Movalis, 15 mg/1.5 ml 1.5 ml 5 pcs.

Movalis is a non-steroidal anti-inflammatory drug, refers to enolic acid derivatives and has anti-inflammatory, analgesic and antipyretic effects. The pronounced anti-inflammatory effect of meloxicam was established in all standard models of inflammation. The mechanism of action of meloxicam is its ability to inhibit the synthesis of prostaglandins – known mediators of inflammation.

In vivo meloxicam inhibits prostaglandin synthesis at the site of inflammation to a greater extent than in the gastric mucosa or kidney.
These differences are due to more selective inhibition of cyclooxygenase-2 (COX-2) compared to cyclooxygenase-1 (COX-1). Inhibition of COX-2 is thought to provide the therapeutic effect of NSAIDs, whereas inhibition of the ever-present COX-1 isoenzyme may cause gastric and renal side effects.

The selectivity of meloxicam against COX-2 has been confirmed in various test systems, both in vitro and ex vivo. The selective ability of meloxicam to inhibit COX-2 was shown when using human whole blood as a test system in vitro. Ex vivo, meloxicam (at doses of 7.5 and 15 mg) was found to be more active in inhibiting COX-2, having a greater inhibitory effect on lipopolysaccharide-stimulated prostaglandin E2 production (COX-2-controlled response) than on thromboxane production involved in blood clotting (COX-1-controlled response). These effects were dose-dependent. Ex vivo, meloxicam at the recommended doses was shown to have no effect on platelet aggregation and bleeding time, in contrast to indomethacin, diclofenac, ibuprofen and naproxen, which significantly inhibited platelet aggregation and increased bleeding time.

In clinical trials, gastrointestinal (GI) side effects were generally less frequent with meloxicam 7.5 and 15 mg than with the other NSAIDs compared. This difference in the frequency of gastrointestinal side effects is mainly due to the fact that such phenomena as dyspepsia, vomiting, nausea, and abdominal pain were observed less frequently while taking meloxicam. The frequency of upper gastrointestinal perforations, ulcers and bleeding associated with the use of meloxicam was low and depended on the size of the dose of the drug.

Pharmacokinetics:

Meloxicam is completely absorbed after intramuscular administration. The relative bioavailability compared to the bioavailability with oral administration is almost 100%. Therefore, no dose adjustment is required when switching from injectable to oral forms. After administration of 15 mg of the drug intramuscularly, the peak plasma concentration of about 1.62 mcg/ml is reached within about 60 minutes.

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

Metabolism
Meloxicam is almost completely metabolized in the liver to form 4 pharmacologically inactive derivatives. 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 CYP 2C9 plays an important role in this metabolic transformation, CYP 3A4 isoenzyme has additional importance. Peroxidase, the activity of which probably varies individually, is involved in the formation of the other two metabolites (which are, respectively, 16% and 4% of the drug dose).

Elimation
It is excreted equally in the feces and urine, mainly as metabolites. Less than 5% of daily dose is excreted unchanged in feces, the drug is excreted unchanged in urine only in trace amounts. The average half-life of meloxicam is 20 hours. Plasma clearance averages 8 ml/min. Meloxicam exhibits linear pharmacokinetics at doses of 7.5 to 15 mg when administered orally or intramuscularly.

Hepatic and/or renal function deficiencies
Liver function deficiencies 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, so in these patients the daily dose should not exceed 7.5 mg.

Elderly patients
Elderly patients have slightly lower mean plasma clearance during steady state pharmacokinetics than younger patients.

Indications

The drug Movalis in dosage form solution for intramuscular injection is indicated for the initial treatment and short-term symptomatic therapy of pain syndrome in rheumatoid arthritis, osteoarthritis, ankylosing spondylitis.

Active ingredient

Composition

Active substance:

meloxicam15 mg;

Associates:

Meglumine;

Glycofurole;

Poloxamer 188 (Pluronic F68);

Sodium chloride;

Glycine;

Sodium hydroxide;

Injectable water.

How to take, the dosage

Intravenous administration of the drug is indicated only during the first 2-3 days of therapy. Subsequently the treatment is continued with enteral forms. The recommended dose is 7.5 mg or 15 mg once daily, depending on the intensity of pain and severity of the inflammatory process.

The maximum recommended daily dose is 15 mg.

The drug is administered by deep intravenous injection.

In view of possible incompatibilities, the contents of Movalis® ampoules should not be mixed with other medicinal products in the same syringe.

Kidney function disorders. In patients with severe renal impairment who are on hemodialysis, the dose should not exceed 7.5 mg/day.

The drug should not be administered intravenously.

Interaction

Other GH synthesis inhibitors, including GK and salicylates, when taken concomitantly with meloxicam increase the risk of gastrointestinal ulcers and bleeding (due to synergistic action) and therefore their combination is not recommended. Simultaneous use with other NSAIDs is not recommended.

SIOZS – increased risk of gastrointestinal bleeding.

Lithium drugs – NSAIDs increase plasma lithium concentrations by reducing renal excretion. It is recommended that lithium concentrations be monitored during the administration of Movalis®, when the dose of lithium drugs is changed and when they are withdrawn.

Methotrexate – NSAIDs decrease tubular secretion of methotrexate, thereby increasing its plasma concentrations and hematological toxicity, the pharmacokinetics of methotrexate is not altered. In this regard, concomitant administration of Movalis® and methotrexate in dose more than 15 mg/day is recommended. The risk of interaction between NSAIDs and methotrexate may also occur in patients using methotrexate in low doses, especially in patients with impaired renal function. Therefore, continuous monitoring of blood cell count and renal function is necessary.

The concomitant use of meloxicam had no effect on the pharmacokinetics of methotrexate at a dose of 15 mg per week, but it should be taken into account that the hematological toxicity of methotrexate is increased by concomitant administration of NSAIDs.

The co-administration of meloxicam and methotrexate for 3 days increases the risk of increased toxicity of the latter.

Contraception – NSAIDs reduce the effectiveness of intrauterine contraceptive devices.

Diuretics – the use of NSAIDs in patients who are dehydrated is accompanied by a risk of acute renal failure.

In patients receiving Movalis® and diuretics, adequate hydration must be maintained. Renal function should be investigated prior to initiation of treatment.

Antihypertensive agents (beta-adrenoblockers, ACE inhibitors, vasodilators, diuretics) – NSAIDs reduce the effect of antihypertensive agents, due to inhibition of GHG, which have vasodilatory properties.

Angiotensin II receptor antagonists when combined with NSAIDs increase decrease of glomerular filtration, which may lead to acute renal failure, especially in patients with impaired renal function. In case of combined therapy, renal function should be monitored.

The NSAIDs may increase the nephrotoxicity of cyclosporine by acting on renal GHGs.

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

The possibility of interaction with hypoglycemic drugs for oral administration cannot be excluded.

When concomitant use of antacids, cimetidine, digoxin and furosemide, no significant pharmacokinetic interactions have been found.

Special Instructions

Caution should be exercised (as with other NSAIDs) when treating patients with a history of gastrointestinal disorders. Patients with gastrointestinal symptoms should be monitored regularly. If gastrointestinal ulceration or gastrointestinal bleeding occurs, Movalis® should be discontinued.
As with other NSAIDs, gastrointestinal bleeding, ulcers and perforations potentially life-threatening to the patient may occur during treatment at any time, either with or without a history of warning symptoms or serious gastrointestinal complications.

The consequences of these complications are generally more serious in the elderly. Particular attention should be paid to patients who report developing skin and mucous membrane adverse events. In such cases, discontinuation of Movalis should be considered.

The NSAIDs inhibit in the kidneys the synthesis of prostaglandins, which are involved in maintaining renal perfusion. Use of NSAIDs in patients with decreased renal blood flow or reduced circulating blood volume may lead to decompensation of latent renal insufficiency. After discontinuation of NSAIDs, renal function usually returns to baseline.

The risk of developing this reaction is greatest in elderly patients; patients with dehydration, congestive heart failure, cirrhosis of the liver, nephrotic syndrome, or overt renal disease;
patients receiving diuretics, ACE inhibitors, angiotensin II receptor antagonists, as well as patients who have undergone serious surgical interventions leading to hypovolemia. Diuresis and renal function should be carefully controlled in such patients at the beginning of therapy.

In rare cases, NSAIDs may cause interstitial nephritis, glomerulonephritis, medullary renal necrosis, or nephrotic syndrome.
In patients with end-stage renal failure who are on hemodialysis, the dose of Movalis® should not exceed 7.5 mg. In patients with small or moderate renal dysfunction (ie, if creatinine clearance is more than 25 ml/min) dose reduction is not required.

When using Movalis® (as well as most other NSAIDs), occasional increases in serum levels of transaminases or other indicators of liver function have been reported. In most cases, these increases were small and transient. If the changes detected are significant or do not decrease over time, Movalis® should be discontinued and the laboratory changes detected should be monitored.

In patients with clinically stable cirrhosis, no dose reduction of the drug is required.

Weakened or debilitated patients may have a worse tolerance to adverse events, so these patients should be closely monitored. Caution (as with other NSAIDs) should be exercised when treating elderly patients who are more likely to have impaired renal, hepatic and cardiac function.

The use of NSAIDs together with diuretics may lead to retention of sodium, potassium and water, and affect the natriuretic effect of diuretics. As a result, in predisposed patients there may be increased signs of heart failure or hypertension.

Meloxicam, as well as other NSAIDs can mask the symptoms of infectious disease.

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

Special studies on the effect of the drug on the ability to drive vehicles and mechanisms have not been conducted. Patients with visual impairment and patients who have noted somnolence or other disorders of the central nervous system should be refrained from this activity.

Contraindications

Side effects

Hematopoietic organs: changes in the number of blood cells, including changes in the leukocytic formula, leukopenia, thrombocytopenia, anemia. A predisposing factor for the occurrence of cytopenias seems to be the simultaneous use of potentially myelotoxic drugs, in particular methotrexate.

Immune system disorders: anaphylactic shock, anaphylactoid/anaphylactic reactions, other immediate-type hypersensitivity reactions.

CNS disorders: headache, dizziness, tinnitus, drowsiness, confusion, disorientation, mood changes.

Gastrointestinal disorders: Gastrointestinal perforation, hidden or overt gastrointestinal bleeding, possibly fatal, gastroduodenal ulcers, colitis, gastritis, esophagitis, stomatitis, abdominal pain, dyspepsia, diarrhea, nausea, vomiting, constipation, bloating, belching, transient changes in liver function parameters (such as increased transaminase or bilirubin activity), hepatitis.

Skin and skin appendages: toxic epidermal necrolysis, Stevens-Johnson syndrome, angioedema, bullous dermatitis, erythema multiforme, pruritus, skin rash, urticaria, photosensitization.

Respiratory system disorders: bronchial asthma in patients with allergy to acetylsalicylic acid or other NSAIDs.

Systemic diseases: increase in blood pressure, palpitations, blood rush to the face, edema.

Urogenital system disorders: acute renal failure, changes in renal function (increased serum creatinine and/or serum urea levels), urinary disorders, including acute urinary retention.

Visual organs: conjunctivitis, visual disturbances, including blurred vision.

Overdose

The antidote is not known, in case of overdose of the drug should be carried out: gastric lavage and general supportive therapy.

In clinical studies it has been shown that cholestyramine accelerates excretion of meloxicam.

Similarities