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

Excipients: meglumine - 9.375 mg glikofurfurol - 150 mg poloxamer 188 - 75 mg Sodium chloride - 4.5 mg glycine - 7.5 mg Sodium hydroxide - 0.228 mg, water for injection - 1279.482 mg.

Description:Transparent yellow with a green hue of color solution, virtually free of particles, in clear ampoules of 2 ml.

Pharmacotherapeutic group:Non-steroidal anti-inflammatory drug - NSAIDs

ATX: & nbsp

M.01.A.C.06 Meloksikam

M.01.A.C Oksikamy

Pharmacodynamics:

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.

Meloksikam in vivo 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 therapeutic effects of NSAIDs, whereas inhibition of the persistent COX-1 iso-enzyme may be responsible for side effects from the stomach and kidneys.The selectivity of meloxicam for COX-2 has been confirmed in various test systems, both in vitro and in vivo. The selective ability of meloxicam to inhibit COX-2 is shown when using human whole blood in vitro as a test system. Determined that meloxicam (in doses of 7.5 and 15 mg) inhibited COX-2 more actively, exerting a greater inhibitory effect on the production of prostaglandin E2 stimulated by lipopolysaccharide (a reaction controlled by COX-2) than on the production of thromboxane involved in blood coagulation (reaction controlled COX-1). These effects depended on the size of the dose.

In ex vivo studies, it has been shown that meloxicam (in doses of 7.5 mg and 15 mg) does not affect the aggregation of platelets and bleeding time.

In clinical trials, side effects from the gastrointestinal tract (GI tract) as a whole occurred less often with meloxicam 7.5 and 15 mg than with other NSAIDs that were compared. 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:

Absorption

Meloksikam is completely absorbed after intramuscular injection. The relative bioavailability compared with the bioavailability with oral administration is almost 100%. Therefore, when switching from an injection to an oral form, the dose is not required. After administration of 15 mg of the drug intramuscularly, a peak plasma concentration of about 1.6 to 1.8 μg / ml is achieved within about 60 to 96 minutes.

Distribution

Meloksikam very well binds to plasma proteins, mainly with albumin (99%). It penetrates into the synovial fluid, the concentration in the synovial fluid is approximately 50% of the concentration in the plasma. The distribution volume is low, about 11 liters. Interindividual differences account for 7-20%.

Metabolism

Meloksikam is almost completely metabolized in the liver with the formation of 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 degree (9% of the dose value).In vitro studies have shown that CYP2C9 plays an important role in this metabolic transformation, the CYP3A4 isoenzyme plays an additional role. 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.

Excretion

It is excreted equally through the intestines and kidneys, 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 varies from 13 to 25 hours. Plasma clearance is an average of 7 - 12 ml / min after a single application. Meloksikam demonstrates a linear pharmacokinetics in doses of 7.5-15 mg when administered intramuscularly.

Liver and / or kidney failure

Lack of liver function, as well as mild renal failure, does not significantly affect the pharmacokinetics of meloxicam. The rate of excretion of meloxicam from the body is much higher in patients with moderate renal insufficiency. Meloksikam worse binds to plasma proteins in patients with terminal renal failure.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

Older patients have similar pharmacokinetic parameters in comparison with young patients. In elderly patients, the average plasma clearance during the equilibrium state of pharmacokinetics is slightly lower than in young patients. Older women have higher AUC values (area under the concentration-time curve) and a longer half-life, compared to young patients of both sexes.

Indications:

Start therapy and short-term symptomatic treatment with:

osteoarthritis (arthrosis, degenerative joint diseases);

rheumatoid arthritis;

ankylosing spondylitis;

other inflammatory and degenerative diseases of the musculoskeletal system, such as arthropathy, dorsopathy (eg, sciatica, lower back pain, shoulder periarthritis, etc.) accompanied by pain.

Contraindications:

Hypersensitivity to the active ingredient or auxiliary components of the drug;

Hypersensitivity (including other non-steroidal anti-inflammatory drugs), complete or partial combination of asthma, recurrent nasal polyposis, and paranasal sinuses, urticaria or angioedema caused by intolerance to acetylsalicylic acid and other non-steroidal anti-inflammatory drugs

because of the existing probability of cross-sensitivity (including in history);

Erosive-ulcerative lesions of the stomach and duodenum in the acute stage or recently transferred;

Inflammatory bowel disease - Crohn's disease or ulcerative colitis in the acute stage;

Severe hepatic and heart failure;

Severe renal failure (if not hemodialysis, creatinine clearance less than 30 mL / min, and when the confirmed hyperkalemia);

Active liver disease;

Active gastrointestinal bleeding, cerebrovascular bleeding recently transferred or established diagnosis of diseases of the blood coagulation system;

Age to 18 years;

Pregnancy;

Breast-feeding;

Therapy of perioperative pain during coronary artery bypass grafting;

Concomitant therapy with anticoagulants, as there is a risk of intramuscular hematoma formation.

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);

cardiac ischemia;

cerebrovascular diseases;

dyslipidemia / hyperlipidemia;

diabetes;

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

diseases of peripheral arteries;

elderly age;

long-term use of NSAIDs;

smoking;

frequent use of alcohol.

Pregnancy and lactation:

The use of Mawalis is contraindicated during pregnancy.

It is known that NSAIDs penetrate into breast milk, so the use of MOVALISA during breastfeeding is contraindicated.

As a preparation inhibiting the synthesis of cyclooxygenase / prostaglandin, MOVALIS can affect fertility, and therefore is not recommended for women planning a pregnancy. Meloksikam can lead to a delay in ovulation.In this regard, women who have problems with conception and undergoing examination for such problems, it is recommended to cancel the admission of MOVALIS.

Dosing and Administration:

Osteoarthritis with pain syndrome: 7.5 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 can be reduced to 7.5 mg per day.

Ankylosing spondylitis: 15 mg per day. Depending on the therapeutic effect, this dose can be reduced to 7.5 mg per day.

In patients with an increased risk of adverse reactions (a history of the gastrointestinal disease, the presence of risk factors for cardiovascular disease), it is recommended to start treatment with a dose of 7.5 mg per day (see Special instructions).

In patients with severe renal failure who are on hemodialysis, the dose should not exceed 7.5 mg per day.

General recommendations

Since 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 application

Do not use the drug simultaneously with other NSAIDs.

The total daily dose of the drug MOVALIS, used in the form of different dosage forms should not exceed 15 mg.

Intramuscular injection of the drug is indicated only during the first few days of therapy. Further treatment is continued with the use of oral dosage 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 drug is administered via a deep intramuscular injection.

The drug can not be administered intravenously.

Given the possible incompatibility, the MOVALIS intramuscular solution should not be mixed in the same syringe with other drugs.

Side effects:

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

Side effects registered with post-marketing use, the relationship of which with taking the drug was regarded as possible, marked *.

Inside the system-organ classes, the following categories are used for the incidence of side effects:

very often (≥ 1/10);

often (≥ 1/100, <1/10);

infrequently (≥ 1 / 1,000, <1/100);

rarely (≥ 1 / 10,000, <1 / 1,000);

very rarely (<1 / 10,000);

not installed.

Violations from the blood and lymphatic system:

Infrequent anemia;

Rarely, leukopenia, thrombocytopenia, changes in the number of blood cells, including changes in the leukocyte formula.

Immune system disorders:

Infrequently, other immediate-type hypersensitivity reactions *;

Not established - anaphylactic shock *, anaphylactoid reactions *.

Disorders of the psyche:

Rarely is a mood change *;

Not established - confusion of consciousness *, disorientation *.

Impaired nervous system:

Often - a headache;

Infrequent - dizziness, drowsiness.

Impaired vision, hearing and labyrinthine disturbances:

Infrequently - vertigo;

Rarely - conjunctivitis *, visual impairment, including blurred vision *, tinnitus.

Violations from the heart and blood vessels:

Infrequent - increased blood pressure, a sense of "tide" of blood to the face;

Rarely - palpitations.

Disturbances from the respiratory system:

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

Disorders from the gastrointestinal tract:

Often - abdominal pain, indigestion, diarrhea, nausea, vomiting;

Infrequent - latent or obvious gastrointestinal bleeding, gastritis *, stomatitis, constipation, bloating, belching;

Rarely gastroduodenal ulcers, colitis, esophagitis;

Very rarely - perforation of the gastrointestinal tract.

Disorders from the liver and bile ducts:

Infrequent - transient changes in liver function indicators (for example, increased activity of transaminases or bilirubin);

Very rarely - hepatitis *.

Disturbances from the skin and subcutaneous tissues:

Infrequent - angio-edema *, itching, skin rash;

Rarely - toxic epidermal necrolysis *, Stevens-Johnson syndrome *, urticaria;

Very rarely - bullous dermatitis *, erythema multiforme *;

Not established - photosensitivity.

Disorders from the kidneys and urinary tract:

Infrequent changes in the indices of kidney function (increased serum creatinine and / or urea levels), urination disorders, including acute urinary retention *;

Very rarely - acute renal failure *.

Violations of the genitals and mammary glands:

Infrequently - 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.

Joint application with drugs that depress the bone marrow (for example, methotrexate) can provoke cytopenia.

Gastrointestinal bleeding, ulcer or perforation can lead to death.

As for other NSAIDs, the possibility of interstitial nephritis, glomerulonephritis, renal medullary necrosis, nephrotic syndrome is not ruled out.

Overdose:

Data on cases associated with drug overdose accumulated insufficiently. Probably, there will be symptoms typical of overdose of NSAIDs 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. It is known that colestramine accelerates the excretion of meloxicam.

Interaction:

Other inhibitors of prostaglandin synthesis, including glucocorticoids and salicylates - concurrent administration with meloxicamincreases the risk of ulceration in the gastrointestinal tract and gastrointestinal bleeding (due to synergism of action). Simultaneous reception with other NSAIDs is not recommended.

Anticoagulants for oral administration, heparin for systemic use, thrombolytic agents - simultaneous administration with meloxicam increases the risk of bleeding. In the case of simultaneous use, careful monitoring of the blood coagulation system is necessary.

Antiplatelet agents, serotonin reuptake inhibitors - simultaneous administration with meloxicam increases the risk of bleeding due to inhibition of platelet function. In the case of simultaneous use, careful monitoring of the blood coagulation system is necessary.

Lithium preparations - NSAIDs increase the level of lithium in plasma, by reducing the excretion of it by the kidneys. The simultaneous use of meloxicam with lithium preparations is not recommended. In case of need for simultaneous use, careful monitoring of lithium concentration in plasma is recommended during the whole course of lithium preparations.

Methotrexate - NSAIDs decrease the secretion of methotrexate by the kidneys, thereby,increasing its concentration in the plasma. The simultaneous use of meloxicam and methotrexate (at a dose of more than 15 mg per week) is not recommended. In the case of simultaneous use, careful monitoring of kidney function and the blood formula is necessary.

Meloxicam may increase the hematologic 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.

Diuretics - the use of NSAIDs in the case of dehydration of patients is accompanied by a risk of developing acute renal failure.

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

Angiotensin II receptor antagonists, as well as angiotensin-converting enzyme inhibitors when combined 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.

Kolestyramin, tying meloxicam in the gastrointestinal tract, leads to its faster excretion.

Pemetrexed - with the simultaneous use of meloxicam and pemetrexed in patients with creatinine clearance from 45 to 79 ml / min, meloxicam should be discontinued five days before the start of pemetrexed and may be resumed 2 days after the end of the procedure. If there is a need for the combined use of meloxicam and pemetrexed, such patients should be closely monitored, especially with respect to myelosuppression and the occurrence of side effects from the gastrointestinal tract. In patients with creatinine clearance less than 45 ml / min, meloxicam is not recommended together with pemetrexed.

NSAIDs, acting on renal prostaglandins, can enhance the nephrotoxicity of cyclosporine.

When used in combination 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), such as sulfonylureas or probenecid derivatives, pharmacokinetic interaction should be considered.

When combined with antidiabetic agents for oral administration (for example, derivatives of sulfonylurea, nateglinide), interactions mediated by CYP 2C9 are possible, which may lead to an increase in the concentration of both these drugs and meloxicam in the blood. Patients simultaneously taking meloxicam with preparations of sulfonylurea or nateglinide, should carefully monitor blood sugar levels because of the possibility of developing hypoglycemia.

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

Special instructions:

Patients suffering from diseases of the gastrointestinal tract should be observed regularly. If there is a ulcerative lesion of the gastrointestinal tract or gastrointestinal bleeding, MOVALIS must be canceled.

Gastrointestinal ulcers, perforation or bleeding can occur during the use of NSAIDs at any time, as with the presence of alarming symptoms or information about serious gastrointestinal complications in the history, and in their absence.The consequences of these complications are generally more serious in the elderly.

When applying the drug MOVALIS can develop such serious reactions from the skin, as exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis. Therefore, special attention should be given to patients reporting the development of undesirable skin and mucous membrane phenomena, as well as hypersensitivity reactions to the drug, especially if similar reactions were observed during previous courses of treatment. The development of such reactions is observed, as a rule, during the first month of treatment. In the case of the appearance of the first signs of skin rash, changes in mucous membranes or other signs of hypersensitivity, the issue of discontinuing the use of MOVALIS preparation should be considered.

Cases when taking NSAIDs increase the risk of developing serious cardiovascular thrombosis, myocardial infarction, an attack of angina pectoris, possibly with a fatal outcome are described. This risk increases with prolonged use of the drug, as well as in patients with the aforementioned diseases in the history and predisposed to such diseases.

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 a reduced volume of circulating blood can lead to decompensation of the secretive renal failure. After the abolition of NSAIDs, the kidney function is usually restored to its original level. The elderly patients, patients with dehydration, congestive heart failure, cirrhosis, nephrotic syndrome or acute renal dysfunction, patients concurrently taking diuretic drugs, ACE inhibitors, angiotensin II receptor antagonists, and elderly patients are most at risk of developing this reaction. also patients who underwent serious surgical interventions that lead to hypovolemia. In such patients at the beginning of therapy, diuresis and renal function should be carefully monitored.

The use of NSAIDs in conjunction with diuretics can lead to a delay in sodium, potassium and water, as well as a decrease in natriuretic action of diuretics. As a result, predisposing patients may have signs of heart failure or hypertension.Therefore, careful monitoring of the condition of such patients is needed, and adequate hydration should be maintained. Before the beginning of treatment it is necessary to study the function of the kidneys.

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

When using the drug MOVALIS (as well as most other NSAIDs), it is possible to occasionally increase the activity of transaminases in the blood serum or other indicators of liver function. In most cases, this increase was small and transient. If the identified changes are significant or do not decrease over time, MOVALIS should be abolished, and monitored for laboratory changes identified.

Weakened or debilitated patients can tolerate undesirable events worse, which is why such patients should be carefully observed.

Like other NSAIDs, MOVALIS can mask the symptoms of a major infectious disease.

As a preparation inhibiting the synthesis of cyclooxygenase / prostaglandin, MOVALIS can affect fertility, and therefore is not recommended for women who have difficulty with conception.In this regard, women who are undergoing examination in this regard, it is recommended to cancel the drug MOVALIS.

In patients with mild or moderate renal failure (creatinine clearance more than 25 ml / min), dose adjustment is not required.

In patients with cirrhosis of the liver (compensated), dose adjustment is not required.

Effect on the ability to drive transp. cf. and fur:Special clinical studies of the effect of the drug on the ability to control the car and mechanisms were not carried out. However, when driving and with machinery, the possibility of developing dizziness, drowsiness, visual impairment, or other disorders from the central nervous system should be taken into account. During the period of treatment, patients need to be careful when driving vehicles and engaging in other potentially dangerous activities that require increased attention and speed of psychomotor reactions.

Form release / dosage:

Solution for intramuscular injection 15 mg / 1.5 ml.

Packaging:

For 1.5 ml in a vial of colorless hydrolytic glass class 1 with a ring of yellow over the fracture line of the ampoule.

By 3 or 5 ampoules per pallet of plastic with an upper individual recess for the medium ampoule or with two upper individual recesses for the side ampoules. The pallet in a cardboard box together with the instruction on application.

Packaging for hospitals: 1.5 ml per ampoule of colorless hydrolytic glass class 1 with a ring of yellow color above the fracture line of the ampoule. 5 ampoules per pallet of plastic with an upper individual recess for the medium ampoule or with two upper individual recesses for the side ampoules. Two pallets in a cardboard box with instructions for use. For 5 cartons in a film of polypropylene.

Storage conditions:

In the dark place at a temperature of no higher than 30 ⁰FROM.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:П N014482 / 01

Date of registration:07.09.2011 / 02.04.2015

Expiration Date:Unlimited

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

Manufacturer: & nbsp

BOEHRINGER INGELHEIM ESPANA, S.A. Spain

Representation: & nbspBehringer Ingelheim, LLCBehringer Ingelheim, LLC

Information update date: & nbsp11.07.2017

Illustrated instructions

Instructions

Movalis® (Movalis®)