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 when 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 has no effect on the progression of the disease.

Short-term symptomatic therapy in osteoarthritis (arthrosis degenerative joint disease) rheumatoid arthritis ankylosing spondylitis other inflammatory and degenerative diseases of the musculoskeletal system such as arthropathies dorsopathies (e.g. sciatica lower back pain shoulder periarthritis and others) accompanied by pain.

Active ingredient

Composition

1 ml of the solution contains:

active ingredients:

meloxicam 10.00 mg/mL

excipients:

glycine (aminoacetic acid),

macrogol (polyethylene glycol 400),

meglumine (N-methyl-D-glucamine),

/p>

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

1,2 – propylene glycol,

sodium hydroxide,

water for injection.

How to take, the dosage

The drug is administered by deep intramuscular injection. The drug should not be given 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 may be reduced to 75 mg per day

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

In patients with an increased risk of adverse reactions (history of gastrointestinal disease, presence of cardiovascular risk factors, it is recommended to start treatment with a dose of 75 mg per day.

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

General recommendations

Because 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

The drug should not be used concomitantly with other NSAIDs.

The total daily dose of Meloxicam used in different dosage forms must not exceed 15 mg.

Intramuscular administration of the drug is indicated only during the first 2-3 days of therapy. Thereafter, 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.

With regard to possible incompatibilities, the drug should not be mixed in the same syringe with other medicinal products.

Interaction

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

Anticoagulants for oral heparin for systemic use thrombolytic agents. Simultaneous use with meloxicam increases the risk of bleeding. In case of concomitant use, close monitoring of the clotting system is necessary.

The antiplatelet drugs serotonin reuptake inhibitors. Simultaneous use with meloxicam increases the risk of bleeding due to inhibition of platelet function. In case of concomitant use, close monitoring of the clotting 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, it is recommended to carefully monitor the concentration of lithium in plasma throughout the course of use of lithium drugs.

Methotrexate. NSAIDs decrease renal secretion of methotrexate, thereby increasing its plasma concentrations. Simultaneous use of meloxicam and methotrexate (in dose more than 15 mg per week) is not recommended. In case of concomitant use, careful monitoring of renal function and blood counts is required. Meloxicam may increase 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: Because of the theoretical risk of prostaglandin inhibitors altering mifepristone’s effectiveness, NSAIDs should not be used more than 8-12 days after mifepristone withdrawal.

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

Antihypertensives (beta-adrenoblockers angiotensin-converting enzyme inhibitors vasodilators diuretics). NSAIDs reduce the effect of antihypertensive drugs due to inhibition of prostaglandins with vasodilatory properties.

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

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

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

NSAIDs acting on renal prostaglandins may increase nephrotoxicity of cyclosporine.

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

In co-administration with antidiabetic agents for oral administration (e.g. sulfonylurea derivatives nateglinide) CYP2C9-mediated interactions are possible that can lead to increased blood concentrations of both these drugs and meloxicam. Patients concomitantly taking meloxicam with sulfonylurea or nateglinide should carefully monitor blood sugar levels due to the possibility of hypoglycemia.

No significant pharmacokinetic interactions have been found with cimetidine digoxin and furosemide concomitantly.

Special Instructions

Patients suffering from gastrointestinal diseases should be monitored regularly. If gastrointestinal ulceration or gastrointestinal bleeding occurs, the drug should be discontinued.

Gastrointestinal ulcers or bleeding can occur during use of NSAIDs at any time, with or without a history of suspicious symptoms or serious gastrointestinal complications.

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

Serious skin reactions such as exfoliative dermatitis Stevens-Johnson syndrome toxic epidermal necrolysis may develop when using the drug. Therefore, special attention should be paid to patients who report the development of adverse reactions of the skin and mucous membranes and hypersensitivity to the drug, especially if such reactions have been observed during the previous course of treatment. The development of such reactions is usually observed during the first month of treatment. In case of the first signs of skin rash, mucous membrane changes or other signs of hypersensitivity the discontinuation of the drug should be considered.

In cases of increased risk of serious cardiovascular thrombosis of myocardial infarction with possible fatal angina attack have been described when taking NSAIDs. This risk increases with long-term use of the drug, as well as in patients with a history of the above diseases and predisposition to such diseases. NSAIDs inhibit in the kidneys the synthesis of prostaglandins that are involved in maintaining renal perfusion. 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 recovers to baseline levels. Elderly patients; patients with dehydration, chronic heart failure, cirrhosis, nephrotic syndrome, or acute renal impairment; patients taking diuretics concomitantly angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists; and patients undergoing major surgical interventions that cause hypovolemia are at highest risk for this reaction. In such patients, diuresis and renal function should be carefully monitored at the beginning of therapy. The use of NSAIDs in conjunction with diuretics may lead to retention of sodium, potassium and water, as well as to a decrease in the natriuretic effect of diuretics. As a result, in predisposed patients there may be increased signs of heart failure or hypertension. Therefore, close monitoring of such patients is necessary and adequate hydration should be maintained. Prior to initiation of treatment renal function investigation is necessary.

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

When using meloxicam (as well as most other NSAIDs) there may be occasional increases in serum transaminase activity or other indicators of liver function. In most cases, these increases were small and transient. If the changes detected are significant or do not decrease with time, the drug should be discontinued and the laboratory changes detected should be monitored. Weakened or debilitated patients may have a worse tolerance to adverse events, so these patients should be closely monitored.

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

The use of meloxicam as well as other drugs that block cyclooxygenase and prostaglandin synthesis may affect fertility so it is not recommended for women who want to get pregnant. Meloxicam should be considered for withdrawal if women have impaired ability to conceive or are being evaluated for infertility.

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

In patients with cirrhosis (compensated) no dose adjustment is required.

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

As a drug which inhibits the synthesis of cyclooxygenase/prostaglandin, meloxicam can affect fertility and therefore is not recommended for women with difficulties in conception. Therefore, in women undergoing examination for this reason it is recommended to cancel meloxicam.

Special clinical studies on the effect of the drug on the ability to operate vehicles and mechanisms have not been conducted. However, when driving or operating machinery, the possibility of dizziness, drowsiness, visual disturbances or other central nervous system disorders should be taken into account. Patients should exercise caution when driving and operating machinery.

Contraindications

– Hypersensitivity to the active substance or excipients of the drug to acetylsalicylic acid and other NSAIDs;

– Complete or incomplete combination of bronchial asthma with recurrent nasal and paranasal sinus polyposis angioedema or urticaria caused by intolerance to acetylsalicylic acid or other NSAIDs due to possible cross-sensitivity (including history);

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

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

– active gastrointestinal bleeding – recent history of cerebrovascular bleeding or established diagnosis of blood clotting disorders;

– severe hepatic insufficiency or active liver disease;

– severe renal failure (unless hemodialysis is performed with a creatinine clearance of less than 30 mL/min) progressive renal disease including confirmed hyperkalemia;

– significant uncontrolled heart failure;

– therapy for perioperative pain during coronary artery bypass grafting;

– concomitant therapy with anticoagulants because of the risk of intramuscular hematomas;

– pregnancy;

– breastfeeding period;

– age less than 18 years.

– Diseases of the gastrointestinal tract (GIT) in the history (presence of Helicobacterpylori infection); gastric and 12 duodenal ulcers;

– chronic heart failure;

– coronary heart disease;

– arterial hypertension;

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

– progressive liver disease hyperbilirubinemia liver failure;

– cerebrovascular disease;

– dyslipidemia/hyperlipidemia;

– diabetes mellitus;

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

– Bronchial asthma – Tuberculosis – Severe osteoporosis;

– Peripheral artery disease;

– Elderly patients (>65 years) (including those on diuretics).

– long-term use of NSAIDs;

-smoking;

– frequent alcohol use.

To reduce the risk of gastrointestinal (GI) adverse events, the lowest effective dose should be used for the shortest possible course.

Side effects

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

Disorders of the blood and lymphatic system:

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

Disorders of the immune system:

infrequent – other immediate-type hypersensitivity reactions; not established – anaphylactic shock anaphylactoid reactions.

Mental disorders:

rarely – change in mood; not established – confusion disorientation.

Nervous system disorders:

often – headache; infrequent – dizziness drowsiness.

Hearing and labyrinth disorders:

infrequent – vertigo; rare – conjunctivitis visual disturbances including blurred vision tinnitus.

Cardiovascular disorders:

infrequent – increase of blood pressure – feeling of “rush” of blood to the face; rare – feeling of palpitation.

Respiratory system disorders:

Rarely, bronchial asthma in patients allergic to acetylsalicylic acid and other NSAIDs.

Gastrointestinal disorders:

often – abdominal pain dyspepsia diarrhea nausea vomiting; infrequent – latent and overt gastrointestinal bleeding gastritis stomatitis constipation bloating belching; rare – gastroduodenal ulcers colitis esophagitis; very rare – gastrointestinal tract perforation.

Hepatic and biliary tract disorders:

frequent – transient changes in liver function parameters (e.g., increased transaminases or bilirubin activity); very rare – hepatitis.

Skin and subcutaneous tissue disorders:

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

Renal and urinary tract disorders:

frequent – change of renal function parameters (increased serum creatinine and/or urea levels) urinary disorders including acute urinary retention; very rare – acute renal failure.

Gender and mammary gland disorders:

infrequent – late ovulation; not established – infertility in women.

General disorders and disorders at the site of administration:

often – pain and swelling at the injection site; infrequent – edema.

The concomitant use with drugs that suppress bone marrow (e.g., methotrexate) may provoke cytopenia. Gastrointestinal bleeding ulcers or perforations can be fatal.

As with other NSAIDs, do not rule out the possibility of interstitial nephritis glomerulonephritis renal medullary necrosis nephrotic syndrome.

Overdose

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

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

Pregnancy use

The drug is contraindicated during pregnancy. The safety of using this drug during pregnancy has not been proven. The effect of inhibition of 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 by premature closure of Ductus arteriosus Botalli in fetus and increased susceptibility to bleeding in mother and child and increased risk of edema in mother.

It is known that NSAIDs penetrate into breast milk so meloxicam is not recommended during breastfeeding.

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