Movasin, 10 mg/ml 1.5 ml 5 pcs.

NSAIDs. It has analgesic, anti-inflammatory and antipyretic effects. The mechanism of action is related to inhibition of prostaglandin synthesis as a result of selective inhibition of enzymatic activity of cyclooxygenase-2 (COX-2), which participates in biosynthesis of prostaglandins in inflammation area. When administered in high doses, prolonged use and individual characteristics of the body selectivity against COX-2 decreases.

It suppresses prostaglandin synthesis in the area of inflammation to a greater extent than in the gastric mucosa or kidneys, which is associated with relatively selective inhibition of COX-2. Less often causes erosive and ulcerative diseases of the gastrointestinal tract. To a lesser extent, meloxicam acts on cyclooxygenase-1 (COX-1), which is involved in the synthesis of prostaglandins that protect the gastrointestinal mucosa and are involved in the regulation of blood flow in the kidneys.

Pharmacokinetics

Intake

After oral administration of the drug meloxicam is well absorbed from the gastrointestinal tract, the absolute bioavailability is 89%. Concomitant use with food does not change absorption. Magnitude of meloxicam concentration when administered orally in doses of 7.5 and 15 mg is proportional to the dose.

The relative bioavailability is almost 100% after administration in m/m. After an oral dose of 5 mg, Cmax is 1.62 mcg/ml and is reached within approximately 60 min.

Meloxicam exhibits linear pharmacokinetics at doses of 7.5-15 mg when administered by injection.

Distribution

Css are achieved within 3-5 days of regular administration. With long-term use of the drug (more than 1 year), concentrations are similar to those observed after first achieving steady state pharmacokinetics. Binding to plasma proteins (especially albumin) is more than 99%.

The range of differences between maximal and basal concentrations of the drug after its administration once daily is relatively small and amounts to 0.4-1 mcg/ml with 7.5 mg dose and 0.8-2 mcg/ml with 15 mg dose (Cmin and Cmax values are given, respectively).

Meloxicam penetrates the histohematic barriers, the concentration in synovial fluid reaches 50% of the maximum concentration of the drug in plasma.

The Vd is low and is 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 value) is formed by oxidation of the intermediate metabolite 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, CYP3A4 isoenzyme has additional importance. Peroxidase, the activity of which probably varies individually, is involved in the formation of the other two metabolites (constituting, respectively, 16% and 4% of the value of the drug dose).

Extracted equally through the intestine and kidneys, mainly as metabolites. Less than 5% of the daily dose is excreted unchanged in the intestine, the drug is detected only in trace amounts in the urine. T1/2 of meloxicam after oral administration is 15-20 hours, when administered by injection – 20 hours. Plasma clearance averages 8 ml/min.

Pharmacokinetics in special clinical cases

The drug clearance is decreased in elderly persons.

Hepatic or renal insufficiency of moderate severity have no significant effect on the pharmacokinetics of meloxicam.

Indications

Symptomatic therapy:

– osteoarthritis;

– rheumatoid arthritis;

– ankylosing spondylitis (Behterev’s disease).

Active ingredient

Composition

Active substance:

meloxicam – 10 mg,

Associates:

Sodium chloride,

glycine,

glycafurfural (tetraglycol),

p> poloxamer 188,

meglumine (meglumine),

sodium hydroxide,

water for injection.

How to take, the dosage

Intramuscularly. Intramuscular administration of Movasin is indicated only during the first 2-3 days. Later the treatment is continued with the use of oral forms (tablets).

Interaction

Simultaneous use with other NSAIDs (as well as with acetylsalicylic acid) increases the risk of erosive ulcerative lesions and bleeding from the gastrointestinal tract.

In concomitant use with hypotensive drugs, the effectiveness of the latter drugs may decrease.
Concomitant use with lithium preparations may lead to cumulation of lithium and increase its toxic effect (it is recommended to control the lithium concentration in the blood).

In concomitant use with methotrexate there is increased side effect of the latter on the hematopoietic system (risk of anemia and leukopenia, periodic control of total blood count is indicated).

Concomitant use with diuretics and with cyclosporine increases the risk of renal failure.
Concomitant use with intrauterine contraceptives may decrease the effectiveness of the latter.

In concomitant use with anticoagulants (heparin, ticlopidine, warfarin), antiaggregants (acetylsalicylic acid, clopidogrel), as well as with fibrinolytic drugs (streptokinase, fibrinolysin) the risk of bleeding increases (periodic monitoring of blood clotting is necessary).

Concomitant use with selective serotonin reuptake inhibitors increases the risk of gastrointestinal bleeding.

Special Instructions

Caution should be exercised when using the drug in patients with a history of peptic ulcer disease and duodenal ulcer, as well as in patients on anticoagulant therapy. These patients have an increased risk of gastrointestinal erosive-ulcer disease.

We should use the drug with caution and monitor renal function parameters when using in elderly patients, in patients with chronic heart failure with clinical manifestations, in patients with cirrhosis of liver as well as in patients with hypovolemia as a result of surgical interventions.

In patients with renal insufficiency, if the CKR is greater than 30 mL/min, no dosing adjustment is required.
In patients on dialysis, the dosage of the drug should not exceed 7.5 mg/day.

Patients taking diuretics and meloxicam simultaneously should take sufficient fluids.
If allergic reactions occurred during treatment (itching, skin rash, urticaria, photosensitization) it is necessary to consult a physician in order to decide on the question of stopping the use of the drug.

Meloxicam, like other NSAIDs, may mask symptoms of infectious diseases.
Use of meloxicam, as well as other drugs that block the synthesis of prostaglandins, may affect fertility, so it is not recommended for women planning to become pregnant.

Contraindications

– condition after coronary artery bypass grafting;

– decompensated heart failure;

– Complete or incomplete combination of bronchial asthma, recurrent nasal and paranasal sinus polyposis, and intolerance to acetylsalicylic acid and other NSAIDs (includingч. history);

– erosive-ulcerative changes of the mucous coat of the stomach or duodenum, active gastrointestinal bleeding;

– inflammatory bowel disease (ulcerative colitis, Crohn’s disease);

– Cerebrovascular bleeding or other bleeding;

– Significant liver failure or active liver disease;

– Chronic renal failure in non-dialysis patients (CKR less than 30 ml/min), advanced renal disease (includingч.

– childhood under 12 years of age (for tablets);

– childhood under 18 years of age (for solution for intravenous administration);

– pregnancy;

– lactation (breastfeeding);

– hypersensitivity to meloxicam and other components of the drug.

The drug in tablet form contains lactose, so patients with rare hereditary diseases, such as galactose intolerance, lactase deficiency or glucose-galactose malabsorption, should not take the drug.

With cautiousness

– CHD;

– cerebrovascular disease;

– compensated heart failure;

p> – dyslipidemia/hyperlipidemia;

– diabetes mellitus;

– peripheral arterial disease;

– smoking;

– CKD 30-60 mL/min;

– history of gastrointestinal ulceration;

– presence of Helicobacter рylori infection;

– older age;

– prolonged use of NSAIDs;

– frequent alcohol use;

– severe somatic illness;

– concomitant therapy with the following medications: anticoagulants (e.g., warfarin); antiaggregants (e.g., acetylsalicylic acid, clopidogrel); oral GCS (e.g., prednisolone); selective serotonin reuptake inhibitors (e.g., citalopram, fluoxetine, paroxetine, sertraline).

In order to reduce the risk of gastrointestinal adverse events, the lowest effective dose should be used for the shortest possible course.

Side effects

Entestinal system: more than 1 % – dyspepsia, including nausea, vomiting, abdominal pain, constipation, flatulence, diarrhea; 0.1-1 % – transient increase of “liver” transaminases activity, hyperbilirubinemia, belching, esophagitis, gastroduodenal ulcer, GI bleeding (including latent bleeding).

The hemopoietic system: over 1% – anemia; 0.1-1% – blood count changes, including leukopenia, thrombocytopenia.

Skin: more than 1% – itching, skin rash, 0.1-1% – urticaria, less than 0.1% – photosensitization, bullous rashes, erythema multiforme, including Stevens-Johnson syndrome, toxic epidermal necrolysis.

Respiratory system: less than 0.1% – bronchospasm.

Central nervous system (CNS): more than 1% – dizziness, headache, 0.1-1% – vertigo, tinnitus, somnolence; less than 0.1% – confusion, disorientation, emotional lability.

Cardiovascular system (CVS): over 1% – peripheral edema; 0,1-1% – increase of blood pressure (BP), palpitation, “rushes” of blood to the skin.

Urinary system: 0.1-1 % – hypercreatininemia and/or increased serum urea, less than 0.1% – acute renal failure, the relationship with meloxicam usage is not determined – interstitial nephritis, albuminuria, hematuria.

Sensory organs: less than 0.1% – conjunctivitis, visual disturbances, including blurred vision.

Allergic reactions: less than 0.1% – angioedema, anaphylactic/anaphylactoid reactions.

Local reactions: more than 1 % – swelling at the injection site; less than 1 % – painful sensations at the injection site

Overdose

Symptoms: impaired consciousness, nausea, vomiting, epigastric pain, gastrointestinal bleeding, acute renal failure, liver failure, respiratory arrest, asystole.

Treatment: no specific antidote; symptomatic therapy. Forced diuresis, urine alkalinization, hemodialysis are ineffective due to high binding of the drug to blood proteins.

Similarities