Genitron, 10 mg/ml 1.5 ml 5 pcs

Pharmacotherapeutic group: NSAIDs

ATC code: M01AC06

Pharmacodynamics:

Meloxicam is a non-steroidal anti-inflammatory drug with anti-inflammatory antipyretic analgesic effect. It belongs to the class of oxycams and is a derivative of enolic acid.

The mechanism of action – inhibition of prostaglandin (Pg) synthesis as a result of selective inhibition of enzymatic activity of cyclooxygenase 2 (COX-2). When prescribed in high doses with prolonged use and individual characteristics of the body COX-2 selectivity decreases.

Suppresses Pg synthesis in the area of inflammation to a greater extent than in the gastrointestinal mucosa or kidneys due to the relatively selective inhibition of COX-2 whereas inhibition of the ever-present COX-1 isoenzyme may cause gastrointestinal (GI) and renal side effects.

Pharmacokinetics:

Absorption

Meloxicam is completely absorbed after intramuscular administration. The bioavailability of meloxicam is about 100%. After intramuscular administration of 15 mg of meloxicam the maximum concentration of the drug (Cmax) in blood plasma is reached after about 1 hour.

Distribution

Meloxicam binds to plasma proteins (mainly to albumin) to a significant extent – 99%. Passes through the histohematic barriers and penetrates into the synovial fluid. Concentration in synovial fluid is 50% of the plasma concentration of meloxicam. The volume of distribution (Vd) is low and is 11 liters.

Metabolism

Meloxicam is almost completely metabolized in the liver to form four pharmacologically inactive metabolites. The main metabolite, 5-carboxymeloxicam (60% of the administered dose) is formed by oxidation of the intermediate metabolite 5′-hydroxymethylmeloxicam (9% of the administered dose). The formation of the other two metabolites (constituting respectively 16% and 4% of the administered dose of meloxicam) probably involves peroxidase activity of which varies individually.

The significant intestinal-hepatic circulation characteristic of meloxicam does not affect its elimination. Meloxicam is excreted mainly as metabolites equally by the kidneys and the intestine. Less than 5% of meloxicam is excreted unchanged by the intestine and only trace amounts of unchanged meloxicam are detected in the urine.

The average elimination half-life (T1/2) of meloxicam is 20 hours. Plasma clearance averages 8 ml/min.

Patients with impaired hepatic and/or renal function

Lack of hepatic function and mild to moderate renal failure have no significant effect on the pharmacokinetics of meloxicam.

In terminal renal failure, increased volume of distribution may lead to higher concentrations of free meloxicam.

Indications

Short-term symptomatic treatment of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis and other joint diseases accompanied by pain.

The drug is intended to reduce pain and inflammation at the time of use and does not affect the progression of the disease.

Pharmacological effect

Pharmacotherapeutic group: NSAIDs

ATX code: M01AC06

Pharmacodynamics:

Meloxicam is a non-steroidal anti-inflammatory drug with anti-inflammatory, antipyretic, analgesic effects. It belongs to the class of oxicams, a derivative of enolic acid.

The mechanism of action is inhibition of prostaglandin (Pg) synthesis as a result of selective suppression of the enzymatic activity of cyclooxygenase 2 (COX-2). When prescribed in high doses over a long period of time and due to individual characteristics of the body, the selectivity of COX-2 decreases.

Suppresses the synthesis of Pg in the area of ​​inflammation to a greater extent than in the gastric mucosa or kidneys, which is associated with relatively selective inhibition of COX-2, while inhibition of the constantly present COX-1 isoenzyme may cause side effects from the gastrointestinal tract (GIT) and kidneys.

Pharmacokinetics:

Absorption

Meloxicam is completely absorbed after intramuscular administration. The bioavailability of meloxicam is about 100%. After intramuscular administration of 15 mg of meloxicam, the maximum concentration of the drug (Cmax) in the blood plasma is reached after approximately 1 hour.

Distribution

Meloxicam binds to plasma proteins (mainly albumin) to a significant extent – 99%. Passes through histohematic barriers and penetrates into the synovial fluid. The concentration in synovial fluid is 50% of the plasma concentration of meloxicam. The volume of distribution (Vd) is low at 11 L.

Metabolism

Meloxicam is almost completely metabolized in the liver to form four pharmacologically inactive metabolites. The main metabolite, 5-carboxymeloxicam (60% of the administered dose), is formed through the oxidation of the intermediate metabolite 5′-hydroxymethylmeloxicam (9% of the administered dose). In the formation of the other two metabolites (constituting 16% and 4% of the administered dose of meloxicam, respectively), peroxidase, the activity of which varies individually, probably takes part.

Removal

The significant enterohepatic circulation characteristic of meloxicam does not affect its elimination. Meloxicam is excreted primarily in the form of metabolites, equally by the kidneys and intestines. Less than 5% of meloxicam is excreted unchanged by the intestines and only trace amounts of unchanged meloxicam are detected in the urine.

The average half-life (T1/2) of meloxicam is 20 hours. Plasma clearance averages 8 ml/min.

Patients with impaired liver and/or kidney function

Insufficiency of liver function as well as mild or moderate renal failure does not have a significant effect on the pharmacokinetics of meloxicam.

In end-stage renal disease, an increase in volume of distribution may result in higher concentrations of free meloxicam.

Special instructions

Patients suffering from gastrointestinal diseases should be monitored regularly. If ulcerative lesions of the gastrointestinal tract or gastrointestinal bleeding occur, meloxicam should be discontinued.

Ulcers in the gastrointestinal tract, perforation or bleeding can occur during treatment at any time, either in the presence of warning symptoms or a history of serious gastrointestinal complications, or in the absence of these signs. The consequences of these complications are generally more serious in older people.

Particular attention should be paid to patients reporting the development of adverse events from the skin and mucous membranes, as well as hypersensitivity reactions to meloxicam, especially if such reactions were observed during previous courses of treatment.

Like other NSAIDs, meloxicam may increase the risk of developing serious cardiovascular thrombosis, myocardial infarction, and possibly fatal angina. This risk increases with long-term use of the drug, as well as in patients with a history of the above diseases and those 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 reduced circulating blood volume may lead to decompensation of latent renal failure. After discontinuation of NSAIDs, renal function usually returns to baseline levels. Those most at risk for developing this reaction are elderly patients and patients with dehydration, congestive heart failure, cirrhosis of the liver, nephrotic syndrome or acute renal impairment, patients concomitantly taking diuretics, and patients who have undergone major surgical procedures that lead to hypovolemia. In such patients, diuresis and renal function should be carefully monitored when initiating therapy.

The use of NSAIDs in combination with diuretics can lead to sodium, potassium and water retention, as well as a decrease in the natriuretic effect of diuretics. As a result, predisposed patients may experience increased signs of heart failure or hypertension. Therefore, such patients must be closely monitored and adequate hydration maintained. Before starting treatment, a kidney function test is necessary.

In case of combination therapy, renal function should also be monitored.

With the use of meloxicam (as well as most other NSAIDs), occasional increases in serum transaminases or other indicators of liver function have been reported. In most cases, this increase was small and transitory. If the detected changes are significant or do not decrease over time, meloxicam should be discontinued and the detected laboratory changes should be monitored.

Weakened or malnourished patients may be less able to tolerate adverse events and such patients should be monitored closely.

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

The use of meloxicam, like other drugs that inhibit cyclooxygenase/prostaglandin synthesis, may affect fertility and is therefore not recommended for women planning pregnancy.

Impact on the ability to drive vehicles. Wed and fur.:

The use of the drug may cause undesirable effects such as headaches and dizziness and drowsiness. You should refrain from driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Active ingredient

Meloxicam

Composition

For 1 ml:

Active ingredient: meloxicam – 10.0 mg.

Excipients: meglumine (meglumine), glycofurfural (tetraglycol), poloxamer 188, sodium chloride, glycine, 1 M sodium hydroxide solution, water for injection.

Pregnancy

Meloxicam is contraindicated during pregnancy (see section “Contraindications”).

NSAIDs are known to pass into breast milk, so meloxicam is not recommended for use during breastfeeding.

Contraindications

– Hypersensitivity to the active substance or auxiliary components (including other NSAIDs);

– complete or incomplete combination of bronchial asthma, recurrent polyposis of the nasal mucosa and paranasal sinuses and intolerance to acetylsalicylic acid and other NSAIDs (including a history);

– erosive and ulcerative changes in the mucous membrane of the stomach and duodenum; active gastrointestinal bleeding;

– ulcerative colitis Crohn’s disease in the acute stage;

– severe liver failure or active liver disease;

– severe renal failure (if hemodialysis is not performed, creatinine clearance (CC) is less than 30 ml/min and also with confirmed hyperkalemia) progressive kidney disease;

– acute gastrointestinal bleeding, recent cerebrovascular bleeding or an established diagnosis of diseases of the blood coagulation system;

– severe uncontrolled heart failure;

– contraindicated in the period after coronary artery bypass surgery;

– pregnancy;

– breastfeeding period;

– children under 18 years of age.

With caution:

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

To reduce the risk of developing adverse events from the gastrointestinal tract, the minimum effective dose should be used for the shortest possible short course.

Side Effects

The frequency of adverse reactions is given in accordance with the WHO classification: very often – more than 1/10 often – more than 1/100 and less than 1/10 infrequently – more than 1/1000 and less than 1,100 rarely – more than 1/10000 and less than 1/1000 very rarely – less than 1/10000 including individual reports.

From the digestive system: often – dyspepsia nausea vomiting abdominal pain constipation diarrhea flatulence; infrequently – transient changes in liver function indicators (for example, increased activity of transaminases or bilirubin) belching esophagitis gastroduodenal ulcer hidden or obvious gastrointestinal bleeding stomatitis; rarely – perforation of the gastrointestinal tract, colitis, hepatitis, gastritis.

From the hematopoietic organs: often – anemia; infrequently – changes in the blood count, including changes in the leukocyte count, leukopenia, thrombocytopenia.

From the skin: often – itching, skin rash; infrequently – urticaria; rarely – Stevens-Johnson syndrome, toxic epidermal necrolysis; very rarely – photosensitivity, bullous rashes, erythema multiforme.

From the respiratory system: very rarely – bronchospasm.

From the nervous system: often – headache; uncommon – dizziness, drowsiness; very rarely – confusion, disorientation, emotional lability.

From the senses: infrequently – vertigo; rarely – tinnitus, conjunctivitis, visual impairment, incl. blurred vision.

From the cardiovascular system: often – peripheral edema; infrequently – increased blood pressure, a feeling of a “rush” of blood to the skin of the face; rarely – a feeling of rapid heartbeat.

From the genitourinary system: infrequently – changes in kidney function indicators (increased levels of creatinine and/or urea in the blood serum), urinary disturbances including acute retention; very rarely – acute renal failure.

Allergic reactions: very rarely – angioedema and immediate hypersensitivity reactions, incl. anaphylactic/anaphylactoid reactions.

Local reactions: often – swelling and pain at the injection site.

Interaction

Other inhibitors of prostaglandin synthesis, including glucocorticoids 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.

Concomitant use with other NSAIDs is not recommended.

Selective serotonin reuptake inhibitors – increased risk of gastrointestinal bleeding.

Lithium preparations – NSAIDs increase the concentration of lithium in the blood plasma by reducing its excretion at night. It is recommended to monitor lithium concentrations during the period of meloxicam administration when changing the dose of lithium preparations and their discontinuation.

Methotrexate – NSAIDs reduce the tubular secretion of methotrexate, thereby increasing its concentration in the blood plasma and hematological toxicity; the pharmacokinetics of methotrexate do not change. In this regard, the simultaneous use of meloxicam and methotrexate at a dose of more than 15 mg is not recommended. With simultaneous use of drugs, the risk of increased toxicity of methotrexate increases.

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

Contraception – when used simultaneously with intrauterine contraceptives, the effectiveness of the latter may decrease.

Mifepristone – due to the theoretical risk of changes in the effectiveness of mifepristone under the influence of prostaglandin synthesis inhibitors, NSAIDs should not be prescribed earlier than 8-12 days after discontinuation of mifepristone.

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

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

Angiotensin II receptor antagonists, when used together with NSAIDs, increase the reduction in glomerular filtration, which can thereby lead to the development of acute renal failure, especially in patients with impaired renal function.

NSAIDs, by acting on renal prostaglandins, may increase the nephrotoxicity of cyclosporine.

When used concomitantly with meloxicam, drugs that have a known ability to inhibit CYP2C9 and/or CYP3A4 (or are metabolized with the participation of these enzymes) should take into account the possibility of pharmacokinetic interaction.

When taken concomitantly, meloxicam may enhance the effect of oral antidiabetic agents, thereby creating a risk of hypoglycemia.

Meloxicam may reduce the effect of the diuretic digoxin and cortisone.

Overdose

Symptoms: drowsiness, impaired consciousness, nausea, vomiting, epigastric pain, gastrointestinal bleeding, acute renal failure, changes in blood pressure, respiratory arrest, asystole.

Treatment: there is no specific antidote; symptomatic therapy. Forced diuresis, alkalinization of urine, hemodialysis – are ineffective due to the high binding of meloxicam to blood proteins.

Storage conditions

In a place protected from light at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life

5 years.

Do not use after expiration date.

Manufacturer

Velfarm LLC, Russia