant women has not been studied, therefore the use of the drug during pregnancy is contraindicated.
From the 20th week of pregnancy, the use of NSAIDs may cause oligohydramnios due to fetal renal dysfunction. This disorder may occur shortly after the start of treatment and is usually reversible after discontinuation of treatment. In addition, there are reports of narrowing of the ductus arteriosus after treatment in the second trimester of pregnancy, which in most cases was reversible after discontinuation of treatment. Therefore, the drug should not be prescribed during the first and second trimester of pregnancy. If the drug is used by a woman attempting to conceive, the dose should be kept as low and the duration of treatment as short as possible.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may pose risks:
for the fetus:
cardiopulmonary toxicity (premature narrowing/closure of the ductus arteriosus and pulmonary hypertension);
renal dysfunction;
for the mother at the end of pregnancy and for the newborn:
prolongation of bleeding time, antiaggregatory effect, which may occur even at very low doses;
suppression of uterine contractions, leading to delayed or prolonged labor.
It is not known whether the metabolites of amtolmetin guacil are excreted in breast milk, therefore the drug is contraindicated for use in women during breastfeeding.
Ability to influence reaction speed when driving vehicles or other mechanisms
Visual impairment may occur during the use of amtolmetin. Therefore, it is recommended to refrain from driving and/or operating other mechanisms.
Method of administration and doses
Apply internally on an empty stomach.
The recommended dose of the drug for adults is 1 tablet 1-2 times a day, depending on the intensity of the pain syndrome and the course of the disease. The recommended daily dose should not be exceeded. The duration of use depends on the pharmacological effect and the general condition of the patient.
Children. Contraindicated.
Overdose
Cases of overdose of amtolmetin are unknown, as are the methods of treatment in such cases. No specific antidote has been established. In case of overdose, gastric lavage should be performed, an adsorbent (activated charcoal) should be administered, and symptomatic therapy should be carried out.
Symptoms of overdose: abdominal pain, nausea, vomiting, erosive-ulcerative lesions of the gastrointestinal tract, impaired renal function, metabolic acidosis.
Side effects
Adverse reactions are classified according to frequency of occurrence: common (≤ 1/100, < 1/10); uncommon (≥ 1/1000, < 1/100); rare (≥ 1/10,000, < 1/1000); very rare (< 1/10,000).
On the part of the digestive system: due to the gastroprotective properties of amtolmetin guacil, the use of the drug provides a minimal risk of adverse reactions in the gastrointestinal tract; rarely - nausea, vomiting, diarrhea, dyspepsia, abdominal pain, flatulence, anorexia; very rarely - gastritis, gastrointestinal bleeding, vomiting with blood, hemorrhagic diarrhea, melena, gastric or intestinal ulcer (with or without bleeding or perforation), colitis (including hemorrhagic colitis and exacerbation of ulcerative colitis or Crohn's disease), constipation, stomatitis, glossitis, esophageal disorders, diaphragmatic strictures of the intestine, pancreatitis.
From the blood and lymphatic system: very rarely - thrombocytopenia, leukopenia, anemia, agranulocytosis.
Immune system disorders: Rare: hypersensitivity reactions, anaphylactic/anaphylactoid reactions (discolouration of the skin, skin rash, urticaria, pruritus, tachypnea or dyspnea, swelling of the eyelids, lower legs, fingers, periorbital oedema, dyspnoea, respiratory depression, chest tightness, wheezing), including hypotension and anaphylactic shock; very rare: angioedema (including facial oedema); common: increased sweating, lymphadenopathy.
From the side of the central nervous system: common - headache, dizziness; rarely - drowsiness; very rarely - disorientation, depression, insomnia, nightmares, irritability, psychotic disorders, paresthesia, memory impairment, convulsions, anxiety, tremor, aseptic meningitis, taste disorders, cerebral circulation disorders.
From the sensory organs: rarely - tinnitus, visual disturbances, very rarely - blurred vision, diplopia, tinnitus, hearing disorders.
Cardiac: very rarely, common - palpitations, chest pain, heart failure, myocardial infarction.
Vascular disorders: very rarely - arterial hypertension, vasculitis.
Hepatobiliary system: common - increased transaminase levels; rare - hepatitis, jaundice;
Skin and subcutaneous tissue disorders: common - skin rash (including maculopapular rash); rare - urticaria; very rare - bullous rash; eczema, erythema, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), exfoliative dermatitis (fever with or without chills, redness, thickening or peeling of the skin, swelling and/or tenderness of the tonsils), alopecia, photosensitivity reactions, purpura, itching.
From the urinary system: very rarely common - acute renal failure, hematuria, proteinuria, nephrotic syndrome, interstitial nephritis, renal papillary necrosis, increased blood urea nitrogen, urinary tract infections.
Reporting of suspected adverse reactions.
Reporting adverse reactions after registration of a medicinal product is of great importance. This allows monitoring of the benefit/risk ratio when using this medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all cases of suspected adverse reactions and lack of efficacy of a medicinal product via the Automated Information System for Pharmacovigilance at the link: https://aisf.dec.gov.ua
Expiration date
3 years.
Storage conditions
Store in a dry, dark place out of reach of children at a temperature not exceeding 25 ºС.
Packaging
10 tablets in a blister. 1 blister in a cardboard box.
Vacation category
According to the recipe.
Producer
Dr. Reddy's Laboratories Ltd., FTO – II
Location of the manufacturer and address of its place of business.
Station No. 42r, 43, 44r, 45r, 46r, 53, 54, 83, Bachupali Village, Bachupali Mandal, Medchal Malkaigiri District – 500090, Telangana State, India
You can report an adverse reaction or lack of effectiveness when using a medicine by calling (24/7):
+380 44207 51 97 or +380 50414 39 39; and also by e-mail:
DrugSafetyUa@drreddys.com
