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

Excipients: meglumine (TV-glucamine) - 7.0 mg, glycine 6.0 mg, poloxamer 188-50.0 mg, tetrahydrofurfuryl macrogol (glycofurol) 100.0 mg, sodium chloride 3.5 mg, 0.1 M sodium hydroxide solution - up to pH 8.4-8.9, water for injection - up to 1 ml.

Description:PA yellow or greenish-yellow liquid is opaque.

Pharmacotherapeutic group:NSAIDs

ATX: & nbsp

M.01.A.C.06 Meloksikam

M.01.A.C Oksikamy

Pharmacodynamics:

Non-steroidal anti-inflammatory drug (NSAID), has anti-inflammatory, antipyretic, analgesic effect. It belongs to the class of oxicams, a derivative of enolic acid.

The mechanism of action is the inhibition of prostaglandin synthesis (Pg) as a result of selective suppression of the enzymatic activity of cyclooxygenase 2 (COX-2). At the appointment in high doses, long-term use and individual characteristics of the organism, the selectivity of COX-2 decreases. Suppress the synthesis of prostaglandins (Pg) in the inflammation region to a greater extent than in the gastric mucosa or kidneys, which is associated with a relatively selective inhibition of COX-2, while inhibition of the constantly present isoenzyme COX-1 can cause side effects from the gastrointestinal tract and kidneys.

Pharmacokinetics:

Absorption

Meloksikam is completely absorbed after intramuscular injection. Bioavailability of the drug is about 100%.After intramuscular administration of 15 mg meloxicam, the maximum drug concentration (C_mOh) in the plasma is achieved after about 1 hour.

Distribution

Meloksikam binds to plasma proteins (mainly with albumin) to a large extent - 99%. Passes through the histogematic barriers, penetrates into the synovial fluid. The concentration in the synovial fluid is 50% of the plasma concentration of the drug. Volume of distribution (V_d) is low and is 11 liters.

Metabolism

Meloksikam is almost completely metabolized in the liver with the formation of four pharmacologically inactive metabolites. The main metabolite 5'-carboxymelloxicam (60% of the administered dose) is formed by oxidation of the intermediate metabolite 5'-hydroxymethylmeloxicam (9% of the administered dose). In the formation of two other metabolites, which constitute 16% and 4% of the administered dose of the drug, peroxidase, whose activity varies individually, probably takes part.

Elimination

Significant intestinal-hepatic circulation, characteristic of meloxicam, does not affect the elimination of the drug. Meloksikam is excreted mainly in the form of metabolites, equally by the kidneys and intestines. In an unchanged form, less than 5% of meloxicam is excreted by the intestine, and only trace amounts of unchanged drug are detected in the urine.

The mean half-life (T_1/2) meloxicam is 20 hours. Plasma clearance is an average of 8 ml / min.

Dysfunction of the liver / kidney

Dysfunction of the liver, as well as renal failure of mild to moderate severity, has no significant effect on the pharmacokinetics of meloxicam. In terminal renal failure, an increase in the volume of distribution can lead to higher concentrations of free meloxicam.

Elderly patients

Elderly patients compared with younger patients patientshave similar pharmacokinetic parameters. In elderly patients, the average plasma clearance during the equilibrium state of pharmacokinetics is slightly lower than in young patients.

Older women have higher AUC values (area under the concentration-time curve) and a longer half-life, compared to young patients of both sexes.

Indications:

Short-term symptomatic therapy of rheumatoid arthritis, osteoarthrosis, ankylosing spondylitis and other joint diseases accompanied by pain syndrome.

Designed to reduce pain and inflammation at the time of use, the progression of the disease is not affected.

Contraindications:

- Hypersensitivity to the active substance or ancillary components (including other non-steroidal anti-inflammatory drugs (NSAIDs));

- complete or incomplete combination of bronchial asthma, recurrent polyposis of the nasal mucosa and paranasal sinuses and intolerance to acetylsalicylic acid and other non-steroidal anti-inflammatory drugs (including in history);

- erosive and ulcerative changes in the mucous membrane of the stomach and duodenum, active gastrointestinal hemorrhage;

- ulcerative colitis, Crohn's disease in the acute stage;

- severe hepatic impairment or active liver disease;

- severe renal failure with creatinine clearance less than 30 ml / min (in patients not undergoing hemodialysis, with confirmed hyperkalemia), progressive kidney disease;

- acute gastrointestinal bleeding, recent cerebrovascular bleeding or a confirmed diagnosis of blood coagulation system diseases;

- severe decompensated heart failure;

- contraindicated in the period after aortocoronary bypass surgery;

- pregnancy;

- the period of breastfeeding;

- Children under 18 years.

Carefully:

Elderly age, coronary heart disease, chronic heart failure, cerebrovascular disease, dyslipidemia / hyperlipidemia, diabetes mellitus, peripheral arterial disease, smoking, moderate renal insufficiency (creatinine clearance 30-60 ml / min), a history of gastrointestinal disease (presence of infection Helicobacter pylori), long-term use of non-steroidal anti-inflammatory drugs (NSAIDs), frequent alcohol consumption, severe somatic diseases, simultaneous intake of oral glucocorticosteroids (including prednisolone), anticoagulants (including warfarin), antiplatelet agents (including acetylsalicylic acid, clopidogrel), selective serotonin reuptake inhibitors (incl.citalopram, fluoxetine, paroxetine, sertraline); A bronchial asthma, a tuberculosis, the expressed osteoporosis.

To reduce the risk of developing adverse events from the gastrointestinal tract (GIT), a minimum effective dose should be used with the minimum possible short course.

Pregnancy and lactation:

Meloksikam is contraindicated during pregnancy.

It is known that NSAIDs penetrate into breast milk, so meloxicam it is not recommended to use during lactation.

Dosing and Administration:

Intramuscular injection of the drug is indicated only during the first 2-3 days. Further treatment is continued with the use of oral forms (tablets).

The recommended dose is 7.5 mg (0.75 ml) or 15 mg (1.5 ml) once a day, depending on the intensity of pain and the severity of the inflammatory process.

The maximum recommended daily dose is 15 mg (1.5 ml).

The drug is administered via a deep intramuscular injection.

Given the possible incompatibility, meloxicam Do not mix in the same syringe with other medicines.

In patients with an increased risk of adverse reactions and with severe renal disease insufficiency, on hemodialysis, dose not must etceatEggs7 7.5 mg (0,75 ml) per day.

For patients with renal insufficiency mild or moderate severity (creatinine clearance more than 30 ml / min) dose adjustment is not required.

The drug can not be administered intravenously.

Combined application

Do not use the drug simultaneously with other NSAIDs.

The total daily dose of meloxicam, used in the form of tablets, suppositories, suspension for ingestion and injection, should not exceed 15 mg.

Side effects:

The incidence of side effects listed below was determined according to the following (classification of the World Health Organization): very often (more than 10%), often (more than 1% and less than 10%), infrequently (more than 0.1% and less than 1%), rarely (more than 0.01% and less than 0.1%), very rarely (less than 0.01%), including individual reports.

From the gastrointestinal tract:

Often: dyspepsia, nausea, vomiting, abdominal pain, constipation, flatulence, diarrhea.

Infrequent: transient changes in liver function (for example, increased activity of "liver" transaminases, bilirubin concentrations), belching, esophagitis, gastroduodenal ulcer, latent or obvious gastrointestinal bleeding, stomatitis.

Rarely: perforation of the gastrointestinal tract, colitis, hepatitis, gastritis.

On the part of the hematopoiesis system:

Often: anemia.

Infrequently: a change in the blood count, including a change in the leukocyte formula, leukopenia, and thrombocytopenia.

From the skin:

Often: itching, skin rash, angioedema.

Infrequently: urticaria.

Rarely: Stevens-Johnson syndrome, toxic epidermal necrolysis.

Very rarely: photosensitization, bullous eruptions, erythema multiforme.

From the respiratory system:

Very rarely: bronchospasm.

From the side of the central nervous system (including cabout the sides of the organs of hearing, psyche):

Often: headache.

Infrequent: dizziness, drowsiness, vertigo.

Rarely: noise in the ears.

Very rarely: confusion, disorientation, emotional lability.

From the side of the cardiovascular system:

Often: peripheral edema.

Infrequent: increased blood pressure, "tides" of blood to the skin of the face.

Rarely: palpitations.

From the genitourinary system:

Infrequent: changes in renal function (increased serum creatinine and / or urea concentration), impaired urination, including acute urinary retention.

Very rarely: acute renal failure.

From the viewpoint:

Rare: conjunctivitis, visual impairment, incl. blurred vision.

Hypersensitivity reactions:

Very rarely: angioedema and hypersensitivity reactions of immediate type, incl. anaphylactoid / anaphylactic reactions.

Local Reactions:

Often: edema and pain at the injection site.

Overdose:

Symptoms: drowsiness, impaired consciousness, nausea, vomiting, epigastric pain, gastrointestinal bleeding, acute renal failure, arterial hypertension, arterial hypotension, respiratory arrest, asystole.

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 glucocorticosteroids and salicylates, when taken concomitantly with meloxicam, increase the risk of ulceration in the gastrointestinal tract and gastrointestinal bleeding (due to synergistic action) and are therefore not recommended.

Simultaneous reception with other NSAIDs is not recommended.

Selective serotonin reuptake inhibitors - an increased risk of gastrointestinal bleeding.

Lithium preparations - NSAIDs increase the concentration of lithium in plasma, by reducing the excretion of it by the kidneys. It is recommended to monitor the concentration of lithium during the period of administration of meloxicam, with a change in the dose of lithium preparations and their cancellation.

Methotrexate - NSAIDs reduce the tubular secretion of methotrexate, thereby increasing its plasma concentration and hematological toxicity, the pharmacokinetics of methotrexate remain unchanged. In this regard, the simultaneous administration of meloxicam and methotrexate in a dose of more than 15 mg / week is not recommended. With the simultaneous use of drugs, the risk of increasing the toxicity of methotrexate increases.

The risk of developing interaction between NSAIDs and methotrexate may also occur in patients using methotrexate in low doses, especially in patients with impaired renal function. Therefore, constant monitoring of the number of blood cells and the function of the kidneys is necessary.

Contraception - when used simultaneously with intrauterine contraceptives, the effectiveness of the latter may be reduced.

Diuretics - the use of NSAIDs in the case of dehydration of patients is accompanied by a risk of developing acute renal failure.

Antihypertensives (beta adrenoblockers and angiotensin converting enzyme inhibitors, vasodilators, diuretics) - NSAIDs reduce the effect of antihypertensive drugs, due to the inhibition of prostaglandins with vasodilating properties.

Angiotensin II receptor antagonists 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.

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), the possibility of pharmacokinetic interaction should be taken into account.

At simultaneous reception meloxicam can enhance the action of hypoglycemic agents for oral administration, thus there is a dangerthe occurrence of hypoglycemiaand.

Meloksikam can weaken the action of digoxin, cortisone, diuretics.

Special instructions:

Patients suffering from diseases of the gastrointestinal tract should be observed regularly. When there is a ulcerative lesion of the gastrointestinal tract or gastrointestinal bleeding meloxicam necessary cancel.

Ulcers in the gastrointestinal tract, perforation or bleeding can occur during treatment at any time, as with the presence of alarming symptoms or information about serious gastrointestinal complications in the history, and in the absence of these symptoms. The consequences of these complications are generally more serious in the elderly.

Particular attention should be given to patients reporting the development of adverse skin and mucous membrane effects, as well as reactions of hypersensitivity to the drug, especially if similar reactions were observed during previous courses of treatment.

Like other NSAIDs, meloxicam may increase the risk of 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 values. The elderly patients, patients with dehydration, chronic heart failure, liver cirrhosis, nephrotic syndrome or acute renal dysfunction, patients taking diuretics at the same time, as well as patients undergoing 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 of the condition of such patients is needed, and adequate hydration should be maintained. 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 meloxicam (as well as most other NSAIDs) was used, an episodic increase in the activity of "liver" transaminases or other indicators of liver function in serum was reported. In most cases, this increase was small and transient. If the identified changes are significant or do not decrease with time, meloxicam should be abolished, and monitored for identified laboratory changes.

Weakened or debilitated patients can tolerate undesirable events worse, which is why such patients should be carefully observed.

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

The use of meloxicam, like other drugs,inhibitors of cyclooxygenase / prostaglandin synthesis can affect fertility, therefore it is not recommended for women planning a pregnancy.

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

The use of the drug can cause the emergence of unwanted effects in the form of headaches and dizziness, drowsiness. It should abandon the management of vehicles and maintenance of machines and mechanisms that require concentration of attention.

Form release / dosage:

Solution for intramuscular injection, 10.0 mg / ml.

Packaging:

By 1.5 ml into ampoules of colorless neutral glass with a kink ring (or break point). On the ampoules paste labels from paper self-adhesive.

5 ampoules together with the instructions for use are put in a pack of cardboard with a corrugated liner.

For 3 or 5 ampoules are inserted into a blister of PVC film.

For 1 blister with ampoules, together with the instruction for use, they put a pack of cardboard.

Storage conditions:

Store in a dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002562

Date of registration:05.08.2014 / 08.06.2017

Expiration Date:05.08.2019

The owner of the registration certificate:FARMAK, PAO FARMAK, PAO Ukraine

Manufacturer: & nbsp

FARMAK, PAO Ukraine

Representation: & nbspFARMAK PAOFARMAK PAO

Information update date: & nbsp28.02.2018

Illustrated instructions

Instructions

Genitron® (Genitron®)