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

Excipients: sodium citrate dihydrate 15 mg (30 mg), lactose monohydrate 23.5 mg (20 mg), microcrystalline cellulose 102 mg (87.3 mg), povidone K25 10.5 mg (9 mg), silicon dioxide colloid - 3.5 mg (3 mg), crospovidone - 16.3 mg (14 mg), magnesium stearate - 1.7 mg.

Description:

Tablets 7.5 mg

Round, from pale yellow to yellow tablets. One side is convex with a bevelled edge. On the convex side is the firm's logo; on the other side - the code and the concave risk. Roughness of tablets is allowed.

Tablets 15 mg

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 constantly present isoenzyme COX-1 can be responsible for side effects from the stomach and kidneys. The selectivity of meloxicam against COX-2 has been confirmed in various test systems as in vitro, and in vivo. The selective ability of meloxicam to inhibit COX-2 is shown by using human whole blood as a test system in vitro. Determined that meloxicam (in doses of 7.5 and 15 mg) more actively inhibited COX-2, having a greater inhibitory effect on prostaglandin production E2, stimulated lipopolysaccharide (reaction controlled by COX-2) than on the production of thromboxane involved in the process of blood coagulation (reaction controlled by COX-1). These effects depended on the size of the dose. In studies ex vivo 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 (GIT) as a whole occurred less frequently with the use of meloxicam 7.5 and 15 mg,compared with the intake of other NSAIDs with which a comparison was made. 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 well absorbed from the gastrointestinal tract, as evidenced by high absolute bioavailability (90%) after ingestion. After a single application of meloxicam, the maximum plasma concentration in the plasma is reached within 5-6 hours. Simultaneous intake of food and inorganic antacids does not alter absorption. When using the drug inside (in doses of 7.5 and 15 mg), its concentrations are proportional to the doses. Steady state of pharmacokinetics is achieved within 3-5 days. The range of differences between the maximum and basal concentrations of the drug after its administration

once a day is relatively small and amounts to using a dose of 7.5 mg 0.41.0 μg / ml, and when using a dose of 15 mg - 0.8-2.0 μg / ml (the values are given respectively Cmin and Cmax in the period of steady state of pharmacokinetics), although the values beyond this range were also noted.

The maximum concentration of meloxicam in plasma during the steady state of pharmacokinetics is reached 5-6 hours after ingestion.

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 volume of distribution after repeated oral administration of meloxicam (at doses ranging from 7.5 mg to 15 mg) is about 16 liters, with a coefficient of variation from 11 to 32%.

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 extent (9% of the dose value). Research in vitro showed that in this metabolic transformation an important role is played by CYP2C9, an additional value is isoenzyme CYP3A4. 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 dose of meloxicam.

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. With terminal renal failure, an increase in volume 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. In elderly women, higher values AUC (area under the concentration-time curve) and a long half-life, compared with young patients of both sexes.

Indications:

Symptomatic treatment:

osteoarthritis (arthrosis, degenerative joint diseases), including painful component;

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;

Complete or incomplete combination of bronchial asthma,recurrent nasal polyposis and paranasal sinuses, angioedema or urticaria caused by intolerance to acetylsalicylic acid or other non-steroidal anti-inflammatory drugs due to the current likelihood of cross-sensitivity (including 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 impairment;

Severe renal failure (if hemodialysis is not performed, creatinine clearance is less than 30 ml / min, and with confirmed hyperkalemia), progressive kidney disease;

Active gastrointestinal bleeding, recent cerebrovascular bleeding or an established diagnosis of blood coagulation system diseases

Severe uncontrolled heart failure;

Pregnancy;

Breast-feeding;

Therapy of perioperative pain during coronary artery bypass grafting;

Children up to 12 years;

A rare hereditary intolerance of galactose (in the maximum daily dose of the drug with a dosage of meloxicam 7.5 mg and 15 mg contains 47 mg and 20 mg of lactose, respectively).

Carefully:

Diseases of the gastrointestinal tract in the anamnesis (peptic ulcer of stomach and duodenum, liver disease);

congestive heart failure;

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

cardiac ischemia;

cerebrovascular diseases;

dyslipidemia / hyperlipidemia;

diabetes;

concomitant therapy with the following drugs: oral glucocorticosteroids, anticoagulants (including warfarin), antiplatelet agents, selective serotonin reuptake inhibitors (including citalopram, fluoxetine, paroxetine, sertraline);

diseases of peripheral arteries;

elderly age;

long-term use of NSAIDs;

smoking;

frequent use of alcohol.

Pregnancy and lactation:

The use of the drug MOVALIS is contraindicated during pregnancy.

It is known that NSAIDs penetrate into breast milk, so the use of the drug MOVALIS 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 drug 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.

Teens

The maximum dose in adolescents (12-18 years) is 0.25 mg / kg and should not exceed 15 mg.

Use of tablets

The drug is contraindicated for children under 12 years due to the impossibility of selecting the appropriate dosage for this age group.

The total daily dose should be taken at one time, during meals, with water or other liquid.

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.

On the part of the blood and lymphatic system

Infrequent anemia;

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

From the immune system

Infrequently, other immediate-type hypersensitivity reactions *;

Not established - anaphylactic shock *, anaphylactoid reactions *.

From the nervous system

Often - a headache;

Infrequent - dizziness, drowsiness.

Disorders of the psyche

Often - a change in mood *;

Not established - confusion of consciousness *, disorientation *.

From the sense organs

Infrequently - vertigo;

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

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.

From the side of the liver

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

Very rarely - hepatitis *.

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.

From the respiratory system

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

From the cardiovascular system

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

Rarely - palpitations.

From the genitourinary system

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 *.

From the genitals and breast

Infrequently - late ovulation *;

Not established - infertility in women *.

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: the antidote is not known, in case of an overdose of the drug should be carried out: evacuation of the contents of the stomach and general maintenance therapy. Cholestyramine accelerates the excretion of meloxicam.

Interaction:

Other inhibitors of prostaglandin synthesis, including glucocorticoids and salicylates - concurrent administration with meloxicam increases 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. If necessary, simultaneous

It is recommended to carefully monitor the concentration of lithium in the plasma 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. Meloksikam may enhance hematological toxicity of methotrexate, especially in patients with impaired renal function. With the combined use of meloxicam and methotrexate for 3 days, the risk increases the toxicity of the latter.

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 antagonists-II receptors, 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.

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

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

When used in conjunction with meloxicam, drugs that have a known ability to inhibit CYP 2C9 and / or CYP 3A4 (or metabolized with the participation of these enzymes), such as derivatives

sulfonylureas or probenecid, pharmacokinetic interaction should be considered.

When combined with oral antidiabetic agents (for example, sulfonylurea derivatives, nateglinide), mediated interactions are possible CYP 2C9, which can 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.

Ulcers of the gastrointestinal tract, perforation or bleeding may occur during the use of NSAIDs at any time, as in the presence of warning signs or information about serious gastrointestinal complications in history, and in the absence of these signs. 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, angina attack, possibly fatal. Such the risk increases with prolonged use of the drug, as well as in patients with the above mentioned 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 secretively flowing renal failure.After the abolition of NSAIDs, the kidney function is usually restored to its original level. The elderly patients are most at risk of developing this reaction, the use of NSAIDs together with diuretics can lead to a delay in sodium, potassium and water, as well as to a decrease in the natriuretic effect 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 working with machinery, one should take into account the possibility of developing dizziness, drowsiness, visual impairment, or other disorders from the central nervous system.Patients should be careful when driving and controlling machinery.

Form release / dosage:Tablets 7.5 mg or 15.0 mg.

Packaging:

For 10 tablets in a blister of PVC / A1-foil or PVC / PVDC / A1-foil. 1 or 2 blisters together with instructions for use in a cardboard box.

Storage conditions:Tablets at a temperature of no higher than 25 ° 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 N012978 / 01

Date of registration:05.07.2011

Expiration Date:Unlimited

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

Manufacturer: & nbsp

BOEHRINGER INGELHEIM ELLAS, A.E. Greece

BOEHRINGER INGELHEIM PHARMA, GmbH & Co.KG Germany

Representation: & nbspBehringer Ingelheim, LLCBehringer Ingelheim, LLC

Information update date: & nbsp14.07.2017

Illustrated instructions

Instructions

Movalis® (Movalis®)