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

Composition

Active ingredient:

Meloxicam – 10,000 mg

Auxiliary substances:

glycofural (tetraglycol) – 100,000 mg

poloxamer 188-50,000 mg

meglumine-6,250 mg

glycine-5,000 mg

sodium chloride-3,000 mg

sodium hydroxide-0.152 mg

water for injection-up to 1 ml

Pharmacological action

Pharmacodynamics

Meloxicam is a nonsteroidal anti-inflammatory drug that has 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 inflammatory region. To a lesser extent, meloxicam acts on cyclooxygenase-1, which is involved in the synthesis of prostaglandin, which protects the mucous membrane of the gastrointestinal tract (GIT) and is involved in the regulation of blood flow in the kidneys.

Pharmacokinetics

Absorption rate

The 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 (With_max) is 1.62 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,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 the CYP2C9 isoenzyme plays an important role in this metabolic transformation, while the CYP3A4 isoenzyme plays an additional role. 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 faeces and urine, mainly in the form of metabolites. In unchanged form, less than 5% of the daily dose is excreted in the feces, and 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, an increase in the volume of distribution may lead to higher concentrations of free meloxicam, so in patients with hepatic and/or renal insufficiency, the daily dose should not exceed 7.5 mg.

Elderly patients

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

Indications

Initial therapy and short-term symptomatic treatment for osteoarthritis (osteoarthritis, degenerative diseases of the joints), 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, 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 penetrate into breast milk, so meloxicam is not recommended for use during breast-feeding.

Contraindications

– hypersensitivity to the Active ingredient or auxiliary components of the drug, 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 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 disease, 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

– A history of gastrointestinal diseases (presence of Helicobacter pylori infection);

– chronic heart failure;

– coronary heart disease;

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

– cerebrovascular diseases;

– dyslipidemia/hyperlipidemia;

– diabetes mellitus;

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

– bronchial asthma, tuberculosis, severe osteoporosis;

– peripheral artery diseases;

– elderly age;

– 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 changes; not established-confusion, disorientation.

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

Visual, hearing and labyrinth 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 “rush” of blood to the face; rarely-a feeling of palpitation.

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

Gastrointestinal disorders: 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 indicators (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 rarely-bullous dermatitis, erythema multiforme; not established – photosensitization.

Renal 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 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, and nephrotic syndrome is not excluded.

Interaction

Other prostaglandin synthesis inhibitors, including glucocorticoids and salicylates. Simultaneous administration 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 administration, 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, serotonin reuptake inhibitors. Concomitant administration 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 may 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, which have vasodilating properties.

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

Colestyramine binds meloxicam in the gastrointestinal tract, leading 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 administration. If there is a need for the combined use of meloxicam and pemetrexed, then 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 administration (for example, sulfonylureas, 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 sulfonylureas or nateglinide should carefully monitor their blood sugar levels due to the possibility of hypoglycemia.

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

How to take, course of administration and dosage

The drug is administered by deep intramuscular injection.

The drug should not be administered intravenously.

Osteoarthritis with pain syndrome: 7.5 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 7.5 mg per day.

Ankylosing spondylitis: 15 mg daily. Depending on the therapeutic effect, this dose can be reduced to 7.5 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 7.5 mg per day.

In patients with severe renal insufficiency who are on hemodialysis, the dose should not exceed 7.5 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 different dosage forms should not exceed 15 mg.

Intramuscular administration of the drug is indicated only during the first few days of therapy. Further treatment is continued with the use of oral dosage forms. The recommended dose is 7.5 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, coma, convulsions, cardiovascular collapse, cardiac arrest, anaphylactoid reactions.

Treatment: no specific antidote. In case of overdose of the drug, conduct symptomatic therapy. Forced diuresis, urine alkalinization, and hemodialysis are 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, perforations, or bleeding may occur during the course of NSAID use at any time, whether there are alarming 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 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, changes in the mucous membranes 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, and 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 together with diuretics can lead to sodium, potassium and water retention, 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 not tolerate adverse events as well, 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.

Influence on the ability to drive vehicles and mechanisms

During treatment, due to possible side effects from the cardiovascular and nervous systems, care should be taken when driving vehicles and engaging in other potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions.

Storage conditions

Store in a dark place at a temperature not exceeding 25 °C.

Keep out of the reach of children.

Shelf

life is 2 years.

Active ingredient

Meloxicam

Conditions of release from pharmacies

By prescription

Dosage form

solution for injection

Weight

Weight: 12 gr.