Meloxicam solution for intramuscular injection 10mg / ml, 1.5ml No. 3

• Short-term symptomatic therapy of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis and other joint diseases accompanied by pain;

• The drug is intended to reduce pain and inflammation at the time of use, does not affect the progression of the disease.

Intramuscular administration 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 deeply intramuscularly.

Intravenous administration of the drug is prohibited!

Given the possible incompatibility, meloxicam should not be mixed with other drugs in the same syringe.

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 concomitantly with other NSAIDs.

Active ingredient: meloxicam - 10.0 mg.

Excipients: meglumine (meglumine), glycofurfural (tetraglycol), poloxamer 188, sodium chloride, glycine, 1 M sodium hydroxide solution, water for injection.

• Hypersensitivity to the active substance or auxiliary components (including other NSAIDs);

• complete or incomplete combination of bronchial asthma, recurrent polyposis of the nasal mucosa and paranasal sinuses and intolerance to acetylsalicylic acid and other NSAIDs (including a history);

• erosive and ulcerative changes in the mucous membrane of the stomach and duodenum, active gastrointestinal bleeding;

• ulcerative colitis, Crohn's disease in the acute stage;

• severe liver failure or active liver disease;

• severe renal failure (if hemodialysis is not performed, creatinine clearance (CC) less than 30 ml / min, as well as with confirmed hyperkalemia), progressive kidney disease;

• acute gastrointestinal bleeding, recent cerebrovascular bleeding or an established diagnosis of diseases of the blood coagulation system;

• severe uncontrolled heart failure;

• contraindicated in the period after coronary artery bypass grafting;

• pregnancy;

• breastfeeding period;

• children under 18 years of age.

  Carefully

• Elderly age, coronary heart disease, chronic heart failure, cerebrovascular disease, dyslipidemia / hyperlipidemia, diabetes mellitus, peripheral arterial disease, smoking, moderate renal failure (CC 30-60 ml / min), history of gastrointestinal tract disease (presence of Helicobacter infection pylori), long-term use of NSAIDs, frequent alcohol consumption, severe somatic diseases, concomitant use of oral glucocorticosteroids (including prednisolone), anticoagulants (including warfarin), antiplatelet agents (including acetylsalicylic acid, clopidogrel) , selective serotonin reuptake inhibitors (including citalopram, fluoxetine, paroxetine, sertraline); 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.

Pharmacological properties

Pharmacodynamics

Meloxicam is a non-steroidal anti-inflammatory drug that has anti-inflammatory, antipyretic, analgesic effects. Belongs to the class of oxicams, a derivative of enolic acid. The mechanism of action is inhibition of the synthesis of prostaglandins (Pg) as a result of selective suppression of the enzymatic activity of cyclooxygenase 2 (COX-2). When administered in high doses, long-term use and individual characteristics of the body, the selectivity of COX-2 decreases. Suppresses the synthesis of Pg in the area of ??inflammation to a greater extent than in the mucous membrane of the stomach or kidneys, which is associated with a relatively selective inhibition of COX-2, while inhibition of the constantly present isoenzyme COX-1 can cause side effects from the gastrointestinal tract (GIT). ) and kidneys.

Pharmacokinetics

Absorption

Meloxicam is completely absorbed after intramuscular administration. Bioavailability of meloxicam is about 100%. After intramuscular administration of 15 mg of meloxicam, the maximum concentration of the drug (Cmax) in the blood plasma is reached after approximately 1 hour. Distribution Meloxicam binds to blood plasma proteins (mainly albumin) to a large extent - 99%. Passes through the histohematogenous barriers, enters the synovial fluid. The concentration in synovial fluid is 50% of the plasma concentration of meloxicam. The volume of distribution (Vd) is low and is 11 liters. Metabolism Meloxicam is almost completely metabolized in the liver to form four pharmacologically inactive metabolites. The main metabolite is 5'-carboxymeloxicam (60% of the administered dose),is formed by oxidation of the intermediate metabolite 5'-hydroxymethylmeloxicam (9% of the administered dose). The formation of the other two metabolites (constituting, respectively, 16% and 4% of the administered dose of meloxicam) probably involves peroxidase, the activity of which varies individually. Excretion The significant intestinal-hepatic circulation characteristic of meloxicam does not affect its elimination. Meloxicam is excreted mainly in the form of metabolites, equally by the kidneys and intestines. Less than 5% of meloxicam is excreted unchanged by the intestines, and only trace amounts of unchanged meloxicam are detected in urine. The average elimination half-life (T1 / 2) of meloxicam is 20 hours. Plasma clearance averages 8 ml / min. Patients with impaired liver and / or kidney function Lack of liver function,and also mild or moderate renal failure does not have a significant effect on the pharmacokinetics of meloxicam. In end-stage renal disease, an increase in volume of distribution may lead to higher concentrations of free meloxicam

Side effect

Disorders of the blood and lymphatic system: infrequently - anemia; rarely - leukopenia, thrombocytopenia, changes in the number of blood cells, including changes in the leukocyte formula.

Immune system disorders: infrequently - other immediate hypersensitivity reactions; not established - anaphylactic shock, anaphylactoid reactions *.

Mental disorders: rarely - mood changes; not established - confusion of consciousness, disorientation *.

Nervous system disorders: often - headache; infrequently - dizziness, drowsiness.

Violations of the organs of vision, hearing and labyrinthine disorders: infrequently - vertigo; rarely - conjunctivitis, visual impairment, including blurred vision, tinnitus.

Violations of the heart and blood vessels: infrequently - increased blood pressure, a feeling of 'rush' of blood to the face; rarely - palpitations.

Respiratory system disorders: rarely - bronchial asthma in patients with allergies to acetylsalicylic acid and other NSAIDs.

Disturbances from the gastrointestinal tract: 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; not established - pancreatitis.

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

Violations 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 *; not established - photosensitivity.

Renal and urinary tract disorders: infrequently - changes in renal function indicators (increased serum creatinine and / or urea levels), urinary disorders, including acute urinary retention; very rarely - acute renal failure.

Violations of the genitals and mammary glands: infrequently - late ovulation; not established - infertility in women.

General disorders and disorders at the injection site: often - pain and swelling at the injection site; infrequently - edema. 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.

Overdose

Symptoms: drowsiness, impaired consciousness, nausea, vomiting, epigastric pain, gastrointestinal bleeding, acute renal failure, changes in blood pressure, respiratory arrest, asystole.

Treatment: there is no specific antidote; symptomatic therapy. Forced diuresis, urine alkalization, hemodialysis are ineffective due to the high connection of meloxicam with blood proteins.

Interaction with other medicinal products

Other inhibitors of prostaglandin synthesis, including glucocorticoids and salicylates, when taken simultaneously with meloxicam, increase the risk of ulceration in the gastrointestinal tract and gastrointestinal bleeding (due to synergistic action) and are therefore not recommended. Concomitant use with other NSAIDs is not recommended. Selective serotonin reuptake inhibitors - increased risk of gastrointestinal bleeding. Lithium preparations - NSAIDs increase the concentration of lithium in the blood plasma by reducing its excretion by the kidneys. It is recommended to monitor the concentration of lithium during the period of administration of meloxicam, when changing the dose of lithium preparations and their cancellation. Methotrexate - NSAIDs reduce the tubular secretion of methotrexate, thereby increasing its concentration in blood plasma and hematological toxicity, while the pharmacokinetics of methotrexate does not change.In this regard, the simultaneous administration of meloxicam and methotrexate at a dose of more than 15 mg / week is not recommended. With the simultaneous use of drugs, the risk of increased toxicity of methotrexate increases. 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. Therefore, it is necessary to constantly monitor the number of blood cells and kidney function. Contraception - when used simultaneously with intrauterine contraceptives, the effectiveness of the latter may decrease. Mifepristone - due to the theoretical risk of a change in the effectiveness of mifepristone under the influence of inhibitors of prostaglandin synthesis, NSAIDs should not be prescribed earlier than 8-12 days after discontinuation of mifepristone.Diuretics - the use of NSAIDs in the case of dehydration of patients is accompanied by the risk of developing acute renal failure. Antihypertensive drugs (beta-blockers and angiotensin-converting enzyme inhibitors, vasodilators, diuretics) - NSAIDs reduce the effect of antihypertensive drugs due to inhibition of prostaglandins, which have vasodilating properties. Angiotensin II receptor antagonists, when used together with NSAIDs, increase the decrease in glomerular filtration, which, thereby, can lead to the development of acute renal failure, especially in patients with impaired renal function. NSAIDs, acting on renal prostaglandins, can increase the nephrotoxicity of cyclosporine. When used simultaneously with meloxicam drugs,which have a known ability to inhibit CYP2C9 and / or CYP3A4 (or are metabolized with the participation of these enzymes), the possibility of a pharmacokinetic interaction should be taken into account. With the simultaneous administration of meloxicam, it can enhance the effect of oral antidiabetic agents, thereby there is a risk of hypoglycemia. Meloxicam can weaken the action of digoxin, cortisone, diuretics.

special instructions

Patients suffering from gastrointestinal diseases should be monitored regularly. If ulcerative lesions of the gastrointestinal tract or gastrointestinal bleeding occur, meloxicam should be canceled.

Gastrointestinal ulcers, perforation, or bleeding can occur at any time during treatment, with or without a history of alarming symptoms or a history of serious gastrointestinal complications. The consequences of these complications are generally more serious in the elderly.

Particular attention should be paid to patients reporting the development of adverse events from the skin and mucous membranes, as well as hypersensitivity reactions to meloxicam, especially if such reactions were observed during previous courses of treatment.

Like other NSAIDs, meloxicam may increase the risk of developing serious cardiovascular thrombosis, myocardial infarction, angina attack, and possibly fatal outcome. This risk increases with prolonged use of the drug, as well as in patients with a history of the above diseases and predisposed to such diseases. NSAIDs inhibit the synthesis of prostaglandins in the kidney, which are involved in maintaining renal perfusion.

The use of NSAIDs in patients with reduced renal blood flow or reduced blood volume can lead to decompensation of latent renal failure. After the withdrawal of NSAIDs, renal function is usually restored to its original level. The greatest risk of developing this reaction are elderly patients and patients who have dehydration, congestive heart failure, cirrhosis of the liver, nephrotic syndrome or acute renal dysfunction, patients who are taking diuretics at the same time, as well as patients who have undergone major surgical interventions who lead to hypovolemia. In such patients, diuresis and renal function should be carefully monitored at the beginning of therapy. The use of NSAIDs in conjunction with diuretics can lead to sodium, potassium and water retention,as well as to reduce the natriuretic effect of diuretics. As a result, predisposed patients may experience increased signs of heart failure or hypertension. Therefore, careful monitoring of the condition of such patients is necessary, and adequate hydration should also be maintained.

Before starting treatment, a study of renal function is necessary. In the case of combination therapy, renal function should also be monitored.

With the use of meloxicam (as well as most other NSAIDs), an episodic increase in the activity of transaminases or other indicators of liver function in the blood serum has been reported. In most cases, this increase was small and transient. If the identified changes are significant or do not decrease over time, meloxicam should be canceled, and the identified laboratory changes should be monitored.

Weakened or emaciated patients may be less tolerant of adverse events, and therefore, such patients should be carefully monitored. Meloxicam, like other NSAIDs, can mask the symptoms of infectious diseases.

The use of meloxicam, like other drugs that inhibit the synthesis of cyclooxygenase / prostaglandin, can affect fertility, therefore it is not recommended for women planning a pregnancy.

Influence on the ability to drive vehicles, mechanisms

The use of the drug can cause undesirable effects in the form of headaches and dizziness, drowsiness. You should refrain from driving vehicles and engaging in other potentially hazardous activities that require increased concentration of attention and speed of psychomotor reactions.