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

Excipients: lactose monohydrate (200) 92.34 mg, cellulose microcrystalline (101) 12.0 mg, sodium citrate 1.20 mg, povidone (K-17) 3.36 mg, crospovidone 1.20 mg, silicon dioxide colloid (aerosil) 1.20 mg, magnesium stearate 1.20 mg.

In 1 tablet of 15 mg contains:

active substance: meloxicam in terms of 100% dry matter 15.0 mg;

Excipients: lactose monohydrate (200) 122.7 mg, microcrystalline cellulose (101) 30.6 mg, sodium citrate 1.8 mg, povidone (K-17) 4.5 mg, crospovidone 1.8 mg, silicon dioxide colloid (aerosil) 1.8 mg, magnesium stearate 1.8 mg.

Description:

Round, flat cylindrical tablets of yellow color, with a facet and a risk. Marble is allowed on the surface of the tablets.

Pharmacotherapeutic group:NSAIDs

ATX: & nbsp

M.01.A.C.06 Meloksikam

M.01.A.C Oksikamy

Pharmacodynamics:

Meloxicam belongs to the non-steroidal anti-inflammatory drugs (NSAIDs) of the oxicam class, is an enolic acid derivative and has an anti-inflammatory, analgesic and antipyretic effect. 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 COX-2 compared to COX-1. It is believed that inhibition of COX-2 provides a therapeutic effect of NSAIDs, whereas inhibition of the constantly present isoenzyme COX-1 can cause side effects on the part of the stomach and kidneys.

The selectivity of meloxicam against COX-2 was 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 mg and 15 mg) actively inhibited COX-2 by providing a greater inhibitory effect on prostaglandin E2 production stimulated by lipopolysaccharide (reaction controlled by COX-2) than on thromboxane products involved in blood clotting (reaction controlled by 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) had no effect on platelet aggregation, and bleeding time.

Pharmacokinetics:

Absorption

Meloksikam is well absorbed from the digestive tract, as evidenced by high absolute bioavailability (90%) after ingestion. After a single application of meloxicam C_mOh in plasma is reached within 5-6 hours. Simultaneous intake of food and antacids does not change the absorption. When using the drug inside (in doses of 7.5 and 15 mg), its concentrations are proportional to the doses. The equilibrium concentration of pharmacokinetics is achieved within 3-5 days. The range of differences between the maximum and minimum concentrations of the drug after its administration once a day is relatively small and amounts to using a dose of 7.5 mg 0.4-1.0 μg / ml, and when a dose of 15 mg is 0.8-2, 0 μg / ml (the values of C_min and C_max in the period of equilibrium concentration of pharmacokinetics), although the values beyond this range were also noted. The maximum concentration of meloxicam in plasma during the equilibrium concentration of pharmacokinetics is reached within 5-6 hours after ingestion.

Distribution

Meloxicam binds very well to plasma proteins, especially albumin (99%). It penetrates into the synovial fluid, the concentration in the synovial fluid is approximately 50% of the concentration in the plasma. Volume of distribution (V_d) after repeated ingestion of meloxicam (in doses from 7.5 mg to 15 mg) is about 16 liters, with a coefficient of variation of 11% to 32%.

Metabolism

Meloksikam is almost completely metabolized in the liver with the formation of 4 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 degree (9% of the dose value).

Research in vitro showed that in this metabolic transformation an important role is played by the isoenzyme CYP2C9, the isozyme has an additional value CYP3A4. In the formation of two other metabolites (constituting 16% and 4% of the dose, respectively), 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 unchanged form, less than 5% of the daily dose is excreted through the intestine, in the urine, in unchanged form, the drug is found only in trace amounts. Average T_1/2meloxicam varies from 13 to 25 hours. Plasma clearance is an average of 7-12 ml / min after a single dose of meloxicam.

Impaired liver and / or kidney function

Dysfunction of the liver, as well as mild renal insufficiency has no significant effect on 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. With terminal renal failure, an increase V_d 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 longer half-life, compared with young patients of both sexes.

Indications:

Symptomatic treatment:

- osteoarthritis (arthrosis, degenerative joint diseases), including painful component;

- rheumatoid arthritis;

- ankylosing spondylitis (Bekhterev's disease).

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

Contraindications:

- Hypersensitivity to the active substance or auxiliary components of the drug (including other NSAIDs);

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

- erosive and ulcerative lesions of the mucous membrane of the stomach and duodenum in the acute stage or recently transferred;

- inflammatory bowel disease - Crohn's disease or ulcerative colitis in the acute stage;

- severe hepatic impairment or active liver disease;

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

- active gastrointestinal bleeding, recent cerebrovascular bleeding or confirmed diagnosis of blood coagulation, thyroid disease;

- Decompensated heart failure, acute myocardial infarction;

- pregnancy;

- breast-feeding;

- period after aortocoronary shunting;

- children's age till 12 years;

- hereditary lactose intolerance, impaired absorption of glucose and galactose, deficiency of lactase.

Carefully:

- Diseases of the gastrointestinal tract in the anamnesis (peptic ulcer of stomach and duodenum, liver disease), the presence of infection Helicobacter pylori;

- ischemic heart disease, chronic heart failure;

- cerebrovascular diseases;

- renal failure (creatinine clearance 30-60 ml / min);

-dislipidemia / hyperlipidemia;

- diabetes;

- simultaneous administration of oral glucocorticosteroids (including prednisolone), anticoagulants (including warfarin), antiaggregants (including clopidogrel), selective serotonin reuptake inhibitors (including citalopram, fluoxetine, paroxetine, sertraline);

- severe physical illness;

- diseases of peripheral arteries;

- elderly age;

- long-term use of non-steroidal anti-inflammatory drugs;

- smoking;

- frequent use of alcohol;

- bronchial asthma;

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:

The use of the drug Liberum is contraindicated during pregnancy.

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

As a preparation inhibiting the synthesis of cyclooxygenase / prostaglandin, Liberum 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 Libermum.

Dosing and Administration:

Inside, with food, do not chew.

Osteoarthritis

The daily dose is 7.5 mg, if necessary can be increased to 15 mg / day.

Rheumatoid arthritis

The drug is prescribed at 15 mg / day, when the positive therapeutic effect is achieved, the dose can be reduced to 7.5 mg / day.

Ankylosing spondylitis

The drug is prescribed at 15 mg / day, when the positive therapeutic effect is achieved, the dose can be reduced to 7.5 mg / day.

In patients with an increased risk of adverse reactions, the initial treatment dose is 7.5 mg / day.

In patients with severe renal failure who are on hemodialysis, the dose should not exceed 7.5 mg / day.

Side effects:

The adverse events presented below are listed according to anatomophysiological classification and frequency of occurrence.

The frequency of occurrence is determined by WHO and has the following gradation: very often - more than 10%; often more than 1%; infrequently, 0.1-1%; rarely - 0,01-0,1%; very rarely - less than 0.01%, including individual cases.

System-Organ Class	Side effect	Frequency of occurrence
On the part of the system hemopoiesis and lymphatic system	The change in the number of blood cells, including changes in the leukocyte formula	Rarely
	Leukopenia	Rarely
	Thrombocytopenia	Rarely
	Anemia	Infrequently
	Anaphylactic shock	Not installed
From the immune system	Anaphylactoid / anaphylactic reactions	Not installed
	Other hypersensitivity reactions immediate type	Infrequently
	Headache	Often
From the side nervous system	Dizziness	Infrequently
From the side nervous system	Drowsiness	Infrequently
Disorders of the psyche	Confusion, disorientation	Not installed
Disorders of the psyche	Emotional lability	Often
From the sense organs	Conjunctivitis, visual impairment, including blurred vision, tinnitus	Rarely
	Vertigo	Infrequently
	Perforation of the gastrointestinal tract	Rarely
From the gastrointestinal tract	Latent or obvious gastrointestinal bleeding, gastritis, stomatitis, constipation, bloating, belching	Infrequently
	Gastroduodenal ulcers, colitis, esophagitis	Rarely
	Abdominal pain, indigestion, diarrhea, nausea, vomiting	Often
From the side of the liver	Transient changes in liver function (for example, increased activity of transaminases or bilirubin)	Infrequently
	Hepatitis	Rarely
	Toxic epidermal necrolysis, Stevens-Johnson syndrome	Rarely
From the skin and subcutaneous tissue	Angioedema	Infrequently
	Bullous dermatitis, erythema multiforme	Rarely
	Itching, skin rash	Infrequently
	Hives	Rarely
	Photosensitivity	Not installed
From the side respiratory system	Bronchial asthma in patients with allergy to acetylsalicylic acid or other NSAIDs	Rarely
From the side of the cardio-cardiovascular system	Increased blood pressure, a sense of "tide" of blood to the face.	Infrequently
From the side of the cardio-cardiovascular system	Heart palpitations	Rarely
From the side urogenital systems	Acute kidney failure	Rarely
From the side urogenital systems	Change (increased urea in renal function indicators of creatinine and / or blood serum concentrations), urination disorders, including acute urinary retention.	Infrequently

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: impaired consciousness, nausea, vomiting, epigastric pain, gastrointestinal bleeding, acute renal failure, hepatic insufficiency, respiratory arrest, asystole.

Treatment: symptomatic therapy, gastric lavage, reception of activated charcoal. Forced diuresis, alkalinization of urine, hemodialysis are ineffective because of the high connection of the drug with blood proteins. There is no specific antidote.

Interaction:

- Meloxicam, along with other inhibitors of prostaglandin synthesis, including glucocorticosteroids and salicylates, can increase the risk of ulcers of the mucosa in the gastrointestinal tract and gastrointestinal bleeding due to their synergism. The joint administration of meloxicam and other NSAIDs is not recommended.

- Together with anticoagulants, heparin for systemic use, thrombolytic agents meloxicam increases the risk of bleeding. If it is impossible to avoid their simultaneous application, it is necessary to monitor the parameters of the blood coagulation system.

- Simultaneous administration of antiplatelet agents, serotonin reuptake inhibitors 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.

- Meloksikam can reduce renal lithium excretion, which leads to an increase in its concentration in the blood plasma to a toxic level. The simultaneous use of meloxicam with lithium preparations is not recommended. In case of the need for simultaneous use, careful monitoring of the concentration of lithium in plasma during the whole course of lithium preparations is recommended.

- NSAIDs decrease the excretion 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 can enhance hematological toxicity of methotrexate, especially in patients with impaired renal function.

With the combined use of meloxicam and methotrexate for 3 days, the risk increases the toxicity of the latter.

- Contraception: there is evidence that meloxicam may reduce the effectiveness of intrauterine contraceptive devices, but this has not been proven.

- When meloxicam is used together with diuretics, there may be a risk of developing acute renal failure, so you should monitor kidney function and maintain an adequate level of hydration.

- Hypotensive drugs (beta adrenoblockers, angiotensin converting enzyme inhibitors, vasodilators, diuretics): meloxicam reduces the effect of antihypertensive drugs, due to the inhibition of prostaglandins, which have vasodilating properties.

- Meloxicam and angiotensin II receptor antagonists, as well as ACE inhibitors, have a synergistic effect on reducing glomerular filtration. In patients with an existing impairment of renal function, this can lead to acute renal failure.

- Kolestyramin, tying meloxicam in the gastrointestinal tract, leads to its faster excretion.

- Meloksikam, affecting kidney prostaglandins, increases the nephrotoxicity of cyclosporine, which requires enhanced monitoring of kidney function with simultaneous use of drugs.

- Meloksikam is almost completely destroyed by hepatic metabolism, approximately two-thirds of which pass with the participation of cytochrome (CYP) P450 and one third - by peroxidase oxidation.

Possible pharmacokinetic interaction of meloxicam and other drugs at the metabolic stage due to their influence on CYP 2C9 and / or CYP 3A4.

With the simultaneous use of meloxicam with hypoglycemic agents for oral administration, it can intensify their action, thereby contributing to the risk of hypoglycemia.

With the simultaneous administration of meloxicam with antacids, cimetidine, digoxin and furosemide interaction at the pharmacokinetic level is not revealed. Meloksikam can weaken the action of digoxin, cortisone, diuretics.

Special instructions:

Since the potential risk of adverse reactions depends on the dose and duration of treatment, the minimum effective dose should be used with the minimum possible short course.

The duration of the course of treatment is set individually, depending on the course of the disease and the effectiveness of the therapy.

Combined application

Do not use the drug at the same time with other NSAIDs, the total daily dose of meloxicam when applied in the form of different dosage forms should not exceed 15 mg.

Patients with gastrointestinal diseases, when using the drug Libermum should be regularly examined. Do not prescribe the drug Libermum to patients with peptic ulcers or gastrointestinal bleeding. At any time during the treatment, with or without previous symptoms, serious gastrointestinal diseases in history, potentially fatal gastrointestinal bleeding, ulceration, or perforation may occur. If there is a ulcerative lesion of the gastrointestinal tract or gastrointestinal bleeding, the drug Liberum must be canceled. The most serious consequences were observed in elderly people.

In patients with cardiovascular diseases or with risk factors for such diseases, non-steroidal anti-inflammatory drugs may increase the risk of serious cardiovascular thrombotic events, myocardial infarction, angina attack and stroke, which can be fatal. With increasing duration of treatment, this risk may increase.

NSAIDs can enhance the retention of sodium, potassium and water and reduce the natriuretic effects of diuretics.As a consequence, heart failure or hypertension may occur or increase in predisposed patients. Such patients are recommended to conduct clinical monitoring, 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.

In patients with reduced renal blood flow, the use of NSAIDs (NSAIDs inhibit the synthesis of renal prostaglandin, which plays an important role in maintaining renal blood flow) can cause renal failure that occurs when non-steroidal anti-inflammatory therapy is discontinued. The greatest risk of such a reaction occurs in elderly patients, with dehydration, chronic heart failure, liver cirrhosis, nephrotic syndrome, chronic kidney disease who receive concomitant therapy with diuretic drugs, ACE inhibitors or angiotensin II receptor antagonists, or after extensive surgical interventions , which led to hypovolemia.Such patients need control over diuresis and kidney function at the beginning of therapy. In isolated cases, NSAIDs can lead to interstitial nephritis, glomerulonephritis, renal medullary necrosis or the development of nephrotic syndromes.

In the treatment of NSAIDs, isolated cases of an increase in the activity of transaminases or other indicators of liver function, which in most cases were minor and temporary, are described. With a persistent and significant deviation from the norm, treatment with Liberalum should be stopped and control tests performed. In clinically stable patients with cirrhosis of the liver, it is not necessary to reduce the dose of Libermum, it is necessary to monitor the revealed laboratory changes. Weakened patients need more careful observation, because side effects are more severe. As with other NSAIDs, caution should be given to elderly patients who are more likely to have decreased kidney, liver, and heart function.

The drug Libermum, like any other NSAID, can mask the symptoms of a major infectious disease.

The use of the drug Liberum, as well as other drugs that inhibit the synthesis of cyclooxygenase / prostaglandins, can affect fertilization, and therefore is not recommended for use in women who plan pregnancy. It is necessary to refuse from reception of a preparation of Liberum to women who pass inspection in occasion of barreness.

In very rare cases with the use of non-steroidal anti-inflammatory drugs, severe skin reactions (some of them fatal) were observed including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis. A high risk of such reactions is observed at the beginning of the treatment, and in most cases such reactions appear during the first month of treatment. At the first appearance of skin rashes, lesions of mucous membranes or other signs of hypersensitivity, it is necessary to stop using the drug Libermum. Due to possible side effects with localization on the skin and mucous membranes, special attention should be paid to the appearance of the corresponding symptoms. If there are side effects, Liberalum should be discontinued.

The composition of tablets Libermum (7.5 mg and 15 mg) includes lactose. Therefore, this drug is not recommended for patients with congenital lactose intolerance, with a deficiency of lactase or a violation of absorption of glucose or galactose.

In patients with an increased risk of side effects, treatment starts with a dose of 7.5 mg. In the terminal stage of chronic renal failure in patients on dialysis, the dose should not exceed 7.5 mg / day.

In patients with mild to moderate renal insufficiency (creatinine clearance greater than 30 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, it is possible to reduce the speed of mental and motor reactions, so it is necessary to refrain from driving transport and occupations with other potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Tablets, 7.5 and 15 mg.

Packaging:

For 10 tablets in a blister of a film of polyvinyl chloride light-shielded white pigmented and aluminum foil printed lacquered.

For 1 or 2 blisters together with instructions for medical use put in 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 printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-002757

Date of registration:15.12.2014 / 22.06.2017

Expiration Date:15.12.2019

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®)