Movalis, 1.5ml/15mg ampoules, 5pcs

Composition

Active ingredient:

meloxicam 15 mg;

Auxiliary substances:

meglumin;

glycofural;

poloxamer 188 (Pluronic F 68);

sodium chloride;

glycine;

sodium hydroxide;

water for injection

Pharmacological action

Movalis is a non-steroidal anti-inflammatory drug, belongs to the derivatives of enolic acid 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 kidneys. These differences are associated with more selective inhibition of cyclooxygenase-2 (COX-2) compared to cyclooxygenase-1 (COX-1). It is believed that COX-2 inhibition provides a therapeutic effect of NSAIDs, while inhibition of the constantly present COX-1 isoenzyme can cause side effects from the stomach and kidneys.

The selectivity of meloxicam for COX-2 was confirmed in various test systems, both in vitro and ex vivo. The selective ability of meloxicam to inhibit COX-2 has been shown when used as an in vitro human whole blood test system. Ex vivo studies showed that meloxicam (at doses of 7.5 and 15 mg) more actively inhibited COX-2, exerting a greater inhibitory effect on the production of prostaglandin E2 stimulated by lipopolysaccharide (COX-2 controlled reaction) than on the production of thromboxane involved in blood clotting (COX-1 controlled reaction). These effects were dose-dependent. Ex vivo studies showed that meloxicam at the recommended doses did not affect platelet aggregation and bleeding time, in contrast to Indometacin, diclofenac, ibuprofen and naproxen, which significantly suppressed platelet aggregation and increased bleeding time.

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

Pharmacokinetics:  

Meloxicam is completely absorbed after intramuscular use. The relative bioavailability compared to oral bioavailability is almost 100%. Therefore, when switching from injectable to oral forms, no dose adjustment is required. After use 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 albumin (99%). Penetrates the synovial fluid, the concentration in the synovial fluid is approximately 50% of the plasma concentration. The volume of distribution is low, with an average of 11 liters. Interindividual differences are 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), is formed by the oxidation of an intermediate metabolite,5’ – hydroxymethylmeloxicam, which is also excreted, but to a lesser extent (9% of the dose). In vitro studies have shown that CYP 2C9 plays an important role in this metabolic transformation, and the CYP 3A4 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.

Excretion 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. Meloxicam demonstrates linear pharmacokinetics at doses of 7.5 – 15 mg when taken orally or intramuscularly.

Hepatic insufficiency and / or renal insufficiency of liver function, as well as mild or moderate renal insufficiency, do not significantly affect the pharmacokinetics of meloxicam.

In end-stage renal failure, increased volume of distribution may lead to higher concentrations of free meloxicam, so the daily dose should not exceed 7.5 mg in these patients.

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

Indications

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

Contraindications

• Hypersensitivity;
• the symptoms of asthma, nasal polyps, angioedema or urticaria after ingestion of acetylsalicylic acid or other NSAIDs in history;
• peptic ulcer/perforation of stomach and duodenum in the acute stage or recently transferred;
• Crohn’s disease or ulcerative colitis in the acute stage;
• severe hepatic impairment;
• severe renal insufficiency (if not possible hemodialysis, Cl creatinine less than 30 ml/min, and when confirmed hyperkalemia), progressive kidney disease;
• acute gastrointestinal bleeding recent cerebrovascular bleeding or established diagnosis of diseases of the blood coagulation system;
• severe uncontrolled heart failure;
• therapy of perioperative pain in the conduct of bypass grafting of the coronary arteries.

Side effects

From the side of hematopoietic organs:  changes in the number of blood cells, including changes in the leukocyte formula, leukopenia, thrombocytopenia, and anemia. A predisposing factor for the occurrence of cytopenia seems to be the simultaneous use of potentially myelotoxic drugs, in particular methotrexate.

From the immune system:  anaphylactic shock, anaphylactoid / anaphylactic reactions, other immediate hypersensitivity reactions.

From the central nervous system:  headache, dizziness, tinnitus, drowsiness, confusion, disorientation, mood swings.

From the gastrointestinal tract:  gastrointestinal perforation, latent 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 indicators (for example, increased transaminase or bilirubin activity), hepatitis.

From the side of the 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 allergic to acetylsalicylic acid or other NSAIDs.

From the CCC side:  raising Blood pressure, palpitations, flushing of the face, swelling.

From the genitourinary system:  acute renal failure, changes in renal function indicators (increased serum creatinine and/or urea), urinary disorders, including acute urinary retention.

From the side of the visual organ:  conjunctivitis, visual disturbances, including blurred vision.

Interaction

Other PG synthesis inhibitors, including HA and salicylates, when taken concomitantly with meloxicam increase the risk of gastrointestinal ulceration and gastrointestinal bleeding (due to the synergy of action) and therefore their combination is not recommended. Concomitant use with other NSAIDs is not recommended.

SSRIs — increased risk of gastrointestinal bleeding.

Lithium preparations-NSAIDs increase the concentration of lithium in plasma, by reducing its excretion by the kidneys. It is recommended to monitor the concentration of lithium during the appointment of Movalis®, when changing the dose of lithium preparations and their cancellation.

Methotrexate-NSAIDs reduce the tubular secretion of methotrexate, thereby increasing its plasma concentration and hematological toxicity, while the pharmacokinetics of methotrexate do not change. In this regard, simultaneous use of Movalis® and methotrexate at a dose of more than 15 mg/week is not recommended. The risk of interaction between NSAIDs and methotrexate may also occur in patients using low-dose methotrexate, especially in patients with impaired renal function. Therefore, constant monitoring of the number of blood cells and kidney function is necessary.

Concomitant use of meloxicam did not affect 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 increases with simultaneous use of NSAIDs.

With the combined use of meloxicam and methotrexate for 3 days, the risk of increased toxicity of the latter increases.

Contraception-NSAIDs reduce the effectiveness of intrauterine contraceptive devices.

Diuretics-the use of NSAIDs in case of dehydration of patients is associated with the risk of acute renal failure.

Adequate hydration should be maintained in patients receiving Movalis and diuretics. Before starting treatment, a study of renal function is necessary.

Antihypertensive drugs (beta-blockers, ACE inhibitors, vasodilators, diuretics — – NSAIDs reduce the effect of antihypertensive drugs, due to the inhibition of PG, which has vasodilating properties.

Angiotensin II receptor antagonists, when co-administered with NSAIDs, increase the decrease in glomerular filtration, which can lead to the development of acute renal failure, especially in patients with impaired renal function. In the case of combination therapy, renal function should be monitored.

NSAIDs that affect the renal function PG, may increase the nephrotoxicity of cyclosporine.

When using drugs with meloxicam 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 use cannot be excluded.

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

How to take, course of use and dosage

of I / m use of the drug is indicated only during the first 2-3 days of therapy. In the future, treatment is continued with the use of enteral 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.

The maximum recommended daily dose is 15 mg.

The drug is administered by deep intravenous injection.

Due to possible incompatibilities, the contents of Movalis ampoules should not be mixed in the same syringe with other medications.

Impaired renal function. In patients with severe renal insufficiency undergoing hemodialysis, the dose should not exceed 7.5 mg / day.

The drug should not be administered intravenously.

Overdose

The antidote is not known, in case of overdose of the drug, gastric lavage and general maintenance therapy should be performed.

Clinical studies have shown that cholestyramine accelerates the elimination of meloxicam.

Special instructions

Caution should be exercised (as with other NSAIDs) in the treatment of patients with a history of gastrointestinal diseases. Patients with gastrointestinal symptoms should be monitored regularly. If ulcerative lesions of the gastrointestinal tract occur or gastrointestinal bleeding occurs, Movalis® should be discontinued. As with other NSAIDs, gastrointestinal bleeding, ulcers, and perforations that are potentially life-threatening may occur at any time during treatment, 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. Special attention should be paid to patients who report the development of adverse events from the skin and mucous membranes. In such cases, discontinuation of Movalis should be considered.

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, congestive heart failure, cirrhosis of the liver, nephrotic syndrome or obvious kidney disease;patients receiving diuretics, ACE inhibitors, angiotensin II receptor antagonists, as well as patients who have undergone serious surgical interventions leading to hypovolemia. In such patients, diuresis and renal function should be carefully monitored at the beginning of therapy.

In rare cases, NSAIDs can cause interstitial nephritis, glomerulonephritis, medullary renal necrosis, or nephrotic syndrome. In patients with end-stage renal failure undergoing hemodialysis, the dose of Movalis® should not exceed 7.5 mg. In patients with mild to moderate renal impairment (i. e., if creatinine clearance is greater than 25 ml/min), no dose reduction is required.

Episodic increases in serum transaminases or other liver function parameters have been reported when Movalis® is used (as with most other NSAIDs). In most cases, this increase was small and transient. If the detected changes are significant or do not decrease over time, Movalis® should be discontinued, and the detected laboratory changes should be monitored. In patients with clinically stable cirrhosis of the liver, no dose reduction is required.

Debilitated or emaciated patients may not tolerate adverse events as well, so such patients should be carefully monitored. Caution (as with other NSAIDs) should be exercised in the treatment of elderly patients who are more likely to have impaired renal, hepatic, and cardiac function.

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

Meloxicam, like other NSAIDs, can mask the symptoms of an infectious disease.

The use of meloxicam, as well as other drugs that block cyclooxygenase/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.

Special studies on the effect of the drug on the ability to drive vehicles and mechanisms have not been conducted. This activity should be avoided in patients with visual impairments, patients with drowsiness or other central nervous system disorders.

Form of production

Solution for intramuscular use

Storage conditions

In a dark place, at temperatures below 30 °C.

Shelf life

5 years

Active ingredient

Meloxicam

Conditions of release from pharmacies

By prescription

Dosage form

solution for injection

Purpose

For adults as prescribed by a doctor, Children over 15 years of age, Children as prescribed by a doctor

Indications

Rheumatoid Arthritis, Osteoarthritis, Osteoarthritis and Arthritis