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

Excipients: silicon dioxide colloid, hydroxyethylcellulose, sorbitol solution 70%, glycerol 85%, xylitol,sodium phosphate monobasic dihydrate, sodium saccharin, sodium benzoate, citric acid monohydrate, raspberry flavor, purified water.

Description:Yellowish viscous suspension with a green tint, fresh scent of raspberry.

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 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 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 2 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 is at a dose of 7.5 mg, 0.4-1.0 μg / ml, and when using a dose of 15 mg - 0.8-2 , 0 μg / ml, (Cmin and Stax values are given respectively in the steady state of pharmacokinetics), although 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%.

Biotransformation

Meloksikam is almost completely metabolized in the liver with the formation of 4 pharmacologically inactive derivatives. The main meta-bolite, 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 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 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. 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.

Children

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), a tendency to a lower maximum concentration in plasma (C_max, -34%) and AUC_0-∞ (-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:

- osteoarthritis (arthrosis, degenerative joint diseases), including pain component:

- rheumatoid arthritis;

ankylosing spondylitis;

juvenile rheumatoid arthritis;

- other inflammatory and degenerative diseases of the musculoskeletal system,such as arthropathy, dorsopathy (for example, sciatica, lower back pain, shoulder periarthritis and others), 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 probability of cross-sensitivity;

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 stage of exacerbation;

Severe hepatic impairment;

Severe renal insufficiency, CRF in patients not subject to hemodialysis for creatinine clearance 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,accompanied by increased bleeding;

Severe uncontrolled cardiovascular diseases;

Pregnancy;

Breast-feeding;

Therapy of perioperative pain during coronary artery bypass grafting (CABG);

A rare hereditary intolerance to fructose (the maximum daily dose of the drug contains 2.45 g of sorbitol);

It is not recommended for children under 12 years (if the drug is used with indications other than juvenile rheumatoid arthritis) due to the lack of data on efficacy and safety.

Carefully:

- Peptic ulcers of the gastrointestinal tract in the anamnesis;

- Chronic heart failure;

- elderly age;

- 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;

- simultaneous intake of other NSAIDs;

- simultaneous reception of methotrexate in a dosage more than 15 mg / week;

- prolonged use of NSAIDs

- Smoking;

- Alcoholism.

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:

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.

Osteoarthritis with pain syndrome: 7.5 mg per day (= 1 measuring spoon). If necessary, this dose can be increased to 15 mg per day (= 2 scoops).

Rheumatoid arthritis: 15 mg per day (= 2 measuring spoons).Depending on the therapeutic effect, this dose can be reduced to 7.5 mg per day (= 1 measuring spoon).

Ankylosing spondylitis: 15 mg per day (= 2 measuring spoons). Depending on the therapeutic effect, this dose can be reduced to 7.5 mg per day (= 1 measuring spoon).

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 an increased risk of adverse reactions and with severe renal failure who are on hemodialysis: the dose should not exceed 7.5 mg per day.

Teens: the maximum recommended daily dose for adolescents (12-18 years) is 0.25 mg / kg and should not exceed 15 mg.

The maximum recommended daily dose is 15 mg.

The entire daily dose of the drug should be taken only once during meals.

Juvenile rheumatoid arthritis *: 0,125 mg / kg once a day.

* for children under 12 years of age:

The weight	The volume of the suspension	Amount of active substance
12 kg	1.0 ml	1.5 mg
24 kg	2.0 ml	3.0 mg
36 kg	3.0 ml	4.5 mg
48 kg	4.0 ml	6.0 mg
≥60 kg	5.0 ml	7.5 mg

The maximum daily dose of 7.5 mg.

For patients older than 12 years,method of administration and dose for adolescents.

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

Use in patients with impaired renal function

In patients with terminal stage of renal failure who are on hemodialysis and with an increased risk of adverse reactions. the dose of the drug MOVALIS should not exceed 7.5 mg.

In patients with small or moderate renal impairment (creatinine clearance greater than 25 ml / min), a dose reduction is not required.

Use in patients with cirrhosis of the liver

In patients with clinically stable cirrhosis, a dose reduction is not required.

Use in patients with juvenile rheumatoid arthritis

Do not exceed the daily dosage higher than 0.125 mg / kg. The drug should not be administered to patients younger than 2 years.

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 *.

Within 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 rare (<1 / 10.000): not established.

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 - mood change *:

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 *.

Common diseases

Infrequent edema is infrequent.

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:Antidote is unknown, in case of an overdose of the drug should be carried out: evacuation of stomach contents 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, concomitant 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. 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 PPI in the case of dehydration of patients is accompanied by a risk of developing acute renal failure.

- Antihypertensive agents (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.

- Antagonists of angiotensin-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.

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

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

- Sodium polystyrene sulfonate - due to the presence of sorbitol in the composition of the drug MOVALIS, joint administration can cause the risk of developing necrosis of the large intestine, with possible fatal outcome.

- Pemetrexed - with the simultaneous use of meloxicam and pemetrexed in patients with creatinine clearance from 45 to 79 ml / min, the meloxicam should be discontinued five days before the start of pemetrexed and may be resumed 2 days after the end of the drug intake. 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 combined with meloxicam, drugs that have a known ability to inhibit CYP2C9 and / or CYP3A4 (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 CYP2C9 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.

- At simultaneous application of antacids, cimetidine, digoxin and furosemide no significant pharmacokinetic interactions were revealed.

Special instructions:

Patients with diseases of the gastrointestinal tract in a history should be observed regularly with the attending physician. 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.

To reduce the risk of developing adverse events on the part of the gastrointestinal tract, a minimum effective dose should be used with the minimum possible short course.

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 are at the greatest risk of developing this reaction. patients with dehydration, chronic heart failure, cirrhosis, nephrotic syndrome or acute renal dysfunction, patients taking diuretics at the same time, ACE inhibitors, angiotensin II receptor antagonists, and patients who underwent serious surgical interventions that lead to hypovolemia . In such patients at the beginning of therapy, diuresis and the function of the nights 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 and diuresis 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.

The drug contains 2.45 g of sorbitol in the maximum recommended daily dose. Patients with hereditary intolerance to fructose are not recommended to take the drug.

In the case of simultaneous use of anticoagulants for oral administration, ticlopidine, heparin for systemic use, thrombolytic agents, careful monitoring of the effect of anticoagulants is necessary.

It is recommended to monitor the levels of lithium during the period of administration of the drug MOVALIS, when changing the dose of lithium drugs and their cancellation.

In the case of simultaneous administration with methotrexate, strict control of the number of blood cells is recommended.

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 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, patients who report drowsiness or other disorders from the central nervous system.

Form release / dosage:Suspension for oral administration 7.5 mg / 5 ml.

Packaging:

For 100 ml in a bottle of amber glass with a screw cap.

The bottle along with the dispensing spoon and instructions for use are placed in a pack of cardboard.

Storage conditions:In a dry place at a temperature of no higher than 25 ° C, out of the reach of children.

Shelf life:

3 years.

After opening the bottle 6 months.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LS-001185

Date of registration:14.12.2011

Expiration Date:Unlimited

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

Manufacturer: & nbsp

BOEHRINGER INGELHEIM ROXANE Inc. USA

Representation: & nbspBehringer Ingelheim, LLCBehringer Ingelheim, LLC

Information update date: & nbsp10.06.2018

Illustrated instructions

Instructions

Movalis® (Movalis®)