Movalis - instructions for use, doses, side effects, contraindications

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

In vivo meloxicam inhibits the synthesis of prostaglandins at the site of inflammation to a greater extent than in the mucous membrane of the stomach or kidneys.

These differences are associated with a more selective inhibition of cyclooxygenase-2 (COX-2) compared to cyclooxygenase-1 (COX-1). It is believed that inhibition of COX-2 provides a therapeutic effect of NSAIDs, whereas inhibition of the constantly present isoenzyme COX-1 can cause side effects on the part of the stomach and kidneys.

The selectivity of meloxicam for COX-2 has been confirmed in various test systems, both in vitro and ex vivo. The selective ability of meloxicam to inhibit COX-2 is shown when using human whole blood in vitro as a test system. Ex vivo found that meloxicam more actively inhibited COX-2, having a greater inhibitory effect on the production of prostaglandin Eg, stimulated by lipopolysaccharide (a reaction controlled by COX-2) than by the production of thromboxane involved in the coagulation process (a reaction controlled by COX-1). These effects depended on the size of the dose. Ex vivo shows that meloxicam in recommended doses did not affect platelet aggregation and bleeding time, in contrast to indomethacin, diclofenac, ibuprofen and naproxen, which significantly suppressed platelet aggregation and increased bleeding time.

In clinical trials, side effects from the gastrointestinal tract (GIT) as a whole occurred less frequently with meloxicam than with other NSAIDs with which the comparison was performed. This difference in the frequency of side effects from the gastrointestinal tract is mainly due to the fact that when taking meloxicam, there were less frequent phenomena such as dyspepsia, vomiting, nausea, abdominal pain.The frequency of perforations in the upper gastrointestinal tract, ulcers and bleeding that were associated with the use of meloxicam was low and depended on the magnitude of the dose of the drug.

Pharmacokinetics:

With a single dose of the drug, the maximum maximum concentration in the plasma is reached within 5-6 hours. With repeated use, a stable state of pharmacokinetics is achieved in a period of 3 to 5 days.

The range of difference between the maximum (C_max) and basal concentrations (C_m_in) of the drug during the steady state of pharmacokinetics after its administration once a day is relatively small and amounts to 0.4-1.0 μg / ml for a dose of 7.5 mg and 0.8-2.0 μg / ml for a dose 15 mg. The maximum concentration of the drug in plasma during the steady state of pharmacokinetics is reached approximately 5 hours after application of the drug.

Distribution

Meloxicam binds well to plasma proteins (with albumin - 99%) Meloksikam penetrates into the synovial fluid; local concentrations are approximately 50% of the plasma concentrations.

The volume of distribution is low, an average of 11 liters. Individual fluctuations - 30-40%.

Metabolism

Meloksikam is almost completely metabolized in the liver with the formation of 4 pharmacologically inactive derivatives, detectable in urine. 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 degree (9% of the dose value). In vitro studies have shown that CYP 2C9 plays an important role in this metabolic transformation, the CYP isoenzyme ZA4 is of additional importance. In the formation of the other two metabolites (which constitute, respectively, 16% and 4% of the dose), peroxidase takes part, the activity of which probably varies individually. It is excreted equally with feces and urine, mainly in the form of metabolites. In unchanged form with feces less than 5% of the daily dose is excreted, in the urine in unchanged form the drug is found only in trace amounts. The average half-life of meloxicam is 20 hours.

Plasma clearance is an average of 8 ml / min. Meloksikam demonstrates a linear pharmacokinetics in doses of 7.5-15 mg when ingested.

Liver and / or kidney failure

Lack of liver function, as well as mild to moderate renal failure, does not significantly affect the pharmacokinetics of meloxicam. In terminal renal failure, an increase in the volume of distribution can lead to higher concentrations of free meloxicam, so in these patients the daily dose should not exceed 7.5 mg.

Elderly patients

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

During the study of meloxicam in children, the pharmacokinetics of the drug was studied in doses applied at the rate of 0.25 mg / kg. When comparing the parameters in children of different ages (2-6 years, n = 7 and 7-14 years, n = 11), the tendency to a lower maximum concentration in plasma (C_max, -34%) and AUC₀_-_∞(-28%) in young children, and the clearance of the drug (adjusted for body weight) in this group of children was higher. Concentrations of meloxicam in plasma in older children and adults are similar. In children of both age groups, the half-lives of meloxicam from plasma were similar (13 hours) and somewhat shorter than in adults (15-20 hours).

Indications:Symptomatic treatment of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis.

Contraindications:

- Hypersensitivity to the active ingredient or auxiliary components of the drug. There is a possibility of cross-sensitivity to acetylsalicylic acid and other NSAIDs;

- Symptoms of bronchial asthma, polyps of the nose, angioedema or urticaria after taking acetylsalicylic acid or other NSAIDs in the anamnesis;

- Peptic ulcer / perforation of the 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 failure (if hemodialysis is not performed, creatinine clearance is less than 30 ml / min, and with confirmed hyperkalemia), progressive kidney disease;

- Acute gastrointestinal bleeding, recent cerebrovascular bleeding or an established diagnosis of blood coagulation system diseases;

- Expressed uncontrolled heart failure;

- Children under 12 years;

- Pregnancy;

- Breast-feeding;

- Therapy of perioperative pain during coronary artery bypass grafting.

Carefully:

- Diseases of the gastrointestinal tract in the anamnesis (presence of H.pylori infection);

congestive heart failure;

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

- ischemic heart disease (as well as risk factors associated with it);

- cerebrovascular diseases;

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

- elderly age;

- prolonged use of NSAIDs;

- frequent use of alcohol.

Pregnancy and lactation:Contraindicated in pregnancy and lactation.

Dosing and Administration:

Osteoarthritis: The maximum daily dose of 15 mg per day.

Rheumatoid arthritis: 15 mg per day.

Ankylosing spondylitis: 15 mg per day.

Adolescents: The maximum dose in adolescents is 0.25 mg / kg.

A minimum effective dose should be used with the minimum possible short course.

Combined application. The total daily dose of the drug Movalis, used in the form of tablets, suppositories, suspension for ingestion and injection, should not exceed 15 mg.

Side effects:

Below are described the side effects, the relationship of which with the use of the drug Movalis, was regarded as possible.

Undesirable effects, the relationship of which with taking the drug was regarded as possible, and which were recorded with a wide application of the drug, are marked with *.

On the part of the hematopoiesis system

Change in the blood formula, including changes in the leukocyte formula, leukopenia, thrombocytopenia, anemia.

The predisposing factor for the onset of cytopenia appears to be the simultaneous use of potentially myelotoxic drugs, in particular methotrexate.

Allergic reactions

Anaphylactic reactions *, anaphylactoid reactions * and other immediate-type hypersensitivity reactions * toxic epidermal necrolysis *, Stevens-Johnson syndrome *, angioedema *, bullous dermatitis *, erythema multiforme * rash, hives, photosensitivity, pruritus. on the part of IIHC: nausea, drowsiness, headache, confusion *, disorientation *, mood changes *.

From the sense organs

Dizziness, tinnitus, visual impairment, including blurred vision *, conjunctivitis *.

From the side of the cardiovascular system

Palpitation, swelling, increased blood pressure, a sense of tidal blood to the face.

From the respiratory system

Bronchial asthma (bronchospasm) in patients with allergy to aspirin or other NSAIDs.

From the gastrointestinal tract

Perforation of the gastrointestinal tract, latent or obvious gastrointestinal bleeding, gastroduodenal ulcer, colitis, gastritis *, esophagitis, stomatitis, abdominal pain, indigestion, diarrhea, nausea, vomiting, constipation, bloating, belching. Gastrointestinal bleeding, ulcer or perforation can lead to death. Hepatitis *, changes in liver function (for example, increased levels of transaminases or bilirubin).

From the urinary system

Acute renal failure *, changes in renal function (increased serum creatinine and / or urea levels). The use of NSAIDs can lead to a violation of urination, including acute urinary retention *.

Overdose:

Data on cases associated with drug overdose accumulated insufficiently. Probably, there will be symptoms,In severe cases: drowsiness, impaired consciousness, nausea, vomiting, epigastric pain, gastrointestinal bleeding, acute renal failure, changes in blood pressure, respiratory arrest, asystole.

Treatment: antidote is not known. In case of an overdose of the drug, symptomatic therapy should be used.

Interaction:

-Other inhibitors of the synthesis of prostaglandins, incl. glucocorticosteroids and salicylates (acetylsalicylic acid):

Simultaneous application increases the risk of ulceration in the gastrointestinal tract and gastrointestinal bleeding due to synergistic action. The combined use of meloxicam and other NSAIDs is not recommended. The combined use of aspirin (1000 mg 3 times per day) and meloxicam in healthy volunteers resulted in an increase in AUC (10%) and C_max(24%) meloxicam. The clinical significance of this interaction is unknown.

-Anticoagulants for oral administration, antiaggregants, heparin for systemic use, thrombolytic agents, selective serotonin reuptake inhibitors (SSRIs): increased risk of bleeding.If it is not possible to avoid the simultaneous use of these drugs, careful monitoring of the effect of anticoagulants is necessary.

-Lithium. NSAIDs increase the concentration of lithium in the plasma by decreasing the renal excretion of lithium. The concentration of lithium in plasma can reach toxic values. The combined use of lithium and NSAIDs is not recommended. If necessary, such combination therapy should monitor the concentration of lithium in the plasma at the beginning of treatment, when choosing a dose and canceling meloxicam.

-Metotrexate. NSAIDs can reduce the tubular secretion of methotrexate and thus increase the concentration of methotrexate in the plasma. In this regard, patients receiving high doses of methotrexate (more than 15 mg per week) concurrent use of NSAIDs is not recommended. The risk of interaction with simultaneous use of methotrexate and NSAIDs is also possible in patients receiving low doses of methotrexate, especially in patients with impaired renal function. If necessary, combined therapy should monitor the blood formula and kidney function. Care should be taken if the NSAIDs and methotrexate apply simultaneously for 3 days, because the concentration of methotrexate in the plasma may increase and, as a consequence, toxic effects may occur. Simultaneous use of meloxicam did not affect the pharmacokinetics of methotrexate at a dose of 15 mg per week, however. it should be taken into account that the hematological toxicity of methotrexate is enhanced by the simultaneous administration of NSAIDs.

-Contraception. Earlier reports of a decrease in the effectiveness of intrauterine contraceptive devices when using NSAIDs. This observation requires further confirmation.

-Diuretics. The use of NSAIDs increases the risk of developing acute renal failure in patients with dehydration. Patients receiving Movalis and diuretics should be adequately hydrated.

Before the beginning of treatment it is necessary to study the function of the kidneys.

Antihypertensives (eg, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, vasodilators, diuretics). NSAIDs reduce the effect of antihypertensive drugs, due to the inhibition of prostaglandins, which have vasodilating properties.

- The combined use of NSAIDs and angiotensin II receptor antagonists (as well as ACE inhibitors) enhances the effect of reducing glomerular filtration. In patients with impaired renal function, this can lead to the development of acute renal failure.

-Holestyramine, binding meloxicam in the gastrointestinal tract, leads to its faster excretion.

-CNAP, by acting on renal prostaglandins, can enhance the nephrotoxicity of cyclosporine. In the case of combined therapy, kidney function should be monitored.

Meloksikam is excreted from the body mainly by hepatic metabolism, about 2/3 of the amount of the drug being metabolized in the liver is destroyed by enzymes of the cytochrome P450 system (the main pathway of metabolism is cytochrome 2C9, the additional pathway is cytochrome ZA4), about 1/3 is metabolized by other systems, for example, by peroxidation. When used in conjunction with meloxicam drugs that have a known ability to inhibit CYP 2C9 and / or CYP 3A4 (or are metabolized with the participation of these enzymes), the possibility of pharmacokinetic interaction should be taken into account.

With the simultaneous use of meloxicam and antacids, cimetidine, digoxin or furosemide, no significant pharmacokinetic interactions were identified.

It is impossible to exclude the possibility of interaction with oral antidiabetic agents.

Special instructions:

Care should be taken (as with other NSAIDs) in the treatment of patients with a history of gastrointestinal disease and patients receiving anticoagulants. Patients who have symptoms from the gastrointestinal tract should be observed regularly. If there is a ulcerative lesion of the gastrointestinal tract or gastrointestinal bleeding, Movalis® should be canceled.

Gastrointestinal bleeding, ulcers and perforations, potentially life-threatening to the patient, can occur during treatment at any time, as in the presence of alarming symptoms or information about serious gastrointestinal complications in the history, and in the absence of these symptoms. The consequences of these complications are generally more serious in the elderly.

During the application of NSAIDs, very rarely reported on the development of serious allergic reactions(some of which resulted in the death of patients), including exfoliative dermatitis, syndrome. Stevens-Johnson and, toxic epidermal necrolysis.

The greatest risk of these reactions in patients appears to be observed at the very beginning of the course of treatment, these reactions in most cases started within the first month of treatment. In the event of the appearance of the first signs of skin rash, changes in mucous membranes or any other symptoms of hypersensitivity meloxicam should be abolished.

NSAIDs may increase the risk of serious thrombotic cardiovascular disease, myocardial infarction and stroke, which can lead to death. This risk may increase as the duration of NSAID use increases. The greatest risk can be observed in patients with cardiovascular diseases or in the presence of risk factors for the development of cardiovascular diseases, renal failure, and those on hemodialysis. In patients with small or moderate renal impairment (ie, if creatinine clearance is greater than 25 mL / min), a dose reduction is not required.

When using the drug Movalis (as well as most other NSAIDs), it was reported an episodic increase in the level of transaminases or other indicators of liver function in the serum. In most cases, this increase was small and transient. If the detected changes are significant or do not decrease over time, and also accompanied by other signs of liver damage (itchy skin, yellowing of the skin, nausea, vomiting, abdominal pain, darkening of the urine), Movalis should be abolished, and monitored for identified laboratory and clinical changes . In patients with clinically stable cirrhosis, a dose reduction is not required.

Weakened or depleted patients can tolerate undesirable events worse, so these patients should be carefully observed. Caution (as with other NSAIDs) should be observed in the treatment of elderly patients who are more likely to have impaired renal, hepatic, and cardiac function. The use of NSAIDs in conjunction with diuretics can lead to a delay in sodium, potassium and water, and affect the natriuretic effect of diuretics.As a result, predisposing patients may have signs of heart failure or hypertension. Clinical observation of patients with a risk of developing these complications is recommended.

Meloxicam, as well as other NSAIDs, can mask the symptoms of an infectious disease. The drug is intended for symptomatic therapy, reducing pain and inflammation when used. As with other NSAIDs, combined treatment of the disease is necessary to influence progression.

The use of NSAIDs can negatively affect female fertility and is not recommended for women planning a pregnancy.

Suppositories should not be used in patients with any inflammatory damage to the rectum or anus, or in patients with recent bleeding from the rectum or anus.

Effect on the ability to drive transp. cf. and fur:Special studies on the effect of the drug on the ability to drive vehicles and mechanisms were not carried out. This activity should be refrained to patients with visual impairment, to patients who report drowsiness or other abnormalities from the CNS.

Form release / dosage:Suppositories rectal 15 mg.

Packaging:For 6 suppositories in a contour package of aluminum foil, 1 or 2 contour packs with instructions for use in a pack of cardboard.

Storage conditions:At a temperature not exceeding 30 ° C. Keep out of the reach of children.

Shelf life:3 years. Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N011487 / 01

Date of registration:15.02.2011

Expiration Date:Unlimited

The owner of the registration certificate:Boehringer Ingelheim International GmbHBoehringer Ingelheim International GmbH Germany

Manufacturer: & nbsp

INSTITUTO de ANGELI, S.r.L. Italy

Representation: & nbspBERINGER INGELCHAIM INTERNATIONAL GmbH BERINGER INGELCHAIM INTERNATIONAL GmbH Germany

Information update date: & nbsp07.07.2017

Illustrated instructions

Instructions

Movalis® (Movalis®)