Meloxicam, tablets 15 mg 20 pcs

Osteoarthritis and arthritis, Lumbago, Pain, Back pain, Osteoarthritis, Rheumatoid arthritis, Joint pain (arthralgia), Pain after injuries and operations, Radiculitis, Osteochondrosis, Periarthritis, Sciatica, Pain in the neck

Indications

Symptomatic treatment:
• osteoarthritis (arthrosis, degenerative joint diseases), including with a pain component;
• rheumatoid arthritis;
• ankylosing spondylitis;
• juvenile rheumatoid arthritis (in patients weighing ≥ 60 kg);
• other inflammatory and degenerative diseases of the musculoskeletal system, such as arthropathy, dorsopathies (for example, sciatica, low back pain, shoulder periarthritis and others), accompanied by pain.

Pharmacological effect

Pharmacotherapeutic group: non-steroidal anti-inflammatory drug – NSAID.

ATX code: M01AC06

Pharmacological properties

Pharmacodynamics

The drug Meloxicam is a non-steroidal anti-inflammatory drug, belongs to enolic acid derivatives and has anti-inflammatory, analgesic and antipyretic effects. The pronounced anti-inflammatory effect of meloxicam has been established in all standard models of inflammation.

The mechanism of action of meloxicam is its ability to inhibit the synthesis of prostaglandins, known mediators of inflammation.

Meloxicam in vivo inhibits the synthesis of prostaglandins at the site of inflammation to a greater extent than in the gastric mucosa or kidneys.

These differences are due to more selective inhibition of cyclooxygenase-2 (COX-2) compared with cyclooxygenase-1 (COX-1). Inhibition of COX-2 is thought to mediate the therapeutic effects of NSAIDs, whereas inhibition of the constitutively present isoenzyme COX-1 may be responsible for gastric and renal side effects. 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 has been demonstrated when used as a test system for human whole blood in vitro. It was found that meloxicam (in doses of 7.5 and 15 mg) more actively inhibited COX-2, having a greater inhibitory effect on the production of prostaglandin E2 stimulated by lipopolysaccharide (reaction controlled by COX-2) than on the production of thromboxane involved in the blood coagulation process (reaction controlled by COX-1). These effects were dose dependent. Ex vivo studies have shown that meloxicam (at doses of 7.5 mg and 15 mg) has no effect on platelet aggregation and bleeding time.

In clinical studies, gastrointestinal (GI) adverse reactions (AEs) generally occurred less frequently with meloxicam 7.5 and 15 mg than with other NSAIDs compared. This difference in the frequency of HP from the gastrointestinal tract is mainly due to the fact that when taking meloxicam, such phenomena as dyspepsia, vomiting, nausea, and abdominal pain were observed less often. The incidence of upper gastrointestinal perforations, ulcers, and bleeding associated with meloxicam use was low and dose-related.

Pharmacokinetics

Absorption

Meloxicam is well absorbed from the gastrointestinal tract, as evidenced by its high absolute bioavailability (90%) after oral administration. After a single dose of meloxicam, the maximum plasma concentration of meloxicam (Cmax) is achieved within 5-6 hours. Concomitant intake of food and inorganic antacids does not alter absorption. When using the drug orally (in doses of 7.5 and 15 mg), the concentrations of meloxicam are proportional to the doses. The equilibrium state of pharmacokinetics is achieved within 3-5 days. The range of differences between the maximum and basal concentrations of meloxicam after taking it once a day is relatively small and is 0.4-1.0 mcg/ml when using a dose of 7.5 mg, and 0.8-2.0 mcg/ml when using a dose of 15 mg (the values ​​of the minimum concentration (Cmin) and Cmax during the period of equilibrium state of pharmacokinetics are given, respectively), although values ​​outside the specified range were also noted.

Cmax during the period of equilibrium pharmacokinetics is achieved 5-6 hours after oral administration.

Distribution

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

Biotransformation

Meloxicam is almost completely metabolized in the liver to form 4 pharmacologically inactive derivatives. The main metabolite, 5′-carboxymeloxicam (60% of the dose), is formed by oxidation of the 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 CYP3A4 isoenzyme 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.

Elimination

It is excreted equally through the intestines and kidneys, mainly in the form of metabolites. Less than 5% of the daily dose is excreted unchanged through the intestines; unchanged meloxicam is found in urine only in trace amounts. The average half-life of meloxicam varies from 13 to 25 hours.

Plasma clearance averages 7-12 ml/min after a single dose of meloxicam.

Special patient groups

Patients with impaired liver and/or kidney function

Insufficiency of liver function, as well as mild renal failure, do not have a 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 less well to plasma proteins in patients with end-stage renal failure. In end-stage renal failure, an increase in volume of distribution may result in higher concentrations of free meloxicam, so in these patients the daily dose should not exceed 7.5 mg.

Elderly patients

Elderly patients compared to young patients have similar pharmacokinetic parameters. In elderly patients, the average 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 longer half-life compared to younger patients of both sexes.

Children

Cmax (-34%) and AUC0-∞ (-28%) were lower in younger children (2-6 years) compared to older children (7-14 years), and drug clearance (adjusted for body weight) was higher in younger children. A retrospective comparison with adults showed that meloxicam plasma concentrations were similar in older children and adults. In children of both age groups, the plasma half-life of meloxicam was similar (13 hours) and slightly shorter than in adults (15-20 hours).

Special instructions

Patients with gastrointestinal diseases should be under medical supervision. If ulcerative lesions of the gastrointestinal tract or gastrointestinal bleeding occur, Meloxicam should be discontinued.
Gastrointestinal ulcers, perforation, or bleeding may occur at any time during the use of NSAIDs, with or without warning symptoms or a history of serious gastrointestinal complications. The consequences of these complications are generally more serious in older people.
When using Meloxicam, serious skin reactions such as exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis may develop. Therefore, special attention should be paid to patients reporting the development of adverse events from the skin and mucous membranes, as well as hypersensitivity reactions to the drug, especially if such reactions were observed during previous courses of treatment. The development of such reactions is observed, as a rule, during the first month of treatment. If the first signs of skin rash, changes in the mucous membranes or other signs of hypersensitivity appear, discontinuation of Meloxicam should be considered.
When taking NSAIDs, cases of increased risk of developing serious cardiovascular thrombosis, myocardial infarction, and angina pectoris, possibly fatal, have been described. This risk increases with long-term use of the drug, as well as in patients with a history of the above diseases 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 reduced circulating blood volume may lead to decompensation of latent renal failure. After discontinuation of NSAIDs, renal function usually returns to baseline levels. Those most at risk for developing this reaction are elderly patients, patients with dehydration, CHF, liver cirrhosis, nephrotic syndrome or acute renal impairment, patients concomitantly taking diuretics, ACE inhibitors, angiotensin II receptor antagonists, and patients who have undergone major surgical procedures that lead to hypovolemia.
In such patients, diuresis and renal function should be carefully monitored when initiating therapy.
The use of NSAIDs in combination with diuretics can lead to sodium, potassium and water retention, as well as a decrease in the natriuretic effect of diuretics. As a result, predisposed patients may experience increased signs of heart failure or hypertension. Therefore, such patients should be closely monitored and adequate hydration maintained. Before starting treatment, a kidney function test is necessary. In case of combination therapy, renal function should also be monitored. When using Meloxicam (as well as most other NSAIDs), episodic increases in serum transaminase activity or other indicators of liver function are possible. In most cases, this increase was small and transitory. If the identified changes are significant or do not decrease over time, the drug Meloxicam should be discontinued and the identified laboratory changes should be monitored.
Weakened or malnourished patients may be less able to tolerate adverse events, and therefore such patients should be under medical supervision.
Like other NSAIDs, Meloxicam may mask the symptoms of an underlying infectious disease.

Impact on the ability to drive vehicles and machinery
No special clinical studies have been conducted on the effect of the drug on the ability to drive vehicles and operate machinery. However, when driving vehicles and working with machinery, the possibility of dizziness, drowsiness, visual impairment or other disorders of the central nervous system should be taken into account. Patients should be careful when operating vehicles and machinery.

Active ingredient

Meloxicam

Composition

1 tablet 7.5 mg contains:

Active ingredient: meloxicam – 7.5 mg.

Excipients: lactose monohydrate (milk sugar) – 67.0 mg, microcrystalline cellulose – 15.0 mg, sodium citrate dihydrate – 4.0 mg, crospovidone – 2.0 mg, povidone-K25 – 3.5 mg, magnesium stearate – 1.0 mg.

1 tablet 15 mg contains:

Active ingredient: meloxicam – 15.0 mg.

Excipients: lactose monohydrate (milk sugar) – 134.0 mg, microcrystalline cellulose – 30.0 mg, sodium citrate dihydrate – 8.0 mg, crospovidone – 4.0 mg, povidone-K25 – 7.0 mg, magnesium stearate – 2.0 mg.

Pregnancy

The use of Meloxicam is contraindicated during pregnancy.
It is known that NSAIDs pass into breast milk, therefore the use of Meloxicam during breastfeeding is contraindicated.
As a drug that inhibits cyclooxygenase/prostaglandin synthesis, Meloxicam may have an effect on fertility and is therefore not recommended for use in women planning pregnancy. Meloxicam may delay ovulation. In this regard, in women who have problems conceiving and are undergoing examination for such problems, it is recommended to discontinue taking the drug Meloxicam.

Contraindications

• Hypersensitivity to the active substance or excipients 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 NSAIDs 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 suffered;
• Inflammatory bowel diseases – Crohn’s disease or ulcerative colitis in the acute stage;
• Severe liver failure;
• Severe renal failure (if hemodialysis is not performed, creatinine clearance (CC) less than 30 ml/min, and also with confirmed hyperkalemia), progressive kidney disease;
• Active gastrointestinal bleeding, recent cerebrovascular bleeding or established diagnosis of diseases of the blood coagulation system;
• Severe uncontrolled heart failure;
• Pregnancy;
• Breastfeeding period;
• Therapy of perioperative pain during coronary artery bypass grafting;
• Rare hereditary galactose intolerance, lactase deficiency, glucose-galactose malabsorption (the maximum daily dose of the drug with a meloxicam dosage of 7.5 mg and 15 mg contains 67 mg and 134 mg of lactose, respectively).

With caution
• History of gastrointestinal diseases (peptic ulcer of the stomach and duodenum, liver disease);
• Chronic heart failure (CHF);
• Renal failure (creatinine clearance 30-60 ml/min);
• Coronary heart disease;
• Cerebrovascular diseases;
• Dyslipidemia/hyperlipidemia;
• Diabetes mellitus;
• Concomitant therapy with the following drugs: oral glucocorticosteroids (GCS), anticoagulants (including warfarin), antiplatelet agents, selective serotonin reuptake inhibitors (including citalopram, fluoxetine, paroxetine, sertraline);
• Peripheral arterial diseases;
• Old age;
• Long-term use of NSAIDs;
• Smoking;
• Frequent consumption of alcohol.

Side Effects

The following are descriptions of adverse reactions that were assessed as possible to be associated with the use of meloxicam.

HP registered during post-registration use, the connection with which the drug was considered possible, are marked with *.

Within systemic organ classes, the following categories are used for the incidence of HP: very common (> 1/10), common (> 1/100, < 1/10), uncommon (> 1/1000, < 1/100), rare (> 1/10,000, < 1/1000), very rare (< 1/10,000) and frequency unknown (cannot be estimated from the available data).

Disorders 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: uncommon – other immediate hypersensitivity reactions*; frequency unknown – anaphylactic shock*, anaphylactoid reactions*.

Mental disorders: often – mood changes*; frequency unknown – confusion*, disorientation*.

Nervous system disorders: often – headache; infrequently – dizziness, drowsiness.

Visual disorders: rarely – conjunctivitis*, visual impairment, including blurred vision*.

Hearing and labyrinthine disorders: uncommon – vertigo; rarely – tinnitus.

Cardiac disorders: rarely – palpitations.

Vascular disorders: infrequently – increased blood pressure, a feeling of a “rush” of blood to the face.

Gastrointestinal disorders: often – abdominal pain, dyspepsia, diarrhea, nausea, vomiting; uncommon – hidden or obvious gastrointestinal bleeding, gastritis*, stomatitis, constipation, bloating, belching; rarely – gastroduodenal ulcers, colitis, esophagitis; very rarely – perforation of the gastrointestinal tract.

Disorders of the liver and biliary tract: infrequently – transient changes in liver function indicators (for example, increased transaminase activity or bilirubin concentration); very rarely – hepatitis*.

Skin and subcutaneous tissue disorders: uncommon – angioedema*, itching, skin rash; rarely – toxic epidermal necrolysis*, Stevens-Johnson syndrome*, urticaria; very rarely – bullous dermatitis*, erythema multiforme*; frequency unknown – photosensitivity.

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

Renal and urinary tract disorders: uncommon – changes in renal function (increased levels of creatinine and/or urea in the blood serum), urinary disorders, including acute urinary retention*; very rarely – acute renal failure*.

Disorders of the genital organs and mammary gland: uncommon – late ovulation*; frequency unknown – infertility in women*.

Concomitant use with drugs that suppress bone marrow (for example, methotrexate) may cause cytopenia.

Gastrointestinal bleeding, ulceration, or perforation can be fatal. As with other NSAIDs, the possibility of interstitial nephritis, glomerulonephritis, renal medullary necrosis, and nephrotic syndrome cannot be excluded.

Given that the indication “juvenile rheumatoid arthritis” applies only to a certain group of children weighing more than 60 kg, the safety profile of the drug is expected to be the same as in adults. The safety profile observed in relevant clinical studies in children, as well as post-marketing studies, did not show significant differences in the safety profile with those in adults.

Interaction

Other inhibitors of prostaglandin synthesis, including corticosteroids and salicylates – simultaneous use with meloxicam increases the risk of ulcers 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 use with meloxicam increases the risk of bleeding. In case of simultaneous use, careful monitoring of the blood coagulation system is necessary.

Antiplatelet drugs, serotonin reuptake inhibitors – simultaneous use with meloxicam increases the risk of bleeding due to inhibition of platelet function. In case of simultaneous use, careful monitoring of the blood coagulation system is necessary.

Lithium preparations – NSAIDs increase the concentration of lithium in plasma by reducing its excretion by the kidneys. The simultaneous use of meloxicam with lithium preparations is not recommended. If simultaneous use is necessary, careful monitoring of plasma lithium concentrations is recommended throughout the course of lithium use.

Methotrexate – NSAIDs reduce the secretion of methotrexate by the kidneys, thereby increasing its plasma concentration. 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. When meloxicam and methotrexate are used together for 3 days, the risk of increased toxicity of the latter increases.

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 case of dehydration of patients is accompanied by the risk of developing acute renal failure.

Antihypertensive drugs (beta-blockers, angiotensin-converting enzyme inhibitors, vasodilators, diuretics). NSAIDs reduce the effect of antihypertensive drugs due to inhibition of the synthesis 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 can thereby lead to the development of acute renal failure, especially in patients with impaired renal function.

Cholestyramine, by binding meloxicam in the gastrointestinal tract, leads to its faster elimination.

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

Pemetrexed – with the simultaneous use of meloxicam and pemetrexed in patients with CC from 45 to 79 ml/min, meloxicam should be discontinued five days before starting pemetrexed and can be resumed 2 days after the end of the drug. If there is a need for combined use of meloxicam and pemetrexed, patients should be closely monitored, especially with regard to myelosuppression and the occurrence of gastrointestinal HP. In patients with CC less than 45 ml/min, taking meloxicam with pemetrexed is not recommended.

When co-administering medicinal products with meloxicam that have a known ability to inhibit CYP2C9 and/or CYP3A4 (or are metabolized by these enzymes), such as sulfonylureas or probenecid, the possibility of pharmacokinetic interaction should be taken into account.

When used together with oral hypoglycemic agents (for example, sulfonylureas, 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 taking meloxicam concomitantly with a sulfonylurea or nateglinide should carefully monitor blood glucose concentrations due to the potential for hypoglycemia.

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

Overdose

Symptoms
There is insufficient data on cases involving drug overdose. Symptoms characteristic of an NSAID overdose are likely to be present in severe cases: drowsiness, disturbances of 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 drug overdose, the following should be carried out: evacuation of the stomach contents and general supportive therapy. Cholestyramine accelerates the elimination of meloxicam.

Storage conditions

In a place protected from light at a temperature not exceeding 25 ºС.
Keep out of the reach of children.

Shelf life

3 years. Do not use after expiration date.

Manufacturer

Ozon, Russia