Meloxicam, 10 mg/ml 1.5 ml 5 pcs

Pharmacotherapeutic group

Non-steroidal 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. Anti-inflammatory effect is associated with inhibition of enzymatic activity of cyclooxygenase-2, which is involved in the biosynthesis of prostaglandins in the inflamed area. To a lesser extent meloxicam acts on cyclooxygenase – involved in the synthesis of prostaglandin which protects the mucous membrane of gastrointestinal tract (GIT) and is involved in the regulation of blood flow in the kidneys.

Pharmacokinetics:

Absorption

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

Distribution

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

Metabolism

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

The drug is excreted equally in the feces and urine, mainly as metabolites. Less than 5% of daily dose is excreted unchanged in feces, and only trace amounts of the drug are detected in urine. The average half-life of meloxicam is 20 hours. Plasma clearance averages 8 ml/min.

Hepatic and/or renal insufficiency

Hepatic insufficiency and mild to moderate renal insufficiency have no significant effect on the pharmacokinetics of meloxicam. In terminal renal failure, increased volume of distribution may lead to higher concentrations of free meloxicam; therefore, in patients with hepatic and/or renal insufficiency the daily dose should not exceed 75 mg.

Elderly patients

In elderly patients, average plasma clearance during equilibrium pharmacokinetics is slightly lower than in younger patients.

Indications

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

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

Pharmacological effect

Pharmacotherapeutic group

Nonsteroidal anti-inflammatory drug (NSAID)

ATX code

M01AC06

Pharmacodynamics:

Meloxicam is a non-steroidal anti-inflammatory drug with analgesic, anti-inflammatory and antipyretic effects. Belongs to the class of oxicams, derivatives of enolic acid. The anti-inflammatory effect is associated with inhibition of the enzymatic activity of cyclooxygenase-2 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

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

Distribution

Meloxicam binds well to plasma proteins, especially albumin (99%). Penetrates into synovial fluid; the concentration in synovial fluid is approximately 50% of the plasma concentration of the drug. The distribution volume is low at 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 5′-carboxymeloxicam (60% of the dose) is formed by oxidation of the intermediate metabolite C 5′-hydroxymethylmeloxicam, which is also excreted but 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; the CYP3A4 isoenzyme plays an additional role. Peroxidase, whose activity probably varies individually, takes part in the formation of the other two metabolites (constituting 16% and 4% of the drug dose, respectively).

Removal

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

Insufficiency of liver and/or kidney function

Insufficiency of liver function as well as mild or moderate renal failure does not have a significant effect on the pharmacokinetics of meloxicam. In end-stage renal failure, an increase in the volume of distribution may lead to higher concentrations of free meloxicam; therefore, in patients with impaired liver and/or renal function, the daily dose should not exceed 7.5 mg.

Elderly patients

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

Special instructions

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

Gastrointestinal ulcers, perforation or bleeding can occur during the use of NSAIDs at any time, either in the presence of warning symptoms or a history of serious gastrointestinal complications or in the absence of these signs.

The consequences of these complications are generally more serious in older people.

When using the drug, serious skin reactions such as exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis may develop. Therefore, special attention should be paid to patients reporting 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 a skin rash, changes in the mucous membranes or other signs of hypersensitivity appear, discontinuation of the drug should be considered.

When taking NSAIDs, cases of an increased risk of developing serious cardiovascular thrombosis, myocardial infarction, and an attack of angina pectoris have been described, possibly with a fatal outcome. This risk increases with long-term use of the drug, as well as in patients with a history of the above diseases and those 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 discontinuation of NSAIDs, renal function usually returns to baseline levels. Elderly patients are most at risk of developing this reaction; patients who have dehydration, chronic heart failure, cirrhosis of the liver, nephrotic syndrome or acute renal dysfunction; patients simultaneously taking diuretics, angiotensin-converting enzyme inhibitors, angiotensin-II receptor antagonists, as well as patients who have undergone major surgical interventions that lead to hypovolemia. In such patients, diuresis and renal function should be carefully monitored when initiating therapy. The use of NSAIDs in combination with diuretics can lead to sodium, potassium and water retention, as well as a decrease in 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 must be maintained. Before starting treatment, a kidney function test is necessary.

In case of combination therapy, renal function should also be monitored.

When using meloxicam (as well as most other NSAIDs), episodic increases in serum transaminase activity or other indicators of liver function are possible. In most cases, this increase was small and transitory. 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. Weakened or malnourished patients may be less able to tolerate adverse events and such patients should be monitored closely.

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

The use of meloxicam, like other drugs that block cyclooxygenase and prostaglandin synthesis, can affect fertility and is therefore not recommended for women wishing to become pregnant. If the ability to conceive in women is impaired or when undergoing examination for infertility, it is necessary to consider discontinuing meloxicam.

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

In patients with liver cirrhosis (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 have an effect on fertility and is therefore not recommended for women who have difficulty conceiving. In this regard, it is recommended to discontinue meloxicam in women undergoing examination for this matter.

Impact on the ability to drive vehicles. Wed and fur.:

No special clinical studies have been conducted on the effect of the drug on the ability to drive a car or use machinery. However, when driving a car and working with machinery, one should take into account the possibility of developing dizziness, drowsiness, visual impairment or other disorders of the central nervous system. Patients should be careful when driving a car and operating machinery.

Active ingredient

Meloxicam

Composition

1 ml of solution contains:

active substances:

meloxicam 10.00 mg/ml

excipients:

glycine (aminoacetic acid),

macrogol (polyethylene glycol 400),

meglumine (N-methyl-D-glucamine),

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

1,2 – propylene glycol,

sodium hydroxide,

water for injections.

Pregnancy

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

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

Contraindications

– Hypersensitivity to the active substance 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, angioedema or urticaria caused by intolerance to acetylsalicylic acid or other NSAIDs due to the existing likelihood of cross-sensitivity (including a history);

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

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

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

– severe liver failure or active liver disease;

– severe renal failure (if hemodialysis is not performed, creatinine clearance is less than 30 ml/min) progressive kidney disease, including confirmed hyperkalemia;

– severe uncontrolled heart failure;

– therapy of perioperative pain during coronary artery bypass surgery;

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

– pregnancy;

– breastfeeding period;

– age up to 18 years.

With caution:

– History of gastrointestinal (GIT) diseases (presence of Helicobacter pylori infection); peptic ulcer of the stomach and duodenum;

– chronic heart failure;

– coronary heart disease;

– arterial hypertension;

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

– progressive liver diseases, hyperbilirubinemia, liver failure;

– cerebrovascular diseases;

– dyslipidemia/hyperlipidemia;

– diabetes mellitus;

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

– bronchial asthma tuberculosis severe osteoporosis;

– diseases of peripheral arteries;

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

– long-term use of NSAIDs;

– smoking;

– frequent alcohol consumption.

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

Side Effects

The incidence of side effects is classified according to the recommendations of the World Health Organization and is characterized as: very often (≥ 1/10) often (≥ 1/100 < 1/10) infrequently (≥ 1/1000 < 1/100) rarely (≥ 1/10000 < 1/1000) very rarely (< 1/10000) not established.

Blood and lymphatic system disorders:

infrequently – anemia; rarely – leukopenia thrombocytopenia changes in the number of blood cells including changes in the leukocyte formula.

Immune system disorders:

uncommon – other immediate hypersensitivity reactions; not established – anaphylactic shock, anaphylactoid reactions.

Mental disorders:

rarely – mood changes; not established – confusion, disorientation.

Nervous system disorders:

often – headache; infrequently – dizziness, drowsiness.

Visual, hearing and labyrinthine disorders:

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

Disorders of the heart and blood vessels:

infrequently – increased blood pressure, a feeling of a “rush” of blood to the face; rarely – a feeling of palpitations.

Respiratory system disorders:

rarely – bronchial asthma in patients with allergies to acetylsalicylic acid and other NSAIDs.

Gastrointestinal disorders:

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

Disorders of the liver and biliary tract:

infrequently – transient changes in liver function indicators (for example, increased activity of transaminases or bilirubin); very rarely – hepatitis.

Disorders of the skin and subcutaneous tissues:

uncommon – 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:

uncommon – changes in renal function (increased levels of creatinine and/or urea in the blood serum), urinary disturbances including acute urinary retention; very rarely – acute renal failure.

Disorders of the genital organs 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 – swelling.

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, the possibility of interstitial nephritis, glomerulonephritis, renal medullary necrosis, nephrotic syndrome cannot be excluded.

Interaction

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

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

Antiplatelet drugs are serotonin reuptake inhibitors. Concomitant use with meloxicam increases the risk of bleeding due to inhibition of platelet function. In case of simultaneous use, careful monitoring of the blood coagulation system is necessary.

Lithium preparations. NSAIDs increase plasma lithium levels by decreasing renal excretion. The simultaneous use of meloxicam with lithium preparations is not recommended. If simultaneous use is necessary, careful monitoring of plasma lithium concentrations is recommended throughout the course of lithium use.

Methotrexate. NSAIDs reduce the secretion of methotrexate by the kidneys, 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. In case of simultaneous use, careful monitoring of renal function and blood count is necessary. Meloxicam may increase the hematological toxicity of methotrexate, especially in patients with impaired renal function.

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

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

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

Angiotensin II receptor antagonists. When used together with NSAIDs, they increase the decrease in glomerular filtration, which can thereby lead to the development of acute renal failure, especially in patients with impaired renal function.

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

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

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

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

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

With the simultaneous use of the antacids cimetidine digoxin and furosemide, no significant pharmacokinetic interactions were identified.

Overdose

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

Treatment: there is no specific antidote. In case of drug overdose, carry out symptomatic therapy. Forced diuresis, alkalization of urine, hemodialysis – are ineffective due to the high connection of the drug with blood proteins.

Storage conditions

In a place protected from light at a temperature not exceeding 25 ° C.

Do not freeze.

Keep out of the reach of children.

Shelf life

2 years.

Do not use after expiration date.

Manufacturer

LLC B-Pharm/Kursk biofactory-firm Biok, Russia