Genitron solution for intravenous injection 10mg / ml, 1.5ml No. 5

Short-term symptomatic therapy for:

• osteoarthritis (arthrosis, degenerative joint diseases), incl. with a pain component;

• rheumatoid arthritis;

• ankylosing spondylitis (ankylosing spondylitis).

  Designed to reduce pain and inflammation at the time of use, does not affect the progression of the disease.

The intramuscular injection of the drug is indicated only during the first 2-3 days. In the future, treatment is continued with the use of oral forms (tablets). The drug is injected deep into the / m. The drug should not be administered intravenously. The recommended dose is 7.5 mg (0.75 ml) or 15 mg (1.5 ml) 1 time / day, depending on the intensity of pain and the severity of the inflammatory process. The maximum recommended daily dose is 15 mg (1.5 ml). Given the possible incompatibility, meloxicam should not be mixed in the same syringe with other drugs. In patients with severe renal failure on hemodialysis, and in patients with an increased risk of adverse reactions, the dose should not be exceeded. 7.5 mg (0.75 ml) / day For patients with mild or moderate renal insufficiency (CC more than 30 ml / min), dose adjustment is not required.The drug should not be used concurrently with other NSAIDs. The total daily dose of meloxicam, used in the form of tablets, suppositories, suspension for oral administration and injections, should not exceed 15 mg.

Solution for intramuscular injection of yellow or greenish-yellow color, transparent.

1 ml meloxicam 10 mg

Excipients: meglumine (N-methylglucamine) - 7 mg, glycine - 6 mg, poloxamer 188 - 50 mg, tetrahydrofurfuril macrogol (glycofurol) - 100 mg, sodium chloride - 3.5 mg, 0.1M sodium hydroxide solution - up to pH 8.4-8.9 , water d / i - up to 1 ml.

• Complete or incomplete combination of bronchial asthma, angioedema or urticaria, recurrent polyposis of the nose and paranasal sinuses and intolerance to acetylsalicylic acid and other NSAIDs (including a history);

• erosive and ulcerative lesions of the mucous membrane of the stomach and duodenum in the acute stage or recently transferred;

• inflammatory bowel disease (Crohn's disease or acute ulcerative colitis);

• severe liver failure or active liver disease;

• severe renal failure with CC less than 30 ml / min (in patients not undergoing hemodialysis, with confirmed hyperkalemia);

• progressive kidney disease; active gastrointestinal bleeding;

• recent cerebrovascular bleeding or a confirmed diagnosis of diseases of the blood coagulation system;

• thyroid disease (for tablets);

• decompensated heart failure;

• acute myocardial infarction;

• period after coronary artery bypass grafting;

• pregnancy;

• lactation period (breastfeeding);

• children under 12 years of age (for tablets);

• children and adolescents up to 18 years old (for solution for intramuscular injection);

• hereditary lactose intolerance, impaired absorption of glucose and galactose, lactase deficiency (for tablets);

• hypersensitivity to the active substance or auxiliary components of the drug (including other NSAIDs).

With care: a history of gastrointestinal diseases (gastric ulcer and duodenal ulcer, liver disease), the presence of Helicobacter pylori infection; Ischemic heart disease, chronic heart failure; cerebrovascular diseases; moderate renal failure (CC 30-60 ml / min); dyslipidemia / hyperlipidemia; diabetes; simultaneous administration of oral corticosteroids (including prednisone), anticoagulants (including warfarin), antiplatelet agents (including clopidogrel), selective serotonin reuptake inhibitors (including citalopram, fluoxetine, paroxetine, sertraline); severe somatic diseases; peripheral arterial disease; elderly age; long-term use of NSAIDs; smoking; frequent alcohol consumption; severe somatic diseases; bronchial asthma; tuberculosis; severe osteoporosis.To reduce the risk of developing adverse events from the gastrointestinal tract, the minimum effective dose should be used in the smallest possible short course.

pharmachologic effect

Meloxicam belongs to NSAIDs of the oxicam class, is a derivative of enolic acid and has anti-inflammatory, analgesic and antipyretic effects. The pronounced anti-inflammatory effect of meloxicam has been established in all standard models of inflammation. The mechanism of action of meloxicam is its ability to inhibit the synthesis of prostaglandins (known mediators of inflammation) as a result of selective suppression of the enzymatic activity of COX-2. When administered in high doses, long-term use and individual characteristics of the organism, the selectivity of COX-2 inhibition decreases. Meloxicam in vivo inhibits the synthesis of prostaglandins at the site of inflammation to a greater extent than in the gastric mucosa or kidneys. These differences are associated with a more selective inhibition of COX-2 compared to COX-1. It is believedthat inhibition of COX-2 provides a therapeutic effect of NSAIDs, whereas inhibition of the persistent isoenzyme COX-1 may cause gastric and renal side effects. The selectivity of meloxicam in relation to COX-2 has been confirmed in various test systems, both in vitro and in vivo. The selective ability of meloxicam to inhibit COX-2 has been shown when using human whole blood in vitro as a test system. It was found that meloxicam (at doses of 7.5 mg and 15 mg) inhibited COX-2 more actively, exerting a greater inhibitory effect on the production of prostaglandin E2 stimulated by lipopolysaccharide (a reaction controlled by COX-2) than on the production of thromboxane involved in blood coagulation ( reaction controlled by COX-1). These effects were dose dependent. Ex vivo studies have shownthat meloxicam (at doses of 7.5 mg and 15 mg) had no effect on platelet aggregation and bleeding time.

Pharmacokinetics

Suction

After oral administration, meloxicam is well absorbed from the gastrointestinal tract, as evidenced by the high absolute bioavailability (90%). After a single use of meloxicam, Cmax in plasma is achieved within 5-6 hours. Simultaneous intake of food and antacids does not change absorption. When using the drug inside (in doses of 7.5 and 15 mg), its concentrations are proportional to the doses. Css is reached within 3-5 days. The range of differences between the maximum and minimum concentrations of the drug after taking it 1 time / day is relatively small and amounts to 0.4-1.0 ?g / ml when using the drug at a dose of 7.5 mg, when used at a dose of 15 mg - 0.8-2.0 ?g / ml (the values ??are given, respectively. Cmin and Cmax in equilibrium), although values ??outside the specified range were also noted.Cmax of meloxicam in plasma in an equilibrium state is achieved within 5-6 hours after oral administration. After i / m administration, meloxicam is completely absorbed. The bioavailability of the drug is about 100%. After i / m administration of meloxicam at a dose of 15 mg, Cmax in plasma is reached after approximately 1 hour.

Distribution

Meloxicam binds very well to plasma proteins, especially albumin (99%). Penetrates through histohematogenous barriers, as well as into synovial fluid. The synovial fluid concentration is approximately 50% of the plasma concentration. Vd after repeated oral administration of meloxicam (in doses from 7.5 mg to 15 mg) is about 16 liters, with a coefficient of variation from 11% to 32%, with i / m administration of Vd is 11 liters.

Metabolism

Meloxicam is almost completely metabolized in the liver to form 4 pharmacologically inactive derivatives. The main metabolite, 5'-carboxymeloxicam (60% of the administered dose), is formed by oxidation of the intermediate metabolite, 5'-hydroxymethylmeloxicam, which is also excreted, but to a lesser extent (9% of the administered dose). In vitro studies have shown that the isoenzyme CYP2C9 plays an important role in this metabolic transformation, and the isoenzyme CYP3A4 plays an additional role. In the formation of two other metabolites (making up 16% and 4% of the administered dose of the drug, respectively), peroxidase is involved, the activity of which varies individually. Excretion It is excreted equally through the intestines and by the kidneys, mainly in the form of metabolites. Less than 5% of the daily dose is excreted unchanged through the intestines,in urine in unchanged form, the drug is found only in trace amounts. The average T1 / 2 of meloxicam varies from 13 to 25 hours (with intramuscular injection - 20 hours). Plasma clearance averages 7-12 ml / min after a single dose of meloxicam, with i / m administration - 8 ml / min.

Pharmacokinetics in special patient groups

Liver dysfunction, as well as renal failure of mild and moderate severity, does not significantly affect the pharmacokinetics of meloxicam. The rate of elimination of meloxicam from the body is significantly higher in patients with moderate renal failure. Meloxicam binds to plasma proteins worse in patients with end-stage renal failure. In end-stage renal failure, an increase in Vd can lead to higher concentrations of free meloxicam, therefore, in such patients, the daily dose should not exceed 7.5 mg. Elderly patients in comparison with young patients have similar pharmacokinetic parameters. In elderly patients, the mean plasma clearance at steady state is slightly lower than in younger patients.Elderly women have higher AUC values ??and a prolonged T1 / 2, compared with young patients of both sexes.

Side effect

From the hematopoietic system: infrequently - anemia; rarely - a change in the number of blood cells, including changes in the leukocyte formula, leukopenia, thrombocytopenia.

From the side of the immune system: not established - anaphylactic shock, anaphylactoid / anaphylactic reactions, other hypersensitivity reactions.

From the nervous system: often - headache; infrequently - dizziness, drowsiness. Mental disorders: often - emotional lability; not established - confusion of consciousness, disorientation.

From the side of the organ of vision: rarely - conjunctivitis, visual impairment, including blurred vision.

On the part of the organ of hearing: infrequently - vertigo; rarely - tinnitus.

From the digestive system: often - abdominal pain, dyspepsia, diarrhea, nausea, vomiting; infrequently - latent or overt gastrointestinal bleeding, gastritis, stomatitis, constipation, bloating, belching; rarely - gastroduodenal ulcers, colitis, esophagitis; very rarely - perforation of the gastrointestinal tract.

From the liver and biliary tract: infrequently - transient changes in liver function indicators (for example, an increase in the activity of transaminases or bilirubin); very rarely - hepatitis.

On the part of the skin and subcutaneous tissues: infrequently - angioedema, itching, skin rash; rarely - urticaria, toxic epidermal necrolysis, Stevens-Johnson syndrome; very rarely - bullous dermatitis, erythema multiforme; not established - photosensitivity.

From the respiratory system: rarely - bronchial asthma in patients with allergy to acetylsalicylic acid or other NSAIDs.

From the side of the cardiovascular system: infrequently - increased blood pressure, a feeling of 'rush' of blood to the face; rarely - palpitations.

From the urinary system: infrequently - changes in renal function indicators (increased concentration of creatinine and / or urea in the blood serum), urinary disorders, including acute urinary retention; very rarely - acute renal failure.

Others: often - peripheral edema, edema and pain at the injection site (solution for intramuscular injection). Concomitant use with drugs that depress the bone marrow (for example, methotrexate) can provoke cytopenia. Gastrointestinal bleeding, ulceration, or perforation can be fatal. As with other NSAIDs, they do not exclude the possibility of the appearance of interstitial nephritis, glomerulonephritis, renal medullary necrosis, and nephrotic syndrome.

Application during pregnancy and lactation

The use of the drug is contraindicated during pregnancy. It is known that NSAIDs penetrate into breast milk, therefore, the use of the drug during breastfeeding is contraindicated. As a drug that inhibits the synthesis of COX / prostaglandin, GenitronЃ can affect fertility, therefore it is not recommended for women planning a pregnancy. Meloxicam may delay ovulation. In this regard, in women who have problems with conception and are undergoing examination for such problems, it is recommended that the drug GenitronЃ be canceled.

Application for violations of liver function

The use of the drug is contraindicated in severe hepatic insufficiency or active liver disease. No dose adjustment is required in patients with (compensated) cirrhosis of the liver.

Application for impaired renal function

The use of the drug is contraindicated in severe renal failure with CC less than 30 ml / min (in patients not undergoing hemodialysis, with confirmed hyperkalemia), progressive kidney disease. Patients with moderate renal insufficiency (CC 30-60 ml / min) should be prescribed the drug with caution.

Application in children

The drug is contraindicated for use in children under 12 years of age (tablets), under the age of 18 (solution for intramuscular injection). Use in elderly patients

The drug should be prescribed with caution to elderly patients.

special instructions

Because the potential risk of adverse reactions depends on the dose and the duration of treatment, the minimum effective dose should be used for the minimum possible short course. The duration of the course of treatment is set individually, depending on the course of the disease and the effectiveness of the therapy. Patients with gastrointestinal diseases, when using GenitronЃ, should be examined regularly. The drug should not be prescribed to patients with peptic ulcers or gastrointestinal bleeding. At any time during treatment, with or without previous symptoms and a history of serious gastrointestinal illness, potentially fatal gastrointestinal bleeding, ulceration, or perforation may occur. If ulcerative lesions of the gastrointestinal tract or gastrointestinal bleeding occur, the drug must be canceled.The most serious consequences were observed in the elderly. In patients with cardiovascular diseases or with risk factors for developing such diseases, NSAIDs can increase the risk of serious cardiovascular thrombotic events, myocardial infarction, angina pectoris and stroke, which can be fatal. As the duration of treatment increases, this risk may increase. NSAIDs can increase sodium, potassium and water retention and reduce the natriuretic effects of diuretics. As a result, predisposed patients may develop or worsen heart failure or arterial hypertension. Clinical monitoring is recommended for these patients and adequate hydration should be maintained. Before starting treatment, a study of renal function is necessary.In the case of combination therapy, renal function should also be monitored. In patients with reduced renal blood flow, the use of NSAIDs (NSAIDs inhibit the synthesis of renal prostaglandin, which plays an important role in maintaining renal blood flow) can cause renal failure, which disappears when anti-inflammatory therapy with nonsteroidal drugs is stopped. The greatest risk of such a reaction occurs in elderly patients, with dehydration, with chronic heart failure, liver cirrhosis, nephrotic syndrome, chronic kidney disease, who receive concomitant therapy with diuretics, ACE inhibitors or angiotensin II receptor antagonists, or after major surgical interventions. which led to hypovolemia.Such patients require monitoring of urine output and renal function at the beginning of therapy. In isolated cases, NSAIDs can lead to interstitial nephritis, glomerulonephritis, renal medular necrosis, or the development of nephrotic syndrome. In the treatment of NSAIDs, isolated cases of increased activity of transaminases or other indicators of liver function have been described, which in most cases were insignificant and temporary. In case of persistent and significant deviation from the norm, treatment with GenitronЃ should be discontinued and control tests should be performed. In clinically stable patients with liver cirrhosis, there is no need to reduce the dose of GenitronЃ; laboratory changes should be monitored. Weakened patients need more careful monitoring, since the side effects are more severe.As with the treatment of other NSAIDs, the drug should be used with caution in elderly patients who are more likely to have a decrease in kidney, liver and heart function. The drug GenitronЃ, like any other NSAID, can mask the symptoms of the underlying infectious disease. In very rare cases, serious skin reactions (some of them fatal) have been observed with the use of NSAIDs, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis. A high risk of such reactions is observed at the beginning of treatment, while in most cases such reactions appeared during the first month of treatment. At the first appearance of skin rashes, lesions of the mucous membranes or other signs of hypersensitivity, it is necessary to discontinue the use of GenitronЃ.Due to the possible occurrence of side effects with localization on the skin and mucous membranes, special attention should be paid to the appearance of the corresponding symptoms. If side effects appear, drug treatment should be discontinued. The composition of the drug in the form of tablets (7.5 mg and 15 mg) contains lactose. Therefore, this drug is not recommended for patients with congenital lactose intolerance, lactase deficiency or malabsorption of glucose or galactose. Influence on the ability to drive vehicles and control mechanisms During the period of treatment, a decrease in the speed of mental and motor reactions is possible, therefore, it is necessary to refrain from driving vehicles and engaging in other potentially hazardous activities that require increased concentration of attention and speed of psychomotor reactions.

Overdose

Symptoms: drowsiness, impaired consciousness, nausea, vomiting, epigastric pain, gastrointestinal bleeding, acute renal failure, liver failure, arterial hypertension, arterial hypotension, respiratory arrest, asystole.

Treatment: there is no specific antidote. In case of drug overdose, symptomatic therapy is performed; in case of an overdose of the drug in the form of tablets - gastric lavage, intake of activated carbon. Forced diuresis, alkalization of urine, hemodialysis are ineffective due to the high degree of binding of the drug to blood proteins.

Drug interactions

When used simultaneously with other inhibitors of prostaglandin synthesis, including corticosteroids and salicylates, meloxicam may increase the risk of mucosal ulcers in the gastrointestinal tract and gastrointestinal bleeding due to their synergism. The co-administration of meloxicam and other NSAIDs is not recommended. Together with anticoagulants, heparin for systemic use, thrombolytic agents, meloxicam increases the risk of bleeding. If it is impossible to avoid their simultaneous use, it is necessary to monitor the indicators of the blood coagulation system. Concomitant use with meloxicam of antiplatelet drugs, serotonin reuptake inhibitors increases the risk of bleeding due to inhibition of platelet function. In the case of simultaneous use, careful monitoring of the blood coagulation system is necessary.Meloxicam can reduce the renal excretion of lithium, which leads to an increase in its concentration in the blood plasma to toxic levels. The simultaneous use of meloxicam with lithium preparations is not recommended. If necessary, simultaneous use is recommended to carefully monitor the concentration of lithium in the plasma during the entire course of the use of lithium preparations. NSAIDs reduce renal excretion of methotrexate, thereby increasing its plasma concentration. The simultaneous use of meloxicam and methotrexate (at a dose of more than 15 mg per week) is not recommended. The risk of developing an interaction between NSAIDs and methotrexate may also occur in patients using low-dose methotrexate, especially in patients with impaired renal function. In the case of simultaneous use, careful monitoring of renal function and blood counts is necessary.Meloxicam may increase the hematological toxicity of methotrexate, especially in patients with impaired renal function. With the combined use of meloxicam and methotrexate for 3 days, the risk of increased toxicity of the latter increases. There is evidence that meloxicam may reduce the effectiveness of intrauterine contraceptives, but this has not been proven. When meloxicam is used together with diuretics, there may be a risk of acute renal failure, therefore, kidney function should be monitored and an adequate level of hydration should be maintained. Meloxicam reduces the effect of antihypertensive drugs (beta-blockers, ACE inhibitors, vasodilators, diuretics) due to inhibition of prostaglandins, which have vasodilating properties. Meloxicam and angiotensin II receptor antagonists,as well as ACE inhibitors have a synergistic effect on reducing glomerular filtration. In patients with preexisting renal impairment, this can lead to acute renal failure. Cholestyramine, binding meloxicam in the gastrointestinal tract, leads to its faster excretion. Meloxicam, affecting renal prostaglandins, enhances the nephrotoxicity of cyclosporin, which requires enhanced control of renal function while using drugs. Meloxicam is almost completely destroyed by hepatic metabolism, approximately 2/3 of which pass with the participation of cytochrome (CYP) P450 and 1/3 by peroxidase oxidation. Possible pharmacokinetic interaction of meloxicam and other drugs at the metabolic stage due to their influence on CYP2C9 and / or CYP3A4.When used simultaneously with hypoglycemic agents for oral administration, meloxicam may enhance their effect, thereby contributing to the risk of hypoglycemia. Meloxicam can weaken the action of digoxin, cortisone, diuretics. With the simultaneous administration of meloxicam with antacids, cimetidine, digoxin and furosemide, no interaction at the pharmacokinetic level was detected.