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

Excipients lactose monohydrate 23.50 mg / 20.00 mg, microcrystalline cellulose 102.30 mg / 94.80 mg, sodium citrate 15.00 mg / 18.50 mg, crospovidone 16.00 mg / 16.00 mg, povidone 10 , 50 mg / 10.50 mg, silica colloidal dioxide 3.50 mg / 3.50 mg, magnesium stearate 1.70 mg / 1.70 mg.

Description:

Dosage 7.5 mg: round tablets, light yellow with a weak greenish tinge, on one side - beveled from edge to risk, with engraved "F" and "1" on opposite sides of the risks, on the other hand flat. Insignificant surface roughness of the tablets is allowed.

Dosage of 15 mg: round tablets, light yellow with a weak greenish tinge, on the one hand - beveled from the edge to the risk, with engraved "F" and "2" on either side of the risks, on the other hand flat.

Insignificant surface roughness of the tablets is allowed.

Pharmacotherapeutic group:Non-steroidal anti-inflammatory drug

ATX: & nbsp

M.01.A.C.06 Meloksikam

M.01.A.C Oksikamy

Pharmacodynamics:Non-steroidal anti-inflammatory drug (NSAID), has anti-inflammatory, antipyretic, analgesic effect. Refers to the class of oxycomams; a derivative of enolic acid. The mechanism of action is the inhibition of prostaglandin synthesis as a result of selective suppression of the enzymatic activity of cyclooxygenase-2 (COX2). With the appointment in high doses, long-term use and individual features of the organism, COX2, the selectivity decreases.Suppresses the synthesis of prostaglandins in the inflammatory region to a greater extent than in the mucous membrane of the stomach or kidneys, which is associated with a relatively selective inhibition of COX2. Less often causes erosive and ulcerative diseases of the gastrointestinal tract (GIT).

Pharmacokinetics:

Meloksikam is well absorbed from the digestive tract, as evidenced by high absolute bioavailability (89%) after ingestion. After a single application of meloxicam C_max in plasma is achieved within 5-6 hours. Simultaneous intake of food and inorganic antacids does not change the 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 a dose of 7.5 mg 0.4-1.0 μg / ml, and when a dose of 15 mg is 0.8-2, 0 μg / ml (the values of C_m_in and C_max 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 within 5-6 hours after ingestion.

Distribution

Meloxicam binds very well to plasma proteins, especially 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 ingestion of meloxicam (in doses from 7.5 mg to 15 mg) is about 11 liters, individual fluctuations of 30-40%.

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 the isoenzyme CYP2C9 plays an important role in this metabolic transformation, the isoenzyme CYP3A4 has an additional significance. In the formation of two other metabolites (which make up 16% and 4% of the dose, respectively), 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 20 hours. Plasma clearance is an average of 8 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 Vd 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 (area under the concentration-time curve) and a longer half-life, compared to young patients of both sexes.

Indications:For symptomatic therapy of osteoarthritis (arthrosis, degenerative joint diseases), rheumatoid arthritis, ankylosing spondylitis (Bechterew's disease) in adults and children over 12 years of age. The drug is intended for symptomatic therapy, reducing pain and inflammation at the time of application, the progression of the disease is not affected.

Contraindications:

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

- Complete or incomplete combination of bronchial asthma, angioedema or urticaria, recurrent nasal polyposis and paranasal sinuses and intolerance to acetylsalicylic acid and other non-steroidal anti-inflammatory drugs (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;

- Dysfunction of the liver of a severe degree;

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

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

Decompensated heart failure;

- Pregnancy;

- Breast-feeding;

- Therapy of perioperative pain during coronary artery bypass grafting;

- Children under 12 years;

- Hereditary lactose intolerance, impaired absorption of glucose-galactose, deficiency of lactase.

Carefully:

- Diseases of the gastrointestinal tract in the anamnesis (peptic ulcer of stomach and 12-colon, liver disease); presence of Helicobacter pylori infection;

- ischemic heart disease, chronic heart failure;

- cerebrovascular diseases;

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

- dyslipidemia / hyperlipidemia;

- diabetes;

- simultaneous administration of oral glucocorticosteroids (including prednisolone), anticoagulants (including warfarin), antiaggregants (including clopidogrel), selective serotonin reuptake inhibitors (including citalopram, fluoxetine, paroxetine, sertraline);

- severe physical illnesses; systemic lupus erythematosus and other autoimmune diseases;

- diseases of peripheral arteries;

- elderly age;

- long-term use of non-steroidal anti-inflammatory drugs;

- Smoking;

- frequent use of alcohol.

To reduce the risk of developing adverse events from the gastrointestinal tract (GIT), a minimum effective dose should be used with the minimum possible short course.

Pregnancy and lactation:

Meloksikam is contraindicated during pregnancy. Suppressing the synthesis of prostaglandins can have an undesirable effect on pregnancy and fetal development.

In the III trimester of pregnancy, the use of inhibitors of prostaglandin synthesis can lead to the following violations of fetal development:

- premature closure of the arterial duct and pulmonary hypertension due to toxic effects on the cardiopulmonary system;

- kidney dysfunction, with the further development of renal failure with a decrease in the amount of amniotic fluid.

The mother during the birth can increase the duration of bleeding and decrease the contractile capacity of the uterus, and as a result, the time of delivery increases.

It is known that NSAIDs penetrate into breast milk, so meloxicam it is not recommended to use during lactation.

Dosing and Administration:

Osteoarthritis: 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 and with severe renal failure who are on hemodialysis, the dose should not exceed 7.5 mg per day. Do not combine the drug with other non-steroidal anti-inflammatory drugs.

In adolescents (over 12 years):

The maximum dose in adolescents is 0.25 mg / kg, not more than 15 mg / day.

Tablets should be washed down with water or another liquid and taken with food.

Since the risk of adverse reactions depends on the size of the dose and the duration of application, it should be used during the shortest course possible with the lowest possible effective dose.

The total daily dose of meloxicam applied form of tablets, suppositories, suspension for ingestion and injection, should not exceed 15 mg.

Side effects:

The adverse events presented below are listed according to anatomophysiological classification and frequency of occurrence. The frequency of occurrence is determined by WHO and has the following gradation: very often (> 1/10); often (> 1/100, <1/10); infrequently (> 1/1000, <1/100); rarely (> 1/10000, <1/1000); very rarely (<1/10000); not installed.

Violations from the blood and lymphatic system: rarely - a change in the number of blood cells, including changes in the leukocyte formula: leukopenia, thrombocytopenia, anemia.

Immune system disorders: not established - anaphylactic shock, anaphylactoid / anaphylactic reactions.

Impaired nervous system: often - headache; infrequently - dizziness, drowsiness.

Disorders of the psyche: often - mood changes; not established - confusion, disorientation.

Disorders from the side of the organ of vision: rarely - conjunctivitis, visual impairment, including blurred vision.

Hearing disorders and labyrinthine disturbances: rarely - noise in the ears.

Disorders from the gastrointestinal tract: often - abdominal pain, indigestion, diarrhea, nausea, vomiting; rarely - gastroduodenal ulcers, colitis, esophagitis; infrequently - latent or obvious gastrointestinal bleeding, gastritis, stomatitis, constipation, bloating, belching; very rarely - perforation of the gastrointestinal tract.

Disorders from the liver and bile ducts: infrequently - transient changes in liver function (for example, increased activity of transaminases or bilirubin); very rarely - hepatitis.

Disturbances from the skin and subcutaneous tissues: often - itching, skin rash; infrequently-toxic epidermal necrolysis, very rarely - severe skin reactions (Stevens-Johnson syndrome, Lyell's syndrome), angioedema, not established - allergic dermatitis, photosensitivity.

Disturbances from the respiratory system, chest and mediastinal organs: rarely - bronchial asthma in patients with an allergy to acetylsalicylic acid or other NSAIDs.

Vascular disorders: infrequently - increased blood pressure, a feeling of "tide" of blood to the face;

Heart Disease: rarely - a feeling of palpitations.

Disorders from the kidneys and urinary tract: infrequent - changes in renal function (increased serum creatinine and / or urea levels), urination disorders, including acute urinary retention; very rarely acute renal failure.

Violations of 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:

Symptoms: impaired consciousness, nausea, vomiting, epigastric pain, bleeding from the gastrointestinal tract, acute renal failure, acute liver failure, respiratory arrest, asystole.

Treatment: gastric lavage, reception of activated charcoal, symptomatic therapy. Forced diuresis, alkalization of urine, hemodialysis are ineffective because of the high degree of binding of meloxicam to plasma proteins. There is no specific antidote. Kolestyramine accelerates the excretion of meloxicam from the body.

Interaction:

Other inhibitors of prostaglandin synthesis, including glucocorticosteroids and salicylates: simultaneous administration with meloxicam increases the risk of ulceration in the gastrointestinal tract and gastrointestinal bleeding (due to synergism of action). The combined use of meloxicam and other NSAIDs is not recommended. The combined use of aspirin (1000 mg 3 times daily) and meloxicam in healthy volunteers resulted in an increase in AUC (10%) and C_max (24%) meloxicam. The clinical significance of this interaction is not known.

Anticoagulants for oral administration, antiplatelet agents, heparin for systemic use, thrombolytic agents. Increased risk of bleeding. If it is not possible to avoid the simultaneous use of these drugs, careful monitoring of the effect of anticoagulants is necessary.

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

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

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

Mifepristone: in connection with the theoretical risk of changing the effectiveness of mifepristone under the influence of inhibitors of the synthesis of prostaglandins NSAIDs should not be prescribed earlier than 8-12 days after the withdrawal of mifepristone.

Diuretics. The use of NSAIDs increases the risk of developing acute renal failure in patients with dehydration. In patients receiving meloxicam and diuretics, adequate hydration should be maintained. Before the beginning of treatment it is necessary to study the function of the kidneys.

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

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

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

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

Meloksikam is excreted from the body mainly by hepatic metabolism, about 2/3 of the amount of the drug being metabolized in the liver is destroyed by enzymes of the cytochrome p450 system (the main pathway of metabolism is cytochrome 2C9, the additional pathway is cytochrome ZA4), about 1/3 is metabolized by other systems, for example, by peroxidation. When used in conjunction with meloxicam, drugs that have a known ability to inhibit CYP 2C9 and / or CYP 3A4 (or metabolized with the participation of these enzymes) should be Given simultaneous admission meloxicam can strengthen the action of tablets antidiabetic drugs, thereby there is a risk of hypoglycemia.

Take into account the possibility of pharmacokinetic interaction.

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

Special instructions:

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

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

Particular attention should be given to patients reporting the development of adverse events from the skin and mucous membranes. In such cases, the issue of discontinuing the use of the drug should be considered.

Meloksikam may increase the risk of serious cardiovascular thrombosis, myocardial infarction, angina attack, possibly fatal. 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 are at greatest risk of developing this reaction; patients with dehydration, congestive heart failure, liver cirrhosis,nephrotic syndrome or obvious kidney disease; patients receiving diuretics, ACE inhibitors, angiotensin II receptor antagonists, and patients who underwent serious surgical interventions leading to hypovolemia. In such patients at the beginning of therapy, diuresis and renal function should be carefully monitored.

In rare cases, NSAIDs can cause interstitial nephritis, glomerulonephritis, medullary kidney necrosis or nephrotic syndrome.

In patients with terminal stage of renal failure who are on hemodialysis, the dose of the drug should not exceed 7.5 mg. In patients with small or moderate renal impairment (ie, if creatinine clearance is greater than 30 mL / min), a dose reduction is not required.

When meloxicam (as well as most other NSAIDs) was used, an episodic increase in the level of transaminases or other indicators of liver function in serum was reported. In most cases, this increase was small and transient. If the changes identified are significant or do not decrease over time, the drug should be withdrawn and monitored for laboratory changes identified.

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

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

Meloxicam, as well as other NSAIDs, can mask the symptoms of an infectious disease.

The use of meloxicam, like other preparations blocking cyclooxygenase / synthesis of prostaglandins, can affect fertility, so it is not recommended for women who want to become pregnant. Meloksikam can lead to a delay in ovulation. In this regard, in women, with a violation of the ability to conceive or conduct a survey of infertility should consider the question of the abolition of meloxicam.

Effect on the ability to drive transp. cf. and fur:Special clinical studies of the effect of the drug on the ability to drive vehicles and work with mechanisms have not been carried out. When driving vehicles 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 vehicles and working with mechanisms.

Form release / dosage:Tablets 7.5 mg or 15 mg.

Packaging:

For 10 tablets in a blister of two-layer PVC / PVDH film / aluminum foil.

1, 2 or 3 blisters together with instructions for use in a cardboard bundle.

Storage conditions:

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

Keep out of the reach of children.

Shelf life:2 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-000200

Date of registration:09.02.2011 / 05.09.2016

Expiration Date:Unlimited

The owner of the registration certificate:Aurobindo Pharma Co., Ltd.Aurobindo Pharma Co., Ltd. India

Manufacturer: & nbsp

AUROBINDO PHARMA, Ltd. India

Representation: & nbspAurobindo Pharma, ZAOAurobindo Pharma, ZAO

Information update date: & nbsp22.04.2018

Illustrated instructions

Instructions

Meloksikam (Meloxicam)