Meloxicam-LF solution for intramuscular injection 15mg/1.5ml in ampoules №3

Name:
Meloxicam-LF solution for intramuscular injection 15mg/1.5ml in amp. in pack. No. 3×1
Description:
Yellow transparent solution with a greenish tinge. The main active ingredient is Meloxicam. Release form Solution for intramuscular injection. Dosage 15 mg / 1.5 ml Pharmacodynamics Meloxicam is a non-steroidal anti-inflammatory drug from the oxicam group and has anti-inflammatory, analgesic and antipyretic effects. The 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 inflammatory mediators. Pharmacokinetics Absorption Meloxicam is completely absorbed after intramuscular administration. The relative bioavailability compared to oral bioavailability is almost 100%, therefore, when switching from injectable to oral forms, dose adjustment is not required. After intramuscular administration of 15 mg of the drug, the peak plasma concentration of about 1.6-1.8 μg / ml is reached within 1-1.6 hours. Following intramuscular administration, dose linearity has been demonstrated over the therapeutic range of 7.5 to 15 mg. Distribution Meloxicam binds very well to plasma proteins, predominantly to albumin. Penetrates into the synovial fluid, the concentration in the synovial fluid is about 50% of the plasma concentration. The volume of distribution is low, averaging 11 liters after intramuscular injection. Individual fluctuations – 30-40%. Metabolism Meloxicam is almost completely metabolized in the liver with the formation of 4 pharmacologically inactive derivatives. The main metabolite 5′-carboxymeloxicam (60% of the dose) is formed by oxidation of the intermediate metabolite 5′-hydroxymethylmeloxicam, which is also excreted, but to a lesser extent (9% of the dose). In vitro studies have shown that CYP 2C9 plays an important role in this metabolic transformation, and the CYP 3A4 isoenzyme is of additional importance. The activity of peroxidase in the patient’s body probably causes the appearance of two other metabolites, which account for 16% and 4%, respectively, of the administered dose. Withdrawal Meloxicam is excreted mainly in the form of metabolites equally with feces and urine. Less than 5% of the daily dose is excreted unchanged in the feces; in the urine, unchanged, the drug is found only in trace amounts. The mean half-life of meloxicam varies from 13 to 25 hours after oral, intramuscular and intravenous administration. The total plasma clearance is about 7-12 ml / min after a single oral, intravenous or rectal administration. Patients with hepatic/renal insufficiency Hepatic insufficiency and moderate renal insufficiency do not significantly affect the pharmacokinetics of meloxicam. In patients with end-stage renal disease, a decrease in plasma protein binding was observed. In end-stage renal disease, an increase in the volume of distribution may lead to higher concentrations of free meloxicam, so in these patients the daily dose should not exceed 7.5 mg. Elderly patients Pharmacokinetic parameters for elderly male patients were similar to pharmacokinetic parameters for younger male patients. In elderly female patients, a higher AUC value and a longer half-life were observed compared with young patients of both sexes. In elderly patients, the mean plasma clearance during steady state pharmacokinetics is slightly lower than in younger patients. Indications for use Symptomatic short-term treatment of exacerbations of rheumatoid arthritis, osteoarthritis and ankylosing spondylitis (Bekhterev’s disease), in cases where oral or rectal administration of meloxicam is not possible. Method of administration and doses Enter intramuscularly. One injection of 15 mg once a day. The daily dose of meloxicam should not exceed 15 mg. The use of the parenteral route of administration, as a rule, is limited to one dose at the beginning of treatment. In justified cases, the maximum duration of treatment may be 2-3 days (for example, if oral or rectal meloxicam is not possible). Special groups of patients Elderly patients and with an increased risk of adverse reactions The recommended daily dose in elderly patients is 7.5 mg (1/2 ampoule). In patients who are at increased risk of adverse events, treatment should be initiated at a dose of 7.5 mg per day. Patients with renal insufficiency In dialysis patients with severe renal insufficiency, the daily dose should not exceed 7.5 mg (1/2 ampoule). In patients with mild or moderate renal impairment (with creatinine clearance greater than 25 ml / min), there is no need to reduce the dose. Use in patients with severe renal insufficiency is contraindicated. Patients with hepatic impairment No dose reduction is necessary in patients with mild or moderate hepatic impairment. Children Safety and efficacy in children and adolescents under 18 years of age have not been established. Method of administration The injection should be given slowly and deeply into the upper outer quadrant of the buttock under strict aseptic conditions. In case of repeated application, alternate application to the left and right buttocks is necessary. Always make sure that the needle is not in a vein before an injection. If significant pain is present during the injection, the administration should be stopped immediately. In patients with a hip replacement, injections should be given on the opposite side. Use during pregnancy and lactation Meloxicam is contraindicated during pregnancy. Inhibition of prostaglandin synthesis can adversely affect pregnancy and/or fetal development. Data from epidemiological studies suggest an increased risk of miscarriage and the development of heart defects and gastrochisis after the use of prostaglandin synthesis inhibitors in early pregnancy. The absolute risk of developing heart defects increases from less than 1% to about 1.5%. This risk is believed to increase with increasing dose and duration of treatment. During the third trimester of pregnancy, all inhibitors of prostaglandin synthesis can create a risk for the fetus: cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension); impaired renal function, may develop into renal failure with oligohydroamnion. Possible risks in the last stages of pregnancy for the mother and newborn: the possibility of prolonging bleeding time, antiaggregation effect even at very low doses; inhibition of uterine contractions, which leads to a delay or delay in childbirth. The use of meloxicam, as well as other drugs that block cyclooxygenase and prostaglandin synthesis, can affect fertility, so this drug is not recommended for women planning to become pregnant. Meloxicam may delay ovulation. In case of violation of the ability to conceive in women or an examination for infertility, it is necessary to raise the question of the abolition of meloxicam. Although there are no specific data on meloxicam, NSAIDs are known to pass into breast milk. Therefore, meloxicam is contraindicated in breastfeeding. Influence on the ability to drive vehicles or potentially dangerous mechanisms There are no special studies of the effect of the drug on the ability to drive a car or work with mechanisms. However, patients who have experienced visual impairment, drowsiness or other disorders of the central nervous system are advised to refrain from driving or working with mechanisms. Precautions As with other NSAIDs, the drug should be used with caution in patients with a history of gastrointestinal disease and taking anticoagulants. Patients who present with symptoms of gastrointestinal disease should be observed. Treatment with the drug should be discontinued if signs of peptic ulcer or gastrointestinal bleeding appear. As with other NSAIDs, potentially fatal gastrointestinal bleeding, ulceration, or perforation may occur at any time during treatment with or without prior symptoms or a history of serious gastrointestinal disease. The consequences of such events are usually more serious in elderly patients. With the use of NSAIDs, serious skin reactions, some of which were fatal, have been observed in very rare cases, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis. A high risk of such reactions was 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 excessive sensitivity, use should be discontinued. The cardiovascular and cerebrovascular effects of NSAIDs may increase the risk of serious cardiovascular thrombolytic events, myocardial infarction and stroke, which can be fatal. With increasing duration of treatment, this risk may increase. This risk may be increased in patients with cardiovascular disease or risk factors for such disease. Appropriate monitoring and consultation of patients with hypertension and / or with a history of mild, moderately severe dodecompensated heart failure is required, as fluid inclusion in the cells and edema have been reported in combination with NSAID therapy. Clinical monitoring of blood pressure is recommended in patients at risk before and, in particular, at the therapeutic initiation of meloxicam. Clinical studies and epidemiological data demonstrate that the use of some NSAIDs, including meloxicam (particularly at high doses and in long-term treatment), may be associated with a slight increased risk of arterial thrombotic events (eg, myocardial infarction or apoplexy). There are no sufficient data to rule out such a risk for meloxicam. In patients with undiagnosed high blood pressure, heart failure, existing coronary artery disease, peripheral arterial disease, and/or cerebrovascular disease, the decision to prescribe meloxicam should only be made after careful consideration. Evaluation should also be undertaken before treating patients with risk factors for cardiovascular disease (eg, high blood pressure, hyperlipidemia, diabetes, smoking). As with most NSAIDs, isolated cases of elevated transaminases or other indicators of liver function have been reported. In most cases, these deviations were significant and temporary. With a stable and significant deviation from the norm of liver function tests, treatment should be stopped and control tests should be carried out. For patients with a clinically stable course of liver cirrhosis, dose reduction is not necessary. Functional renal failure NSAIDs inhibit the synthesis of prostaglandins in the kidneys, which are involved in maintaining renal perfusion. The use of NSAIDs in patients with reduced renal blood flow or reduced circulating blood volume may lead to decompensation of renal failure. After discontinuation of NSAIDs, renal function usually returns to baseline. Elderly patients are most at risk of developing this reaction; patients who have dehydration, congestive heart failure, cirrhosis of the liver, nephrotic syndrome, or clinically manifested kidney disease; patients simultaneously taking diuretics, ACE inhibitors, angiotensin II receptor antagonists, as well as patients who have undergone major surgical interventions leading to hypovolemia. In such patients, diuresis and renal function should be carefully monitored at the beginning of therapy. In rare cases, NSAIDs can cause interstitial nephritis, glomerulonephritis, medullary renal necrosis, or nephrotic syndrome. In patients with end-stage renal disease who are on hemodialysis, the dose of meloxicam should not exceed 7.5 mg. In patients with mild or moderate renal impairment (CC more than 25 ml / min), dose reduction is not required. NSAIDs may increase sodium, potassium, water retention and affect the natriuretic effect of diuretics, and may cause or exacerbate heart failure or hypertension. Clinical monitoring is recommended for such patients. Hyperkalemia Hyperkalemia may be caused by diabetes or concomitant therapy with drugs that increase plasma potassium levels. Combination with pemetrexed In patients with mild to moderate renal insufficiency taking pemetrexed, meloxicam should be discontinued at least 5 days before the start of pemetrexed therapy and resumed 2 days after the end of pemetrexed. Meloxicam, like any other NSAID, can mask the symptoms of infectious diseases. The use of meloxicam, as well as other drugs that inhibit the synthesis of COX / prostaglandins, can adversely affect reproductive function and is not recommended for women who want to become pregnant. Therefore, for women who want to become pregnant or who are being tested for infertility, discontinuation of meloxicam should be considered. For significant drug interactions that require special attention, see the Interaction with other medicinal products section. Interaction with other drugs Drug interaction studies have only been conducted in adults. Risks associated with hyperkalemia: Some drugs, when used together, can cause hyperkalemia: potassium salts, potassium-sparing diuretics, angiotensin II receptor antagonists, NSAIDs, heparins (low molecular weight or unfractionated), cyclosporine, tacrolimus, trimethoproim. Pharmacodynamic interaction Other NSAIDs, including salicylates (acetylsalicylic acid): the simultaneous use of NSAIDs increases the risk of ulceration in the gastrointestinal tract and gastrointestinal bleeding due to synergistic action. Co-administration with acetylsalicylic acid administered in anti-inflammatory doses (> 1 g single dose or > 3 g total daily dose) is not recommended. Corticosteroids: Concomitant use of corticosteroids requires caution due to an increased risk of gastrointestinal bleeding and ulceration. Anticoagulants or heparin: combined use increases the risk of bleeding due to inhibition of platelet function and damage to the mucous membrane of the stomach and intestines. The simultaneous use of NSAIDs and oral anticoagulants or heparin is not recommended for elderly patients. If it is impossible to avoid the simultaneous use of these drugs, careful monitoring of the effect of anticoagulants is necessary. Thrombolytic drugs and antiplatelet agents: when combined with meloxicam, an increased risk of bleeding is possible (periodic monitoring of blood coagulation parameters is necessary). Selective serotonin reuptake inhibitors: increased risk of gastrointestinal bleeding. Diuretics, ACE inhibitors and angiotensin II antagonists: The use of NSAIDs increases the risk of developing acute renal failure in patients with dehydration. Patients taking diuretics should be adequately hydrated. Before starting treatment, a study of kidney function is necessary. In some patients with impaired renal function (eg, patients with dehydration or elderly patients with impaired renal function), the concomitant use of an ACE inhibitor or angiotensin II antagonist and cyclooxygenase inhibitors may lead to further deterioration of renal function, including the possibility of developing acute renal failure, usually , reversible. This combination should be administered with caution, especially in elderly patients. Adequate hydration of the patient and monitoring of renal function are recommended after initiation of concomitant therapy and periodically during treatment. Antihypertensive agents (?-blockers): NSAIDs reduce the effect of antihypertensive agents due to inhibition of prostaglandins, which have vasodilating properties. Calcineurin inhibitors (tacrolimus, cyclosporine): increased nephrotoxic effect. In the case of combination therapy, renal function should be monitored (especially in elderly patients). Deferasirox: concomitant use requires caution due to an increased risk of gastrointestinal side effects. Pharmacokinetic interaction Lithium: NSAIDs increase the concentration of lithium in the blood plasma by reducing the renal excretion of lithium. The concentration of lithium in plasma can reach toxic values. The combined use of lithium and NSAIDs is not recommended. If such combination therapy is necessary, the serum lithium content should be carefully monitored before, during and after the end of the course of therapy with meloxicam and lithium preparations. Methotrexate: NSAIDs may reduce tubular secretion of methotrexate and thus increase the plasma concentration of methotrexate. In this regard, patients receiving high doses of methotrexate (more than 15 mg per week), the simultaneous use of NSAIDs is not recommended. The risk of interaction with the simultaneous use of methotrexate and NSAIDs is also possible in patients receiving low doses of methotrexate, especially in patients with impaired renal function. If combination therapy is necessary, the blood count and kidney function should be monitored. Care must be taken if NSAIDs and methotrexate are used simultaneously for 3 days, because. plasma methotrexate concentrations may be exceeded and, as a result, toxic effects may occur. The simultaneous use of meloxicam did not affect the pharmacokinetics of methotrexate at a dose of 15 mg per week, however, it should be taken into account that the hematological toxicity of methotrexate increases with the simultaneous use of NSAIDs. Pemetrexed: For concomitant use of meloxicam with pemetrexed in patients with creatinine clearance between 45 and 79 ml/min, meloxicam should be withheld 5 days before, on the day of, and 2 days after, pemetrexed. If the combination of meloxicam with pemetrexed is necessary, patients should be closely monitored, especially for myelosuppression and gastrointestinal adverse reactions. In patients with creatinine clearance below 45 ml/min, the concomitant use of meloxicam with pemetrexed is not recommended. Cholestyramine: cholestyramine accelerates the elimination of meloxicam, increasing the clearance of meloxicam by 50%, reduces its half-life by 13 ± 3 hours. This interaction is of clinical importance. When taken simultaneously with antacids, cimetidine and digoxin, no significant clinical interaction is noted. Contraindications Known hypersensitivity to meloxicam or any component of the drug; there is a possibility of developing cross-sensitivity to acetylsalicylic acid or other NSAIDs. Patients who have previously experienced symptoms of bronchial asthma, nasal polyps, angioedema or urticaria after taking acetylsalicylic acid or other NSAIDs. Contraindicated for the treatment of intraoperative pain in coronary artery bypass grafting (CABG). Acute or recent gastrointestinal ulcer/perforation (two or more confirmed episodes). Nonspecific inflammatory bowel disease in the acute phase (Crohn’s disease, ulcerative colitis). Severe liver failure. Severe renal failure (if hemodialysis is not performed). Open gastrointestinal bleeding, recent cerebrovascular bleeding or other identified somatic disorders accompanied by bleeding. Severe uncontrolled heart failure. Children and teenagers up to 18 years old. Third trimester of pregnancy. Patients with impaired hemostasis or taking anticoagulants: intramuscular hematomas may form. Composition One ampoule contains: Active substance: meloxicam – 15.0 mg. Excipients: meglumine, glycofurol, poloxamer 188, glycine, sodium chloride, sodium hydroxide (in the form of a 1M solution), water for injection. Overdose Increased dose-dependent side effects. Symptoms: impaired consciousness, nausea, vomiting, epigastric pain, bleeding from the gastrointestinal tract, acute renal failure, acute liver failure, respiratory arrest, asystole. Treatment: symptomatic therapy. Forced diuresis, alkalization of urine, hemodialysis are ineffective due to the high degree of meloxicam binding to plasma proteins. There is no specific antidote. Side effects Clinical studies and epidemiological data suggest that the use of some NSAIDs (especially at high doses and in long-term treatment) may be associated with a slight increased risk of arterial thrombosis (eg, myocardial infarction or stroke). It was reported about the development of edema, arterial hypertension, heart failure associated with the use of NSAIDs. The most common adverse reactions are gastrointestinal disorders. Complications of peptic ulcer may develop: perforation or gastrointestinal bleeding, sometimes fatal, especially in the elderly. Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena, bloody vomiting, ulcerative stomatitis, exacerbation of ulcerative colitis and Crohn’s disease, and less often gastritis have been reported. Within the systemic organ classes, the following categories are used in terms of the incidence of side effects: very often (?1/10); often (?1/100, <1/10); infrequently (?1/1000, <1/100); rarely (?1/10,000, <1/1000); very rarely (<1/10,000); not installed. From the hemopoietic system: infrequently: anemia; rarely: a change in the blood count (including a change in the leukocyte formula), leukopenia, thrombocytopenia. In very rare cases, agranulocytosis. From the immune system: infrequently: allergic reactions; frequency not established: anaphylactic shock, anaphylactoid / anaphylactic reactions. On the part of the psyche: rarely: mood changes, nightmares; frequency not established: confusion, disorientation. From the nervous system: often: headache; infrequently: dizziness, drowsiness. On the part of the organs of vision: rarely: blurred vision, blurred vision, conjunctivitis. On the part of the hearing organs and the labyrinth: infrequently: dizziness; rarely: ringing in the ears. From the side of the heart: rarely - palpitations. There have been reports of heart failure associated with the use of NSAIDs. From the side of the vessels: infrequently: increased blood pressure, a feeling of "tides". On the part of the respiratory system, chest organs and mediastinum: rarely - bronchial asthma (in patients allergic to acetylsalicylic acid or other NSAIDs). From the gastrointestinal tract: often: abdominal pain, dyspepsia, diarrhea, nausea, vomiting; infrequently: hidden or obvious gastrointestinal bleeding, gastritis, stomatitis, constipation, bloating, belching; rarely: gastroduodenal ulcers, colitis, esophagitis; very rarely: perforation of the gastrointestinal tract. Gastrointestinal bleeding, perforation, gastric ulcer can be severe and potentially fatal, especially in elderly patients. From the side of the liver and biliary tract: infrequently: transient changes in liver function tests (for example, increased activity of transaminases or bilirubin); very rare: hepatitis. On the part of the skin and subcutaneous tissues: infrequently: angioedema, itching, skin rash; rarely: toxic epidermal necrolysis, Stevens-Johnson syndrome, urticaria; very rarely: bullous dermatitis, erythema multiforme; frequency not established: photosensitivity. From the urinary system: infrequently: potassium and water retention, hyperkalemia, changes in indicators of kidney function (increased levels of creatinine and / or urea in the blood serum); very rarely: acute renal failure, especially in patients with risk factors. General disorders and disorders at the injection site: often: pain and swelling at the injection site; infrequently: edema. Co-administration with drugs that depress the bone marrow (eg, methotrexate) may cause cytopenia. As with other NSAIDs, the possibility of interstitial nephritis, glomerulonephritis, renal medullary necrosis, and nephrotic syndrome cannot be ruled out. Storage conditions In a place protected from moisture and light at a temperature not exceeding 25 ° C. Keep out of the reach of children. Buy Meloxicam-LF solution for intramuscular injection 15mg/1.5ml in ampoules No. 3 -LF solution for intramuscular injection 15mg/1.5ml in ampoules No. 3