Arthrosan, tablets 15 mg 10 pcs

Pharmacotherapeutic group: Non-steroidal anti-inflammatory drug

ATX code: M01AC06

Pharmacological properties

Pharmacodynamics

Arthrosan

sup>® is a nonsteroidal anti-inflammatory drug (NSAID) with anti-inflammatory, antipyretic and analgesic effects.

It belongs to the class of oxycams and is a derivative of enolic acid.

The mechanism of action is related to inhibition of prostaglandin synthesis due to selective inhibition of enzymatic activity of cyclooxygenase of second type (COX-2), which participates in biosynthesis of prostaglandins in inflammatory area. When prescribed in high doses, prolonged use and individual characteristics of the body, selectivity against COX-2 is reduced. To a lesser extent, it acts on cyclooxygenase type 1 (COX-1), which is involved in the synthesis of prostaglandins that protect the mucosa of the gastrointestinal tract and is involved in the regulation of blood flow in the kidneys. Due to the above selective inhibition of COX-2 activity, the drug less often causes erosive-ulcerative lesions of the gastrointestinal tract.

Pharmacokinetics

It is well absorbed from the gastrointestinal tract, the absolute bioavailability is 89%. Simultaneous intake of food does not change the absorption of the drug. When using the drug orally in doses of 7.5 and 15 mg, its concentrations are proportional to the doses. Equilibrium concentrations are reached within 3-5 days of treatment. With long-term use of the drug (more than 1 year) the concentrations are similar to those observed after the first achievement of steady state pharmacokinetics.

The binding to plasma proteins is 99%. At a dose of 7.5 mg, the minimum concentration (C_min) is 0.4 µg/mL, the maximum concentration (C_max) is 1.0 µg/mL; when using a 15 mg dose, C_min is 0.8 µg/mL, C_max is 2.0 µg/mL. It is almost completely metabolized in the liver to form four 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 extent (9% of the dose value). In vitro studies have shown that CYP 2C9 isoenzyme plays an important role in this metabolic transformation, CYP3A4 isoenzyme has additional importance. Peroxidase, the activity of which probably varies, is involved in the formation of the other two metabolites (constituting, respectively, 16% and 4% of the drug dose).

The drug penetrates the histohematic barriers, the concentration in the synovial fluid is 50% of the maximum concentration in plasma.

Plasma clearance averages 8 ml/min. In elderly persons the drug clearance is decreased. The volume of distribution is low and averages 11 L. Hepatic or renal insufficiency of moderate severity has no significant effect on the pharmacokinetics of meloxicam.

Extracted in equal proportions in the feces and urine, mainly as metabolites. Less than 5% of the daily dose is excreted unchanged in the intestine, the drug is detected only in trace amounts in the urine. The half-life (T_1/2) of meloxicam is 15-20 hours.

Indications

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

Symptomatic therapy:

• osteoarthritis (osteoarthritis, degenerative joint diseases), including with a pain component;
• rheumatoid arthritis;
• ankylosing spondylitis.

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Active ingredient

Meloxicam

Composition

On 1 tablet:

the active ingredient: meloxicam – 7.5 mg or 15.0 mg;

excipients:

for dosage 7.5 mg: potato starch – 64.5 mg, lactose monohydrate – 100.0 mg, povidone (polyvinylpyrrolidone, povidone K-25) – 3.2 mg, sodium citrate – 18.8 mg, magnesium stearate – 2.0 mg, colloidal silicon dioxide (aerosil) – 4.0 mg;

for dosage 15.0 mg: potato starch – 94.5 mg, lactose monohydrate – 150.0 mg, povidone (polyvinylpyrrolidone, povidon K-25) – 4.5 mg, sodium citrate – 27.0 mg, magnesium stearate – 3.0 mg, colloidal silica (aerosil) – 6.0 mg.

How to take, the dosage

Ingestion.

The drug is taken with meals in a daily dose of 7.5-15 mg.

The recommended dosing regimen:

Rheumatoid arthritis:

15 mg daily. If necessary, the dose can be reduced to 7.5 mg per day.

Osteoarthritis, Osteochondrosis and other inflammatory and degenerative diseases of the musculo-articular system accompanied by pain syndrome:

7.5 mg daily. If ineffective, the dose may be increased to 15 mg per day.

Ankylosing spondylitis:

15 mg daily.

The maximum daily dose should not exceed 15 mg.

In patients at increased risk of side effects, and in patients with significant renal impairment who are on hemodialysis, the dose should not exceed 7.5 mg daily.

Interaction

• Concomitant use with other non-steroidal anti-inflammatory drugs (including acetylsalicylic acid) increases the risk of erosive ulcerative lesions and gastrointestinal bleeding;
• Concomitant use with hypotensive medications may decrease the effectiveness of the latter;
• co-administration with methotrexate may increase the side effect of the latter on the hematopoietic system (risk of anemia and leukopenia, periodic control of total blood count is indicated)
• co-administration with diuretics may lead to increased risk of anemia and leukopeniaconcomitant use with diuretics and cyclosporine may increase the risk of renal failure.
• Concomitant use with intrauterine contraceptives may decrease the effectiveness of the latter.
• Simultaneous use with anticoagulants (heparin, warfarin), thrombolytics (streptokinase, fibrinolysin), and antiaggregants (ticlopidine, clopidogrel, acetylsalicylic acid) increases the risk of bleeding (periodic monitoring of blood clotting is necessary);
• Concomitant use with colestiramine accelerates gastrointestinal excretion of meloxicam;
• concomitant use with selective serotonin reuptake inhibitors increases the risk of gastrointestinal bleeding.
• Start NSAIDs at least 8-12 days after mifepristone administration because NSAIDs may decrease the effectiveness of mifepristone

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Special Instructions

• Caution should be exercised when using the drug in patients with a history of peptic ulcer and duodenal ulcer, and in patients on anticoagulant therapy. These patients have an increased risk of gastrointestinal erosive ulcers.
• Cautious use and monitoring of daily urine output and renal function is recommended in elderly patients with decreased blood circulation and glomerular filtration (dehydration, chronic heart failure, cirrhosis, nephrotic syndrome, clinically significant renal disease, use of diuretics, dehydration after major surgery).
• In patients with mild to moderate renal function impairment (creatinine clearance 30-60 mL/min), no dose adjustment is required.
• Patients taking diuretics and meloxicam simultaneously should take adequate fluids.
• In case of allergic reactions (itching, skin rash, urticaria, photosensitization) during treatment, a physician should be consulted to decide whether to discontinue the drug.
• Meloxicam, like other NSAIDs, may mask symptoms of infectious diseases.
• The use of meloxicam, as well as other drugs that block the synthesis of prostaglandins, may affect fertility, so it is not recommended for women who plan to become pregnant.

Influence on ability to drive vehicles, mechanisms

Due to the possibility of headache, dizziness and somnolence, during the treatment period the patients should avoid driving vehicles and performing other potentially dangerous activities requiring increased concentration and rapid psychomotor reactions.

Synopsis

Tablets from light yellow to yellow in color, round, flat cylindrical, beveled and ribbed. Slight marbling is allowed.

Contraindications

• Hypersensitivity to meloxicam or excipients of the drug;
• heart failure in decompensation;
• early postoperative period after coronary artery bypass grafting;
• complete or incomplete combination of bronchial asthma, recurrent polyposis of the nose and sinuses, and intolerance to acetylsalicylic acid or other NSAIDs (incl.ч. history)
• acute gastric or duodenal ulcer; active gastrointestinal bleeding;
• cerebrovascular bleeding or other bleeding;
• explicit hepatic insufficiency or active liver disease;
• chronic renal failure (in patients not undergoing hemodialysis (creatinine clearance less than 30 ml/min); advanced renal disease, includingч. confirmed hyperkalemia;
• children under 15 years of age;
• pregnancy;
• lactose intolerance, lactase deficiency and glucose-galactose malabsorption

Cautions

The drug should be used with caution in elderly patients and in the presence of the following medical history: CHD, congestive heart failure, cerebrovascular disease, dyslipidemia/hyperlipidemia, diabetes mellitus, peripheral vascular disease, CKD with creatinine clearance 30-60 ml/min; gastrointestinal ulceration, presence of Helicobacter pylori infection.

. Prolonged use of NSAIDs, alcohol abuse, concomitant therapy with anticoagulants (e.g., warfarin), antiaggregants (e.g., acetylsalicylic acid, clopidogrel), oral glucocorticosteroids (e.g, Prednisolone), selective serotonin reuptake inhibitors (e.g., citalopram, fluoxetine, sertraline, paroxetine) should always be considered when prescribing meloxicam.

In order to reduce the risk of gastrointestinal adverse events, the lowest effective dose should be used for as short a course as possible.

Side effects

The following categories are used within the system-organ classes for frequency of adverse effects: very common (≥ 1/10); common (≥ 1/100, < 1/10); infrequent (≥ 1/1,000, < 1/100); rare (≥ 1/10,000, < 1/1,000); very rare (< 1/10,000); not established.

Blood and lymphatic system disorders:

not infrequently: anemia;

rarely: Changes in blood cell count, including changes in the leukocyte formula, leukopenia, thrombocytopenia.

From the immune system:

not infrequently: Other immediate-type hypersensitivity reactions;

frequency unknown: anaphylactic shock, anaphylactoid/anaphylactic reactions.

Mental side:

often: Mood changes;

frequency unknown: confusion, disorientation.

Nervous system side:

often: Headache;

infrequent: dizziness, drowsiness.

Visual organ:

frequently: conjunctivitis, visual disturbances, including blurred vision.

Hearing organ and labyrinth disorders:

not infrequently: vertigo;

not infrequently: tinnitus.

Cardiac side:

not infrequently: palpitations.

vascular side:

infrequent: increase in blood pressure, “rushes” of blood to the face.

Respiratory system, thoracic and mediastinal organs:

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

Gastrointestinal tract:

often: abdominal pain, dyspepsia, diarrhea, nausea, vomiting;

infrequent: latent or overt gastrointestinal bleeding, gastritis, stomatitis, constipation, abdominal bloating, belching;

rarely: gastroduodenal ulcers, colitis, esophagitis;

very rarely: gastrointestinal perforation.

From the liver and biliary tract:

not infrequently: Transient changes in liver function parameters (e.g., increased transaminase or bilirubin activity);

very rarely: hepatitis.

Skin and subcutaneous tissue:

not infrequently: angioedema, pruritus, skin rash;

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

very rarely: bullous dermatitis, erythema multiforme;

frequency unknown: photosensitization.

Kidney and urinary tract disorders:

infrequent: Changes in renal function parameters (increased serum creatinine and/or urea levels), urinary disorders, including acute urinary retention;

very frequently: acute renal failure.

Combined use with medications that depress bone marrow (e.g., methotrexate) may provoke cytopenia. Gastrointestinal bleeding, ulceration or perforation may be fatal.

As with other NSAIDs, do not rule out the possibility of interstitial nephritis, glomerulonephritis, renal medullary necrosis, and nephrotic syndrome.

Overdose

Symptoms: impaired consciousness, nausea, vomiting, epigastric pain, gastrointestinal bleeding, acute renal failure, liver failure, respiratory arrest, asystole. Treatment: there are no specific antidotes and antagonists. In case of drug overdose – gastric lavage, activated charcoal intake (within the next hour), symptomatic therapy. Forced diuresis, urine alkalinization, hemodialysis are ineffective due to high binding of the drug to blood proteins.

Pregnancy use

The drug is contraindicated in pregnancy and during breastfeeding. If it is necessary to use during breastfeeding, discontinue breastfeeding should be decided.

Similarities

Movalis, Meloxicam, Amelotex, Movasin, Arthrosan, Meloxicam-Teva, Meloxicam DS, Meloxicam Stada, Petcam Tabs, Meloxidil, Elox-SOLofar