Mesipol - instructions for use, dose, side effects, contraindications

Excipients: meglumine 6.25 mg, glycofurol 100.00 mg, poloxamer 188 50.00 mg, sodium chloride 3.00 mg, glycine 5.00 mg, sodium hydroxide 0.152 mg, water for injection up to 1 ml .

Description:

Transparent solution of yellow or greenish-yellow color with a characteristic odor.

Pharmacotherapeutic group:Non-steroidal anti-inflammatory drug

ATX: & nbsp

M.01.A.C.06 Meloksikam

M.01.A.C Oksikamy

Pharmacodynamics:

Meloxicam is a non-steroidal anti-inflammatory drug (NSAID), which has analgesic, anti-inflammatory and antipyretic effects. Anti-inflammatory effect is associated with inhibition of the enzymatic activity of cyclooxygenase-2 (COX-2), involved in the biosynthesis of prostaglandins in the inflammatory region. Less meloxicam It acts on cyclooxygenase-1 (COX-1) involved in prostaglandin synthesis, protecting the mucosa of the gastrointestinal tract (GIT) and participate in the regulation of blood flow in the kidney.

Pharmacokinetics:

Absorption

Meloksikam is almost completely absorbed after intramuscular injection. Bioavailability of the drug is about 100%. After intramuscular administration of 15 mg meloxicam, the maximum drug concentration (C_m_Oh) in plasma, which is 1.62 μg / ml, is reached after about 1 hour.

Distribution

Meloksikam binds to plasma proteins (mainly with albumin) to a large extent - 99%. Passes through the histogematic barriers, penetrates into the synovial fluid. The concentration in the synovial fluid is 50% of the plasma concentration of the drug. The volume of distribution (Vd) is low and is 11 liters.

Metabolism

Meloksikam is almost completely metabolized in the liver with the formation of four pharmacologically inactive metabolites. The main metabolite, 5'-carboxymeloxicam (60% of the administered dose), is formed by oxidation of the intermediate metabolite, 5'-hydroxymethylmeloxicam (9% of the administered dose). In vitro studies have shown that in this metabolic transformation an important role is played by the isoenzyme CYP2C9 and the isozyme has an additional value CYP3A4. In the formation of two other metabolites, which constitute 16% and 4% of the administered dose of the drug, peroxidase, whose activity varies individually, probably takes part.

Elimination

Significant intestinal-hepatic circulation, characteristic of meloxicam, does not affect the elimination of the drug. Meloksikam is excreted mainly in the form of metabolites, equally by the kidneys and intestines. In unchanged form, less than 5% of the daily dose of meloxicam is excreted through the intestine, and only trace amounts of unchanged drug are detected in the urine.

The mean half-life (T_1/2) meloxicam is 20 hours. Plasma clearance is an average of 8 ml / min.

Indications:

Symptomatic short-term treatment of exacerbations of rheumatoid arthritis and ankylosing spondylitis (Bechterew's disease) with the inability to use oral or rectal forms.

Contraindications:

- hypersensitivity to meloxicam, other NSAIDs, acetylsalicylic acid, excipients;

- complete or incomplete combination of bronchial asthma, recurrent nasal polyposis and paranasal sinuses and intolerance to acetylsalicylic acid and other NSAIDs (including in the anamnesis);

- erosive and ulcerative changes in the mucous membrane of the stomach or duodenum in the acute stage or a relapsing form;

- gastrointestinal bleeding;

- inflammatory bowel disease (ulcerative colitis, Crohn's disease) in the stage of exacerbation;

- period after aortocoronary shunting;

- Decompensated heart failure;

- cerebrovascular bleeding or other bleeding;

- severe hepatic impairment or active liver disease;

- severe renal failure in patients not undergoing hemodialysis (creatinine clearance less than 30 ml / min), progressive kidney disease, including confirmed hyperkalemia;

- violations of blood coagulation or simultaneous reception of anticoagulants;

- disturbance of homeostasis or simultaneous administration of anticoagulants;

- pregnancy;

- the period of breastfeeding;

- children's age till 18 years.

Carefully:Elderly age, ischemic heart disease, chronic heart failure, cerebrovascular disease, dyslipidemia / hyperlipidemia, diabetes mellitus, peripheral arterial disease, bronchial asthma, smoking, mild and moderate renal function impairment (creatinine clearance 30-60 ml / min), ulcerative lesions of the gastrointestinal tract in an anamnesis, presence of an infection Helicobacter pylori, long-term use of NSAIDs, frequent use of alcohol, severe somatic diseases, simultaneous intake of oral glucocorticosteroids (including prednisolone), anticoagulants (incl.warfarin), antiplatelet agents (including acetylsalicylic acid, clopidogrel), selective serotonin reuptake inhibitors (including citalopram, fluoxetine, paroxetine, sertraline).

Pregnancy and lactation:

The drug is contraindicated in pregnancy and during breastfeeding.

Like other inhibitors of cyclooxygenase and prostaglandin synthesis, meloxicam can have a negative impact on the fertility of women, so it is not recommended for women seeking to become pregnant. If a woman can not become pregnant or is on a test for infertility, consideration should be given to abolishing meloxicam treatment.

Dosing and Administration:

Intramuscularly. The drug is usually administered once, at the beginning of the course of treatment, in exceptional cases, the maximum course duration of intramuscular injection is no more than 2-3 days, if necessary (if oral or rectal administration is not possible). Further treatment is continued with the use of oral forms (tablets).

Rheumatoid arthritis

The recommended dose is 15 mg per day (1 ampoule).Depending on the therapeutic effect, the dose can be reduced to 7.5 mg per day (1/2 ampoule).

Ankylosing spondylitis

The recommended dose is 15 mg per day (1 ampoule). Depending on the therapeutic effect, the dose can be reduced to 7.5 mg per day (1/2 ampoule).

The maximum daily dose of meloxicam is 15 mg.

The drug is administered via a deep intramuscular injection. With repeated injections alternate injections into the left and right buttocks.

If severe pain occurs during the administration of the drug, discontinue the injection immediately.

Given the possible incompatibility, the contents of the ampoules of the Mesipol® preparation should not be mixed in the same syringe with other medicines.

In elderly patients, patients with an increased risk of adverse reactions, as well as in patients with severe renal failure who are on hemodialysis, the dose should not exceed 7.5 mg per day.

For patients with mild to moderate renal insufficiency (creatinine clearance 30-60 ml / min), dose adjustment is not required.

For patients with mild or moderate hepatic insufficiency, dose adjustment is not required.

The drug can not be administered intravenously.

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

Side effects:

Available data suggest that the use of certain NSAIDs (especially in high doses and long-term treatment) may be associated with a slight increase in the risk of developing arterial thrombosis (eg, myocardial infarction or stroke).

The frequency of adverse reactions listed below was determined according to the following criteria: very often (≥ 10%); often (≥ 1%, <10%); infrequently (≥ 0.1%, <1%); rarely (≥ 0.01%, <0.1%); very rarely (<0.01%); the frequency is unknown (it is impossible to estimate the frequency from the available data).

From the digestive system: often - dyspepsia, nausea, vomiting, abdominal pain, diarrhea; infrequently - concealed or obvious bleeding, gastritis, stomatitis, constipation, flatulence, belching; rarely - colitis, erosive and ulcerative lesions of the gastrointestinal tract, hyperbilirubinemia, transient liver dysfunction (increased activity of transaminases and bilirubin), esophagitis, stomatitis; very rarely - perforation of the digestive tract, hepatitis.

On the part of the hematopoiesis system: infrequently, anemia; rarely - a change in the blood formula, incl.leukopenia, thrombocytopenia; very rarely - agranulocytosis.

From the skin: infrequently - vascular edema, itching, skin rash; rarely Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria; very rarely - bullous eruptions, erythema multiforme; the frequency is unknown - the photosensitization reaction.

From the respiratory system: rarely - an asthmatic attack in patients with an allergy to NSAIDs and acetylsalicylic acid.

From the central nervous system: often - headache; infrequently - dizziness, drowsiness.

From the side of the organ of hearing and balance: infrequently - vertigo, rarely - noise in the ears.

From the side of the organ of vision: rarely - visual impairment (including, blurred vision), conjunctivitis.

From the side of the psyche: rarely - emotional lability, "nightmarish" dreams; frequency is unknown - confusion, disorientation.

From the side of the cardiovascular system: infrequently - increased blood pressure, "hot flashes" of blood to the skin of the face; rarely - a feeling of palpitations.

From the urinary system: infrequently - sodium and water retention, hyperkalemia, hypercreatininaemia and / or urea increase in blood serum; very rarely acute renal failure.

From the immune system: infrequently - allergic reactions (except anaphylactic or anaphylactoid reactions); frequency unknown - anaphylactic shock, anaphylactoid reactions, anaphylactic reactions.

Local reactions: often - densification and pain at the injection site.

General reactions: infrequently - edema, including swelling of the lower extremities.

Overdose:

Symptoms: lethargy, drowsiness, nausea, vomiting, epigastric pain, gastrointestinal bleeding, increased blood pressure, acute renal failure, hepatic failure, respiratory arrest, coma, convulsions, cardiovascular collapse, cardiac arrest, anaphylactoid reactions.

Treatment: There is no specific antidote. Symptomatic therapy is recommended. In clinical studies it was shown that colestramine accelerates the excretion of meloxicam.

Interaction:

Interactions with other medications have been studied only for adults. Simultaneous use with other NSAIDs (including acetylsalicylic acid in a dose of 1 g or more per reception or Zgi more per day) is not recommended because of the high risk of development of erosive-ulcerative lesions and bleeding of the gastrointestinal tract.

When used simultaneously with glucocorticosteroids, the risk of erosive and ulcerative lesions and gastrointestinal bleeding increases.

With simultaneous use with diuretics and antihypertensive drugs, it is possible to reduce the effectiveness of the latter. In some patients with impaired renal function (eg, in patients with dehydration or in elderly patients with decreased renal function) concurrent use of angiotensin converting enzyme or angiotensin-II and cyclooxygenase inhibitors can lead to further impairment of renal function, usually reversible.

With the simultaneous use of NSAIDs and calcineurin inhibitors (ciclosporin, tacrolimus) nephrotoxicity of the latter may increase. Kidney function should be monitored.

With the simultaneous use of meloxicam with hypoglycemic agents for oral administration, it can intensify their action, thereby contributing to the risk of hypoglycemia.

Simultaneous use with lithium preparations is not recommended because of the accumulation of lithium and the increase in its toxic effect due to decreased renal excretion.If the use of both drugs is necessary, the plasma lithium concentrations should be monitored at the onset of combined treatment with meloxicam, dose adjustment and meloxicam cancellation.

NSAIDs can reduce the tubular secretion of methotrexate, thus increasing the concentration of methotrexate in the blood plasma. In this regard, the use of meloxicam in patients taking high doses of methotrexate (more than 15 mg per week) is not recommended. The risk of interaction between NSAIDs and methotrexate should also be considered in patients taking low doses of methotrexate, especially if the kidney function is impaired. If necessary, this combination should regularly monitor the blood picture and kidney function. Care should be taken when using both drugs for 3 days, as the concentration of methotrexate in the plasma may increase, which can cause an increase in its toxic effect. The pharmacokinetics of methotrexate (at a dose of 15 mg per week) did not change with the simultaneous use of meloxicam, however the hematological toxicity of methotrexate may increase with the use of NSAIDs.

With simultaneous use with intrauterine contraceptives, the effectiveness of the latter may be reduced.

Simultaneous use of NSAIDs with anticoagulants or heparin (warfarin) in geriatric or therapeutic doses is not recommended, as it leads to a significant increase in the risk of bleeding. In other cases of joint use of heparin and NSAIDs, care should be taken (regular monitoring of blood clotting parameters is necessary).

With simultaneous use with thrombolytic drugs (streptokinase, fibrinolysin) increases the risk of bleeding.

With simultaneous application with colestyramine, as a result of binding meloxicam, the excretion of meloxicam through the digestive tract increases by 50%, while the half-life decreases to 13 ± 3 hours. This interaction is of clinical importance.

Clinically insignificant pharmacokinetic interactions were detected with simultaneous use of meloxicam and antacids, cimetidine and digoxin.

When used simultaneously with selective serotonin reuptake inhibitors, the risk of developing gastrointestinal bleeding increases.

Special instructions:

Care should be taken when using the drug in patients who have a history of esophagitis, gastritis, peptic ulcer and duodenal ulcer, as well as patients who are on anticoagulant therapy. In such patients, the risk of ulcerative-erosive gastrointestinal diseases is increased. Gastrointestinal bleeding, ulcerative-erosive disease of the gastrointestinal tract or its perforation due to the use of NSAIDs can be absolutely sudden, without anamnestic prerequisites, and be fatal to the patient. The risk of such events increases with an increase in the dose of NSAIDs; it is also higher in patients with history of a history of ulcerative erosion, especially with bleeding or perforation, as well as in elderly patients. Such patients should begin treatment with the lowest therapeutic doses. Consideration should be given to assigning patients to the risk group, as well as patients taking low dosages of acetylsalicylic acid, combined therapy with misoprostol or proton pump inhibitors. Care should be taken to monitor any unusual reactions from the gastrointestinal tract in these patients, especially at the beginning of treatment, so as not to miss serious side effects (especially bleeding).Care must be taken in patients taking medications that increase the risk of erosive ulcerative lesions and bleeding:

- heparin;

- anticoagulants (eg, warfarin);

- other NSAIDs (including acetylsalicylic acid in doses of at least 1 g at a time or at least 3 grams per day.

If, during treatment with meloxicam, the patient has bleeding from the digestive tract, immediately discontinue the drug.

Caution should be used to prescribe NSAIDs for patients with gastrointestinal ailments in history (ulcerative colitis, Crohn's disease).

Care should be taken to monitor patients with a history of high blood pressure and / or congestive heart failure of mild and moderate severity, as there are reports of fluid retention and swelling in the use of NSAIDs. It is necessary to control blood pressure in such patients before treatment, and also at the beginning of therapy with meloxicam. There is evidence that the use of NSAIDs, especially in high doses and for a long time, may be associated with a slight increase in the risk of developing arterial thrombosis (for example, in the form of myocardial infarction or stroke).All risks should be weighed carefully before starting treatment with meloxicam in patients with uncompensated hypertension, congestive heart failure. Particular caution should be exercised in the appointment of meloxicam in patients with uncontrolled hypertension, congestive heart failure, confirmed by coronary heart disease, peripheral arterial disease and disorders of cerebral circulation. It is also necessary to evaluate the risks associated with the appointment of a long course of treatment for patients with risk factors for cardiovascular disease (such as hypertension, hyperlipidemia, diabetes mellitus, smoking).

Very rare cases of serious (including fatal) adverse reactions on the part of the skin when applying NSAIDs, including exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis. Most of these reactions occur within the first month after the start of treatment. It should immediately stop the use of meloxicam at the first signs of skin rashes, damage to the mucous membranes or any manifestations of hypersensitivity.If a patient develops Stevens-Johnson syndrome or toxic epidermal necrolysis with meloxicam, treatment with this drug should be immediately discontinued and should not be resumed under any circumstances.

In the application of meloxicam, as well as other NSAIDs, there have been isolated cases of increased serum transaminase activity, bilirubin concentration and changes in other parameters of liver function, as well as an increase in the concentration of creatinine, urea nitrogen in the blood, and other laboratory indicators. Most of these changes are mild and transient. If the laboratory deviations are significant and long-lasting, then meloxicam should be discontinued and the patient should be examined.

In connection with the inhibition of vasodilation caused by prostaglandin of the kidneys, NSAIDs can cause functional renal failure due to a decrease in glomerular filtration. This effect of NSAIDs is dose-dependent. Should carefully monitor diuresis and renal function at the beginning of treatment with NSAIDs and after increasing the dose in patients with the following risk factors:

- elderly age;

- combined therapy with angiotensin converting enzyme inhibitors, angiotensin-II, derivatives of sartan, diuretics;

- hypovolemia;

- chronic heart failure;

- kidney failure;

- nephrotic syndrome;

- lupus nephropathy;

- serious impairment of liver function (serum albumin <25 g / l or expression ≥ 10 on the Child-Pugh scale).

In rare cases, NSAIDs cause interstitial nephritis, glomerulonephritis, renal medullary necrosis or nephrotic syndrome. In patients with end-stage renal failure or hemodialysis, the dose of meloxicam should not exceed 7.5 mg.

Patients with impaired renal function of mild and moderate severity (creatinine clearance 30-60 ml / min) dose adjustment of meloxicam is not required.

Taking NSAIDs can cause sodium, potassium and water retention in the body and weakening of the natriuretic effect of diuretics. There may also be a decrease in the antihypertensive effect of drugs used to treat hypertension. In this regard, some patients may develop or develop edema, heart failure and hypertension.It is necessary to ensure thorough medical supervision of patients at risk.

Hyperkalemia can worsen in diabetes mellitus, as well as in the appointment of combination therapy with drugs that increase the concentration of potassium in the blood. In such cases, the concentration of potassium in the blood should be monitored regularly.

Adverse reactions are often worse tolerated by elderly or weakened patients, so they need special attention. As with other NSAIDs, elderly patients are more likely to have liver, kidney and heart failure, so they need special control. In addition, this age group of patients increased the incidence of such adverse reactions with NSAIDs, such as gastrointestinal bleeding and perforation of ulcers that can lead to death.

Meloksikam, as well as other NSAIDs, can mask the symptoms of infectious diseases.

The use of meloxicam, as well as other drugs blocking the synthesis of prostaglandins, can affect fertility, so it is not recommended for women who want to become pregnant.

Effect on the ability to drive transp. cf. and fur:

During the treatment period, it is possible to reduce the speed of mental and motor reactions, so it is necessary to refrain from driving transport and occupations with other potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Solution for intramuscular injection 10 mg / ml.

Packaging:

For 1.5 ml of solution in glass ampoules of the 1st type, a capacity of 2 ml with a coding ring of green color applied to the surface of the ampoule.

For 3 or 5 ampoules together with instructions for medical use in a cardboard box.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:PL-000555

Date of registration:14.07.2011

Expiration Date:14.07.2016

The owner of the registration certificate:Pharmaceutical factory "POLFARMA" JSCPharmaceutical factory "POLFARMA" JSC Poland

Manufacturer: & nbsp

POLPHARMA, S.A. Poland

Representation: & nbspAKRIKHIN OJSC AKRIKHIN OJSC Russia

Information update date: & nbsp14.07.2016

Illustrated instructions

Instructions

Mesipol® (Mesipol®)