Meloxicam solution 10mg/ml 1.5ml ampoules, 5pcs

Composition

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1 ml of the solution contains:

active ingredients:

meloxicam 10.00 mg / ml

excipients:

glycine (aminoacetic acid),

macrogol (polyethylene glycol 400),

meglumin (N-methyl-D-glucamine),

povidone-K 17 (plasdon C-15 or collidone 17 F),

1,2-propylene glycol,

sodium hydroxide,

water for injection.

Pharmacological action

Pharmacotherapy group

Nonsteroidal Anti-inflammatory drug (NSAID)

ATX code

M01AC06

Pharmacodynamics :

Meloxicam is a nonsteroidal anti-inflammatory drug with analgesic anti-inflammatory and antipyretic effects. It belongs to the class of oxycams derived from enolic acid. The anti-inflammatory effect is associated with inhibition of the enzymatic activity of cyclooxygenase-2, which is involved in the biosynthesis of prostaglandins in the area of inflammation. To a lesser extent, meloxicam acts on cyclooxygenase, which is involved in the synthesis of prostaglandin, which protects the mucous membrane of the gastrointestinal tract (GIT) and takes part in the regulation of blood flow in the kidneys.

Pharmacokinetics:

Absorption rate

The relative bioavailability is about 100%. After intramuscular use of the drug at a dose of 15 mg, the maximum concentration of the drug in plasma (Cmax) is 162 mcg / ml and is reached within approximately 60 minutes.

Distribution

Meloxicam binds well to plasma proteins, especially albumin (99%). Penetrates the synovial fluid the concentration in the synovial fluid is approximately 50% of the plasma concentration of the drug. The volume of distribution is low approximately 11 liters. Interindividual differences are 30-40%.

Metabolism

Meloxicam is almost completely metabolized in the liver to form four pharmacologically inactive metabolites. The main metabolite of 5 ‘- carboxymeloxicam (60% of the dose) is formed by the oxidation of an intermediate metabolite with 5’ – hydroxymethylmeloxicam, which is also excreted to a lesser extent (9% of the dose). In vitro studies have shown that the CYP2C9 isoenzyme plays an important role in this metabolic transformation and the CYP3A4 isoenzyme is of additional importance. The formation of the other two metabolites (which make up 16% and 4% of the drug dose, respectively) involves peroxidase, the activity of which probably varies individually.

Deduction

It is excreted equally in the feces and urine, mainly in the form of metabolites. In unchanged form, less than 5% of the daily dose is excreted in the feces in the urine. In unchanged form, the drug is detected only in trace amounts. The average elimination half-life of meloxicam is 20 hours. The average plasma clearance is 8 ml/min.

Insufficient liver and/or kidney function

Hepatic insufficiency as well as mild or moderate renal insufficiency does not significantly affect the pharmacokinetics of meloxicam. In end-stage renal failure, increased volume of distribution may lead to higher concentrations of free meloxicam, so in patients with liver and/or kidney failure, the daily dose should not exceed 75 mg.

Elderly patients

In elderly patients, the mean plasma clearance during steady-state pharmacokinetics is slightly lower than in young patients.

Indications

The drug is recommended if it is impossible to use meloxicam in other dosage forms. The drug is intended for symptomatic therapy of reducing pain and inflammation at the time of use, it does not affect the progression of the disease.

Short-term symptomatic therapy for osteoarthritis (osteoarthritis degenerative joint diseases) rheumatoid arthritis ankylosing spondylitis other inflammatory and degenerative diseases of the musculoskeletal system such as arthropathy dorsopathy (for example sciatica lower back pain shoulder periarthritis and others) accompanied by pain.

Use during pregnancy and lactation

The drug is contraindicated during pregnancy. The safety of using this drug during pregnancy has not been proven. The effect of delayed prostaglandin synthesis on embryogenesis during the first two trimesters of pregnancy is not clear. In the last trimester of pregnancy, the mechanism of action of meloxicam is characterized by inhibition of labor activity, premature closure of Ductus arteriosus Botalli in the fetus, increased predisposition to bleeding in the mother and child, and increased risk of edema in the mother.

It is known that NSAIDs pass into breast milk, so meloxicam is not recommended for use during lactation.

Contraindications

– hypersensitivity to the Active ingredient or auxiliary components of the drug to acetylsalicylic acid and other NSAIDs;

– complete or incomplete combination of bronchial asthma, recurrent polyposis of the nasal mucosa and paranasal sinuses of angioedema or urticaria caused by intolerance to acetylsalicylic acid or other NSAIDs because of the probability of cross-sensitivity (including in the anamnesis);

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

– inflammatory bowel disease – Crohn’s disease or ulcerative colitis in the acute stage;

– active gastrointestinal bleeding, recent cerebrovascular bleeding or established diagnosis of diseases of the blood coagulation system;

– severe hepatic impairment or active liver disease;

– severe renal insufficiency (if not possible, dialysis creatinine clearance less than 30 ml/min), progressive kidney diseases including confirmed hyperkalemia;

– severe uncontrolled heart failure;

therapy of perioperative pain in the conduct of bypass grafting of the coronary arteries;

– concomitant therapy with anticoagulants as there is a risk of intramuscular hematomas;

– pregnancy;

– the period of breastfeeding;

– age up to 18 years.

With caution:

– Diseases of the gastrointestinal tract (GIT) disease (infection Helicobacterpylori); gastric ulcer and 12 duodenal ulcer;

chronic heart failure;

ischemic heart disease;

– arterial hypertension;

– renal insufficiency (creatinine clearance 30-60 ml/min);

– progressing liver disease, hyperbilirubinemia, hepatic failure;

– cerebrovascular disease;

– dyslipidemia/hyperlipidemia;

– diabetes;

– concomitant therapy with the following drugs: oral anticoagulants glucocorticosteroids antiplatelet agents selective serotonin reuptake inhibitors;

– bronchial asthma tuberculosis severe osteoporosis;

– peripheral arterial diseases;

– elderly patients (over 65 years of age) (including those receiving diuretics, weakened patients and low body weight);

– long – term use of NSAIDs;

– smoking;

– frequent alcohol consumption.

To reduce the risk of adverse events from the gastrointestinal tract (GIT), the minimum effective dose should be used in the shortest possible course.

Side effects

The frequency of side effects is classified according to the recommendations of the World Health Organization characterized as: very common (≥ 1/10) common (≥ 1/100 <1/10) infrequent (≥ 1/1000 <1/100) rare (≥ 1/10000 <1/1000) very rare (

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 swings; not established – confusion disorientation.

Nervous system disorders:

often – headache; infrequently-dizziness and drowsiness.

Visual hearing disorders and labyrinth disorders:

infrequently-vertigo; rarely-conjunctivitis visual disturbances including blurred vision tinnitus.

Disorders of the heart and blood vessels:

infrequently-an increase in blood pressure, a feeling of “rush” of blood to the face; rarely-a feeling of palpitation.

Respiratory system disorders:

rarely-bronchial asthma in patients allergic to acetylsalicylic acid and other NSAIDs.

Disorders of the gastrointestinal tract:

often – abdominal pain dyspepsia diarrhea nausea vomiting; infrequently-latent and obvious gastrointestinal bleeding gastritis stomatitis constipation bloating belching; rarely-gastroduodenal ulcers colitis esophagitis; very rarely – perforation of the gastrointestinal tract.

Liver and biliary tract disorders:

infrequently-transient changes in liver function parameters (for example, increased transaminase or bilirubin activity); very rarely – hepatitis.

Skin and subcutaneous tissue disorders:

infrequently-angioedema pruritus skin rash; rarely-toxic epidermal necrolysis Stevens-Johnson syndrome urticaria; very rare-bullous dermatitis erythema multiforme; not established-photosensitization.

Kidney and urinary tract disorders:

infrequently-changes in renal function indicators (increased serum creatinine and/or urea) impaired urination including acute urinary retention; very rarely – acute renal failure.

Disorders 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.

Combined use with drugs that depress bone marrow (for example, methotrexate) can provoke cytopenia. Gastrointestinal bleeding an ulcer or perforation can be fatal.

As with other NSAIDs, the possibility of interstitial nephritis, glomerulonephritis, renal medullary necrosis, and nephrotic syndrome is not excluded.

Interaction

Other prostaglandin synthesis inhibitors including glucocorticoids and salicylates. Simultaneous use with meloxicam increases the risk of ulceration in the gastrointestinal tract and gastrointestinal bleeding (due to the synergy of action). Concomitant use with other NSAIDs is not recommended.

Anticoagulants for oral use heparin for systemic use thrombolytic agents. Concomitant use with meloxicam increases the risk of bleeding. In the case of simultaneous use, careful monitoring of the blood coagulation system is necessary.

Antiplatelet drugs are serotonin reuptake inhibitors. Concomitant use of meloxicam 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.

Lithium preparations. NSAIDs increase the level of lithium in plasma by reducing its excretion by the kidneys. Concomitant use of meloxicam with lithium preparations is not recommended. If concomitant use is necessary, careful monitoring of the plasma lithium concentration is recommended throughout the course of lithium preparations.

Methotrexate. NSAIDs reduce the secretion of methotrexate by the kidneys, thereby increasing its concentration in plasma. Simultaneous use of meloxicam and methotrexate (at a dose of more than 15 mg per week) is not recommended. In the case of simultaneous use, careful monitoring of renal function and blood formula is necessary. Meloxicam may increase the hematological toxicity of methotrexate, especially in patients with impaired renal function.

Contraception. There is evidence that NSAIDs can reduce the effectiveness of intrauterine contraceptive devices, but this has not been proven. Mifepristone: due to the theoretical risk of changing the effectiveness of mifepristone under the influence of prostaglandin synthesis inhibitors, NSAIDs should not be prescribed earlier than 8-12 days after mifepristone withdrawal.

Diuretics. The use of NSAIDs increases the risk of acute renal failure in patients with dehydration.

Antihypertensive agents (beta-blockers angiotensin converting enzyme inhibitors vasodilators diuretics). NSAIDs reduce the effect of antihypertensive drugs due to the inhibition of prostaglandins with vasodilating properties.

Angiotensin-II receptor antagonists. Concomitant use with NSAIDs increases glomerular filtration rate, which may lead to the development of acute renal failure, especially in patients with impaired renal function.

Colestyramine binding meloxicam in the gastrointestinal tract leads to its faster elimination.

Pemetrexed. When meloxicam and pemetrexed are co-administered in patients with a creatinine clearance of 45 to 79 ml/min, meloxicam should be discontinued 5 days before the start of pemetrexed and possibly resumed 2 days after the end of use. If there is a need for the combined use of meloxicam and pemetrexed, patients should be carefully monitored, especially with regard to myelosuppression and the occurrence of gastrointestinal side effects. In patients with creatinine clearance less than 45 ml/min, meloxicam is not recommended in combination with pemetrexed.

NSAIDs acting on renal prostaglandins may increase the nephrotoxicity of cyclosporine.

When using medicinal products with meloxicam that have a known ability to inhibit CYP2C9 and / or CYP3A4 (or are metabolized with the participation of these enzymes), such as sulfonylureas or probenecid, the possibility of pharmacokinetic interaction should be taken into account.

When combined with antidiabetic agents for oral use (for example, sulfonylurea derivatives nateglinide), interactions mediated by CYP2C9 are possible that can lead to an increase in the concentration of both these drugs and meloxicam in the blood. Patients taking meloxicam concomitantly with sulfonylureas or nateglinide should carefully monitor their blood sugar levels due to the possibility of hypoglycemia.

No significant pharmacokinetic interactions were observed with the concomitant use of the antacids cimetidine digoxin and furosemide.

How to take, course of use and dosage

The drug is administered by deep intramuscular injection. The drug should not be administered intravenously.

Osteoarthritis with pain syndrome: 75 mg per day. If necessary, this dose can be increased to 15 mg per day.

Rheumatoid arthritis: 15 mg per day. Depending on the therapeutic effect, this dose can be reduced to 75 mg per day.

Ankylosing spondylitis: 15 mg daily. Depending on the therapeutic effect, this dose can be reduced to 75 mg per day.

In patients with an increased risk of adverse reactions (gastrointestinal diseases in the anamnesis, the presence of risk factors for cardiovascular diseases), it is recommended to start treatment with a dose of 75 mg per day.

In patients with severe renal insufficiency who are on hemodialysis, the dose should not exceed 75 mg per day.

General recommendations

Since the potential risk of adverse reactions depends on the dose and duration of treatment, the lowest possible dose and duration of use should be used.

The maximum recommended daily dose is 15 mg.

Combined use

Do not use the drug simultaneously with other NSAIDs.

The total daily dose of Meloxicam used in various dosage forms should not exceed 15 mg.

Intramuscular use of the drug is indicated only during the first 2-3 days of therapy. Further treatment is continued with the use of oral dosage forms. The recommended dose is 75 mg or 15 mg once a day, depending on the intensity of pain and the severity of the inflammatory process.

Due to possible incompatibilities, the drug should not be mixed in the same syringe with other medications.

Overdose

Symptoms: nausea vomiting epigastric pain gastrointestinal bleeding acute renal failure liver failure respiratory arrest asystole lethargy drowsiness changes in blood pressure comatose state convulsions cardiovascular collapse cardiac arrest anaphylactoid reactions.

Treatment: there is no specific antidote. In case of overdose of the drug, conduct symptomatic therapy. Forced diuresis alkalinization of urine hemodialysis – ineffective due to the high binding of the drug to blood proteins.

Special instructions

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

Gastrointestinal ulcers perforation or bleeding may occur during the course of NSAID use at any time, either in the presence of alarming symptoms or in the absence of a history of serious gastrointestinal complications.

The consequences of these complications are generally more serious in the elderly.

When using the drug, such serious skin reactions as exfoliative dermatitis Stevens-Johnson syndrome toxic epidermal necrolysis may develop. Therefore special attention should be paid to patients who report the development of adverse events from the skin and mucous membranes as well as hypersensitivity reactions to the drug especially if such reactions were observed during previous courses of treatment. The development of such reactions is usually observed during the first month of treatment. If the first signs of skin rash, mucosal changes or other signs of hypersensitivity appear, discontinuation of the drug should be considered.

When taking NSAIDs, cases of increased risk of developing serious cardiovascular thrombosis, myocardial infarction, angina attack, possibly with a fatal outcome, have been described. 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 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 latent renal failure. After NSAID withdrawal, renal function usually returns to its original level.Elderly patients are most at risk of developing this reaction; patients with dehydration, chronic heart failure, cirrhosis of the liver, nephrotic syndrome or acute renal function disorders; patients who are simultaneously taking diuretics, angiotensin-converting enzyme inhibitors, angiotensin-II receptor antagonists, and patients who have undergone serious surgical interventions that lead to hypovolemia. In such patients, diuresis and renal function should be carefully monitored at the beginning of therapy. The use of NSAIDs in combination with diuretics can lead to a delay in sodium potassium and water, as well as to a decrease in the natriuretic effect of diuretics. As a result, predisposed patients may have increased signs of heart failure or hypertension. Therefore, the condition of such patients should be carefully monitored 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.

When using meloxicam (as well as most other NSAIDs), an episodic increase in serum transaminase activity or other indicators of liver function may occur. In most cases, this increase was small and transient. If the detected changes are significant or do not decrease over time, the drug should be discontinued and the detected laboratory changes should be monitored. Debilitated or emaciated patients may have a worse tolerance for adverse events, and such patients should be carefully monitored.

Like other NSAIDs, meloxicam can mask the symptoms of an underlying infectious disease.

The use of meloxicam as well as other drugs that block cyclooxygenase and prostaglandin synthesis can affect fertility, so it is not recommended for women who want to become pregnant. If the ability to conceive in women is impaired or an infertility test is performed, you should consider canceling meloxicam.

In patients with mild or moderate renal insufficiency (creatinine clearance greater than 25 ml/min), no dose adjustment is required.

In patients with cirrhosis of the liver (compensated), no dose adjustment is required.

In patients with a hip replacement, injections should be given in the other buttock.

As a drug that inhibits cyclooxygenase/prostaglandin synthesis, meloxicam may affect fertility and is therefore not recommended for women who have difficulty conceiving. In this regard, in women undergoing examination for this reason, it is recommended to cancel meloxicam.

Influence on the ability to drive vehicles and mechanisms:

Special clinical studies of the effect of the drug on the ability to drive a car and mechanisms have not been conducted. However, when driving a car and working with mechanisms, you should take into account the possibility of developing dizziness, drowsiness, visual disturbances or other disorders of the central nervous system. Patients should be careful when driving a car and operating mechanisms.

Storage conditions

In a dark place at a temperature not exceeding 25 °C.

Do not freeze it.

Keep out of reach of children.

Shelf

life is 2 years.

Do not use after the expiration date.

Active ingredient

Meloxicam

Conditions of release from pharmacies

By prescription

Dosage form

solution for injection