Arthrosan - instructions for use, dose, side effects, contraindications

Excipients: meglumine - 3.75 mg, poloxamer 188-50.00 mg, tetrahydrofurfuryl macrogol (glycofurol) 100.00 mg, glycine 5.00 mg, sodium chloride 3.00 mg, 1M sodium hydroxide solution to pH 8.2 -8.9, water for injection - up to 1 ml.

One ampoule (2.5 ml) contains 15 mg meloxicam.

Description:Transparent greenish-yellow liquid.

Pharmacotherapeutic group:Non-steroidal anti-inflammatory drug

ATX: & nbsp

M.01.A.C.06 Meloksikam

M.01.A.C Oksikamy

Pharmacodynamics:

Meloksikam is a non-steroidal anti-inflammatory drug (NSAID), belongs to the derivatives of enolic acid and has anti-inflammatory, analgesic and antipyretic effects. The pronounced anti-inflammatory effect of meloxicam is established on all standard models of inflammation. The mechanism of action of meloxicam is its ability to inhibit the synthesis of prostaglandins - known inflammatory mediators. Meloksikam in vivo inhibits the synthesis of prostaglandins at the site of inflammation to a greater extent than in the mucous membrane of the stomach or kidneys.

These differences are associated with a more selective inhibition of cyclooxygenase-2 (COX-2) compared to cyclooxygenase-1 (COX-1). It is believed that inhibition of COX-2 provides the therapeutic effects of NSAIDs, whereas inhibition of the constantly present isoenzyme COX-1 can be responsible for side effects from the stomach and kidneys.The selectivity of meloxicam against COX-2 has been confirmed in various test systems as in vitro, and in vivo. The selective ability of meloxicam to inhibit COX-2 is shown by using human whole blood as a test system in vitro. Determined that meloxicam (in doses of 7.5 and 15 mg) inhibited 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 coagulation (reaction controlled COX-1). These effects depended on the size of the dose. In studies ex vivo shown, that meloxicam (in doses of 7.5 mg and 15 mg) does not affect the aggregation of platelets and bleeding time.

In clinical trials, side effects from the gastrointestinal tract (GIT) as a whole occurred less often with meloxicam 7.5 and 15 mg than with other NSAIDs with which the comparison was made. This difference in the frequency of side effects from the gastrointestinal tract is mainly due to the fact that when taking meloxicam, there were less frequent phenomena such as dyspepsia, vomiting, nausea, abdominal pain.The frequency of perforations in the upper gastrointestinal tract, ulcers and bleeding that were associated with the use of meloxicam was low and depended on the magnitude of the dose of the drug.

Pharmacokinetics:

Absorption

Meloksikam is completely absorbed after intramuscular injection. The relative bioavailability compared with the bioavailability with oral administration is almost 100%. Therefore, when switching from an injection to an oral form, the dose is not required. After administration of 15 mg of the drug intramuscularly, the peak plasma concentration (about 1.6 to 1.8 μg / ml) is achieved within approximately 60 to 96 minutes.

Distribution

Meloksikam very well binds to plasma proteins, mainly with albumin (99%). It penetrates into the synovial fluid, the concentration in the synovial fluid is approximately 50% of the concentration in the plasma. The distribution volume is low, about 11 liters. Individual differences make up 7-20 %.

Metabolism

Meloksikam is almost completely metabolized in the liver with the formation of 4 pharmacologically inactive derivatives. The main metabolite, 5-carboxy-meloxicam (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 value). Research in vitro showed that in this metabolic transformation an important role is played by the isoenzyme CYP2C9, an additional value is isoenzyme CYP3A4. In the formation of the other two metabolites (which constitute, respectively, 16% and 4% of the dose), 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 the unaltered 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 13 to 25 hours.

Plasma clearance is an average of 7-12 ml / min after a single application. Meloksikam demonstrates linear pharmacokinetics in doses of 7.5-15 mg with intramuscular injection.

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 the volume of distribution 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. In elderly women, higher values AUC (area under the concentration-time curve) and a long half-life, compared with young patients of both sexes.

Indications:

Start therapy and short-term symptomatic treatment with:

- osteoarthritis (arthrosis, degenerative joint diseases);

- rheumatoid arthritis;

ankylosing spondylitis;

- Other inflammatory and degenerative diseases of the musculoskeletal system, such as arthropathy, dorsopathy (eg sciatica, lower back pain, shoulder periarthritis, etc.) accompanied by pain.

Contraindications:

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

Hypersensitivity (including other non-steroidal anti-inflammatory drugs).

Complete or incomplete combination of bronchial asthma, recurrent nasal polyposis and paranasal sinuses, angioedema or urticaria caused by intolerance to acetylsalicylic acid or other non-steroidal anti-inflammatory drugs due to the existing probability of cross-sensitivity (including 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 stage of exacerbation.

Severe hepatic and heart failure.

Severe renal insufficiency (if hemodialysis is not performed, creatinine clearance is less than 30 ml / min, and also with confirmed hyperkalemia).

Active liver disease.

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

Age to 18 years.

Pregnancy.

Breastfeeding period.

Therapy of postoperative pain during coronary artery bypass grafting.

Concomitant therapy with anticoagulants, as there is a risk of intramuscular hematoma formation.

Carefully:

Diseases of the gastrointestinal tract in the anamnesis (presence of infection Helicobacter pylori).

Congestive heart failure.

Renal failure (creatinine clearance 30-60 ml / min).

Cardiac ischemia.

Cerebrovascular diseases.

Dyslipidemia / hyperlipidemia.

Diabetes.

Concomitant therapy with anticoagulants, oral glucocorticosteroids, antiaggregants, selective serotonin reuptake inhibitors.

Diseases of peripheral arteries.

Elderly age.

Prolonged use of NSAIDs.

Smoking.

Frequent use of alcohol.

Pregnancy and lactation:

Use of Arthrosan® is contraindicated during pregnancy.

It is known that NSAIDs penetrate into breast milk, so the use of Arthrosan® during breastfeeding is contraindicated.

As a preparation inhibiting the synthesis of cyclooxygenase / prostaglandin, meloxicam can affect fertility, and therefore is not recommended for women planning a pregnancy. Meloksikam can lead to a delay in ovulation.In this regard, women who have problems with conception and undergoing examination for such problems, it is recommended to cancel the drug.

Dosing and Administration:

Osteoarthritis with pain syndrome: 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 (a history of gastrointestinal disease, the presence of risk factors for cardiovascular disease), it is recommended to start treatment with a dose of 7.5 mg per day (see section "Special instructions").

In patients with severe renal failure who are 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 application

Do not use the drug simultaneously with other NSAIDs. The total daily dose of the drug Arthrosan®, used in the form of different dosage forms, should not exceed 15 mg.

Intramuscular injection of the drug is indicated only during the first few days of therapy. Further treatment is continued with the use of oral dosage forms. The recommended dose is 7.5 mg or 15 mg once a day, depending on the intensity of pain and the severity of the inflammatory process.

The drug is administered via a deep intramuscular injection.

The drug can not be administered intravenously.

Given the possible incompatibility, Arthrosan®, the solution for intramuscular injection should not be mixed in the same syringe with other medicines.

Side effects:

Below are described the side effects, the relationship of which with the use of meloxicam, was regarded as possible.

The side effects registered with post-marketing application, the connection of which with taking meloxicam was regarded as possible, are marked with a * sign.

Inside the system-organ classes, the following categories are used for the incidence of side effects:

very often (≥ 1/10);

often (≥ 1/100, <1/10);

infrequently (≥ 1 / 1,000, <1/100);

rarely (≥ 1 / 10,000.<1 / 1,000);

very rarely (<1 / 10,000);

not installed.

Violations from the blood and lymphatic system:

Infrequent anemia;

Rarely, leukopenia, thrombocytopenia, changes in the number of blood cells, including changes in the leukocyte formula.

Immune system disorders:

Infrequently, other immediate-type hypersensitivity reactions *;

Not established - anaphylactic shock *, anaphylactoid reactions.

Disorders of the psyche:

Rarely is a mood change *;

Not established - confusion of consciousness *, disorientation *.

Impaired nervous system:

Often - a headache;

Infrequent - dizziness, drowsiness.

Vision disorders, hearing and labyrinthine disorders:

Infrequently - vertigo;

Rarely - conjunctivitis *, visual impairment, including blurred vision *, tinnitus.

Violations from the heart and blood vessels:

Infrequent - increased blood pressure, a sense of "tide" of blood to the face;

Rarely - palpitations.

Disturbances from the respiratory system:

Rarely, bronchial asthma in patients with allergy to acetylsalicylic acid and other NSAIDs.

Disorders from the gastrointestinal tract:

Often - abdominal pain, indigestion, diarrhea, nausea, vomiting;

Infrequent - latent or obvious gastrointestinal bleeding, gastritis *, stomatitis, constipation, bloating, belching;

Rarely gastroduodenal ulcers, colitis, esophagitis;

Very rarely - perforation of the gastrointestinal tract.

Disorders from the liver and bile ducts:

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

Very rarely - hepatitis *.

Disturbances from the skin and subcutaneous tissues:

Infrequent - angio-edema *, itching, skin rash;

Rarely - toxic epidermal necrolysis *, Stevens-Johnson syndrome *, urticaria;

Very rarely - bullous dermatitis *, erythema multiforme *;

Not established - photosensitivity.

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 mammary glands:

Infrequently - late ovulation *;

Not established - infertility in women *.

General disorders and disorders at the site of administration:

Often - pain and swelling at the injection site;

Infrequent - edema.

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:

Data on cases associated with drug overdose accumulated insufficiently. Presumably, symptoms typical of overdose of NSAIDs will be present in severe cases: drowsiness, mental disturbances, nausea, vomiting, epigastric pain, gastrointestinal bleeding, acute renal failure, changes in blood pressure, respiratory arrest, asystole.

Treatment: antidote is not known. In case of an overdose of the drug, symptomatic therapy should be used. It is known that colestramine accelerates the excretion of meloxicam.

Interaction:

Other inhibitors of prostaglandin synthesis, including glucocorticoids and salicylates - concurrent administration with meloxicam increasesrisk of ulceration in the gastrointestinal tract and gastrointestinal bleeding (due to synergistic action). Simultaneous reception with other NSAIDs is not recommended.

Anticoagulants for oral administration, heparin for systemic use, thrombolytic agents - simultaneous administration with meloxicam increases the risk bleeding. In the case of simultaneous use, careful monitoring of the blood coagulation system is necessary.

Antiplatelet agents, serotonin reuptake inhibitors, concurrent 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 level of lithium in plasma, by reducing the excretion of it by the kidneys. The simultaneous use of meloxicam with lithium preparations is not recommended. In case of need for simultaneous use, careful monitoring of lithium concentration in plasma is recommended during the whole course of lithium preparations.

Methotrexate - NSAIDs decrease the secretion of methotrexate by the kidneys, thereby increasing its concentration in the plasma.The 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 kidney function and the blood formula is necessary. Meloksikam may enhance hematological toxicity of methotrexate, especially in patients with impaired renal function.

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

Antihypertensives (beta-blockers, inhibitors angiotensin-converting enzyme, 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 combined with NSAIDs, increase the decrease in glomerular filtration, which can lead to the development of acute renal failure, especially in patients with impaired renal function. Kolestyramine, tying meloxicam in the gastrointestinal tract, leads to its faster excretion.

Pemetrexed - with the simultaneous use of meloxicam and pemetrexed in patients with a clearance of 45 to 79 ml / min, meloxicam should be discontinued five days before the start of pemetrexed and can be resumed 2 days after the end of admission. If there is a need for the combined use of meloxicam and pemetrexed, these patients should be carefully monitored, especially for myelosuppression and gastrointestinal side effects. In patients with creatinine clearance less than 45 ml / min, meloxicam is not recommended together with pemetrexed.

NSAIDs, acting on renal prostaglandins, can enhance nephrotoxicity of cyclosporine.

When used in conjunction with meloxicam, drugs that have a known ability to inhibit CYP 2C9 and / or CYP 3A4 (or metabolized starring these enzymes), such as derivatives sulfonylureas or probenecid, pharmacokinetic interaction should be considered.When combined with antidiabetic agents for oral administration (for example, derivatives of sulfonylurea, nateglinide), interactions mediated by CYP 2C9, which can lead to an increase in the concentration of both these drugs and meloxicam in the blood. Patients simultaneously taking meloxicam with preparations of sulfonylurea or nateglinide, should carefully monitor blood sugar levels because of the possibility of developing hypoglycemia.

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

Special instructions:

The drug can change the properties of platelets, but does not replace the preventive effect of acetylsalicylic acid in cardiovascular diseases.

Caution should be exercised when using the drug in patients who have a history of gastric ulcer and duodenal ulcer and patients on anticoagulant therapy. In such patients, the risk of erosive and ulcerative diseases of the gastrointestinal tract is increased.

Caution should be exercised and daily diuresis and renal function should be monitored when the drug is used in the elderly and in patients with reduced circulating blood volume and reduced glomerular filtration (dehydration, chronic heart failure, liver cirrhosis, nephrotic syndrome, clinically expressed kidney disease, diuretics, dehydration after large surgical operations).

When there are signs of liver damage (skin itch, yellowing of the skin, nausea, vomiting, abdominal pain, darkening of urine, persistent and significant increase the level of transaminases and changes in other indicators of liver function), the drug should be discontinued and consulted by your doctor.

After two weeks of using the drug, it is necessary to monitor the activity of "liver" enzymes.

In patients with a slight or moderate decrease in renal function (creatinine clearance ≥ 30 ml / min), dose adjustment is not required.

Patients taking both diuretics and meloxicam, should take a sufficient amount of fluid.

When allergic reactions occur (itching, skin rash, hives,photosensitization), it is necessary to consult a doctor in order to decide whether to stop taking the drug.

Meloksikam, like other NSAIDs, can mask the symptoms of infectious diseases.

The use of meloxicam, as well as other drugs that block the synthesis of prostaglandins, can affect fertility, so it is not recommended for admission to women planning a pregnancy.

Do not use the drug simultaneously with other NSAIDs.

Effect on the ability to drive transp. cf. and fur:

Special clinical studies of the effect of the drug on the ability to control the car and mechanisms were not carried out. However, it should take into account the possibility of developing dizziness and drowsiness, visual impairment and other disorders of the central nervous system. During treatment, patients need to be careful when driving vehicles and engaging in other activities that require increased concentration of attention and quick reaction.

Form release / dosage:

Solution for intramuscular injection 6 mg / ml.

Packaging:

For 2.5 ml of the drug in 5 ml ampoules from glass 1 of hydrolytic class with two rings of green and yellow in the upper part of the ampoule.

By 3 or 5 ampoules are placed in a contour mesh package made of a polyvinyl chloride film without foil. 1 or 2 contour packs of 5 ampoules or 1 circuit cell pack of 3 ampoules together with instructions for use are placed in a pack of cardboard.

Storage conditions:

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

Keep out of the reach of children.

Shelf life:

5 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-004856/10

Date of registration:28.05.2010 / 18.12.2015

Expiration Date:Unlimited

The owner of the registration certificate:PHARMSTANDART-UFIM VITAMIN FACTORY, OJSC PHARMSTANDART-UFIM VITAMIN FACTORY, OJSC Russia

Manufacturer: & nbsp

FARMSTANDART-UFAVITA, JSC Russia

Information update date: & nbsp09.10.2017

Illustrated instructions

Instructions

Arthrosan® (Artrozan®)