Meloxicam-SOLOfarm - instructions for use, doses, side effects, contraindications

Meloxicam is a non-steroidal anti-inflammatory drug with analgesic, anti-inflammatory and antipyretic effects. Refers to class oxicam, the derivatives of enolic acid. The anti-inflammatory effect is associated with inhibition of the enzymatic activity of cyclooxygenase-2, which participates in the biosynthesis of prostaglandins in the inflammatory region. Less meloxicam acts on cyclooxygenase-1, involved in the synthesis of prostaglandin, which protects the mucous membrane of the gastrointestinal tract and takes part in the regulation of blood flow in the kidneys.

Pharmacokinetics:

Absorption

The relative bioavailability is about 100%. After intramuscular injection of the drug at a dose of 15 mg, the maximum concentration of the drug in the plasma (Cmax) is 1.62 μg / ml and is achieved within about 60 minutes.

Distribution

Meloxicam binds well to plasma proteins, especially albumin (99%).It penetrates into the synovial fluid, the concentration in the synovial fluid is about 50 % concentration in plasma. The distribution volume is low, about 11 liters. Interindividual differences account for 30-40%.

Metabolism

Meloksikam is almost completely metabolized in the liver with the formation of four pharmacologically inactive metabolites. 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 degree (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 with feces and urine, mainly in the form of metabolites. In unchanged form with feces less than 5% of the daily dose is excreted, in the urine the drug remains unchanged only in trace amounts. The average half-life of meloxicam is 20 hours.Plasma clearance is an average of 8 ml / min.

Meloxicam demonstrates linear pharmacokinetics in doses of 7.5-15 mg with intramuscular injection.

There are reports that oral administration for meloxicam is characterized by enterohepatic recirculation. When taking dosage forms of meloxicam for oral administration, the average period of time until the maximum plasma concentration of the drug in the blood plasma (TCmah) is 5-6 hours, with a violation for some reason of enterohepatic recirculation may increase the elimination of meloxicam and reduce its half-life to 13 hours or more (if ingested).

Liver and / or kidney failure

Insufficiency of liver function, as well as easy or moderately expressed renal failure, does not significantly affect the pharmacokinetics of meloxicam. 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

In elderly patients, the mean plasma clearance during the equilibrium state of pharmacokinetics is slightly lower than in young patients.

Indications:

Initial therapy and short-term symptomatic treatment for osteoarthritis (arthrosis, degenerative joint diseases), rheumatoid arthritis, ankylosing spondylitis, other inflammatory and degenerative diseases of the musculoskeletal system such as arthropathies, dorsopathies (eg sciatica, lower back pain, shoulder periarthritis and others ), accompanied by pain.

Contraindications:

- Hypersensitivity to the active ingredient and auxiliary components of the drug, to acetylsalicylic acid or other NSAIDs.

- Complete or incomplete combination of bronchial asthma, recurrent nasal polyposis and paranasal sinuses, angioedema or urticaria caused by intolerance to acetylsalicylic acid or other NSAIDs due to the current probability of cross-sensitivity (including in anamnesis).

- 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 failure (if hemodialysis is not performed, creatinine clearance is less than 30 ml / min), progressive kidney disease, including confirmed hyperkalemia.

Active liver disease.

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

- Age to 18 years.

- Therapy of perioperative pain during coronary artery bypass grafting.

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

- Pregnancy.

- The period of breastfeeding.

Carefully:

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

- Congestive heart failure.

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

- Cardiac ischemia.

- Cerebrovascular diseases.

- Dyslipidemia / hyperlipidemia.

- Diabetes.

- Concomitant therapy with the following drugs: 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:

The drug is contraindicated in pregnancy.

If it is necessary to prescribe the drug during breastfeeding, breastfeeding should be discontinued.

It is not recommended to use meloxicam in women planning pregnancy, as well as in women participating in infertility or birth control studies. Safety of use during pregnancy of this drug is not proven. The effect of delayed synthesis of prostaglandins on embryogenesis during the first two trimesters of pregnancy is not clear. In the last trimester of pregnancy, the mechanism of action of meloxicam is characterized by inhibition of labor, premature closure Ductus arteriosus Botalli the fetus, the predisposition to bleeding in the mother and child increases and the risk of edema in the mother is increased. Meloksikam in small quantities penetrates into the mother's milk, and in the case of breastfeeding meloxicam can be detected in the infant's plasma.

As a preparation inhibiting the synthesis of cyclooxygenase / prostaglandin, meloxicam can affect fertility, and therefore is not recommended for women who have difficulty with conception. In this regard, women who are undergoing examination in this regard, it is recommended to cancel the drug.

Dosing and Administration:

The drug is administered via a deep intramuscular injection.

The drug can not be administered intravenously.

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 GI disease, the presence of risk factors for cardiovascular disease), it is recommended to start treatment with a dose of 7.5 mg per day.

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 reactionsdepending 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.

Total daily dose of the drug Meloksikam, 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.

Given the possible incompatibility, the drug should not be mixed in the same syringe with other medicines.

The procedure for working with a polymer ampoule:

1 Take an ampoule and shake it, holding it by the neck.

2 Press the ampoule with your hand, while the drug should not be isolated, and rotate and separate the valve with rotating movements.

3 Through the formed hole, immediately connect the syringe with the ampoule.

4 Turn the ampoule over and slowly put the contents into the syringe.

5 Put the needle on the syringe.

Side effects:

The following side effects are described, the relationship of which with the use of the drug was regarded as possible. Side effects, registered with post-marketing application, the connection of which with taking the drug was regarded as possible, marked with *.

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 (≥ 1/1000, <1/100), rarely (≥ 1/10000, <1/1000), very rarely (<1/10000), is not established.

Violations of 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 *.

Disturbances from the nervous system

Often - a headache;

infrequently - 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 - a feeling of 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;

infrequently - latent and obvious gastrointestinal bleeding, gastritis *, stomatitis, constipation, bloating, belching;

rarely - gastroduodenal ulcers, colitis, esophagitis;

very rarely - perforation of the gastrointestinal tract.

Disturbances 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 the indices of kidney 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;

rarely - swelling.

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:

Symptoms: nausea, vomiting, epigastric pain, gastrointestinal bleeding, acute renal failure, hepatic failure, respiratory arrest, asystole, lethargy, drowsiness,increased blood pressure, coma, convulsions, cardiovascular collapse, cardiac arrest, anaphylactoid reactions.

Treatment: there is no specific antidote. In case of an overdose of the drug, symptomatic therapy should be performed. Forced diuresis, alkalinization of urine, hemodialysis - ineffective because of the high connection of the drug with blood proteins.

Interaction:

- Other inhibitors of prostaglandin synthesis, including glucocorticoids and salicylates - concurrent administration with meloxicam increases the risk of ulceration in the gastrointestinal tract and gastrointestinal bleeding (due to synergism actions). Simultaneous reception with other ngTV 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 agents, 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 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 case of dehydration of patients is accompanied by a risk of acute renal failure.

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

- Antagonists of angiotensin-II receptors, 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 removal.

- Pemetrexed - with concomitant use of meloxicam and pemetrexed in patients with creatinine clearance from 45 to 79 ml / min, meloxicam should be discontinued 5 days before the start of pemetrexed and may be resumed 2 days after the end of admission. If there is a need for the combined use of meloxicam and pemetrexed, such patients should be closely monitored, especially with respect to myelosuppression and the occurrence of side effects from the gastrointestinal tract.In patients with creatinine clearance less than 45 ml / min, meloxicam is not recommended together with pemetrexed.

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

When used in conjunction with meloxicam, drugs that have a known ability to inhibit CYP2C9 and / or CYP3A4 (or metabolized with the participation of these enzymes), such as sulfonylureas or probenecid derivatives, pharmacokinetic interaction should be considered.

When combined with oral antidiabetic agents (for example, sulfonylurea derivatives, nateglinide), interactions, mediated CYP2C9, 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:

Patients suffering from diseases of the gastrointestinal tract should be observed regularly. If there is a ulcerative lesion of the gastrointestinal tract or gastrointestinal bleeding, the drug must be canceled.

Gastrointestinal ulcers, perforation or bleeding may occur during the use of NSAIDs at any time, as in the presence of alarming symptoms or information about serious gastrointestinal complications in the history, and when absence of these signs. The consequences of these complications are generally more serious in the elderly.

When applying the drug, such serious skin reactions as exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis can develop. Therefore, special attention should be given to patients reporting the development of undesirable skin and mucous membrane phenomena, as well as hypersensitivity reactions to the drug, especially if similar reactions were observed during previous courses of treatment. The development of such reactions is observed, as a rule, during the first month of treatment.In the event of the appearance of the first signs of skin rash, changes in mucous membranes or other signs of hypersensitivity, the question of discontinuing the use of the drug should be considered.

Cases when taking NSAIDs increase the risk of developing serious cardiovascular thrombosis, myocardial infarction, angina attack, possibly fatal. This risk increases with prolonged use of the drug, as well as in patients with the aforementioned diseases in the history 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 a reduced volume of circulating blood can lead to decompensation of the secretive renal failure. After the abolition of NSAIDs, the kidney function is usually restored to its original level. The elderly patients, patients with dehydration, congestive heart failure, liver cirrhosis, nephrotic syndrome or acute renal dysfunction, patients,simultaneously taking diuretic drugs, angiotensin-converting enzyme inhibitors, angiotensin-II receptors, as well as patients who underwent serious surgical interventions that lead to hypovolemia. In such patients at the beginning of therapy, diuresis and renal function should be carefully monitored. The use of NSAIDs in conjunction with diuretics can lead to a delay in sodium, potassium and water, as well as a decrease in natriuretic action of diuretics. As a result, predisposing patients may have signs of heart failure or hypertension. Therefore, careful monitoring is necessary the condition of such patients, and they should be supported by adequate hydration. Before the beginning of treatment it is necessary to study the function of the kidneys.

In the case of combined therapy, kidney function should also be monitored.

When using meloxicam (as well as most other NSAIDs), an occasional increase in the activity of transaminases in the serum or other indicators of liver function is possible. In most cases, this increase was small and transient.If the changes identified are significant or do not decrease over time, the drug should be withdrawn and observed for identified laboratory changes.

Weakened or debilitated patients can tolerate undesirable events worse, and such patients must be carefully observed.

Like other NSAIDs, meloxicam can mask the symptoms of a major infectious disease.

The use of meloxicam, as well as other preparations that inhibit the synthesis of cyclooxygenase / prostaglandin, can affect fertility, therefore it is not recommended for women who have difficulty with conception.

In patients with mild or moderate renal failure (creatinine clearance more than 25 ml / min), dose adjustment is not required.

In patients with cirrhosis of the liver (compensated), dose adjustment is not required.

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

During the treatment period, due to possible side effects from the cardiovascular and nervous system, care must be taken when driving vehicles and engaging in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions.

Form release / dosage:

Solution for intramuscular injection 10 mg / ml.

Packaging:

By 1.5 ml into ampoules of low-density polyethylene or polypropylene, or into ampoules of colorless or colored glass.

For 3 or 5 ampoules of low-density polyethylene or polypropylene together with instructions for use in a pack of cardboard.

By 3 or 5 ampoules of glass in a contoured cell pack of a polyvinyl chloride film with a polymer film or a foil of aluminum lacquered, or without a film of polymer and aluminum foil lacquered, or in a (pre-manufactured) form of cardboard with cells for laying ampoules.

On 1 contour acheikovoj packing or the form from a cardboard together with the instruction on application and skarifikatorom ampulnym, or without scarifier ampullum in a pack from a cardboard.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:

5 years.

Do not use after the expiration date!

Terms of leave from pharmacies:On prescription

Registration number:LP-004221

Date of registration:30.03.2017

Expiration Date:30.03.2022

The owner of the registration certificate:GROTEKS, LLC GROTEKS, LLC Russia

Manufacturer: & nbsp

GROTEKS, LLC Russia

Information update date: & nbsp11.05.2017

Illustrated instructions

Instructions

Meloxicam-SOLOFARM (Meloxicam-SOLOfarm)