Meloxicam pills 7.5mg, 20pcs – Vertex

Composition

Active ingredient:

meloxicam – 7.5 mg;

excipients:

lactose monohydrate – 88.0 mg;

microcrystalline cellulose-62.4 mg;

sodium citrate dihydrate-7.5 mg;

sodium carboxymethyl starch-7.2 mg;

povidone K-30-3.6 mg;

colloidal silicon dioxide-2.0 mg;

calcium stearate-1.8 mg

Pharmacological action

Meloxicam is a nonsteroidal anti-inflammatory drug (NSAID) that has analgesic, anti-inflammatory and antipyretic effects. It belongs to the class of oxycams; it is a derivative of enolic acid. The pronounced anti-inflammatory effect of meloxicam was established in all standard models of inflammation. The mechanism of action of meloxicam is to inhibit the synthesis of prostaglandins-inflammatory mediators.

Meloxicam in vivo inhibits prostaglandin synthesis in the area of inflammation to a greater extent than in the gastric mucosa or kidneys, which is associated with a relatively selective inhibition of the enzyme cyclooxygenase-2 (COX-2) compared to cyclooxygenase-1 (COX-1). It is believed that COX-2 inhibition provides a therapeutic effect of NSAIDs, while inhibition of the constantly present COX-1 isoenzyme can cause side effects from the stomach and kidneys.

The selectivity of meloxicam for COX-2 was confirmed in various test systems, both in vitro and in vivo. The selective ability of meloxicam to inhibit COX-2 has been shown when used as an in vitro human whole blood test system. In vivo, meloxicam (at doses of 7.5 mg and 15 mg) was found to inhibit 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 clotting (a reaction controlled by COX-1). These effects were dose-dependent. In vivo studies showed that meloxicam (at doses of 7.5 mg and 15 mg) had no effect on platelet aggregation and bleeding time.

Indications

• rheumatoid arthritis;
• osteoarthritis;
• ankylosing spondylitis (Ankylosing spondylitis) and other inflammatory and degenerative joint diseases accompanied by pain syndrome.

 The drug is intended for symptomatic therapy, reducing pain and inflammation at the time of use, and does not affect the progression of the disease.

Recommendations for use

Inside, while eating, without chewing, with water or other liquid. The frequency of reception is once a day. Rheumatoid arthritis 15 mg per day. After achieving a therapeutic effect, the dose can be reduced to 7.5 mg per day. Osteoarthritis 7.5 mg per day. If necessary, the dose can be increased to 15 mg per day. Ankylosing spondylitis 15 mg per day. After achieving a therapeutic effect, the dose can be reduced to 7.5 mg per day. The maximum daily dose should not exceed 15 mg. The initial dose in patients with an increased risk of side effects is 7.5 mg per day. In patients with severe renal insufficiency who are on hemodialysis, the dose should not exceed 7.5 mg per day. Teenagers over 12 years of age The maximum dose in adolescents is 0.25 mg / kg of body weight. The maximum recommended daily dose is 15 mg.

Contraindications

• hypersensitivity to the Active ingredient or auxiliary components of the drug (including other NSAIDs);
• lactase deficiency, lactose intolerance, glucose-galactose malabsorption;
• complete or incomplete combination of bronchial asthma, recurrent polyposis of the nose and paranasal sinuses and intolerance of acetylsalicylic acid and other NSAIDs (including in the anamnesis);
• exacerbation of peptic ulcer of stomach and duodenum; 
• gastrointestinal bleeding, a recent hemorrhagic stroke or a confirmed diagnosis of blood coagulation disorders;
• inflammatory bowel diseases (ulcerative colitis, Crohn’s disease);
• severe liver failure or active liver disease; 
• severe renal insufficiency in patients not undergoing hemodialysis (creatinine clearance less than 30 ml/min), progressive renal diseases, including confirmed hyperkalemia;
• decompensated heart failure;
• post-coronary artery bypass grafting;
• childhood (up to 12 years);
• pregnancy;
• breast-feeding period.

With caution: Coronary heart disease, cerebrovascular diseases, chronic heart failure (CHF), dyslipidemia/hyperlipidemia, diabetes mellitus, peripheral artery disease, smoking, creatinine clearance less than 60 ml / min. Anamnestic data on the development of ulcerative lesions of the gastrointestinal tract, the presence of Helicobacter pylori infections, old age, long-term use of NSAIDs, frequent alcohol consumption, severe somatic diseases, concomitant therapy with the following drugs:

• anticoagulants (e. g., warfarin);
• antiplatelet agents (e. g., acetylsalicylic acid, clopidogrel);
• oral glucocorticosteroids (e. g., prednisone);
• selective serotonin reuptake inhibitors (e. g., citalopram, fluoxetine, paroxetine, sertraline).

To reduce the risk of gastrointestinal adverse events, the minimum effective dose should be used in the shortest possible course.

Side effects

Classification of the frequency of side effects according to the recommendations of the World Health Organization (WHO):

very often > 1/10;>

often from > 1/100 to >< 1/10;

infrequently from > 1/1000 to >< 1/100;

rarely from > 1/10000 to >< 1/1000;

very rarely < 1/10000, including individual messages;

frequency unknown – according to available data, it is not possible to determine the frequency of occurrence.

From the side of hematopoietic organs:

rarely-changes in the number of blood cells, including changes in the leukocyte formula; leukopenia, thrombocytopenia;

infrequently-anemia.

Allergic reactions:

frequency unknown – anaphylactic shock, anaphylactoid / anaphylactic reactions, other immediate hypersensitivity reactions.

Nervous system disorders:

often – headache, emotional lability;

infrequently-dizziness, drowsiness;

frequency unknown-confusion, disorientation.

From the side of the senses:

rarely-conjunctivitis; visual disturbances, including blurred vision; tinnitus;

infrequently-vertigo.

From the digestive system:

often-abdominal pain, dyspepsia, diarrhea, constipation, flatulence, nausea, vomiting;

rarely-gastroduodenal ulcers, colitis, esophagitis;

infrequently-hidden or obvious gastrointestinal bleeding, gastritis, stomatitis, constipation, bloating, belching;

very rarely – perforation of the gastrointestinal tract.

From the liver:

very rarely-hepatitis;

infrequently-transient changes in liver function indicators (for example, increased activity of transaminases or bilirubin).

From the side of the skin:

infrequently-angioedema, pruritus, skin rash;

rarely-toxic epidermal necrolysis, Stevens-Johnson syndrome, urticaria;

very rarely-bullous dermatitis, erythema multiforme;

frequency unknown-photosensitization.

Respiratory system disorders:

rarely-bronchial asthma in patients allergic to acetylsalicylic acid or other NSAIDs.

From the cardiovascular system:

often-peripheral edema;

infrequently-increased blood pressure, a feeling of “rush” of blood to the face;

rarely-a feeling of palpitation.

From the genitourinary system:

infrequently-changes in renal function indicators (increased creatinine and/or urea concentrations in blood plasma); urinary disorders, including acute urinary retention;

very rarely – acute renal failure.

As with other NSAIDs, the possibility of interstitial nephritis, glomerulonephritis, renal medullary necrosis, and nephrotic syndrome is not excluded.

Combined use with drugs that depress the bone marrow (for example, methotrexate) can provoke cytopenia.

Interaction

Other prostaglandin synthesis inhibitors, including glucocorticoids and salicylates

Concomitant administration of prostaglandin synthesis inhibitors with meloxicam increases the risk of gastrointestinal ulceration and gastrointestinal bleeding (due to the synergistic effect). Concomitant administration of meloxicam with other NSAIDs is not recommended (see section “With caution”).

Anticoagulants for oral administration, heparin for systemic use, thrombolytic agents

Concomitant use 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

Concomitant administration of 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

When meloxicam is co-administered with lithium preparations, lithium accumulation is possible due to a decrease in renal excretion and an increase in its toxic effect (it is recommended to monitor the concentration of lithium in blood plasma if such combination therapy is necessary).

Methotrexate

NSAIDs reduce the secretion of methotrexate by the kidneys, thereby increasing its concentration in blood plasma. 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 renal function and blood formula 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 three days, the risk of increased toxicity of the latter increases.

Contraception

When used concomitantly with intrauterine contraceptives, the effectiveness of the latter may decrease.

Diuretics

Concomitant use of NSAIDs and diuretics in patients with dehydration is associated with the risk of acute renal failure. Adequate hydration levels should be maintained in patients taking Meloxicam and diuretics.

Antihypertensive agents (beta-blockers, vasodilators, angiotensin-converting enzyme inhibitors, diuretics)

NSAIDs reduce the effect of antihypertensive agents due to the inhibition of prostaglandins with vasodilating properties.

Angiotensin-II receptor antagonists

Concomitant use of NSAIDs and angiotensin II receptor antagonists increases the effect of reduced glomerular filtration, which can lead to the development of acute renal failure, especially in patients with impaired renal function.

Cholestyramine

Cholestyramine binds meloxicam in the gastrointestinal tract, which leads to its faster elimination (see the section “Overdose”).

Cyclosporine

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

Other possible interactions

When using drugs with meloxicam that have a known ability to inhibit CYP2C9 and/or CYP3A4 (or are metabolized with the participation of these enzymes), the possibility of pharmacokinetic interaction should be taken into account.

The possibility of interaction with hypoglycemic drugs for oral use cannot be excluded.

No significant pharmacokinetic interactions were observed with concomitant use of antacids, cimetidine, digoxin, and furosemide.

Overdose

Symptoms

Impaired consciousness, nausea, vomiting, epigastric pain, gastrointestinal bleeding, acute renal failure, liver failure, respiratory arrest, asystole.

Treatment

Symptomatic therapy, gastric lavage, intake of adsorbents (activated carbon). Cholestyramine accelerates the elimination of the drug from the body. There is no specific antidote. Forced diuresis, urine alkalinization, and hemodialysis are ineffective due to the high binding of the drug to blood proteins.

Functional features

Suction

Meloxicam is well absorbed from the gastrointestinal tract( GIT), as evidenced by its high absolute bioavailability (89%) after oral use. Simultaneous intake of food and antacids does not change the absorption. After a single dose of the drug in tablets, the average maximum concentration in blood plasma is reached within 5-6 hours. When taking Meloxicam orally (in doses of 7.5 mg and 15 mg), its concentrations are proportional to the doses. With repeated use, a stable state of pharmacokinetics is achieved within 3 to 5 days.

The range of differences between the maximum and minimum concentrations of the drug after taking it once a day is relatively small and amounts to 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 minimum and maximum values are given during the steady-state pharmacokinetic concentration period, respectively), although values that

Distribution

Meloxicam binds very well to plasma proteins, especially albumin (99%). Penetrates the synovial fluid, the concentration in the synovial fluid is approximately 50% of the concentration in the blood plasma. The volume of distribution after repeated oral use 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 to form four pharmacologically inactive derivatives. The main metabolite of 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 the CYP2C9 isoenzyme plays an important role in this metabolic transformation, while the CYP3A4 isoenzyme plays an additional role. The formation of the other two metabolites (which make up 16% and 4% of the drug dose, respectively) involves peroxidase, the activity of which probably varies individually.

Deduction

Meloxicam is excreted equally through the intestines and kidneys, mainly in the form of metabolites. In unchanged form, less than 5% of the daily dose is excreted through the intestines, and in the urine in unchanged form, the drug is detected 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.

Pharmacokinetics in special patient groups

Patients with impaired renal and/or hepatic function

Impaired liver function, as well as mild renal insufficiency, do not significantly affect the pharmacokinetics of meloxicam. The rate of elimination of meloxicam from the body is significantly higher in patients with moderate renal insufficiency. Meloxicam binds worse to plasma proteins in patients with end-stage renal failure. In end-stage renal failure, an increase in the volume of distribution may lead to higher concentrations of free meloxicam, so in these patients, the daily dose should not exceed 7.5 mg.

Elderly patients

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

Special instructions

The potential risk of side effects depends on the dose and duration of treatment, so the minimum effective dose of Meloxicam should be used in the minimum possible course. The duration of the course of treatment is set individually, depending on the course of the disease and the effectiveness of the therapy. Patients with a history of gastric or duodenal ulcers, as well as patients undergoing anticoagulant therapy, should regularly undergo a medical examination, as such patients have an increased risk of erosive and ulcerative diseases of the gastrointestinal tract. If peptic ulcers or gastrointestinal bleeding occur, as well as if side effects from the skin and mucous membranes develop, the drug should be discontinued. In patients with cardiovascular diseases or risk factors for developing such diseases, NSAIDs may increase the risk of serious cardiovascular thrombosis, myocardial infarction, and angina attack, which can be fatal. As the duration of treatment increases, this risk may increase. 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 NSAID withdrawal, renal function usually returns to its original level. Elderly patients, patients with dehydration, congestive heart failure, cirrhosis of the liver, nephrotic syndrome or acute renal function disorders, patients who are simultaneously taking diuretics, angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, and patients who have undergone major surgical interventions that lead to hypovolemia are most at risk of developing this reaction. In such patients, diuresis and renal function should be carefully monitored at the beginning of therapy. The use of NSAIDs together with diuretics can lead to sodium, potassium and water retention, as well as to a decrease in the natriuretic effect of diuretics. As a result, predisposed patients may have increased signs of heart failure or hypertension. Therefore, the condition of such patients should be carefully monitored and adequate hydration should be maintained. Before starting treatment, a study of renal function is necessary. In patients with mild or moderate renal insufficiency (creatinine clearance greater than 30 ml/min), no dose adjustment is required.In patients with end-stage renal failure undergoing hemodialysis, the dose of Meloxicam should not exceed 7.5 mg per day. When using the drug Meloxicam (as well as most other NSAIDs), an episodic increase in serum transaminase activity or other indicators of liver function may have been noted. In most cases, this increase was small and transient. If the detected changes are significant or do not decrease over time, Meloxicam should be discontinued and the detected laboratory changes should be monitored. In patients with cirrhosis of the liver (compensated), no dose adjustment is required. Debilitated or emaciated patients may have a worse tolerance for adverse events, and such patients should be closely monitored. Like other NSAIDs, meloxicam can mask the symptoms of an underlying infectious disease. Meloxicam, which inhibits cyclooxygenase/prostaglandin synthesis, may affect fertility and is therefore not recommended for women who have difficulty conceiving. In this regard, in women undergoing examination for this reason, it is recommended to cancel taking the drug Meloxicam. In very rare cases, serious skin reactions have been reported with NSAIDs, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis. A high risk of such reactions is observed at the beginning of treatment, and in most cases such reactions appeared during the first month of treatment. At the first appearance of skin rashes, mucosal lesions or other signs of hypersensitivity, it is necessary to stop using the drug Meloxicam. Effects on the ability to drive vehicles and mechanisms The use of Meloxicam may cause the occurrence of adverse reactions in the form of headache, dizziness and drowsiness. During the treatment period, care should be taken when driving vehicles and engaging in other potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions.

Storage conditions

Store in a dark place at a temperature not exceeding 25 ° C. Keep out of reach of children.

Shelf

life is 3 years. Do not use after the expiration date.

Active ingredient

Meloxicam

Conditions of release from pharmacies

By prescription

Dosage form

Tablets