Meloxicam-Teva tablets 7,5mg, No. 20

Symptomatic treatment:

• osteoarthritis (arthrosis, degenerative diseases of the joints), including with a pain component; - rheumatoid arthritis;

• ankylosing spondylitis;

• other inflammatory and degenerative diseases of the musculoskeletal system, such as arthropathies, dorsopathies (for example, sciatica, lower back pain, shoulder periarthritis, and others), accompanied by pain.

Osteoarthritis with pain: 7.5 mg per day. If necessary, this dose can be increased to 15 mg per day.

Rheumatoid arthritis: 15 mg daily. Depending on the therapeutic effect, this dose can be reduced to 7.5 mg per day.

Ankylosing spondylitis: 15 mg daily. 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 (history of gastrointestinal tract disease, presence of risk factors for cardiovascular diseases), it is recommended to start treatment with a dose of 7.5 mg per day (see Special Instructions).

In patients with severe renal failure 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 use

The drug should not be used concomitantly with other NSAIDs. The total daily dose of Meloxicam-Teva used in different dosage forms should not exceed 15 mg.

Teenagers

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

The use of tablets

The drug is contraindicated in children under 12 years of age due to the impossibility of selecting the appropriate dosage for this age group. The total daily dose should be taken at one time, with meals, with water or other liquid.

Active substance:

Meloxicam - 7.5 mg

Excipients: lactose monohydrate 77.2 mg, microcrystalline cellulose 56.0 mg, sodium citrate dihydrate 18.0 mg, povidone-KZO 6.0 mg, crospovidone 12.0 mg, colloidal silicon dioxide 1.5 mg, magnesium stearate 1 , 8 mg.

• Hypersensitivity to the active ingredient or auxiliary components of the drug.

• Complete or incomplete combination of bronchial asthma, recurrent polyposis of the nose and paranasal sinuses, angioedema or urticaria caused by intolerance to acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs due to the existing likelihood of cross-sensitivity (including a history).

• Erosive and 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 liver failure.

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

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

• Severe uncontrolled heart failure.

• Pregnancy.

• Breast-feeding.

• Therapy of perioperative pain during coronary artery bypass grafting.

• Children under 12 years of age.

• Rare hereditary galactose intolerance (in the maximum daily dose of the drug with a dosage of 7.5 mg and 15 mg meloxicam, 47 mg and 20 mg of lactose are contained, respectively).

  Carefully:

• Coronary heart disease; cerebrovascular diseases; chronic heart failure; dyslipidemia / hyperlipidemia; diabetes; peripheral arterial disease, smoking, renal failure (creatinine clearance 30-60 ml / min); anamnestic data on the development of ulcerative lesions of the gastrointestinal tract; presence of Helicobacter pylori infection; elderly age; long-term use of NSAIDs; frequent alcohol consumption, severe somatic diseases; concomitant therapy with the following drugs: anticoagulants (eg, warfarin), antiplatelet agents (eg, acetylsalicylic acid, clopidogrel), oral glucocorticoids (eg, prednisolone), selective serotonin reuptake inhibitors (eg, citalopram, fluoxetine, serlin).

Pharmacodynamics

Meloxicam is a non-steroidal anti-inflammatory drug with anti-inflammatory and antipyretic effects. The anti-inflammatory effect is associated with inhibition of the enzymatic activity of cyclooxygenase-2 (COX-2), which is involved in the biosynthesis of prostaglandin in the area of ??inflammation. To a lesser extent, meloxicam acts on cyclooxygenase-1 (COX-1), which is involved in the synthesis of prostaglandin, which protects the mucous membrane of the gastrointestinal tract (GIT) and takes part in the regulation of blood flow in the kidneys.

Pharmokinetics

Absorption.

Meloxicam is well absorbed from the gastrointestinal tract, as evidenced by the high absolute bioavailability (90%) after oral administration. After a single use of meloxicam, the maximum plasma concentration of the drug is reached within 5-6 hours. The 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. A steady state of pharmacokinetics is achieved within 3-5 days. The range of differences between the maximum and basal concentrations of the drug after taking it once a day is relatively small and amounts to 0.4-1.0 ?g / ml when using a dose of 7.5 mg, and 0.8-2 when using a dose of 15 mg, 0 ?g / ml (the values ??of Cmin and Cmax are given, respectively, during the period of steady state pharmacokinetics),although values ??outside the specified range were also noted. The maximum plasma concentration of meloxicam in the period of steady state pharmacokinetics is achieved 5-6 hours after oral administration.

Distribution.

Meloxicam binds very well to plasma proteins, mainly albumin (99%). Penetrates into the synovial fluid, the concentration in the synovial fluid is approximately 50% of the plasma concentration. The volume of distribution after repeated oral administration of meloxicam (in doses from 7.5 mg to 15 mg) is about 16 liters, with a coefficient of variation from 11 to 32%.

Metabolism.

Meloxicam is almost completely metabolized in the liver with the formation of 4 pharmacologically inactive derivatives. The main metabolite, 5'-carboxymeloxicam (60% of the dose), is formed by oxidation of an intermediate metabolite, 5'-hydroxymethylmeloxicam, which is also excreted, but to a lesser extent (9% of the dose). In vitro studies have shown that CYP2C9 plays an important role in this metabolic transformation, and the isoenzyme CYP3A4 is of additional importance. Peroxidase is involved in the formation of the other two metabolites (constituting, respectively, 16% and 4% of the drug dose), the activity of which probably varies individually.

Excretion.

It is excreted equally through the intestines and by the kidneys, mainly in the form of metabolites. In unchanged form, less than 5% of the daily dose is excreted in the feces, in urine unchanged the drug is found only in trace amounts. The average elimination half-life of meloxicam varies from 13 to 25 hours. Plasma clearance averages 7-12 ml / min after a single dose of meloxicam. Lack of liver and / or kidney function. Lack of liver function, as well as mild renal failure, has no significant effect on the pharmacokinetics of meloxicam. The rate of elimination of meloxicam from the body is significantly higher in patients with moderate renal failure. Meloxicam binds to plasma proteins worse in patients with end-stage renal failure.In end-stage renal failure, an increase in the volume of distribution can lead to higher concentrations of free meloxicam, therefore, in these patients, the daily dose should not exceed 7.5 mg.

Elderly patients.

Elderly patients have similar pharmacokinetic parameters compared to younger patients. In elderly patients, the mean plasma clearance during steady state pharmacokinetics is slightly lower than in younger patients. Elderly women have higher AUC values ??(area under the concentration-time curve) and a long half-life compared with younger patients of both sexes.

Overdose

Symptoms: impaired consciousness, nausea, vomiting, epigastric pain are usually reversible. Gastrointestinal bleeding is possible. Severe poisoning can lead to acute renal failure, liver failure, respiratory arrest, asystole. Treatment: there is no specific antidote; in case of drug overdose, gastric lavage, activated charcoal intake (within the next hour) and symptomatic therapy should be performed. In clinical studies, it has been shown that cholestyramine, by binding meloxicam in the gastrointestinal tract, leads to its more rapid elimination. Forced diuresis, alkalization of urine, hemodialysis are ineffective due to the high connection with blood proteins.

Side effects

Side effects recorded during post-marketing use, the connection of which with the drug intake was regarded as possible, are marked with a *.

On the part of the blood and lymphatic system: infrequently - anemia; rarely - changes in the number of blood cells, including changes in the leukocyte formula, leukopenia, thrombocytopenia.

Immune system disorders: infrequently - other immediate-type hypersensitivity reactions *; not established - anaphylactic shock *, anaphylactoid reactions *.

From the nervous system: often - headache; infrequently - dizziness, drowsiness. Mental disorders: often - mood changes *; not established - confusion *, disorientation *.

From the senses: infrequently - vertigo; rarely - conjunctivitis *, visual impairments, including blurred vision *, tinnitus.

From the gastrointestinal tract: often - abdominal pain, dyspepsia, diarrhea, nausea, vomiting; infrequently - latent or overt gastrointestinal bleeding, gastritis *, stomatitis, constipation, bloating, belching; rarely - gastroduodenal ulcers, colitis, esophagitis; very rarely - perforation of the gastrointestinal tract.

From the liver: infrequently - transient changes in liver function indicators (for example, an increase in the activity of transaminases or bilirubin); very rarely - hepatitis *.

On the part of the skin and subcutaneous tissues: infrequently - angioedema *, 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 side of the cardiovascular system: infrequently - increased blood pressure, a feeling of 'rush' of blood to the face; rarely - palpitations.

From the genitourinary system: infrequently - changes in renal function indicators (increased serum creatinine and / or urea levels), urinary disorders, including acute urinary retention *; very rarely - acute renal failure *.

From the genitals and mammary gland: infrequently - late ovulation *; not established - infertility in women *. Concomitant use with drugs that depress the bone marrow (for example, methotrexate) can provoke cytopenia.

Drug interactions

Other inhibitors of prostaglandin synthesis, including glucocorticoids and salicylates - concomitant use with meloxicam increases the risk of ulceration in the gastrointestinal tract and gastrointestinal bleeding (due to synergistic action). Concomitant use 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 drugs, 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 plasma level of lithium by decreasing its excretion by the kidneys. The simultaneous use of meloxicam with lithium preparations is not recommended. If necessary, simultaneous use is recommended to carefully monitor the concentration of lithium in the plasma during the entire course of the use of lithium preparations.

Methotrexate - NSAIDs reduce the secretion of methotrexate by the kidneys, thereby increasing its concentration in plasma. The simultaneous use of meloxicam and methotrexate (at a dose of more than 15 mg per week) is not recommended. In case of simultaneous use, careful monitoring of renal function and blood count is necessary. Meloxicam may increase the hematological toxicity of methotrexate, especially in patients with impaired renal function. With the combined use of meloxicam and methotrexate for 3 days, the risk of increased toxicity of the latter increases.

Contraception - There is evidence that NSAIDs can 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 the risk of developing acute renal failure.

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

Angiotensin II receptor antagonists, as well as angiotensin-converting enzyme inhibitors, when used together with NSAIDs, increase the decrease in glomerular filtration, which, thereby, can lead to the development of acute renal failure, especially in patients with impaired renal function.

Cholestyramine, binding meloxicam in the gastrointestinal tract, leads to its more rapid elimination.

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

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

When used in conjunction 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 sulfonylurea derivatives or probenecid, should take into account the possibility of pharmacokinetic interactions.

When used together with antidiabetic drugs for oral administration (for example, sulfonylurea derivatives, nateglinide), interactions mediated by CYP2C9 are possible, which can lead to an increase in the concentration of both these drugs and meloxicam in the blood. Patients concurrently taking meloxicam with sulfonylurea or nateglinide preparations should carefully monitor blood sugar levels due to the possibility of hypoglycemia.

With the simultaneous use of antacids, cimetidine, digoxin and furosemide, no significant pharmacokinetic interactions were identified. Gastrointestinal bleeding, ulceration, or perforation can be fatal. As with other NSAIDs, they do not exclude the possibility of the appearance of interstitial nephritis, glomerulonephritis, renal medullary necrosis, and nephrotic syndrome.