Genitron solution 10mg/ml 1.5ml ampoules, 5pcs

Composition

Per 1 ml:

Active ingredient:  meloxicam – 10.0 mg.

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

Pharmacological action

Pharmacotherapy group: NSAIDs ATX code: M01AC06 Pharmacodynamics :

Meloxicam is a nonsteroidal anti-inflammatory drug with an anti-inflammatory antipyretic analgesic effect. Enolic acid derivative belongs to the class of oxycams.

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, long-term use and individual characteristics of the body, the selectivity of COX-2 decreases.

Inhibits Pg synthesis 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 can cause side effects from the gastrointestinal tract (GI) and kidneys.

Pharmacokinetics:

Absorption rate

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

Distribution

Meloxicam binds to plasma proteins (mainly albumin) to a significant extent-99%. Passes through histohematic barriers and penetrates synovial fluid. The synovial fluid concentration is 50% of the plasma concentration of meloxicam. The volume of distribution (Vd) is low and amounts to 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 (which make up 16% and 4% of the administered dose of meloxicam, respectively) probably involves peroxidase, the activity of which varies individually.

Elimination

The significant intestinal-hepatic circulation characteristic of meloxicam does not affect its elimination. Meloxicam is excreted primarily as 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 elimination half-life (T 1/2) of meloxicam is 20 hours. The average plasma clearance is 8 ml/min.

Patients with impaired liver and/or kidney function

Hepatic insufficiency as well as mild or moderate renal insufficiency does not significantly affect the pharmacokinetics of meloxicam.

In end-stage renal failure, increased volume of distribution may result in higher concentrations of free meloxicam.

Indications

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

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

Use during pregnancy and lactation

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 ingredient or auxiliary components (including other NSAIDs);

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

– erosive and ulcerative changes in the mucous membrane of the stomach and duodenal ulcers, active gastrointestinal bleeding;

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

– severe hepatic impairment or active liver disease;

– severe renal insufficiency (if not possible, dialysis creatinine clearance (CC) of less than 30 ml/min and when confirmed hyperkalemia) progressive kidney disease;

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

– severe uncontrolled heart failure;

– contraindicated in the period after the coronary artery bypass grafting;

– pregnancy;

– the period of breastfeeding;

– children’s age till 18 years.

With caution:

Advanced age ischemic heart disease chronic heart failure cerebrovascular diseases dyslipidemia/hyperlipidemia diabetes mellitus peripheral arterial diseases smoking moderate renal failure (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 concomitant use of oral glucocorticosteroids (including prednisone) anticoagulants (including prednisone) 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 gastrointestinal adverse events, the minimum effective dose should be used in the shortest possible course.

Side effects

The frequency of adverse reactions is given in accordance with the WHO classification: very common-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 rare-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 transaminase or bilirubin activity) belching esophagitis gastroduodenal ulcer hidden or obvious gastrointestinal bleeding stomatitis; rarely-perforation of the gastrointestinal tract colitis hepatitis gastritis.

From the side of hematopoietic organs:  often-anemia; infrequently-a change in the blood formula including a change in the leukocyte formula leukopenia thrombocytopenia.

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

Respiratory system disorders:  very rarely – bronchospasm.

From the nervous system: often-headache; infrequently-dizziness drowsiness; very rarely-confusion disorientation emotional lability.

From the sensory organs: infrequently-vertigo; rarely-tinnitus conjunctivitis visual disturbances including blurred vision.

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

From the genitourinary system:  infrequently-changes in renal function indicators (increased serum creatinine and/or urea) impaired urination, including acute urinary retention; very rarely – acute renal failure.

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

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

Interaction

Other prostaglandin synthesis inhibitors, including glucocorticoids and salicylates, when co-administered with meloxicam increase the risk of gastrointestinal ulceration and gastrointestinal bleeding (due to synergistic effects) and are therefore not recommended.

Concomitant use with other NSAIDs is not recommended.

Selective serotonin reuptake inhibitors increase the 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 the lithium concentration during the use of meloxicam when changing the dose of lithium preparations and canceling them.

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

The risk of interaction between NSAIDs and methotrexate may also occur in patients using low-dose 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 changing the effectiveness of mifepristone under the influence of prostaglandin synthesis inhibitors, NSAIDs should not be prescribed earlier than 8-12 days after mifepristone withdrawal.

Diuretics-the use of NSAIDs in case of dehydration of patients is associated with the risk of acute renal failure.

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

Angiotensin II receptor antagonists, when combined with NSAIDs, increase the decrease in glomerular filtration rate, which may lead to the development of acute renal failure, especially in patients with impaired renal function.

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

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

When taking meloxicam at the same time, it may increase the effect of oral antidiabetic agents, thereby there is a risk of hypoglycemia.

Meloxicam may weaken the effects of digoxin cortisone diuretics.

How to take, course of use and dosage

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

The recommended dose is 75 mg or 15 mg 1 time / day, depending on the intensity of pain and the severity of the inflammatory process.

The maximum recommended daily dose is 15 mg.

The drug is administered deep intramuscularly. Intravenous use of the drug is prohibited!

Due to possible incompatibilities, meloxicam should not be mixed in the same syringe with other medications.

In patients with an increased risk of adverse reactions and severe renal insufficiency who are on hemodialysis, the daily dose should not exceed 75 mg.

No dose adjustment is required for patients with mild or moderate renal insufficiency (creatinine clearance greater than 30 ml / min).

Do not use the drug simultaneously with other NSAIDs.

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

Overdose

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

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

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, both in the presence of alarming symptoms or information about serious gastrointestinal complications in the anamnesis and in the absence of these signs. The consequences of these complications are generally more serious in the elderly.

Special attention should be paid to patients who report skin and mucosal adverse events 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 serious cardiovascular thrombosis, myocardial infarction, and possibly fatal angina attacks. This risk increases with prolonged use of the drug, as well as in patients with a history of the above diseases 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 reduced circulating blood volume may lead to decompensation of latent renal failure. After NSAID withdrawal, renal function usually returns to its original level. Elderly patients and patients with dehydration congestive heart failure cirrhosis of the liver nephrotic syndrome or acute renal function disorders patients taking diuretics at the same time as well as patients who have undergone serious surgical interventions that lead to hypovolemia are most at risk of developing this reaction. In such patients, diuresis and renal function should be carefully monitored at the beginning of therapy.

The use of NSAIDs in combination with diuretics can lead to a delay in sodium potassium and water, as well as to a decrease in the natriuretic effect of diuretics. As a result, predisposed patients may have increased signs of heart failure or hypertension. Therefore, the condition of such patients should be carefully monitored and adequate hydration should be maintained. Before starting treatment, a study of renal function is necessary.

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

When meloxicam is used (as with most other NSAIDs), an occasional increase in transaminase activity or other indicators of liver function in the blood serum has been reported. In most cases, this increase was small and transient. If the detected changes are significant or do not decrease over time, meloxicam should be discontinued and the detected laboratory changes should be monitored.

Debilitated or emaciated patients may have a worse tolerance for adverse events, and such patients should be carefully monitored.

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

The use of meloxicam as well as other drugs that inhibit the synthesis of cyclooxygenase / prostaglandin can affect fertility, so it is not recommended for women planning pregnancy.

Influence on the ability to drive vehicles and mechanisms:

The use of the drug may cause undesirable effects in the form of headache and dizziness drowsiness. You should refrain from driving vehicles and engaging in other potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions.

Storage conditions

Store in a dark place at a temperature not exceeding 25 °C.

Keep out of reach of children.

Shelf

life is 5 years.

Do not use after the expiration date.

Active ingredient

Meloxicam

Conditions of release from pharmacies

By prescription

Dosage form

solution for injection