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 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 has no effect on the progression of the disease.

Active ingredient

Composition

Per 1 ml:

Active ingredient: meloxicam – 10.0 mg.

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

How to take, the dosage

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

The recommended dose is 75 mg or 15 mg once daily depending on the intensity of pain and severity of the inflammatory process.

The maximum recommended daily dose is 15 mg.

The drug is administered deeply intramuscularly. Intravenous administration of the drug is prohibited!

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

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

In patients with mild to moderate renal insufficiency (CKG greater than 30 ml/min), no dose adjustment is required.

The drug should not be used simultaneously with other NSAIDs.

The total daily dose of Meloxicam used as oral suspension tablets and injections should not exceed 15 mg.

Interaction

Other prostaglandin synthesis inhibitors including glucocorticoids and salicylates when taken concomitantly with meloxicam increase the risk of GI ulcers and gastrointestinal bleeding (due to synergistic action) and therefore are not recommended.

Simultaneous use with other NSAIDs is not recommended.

Selective serotonin reuptake inhibitors – increased risk of gastrointestinal bleeding.

Lithium drugs – NSAIDs increase plasma lithium concentration by reducing its excretion overnight. It is recommended to monitor lithium concentrations while prescribing meloxicam when changing the dose of lithium drugs and their withdrawal.

Methotrexate – NSAIDs decrease tubular secretion of methotrexate thereby increasing its plasma concentrations and hematological toxicity methotrexate pharmacokinetics are not altered. In this regard, concomitant use of meloxicam and methotrexate in doses greater than 15 mg per week is not recommended. When concomitant use of the drugs the risk of increased toxicity of methotrexate increases.

The risk of interaction between NSAIDs and methotrexate may also occur in patients using methotrexate in low doses especially in patients with impaired renal function. Therefore, continuous monitoring of blood cell count and renal function is necessary.

Contraception – Simultaneous use with intrauterine contraceptives may decrease the effectiveness of the latter.

Mifepristone – due to the theoretical risk of the effectiveness of mifepristone being affected by prostaglandin synthesis inhibitors, NSAIDs should not be administered earlier than 8-12 days after mifepristone withdrawal.

Diuretics – use of NSAIDs if patients are dehydrated is accompanied by a risk of acute renal failure.

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

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

NSAIDs acting on renal prostaglandins may increase nephrotoxicity of cyclosporine.

When using concomitantly with meloxicam the medicines with 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.

In concomitant administration of meloxicam may increase the effect of oral antidiabetic agents and thus there is a risk of hypoglycemia.

Meloxicam may weaken the effects of digoxin cortisone diuretics.

Special Instructions

Patients suffering from gastrointestinal diseases should be monitored regularly. If gastrointestinal ulceration or gastrointestinal bleeding occurs, meloxicam should be discontinued.

Gastrointestinal ulcers perforation or bleeding can occur during treatment at any time, either in the presence of alarming symptoms or knowledge of serious gastrointestinal complications in the history or in the absence of these signs. The consequences of these complications are generally more serious in older adults.

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

Like other NSAIDs, meloxicam may increase the risk of serious cardiovascular thrombosis myocardial infarction with possible fatal angina attacks. This risk increases with long-term use of the drug as well as in patients with a history of and predisposition to the above diseases.

NSAIDs inhibit the renal synthesis of prostaglandins that are involved in maintaining renal perfusion. Use of NSAIDs in patients with reduced renal blood flow or reduced circulating blood volume can lead to decompensation of latent renal failure. After discontinuation of NSAIDs, renal function usually recovers to baseline levels. Elderly patients and patients with dehydration, congestive heart failure, cirrhosis nephrotic syndrome or acute renal dysfunction, patients taking diuretics simultaneously, and patients who have undergone serious surgical interventions that lead to hypovolemia are at the highest risk of developing this reaction. In such patients, diuresis and renal function should be closely monitored at the beginning of therapy.

The use of NSAIDs in conjunction with diuretics may lead to retention of potassium sodium and water as well as a decrease in the natriuretic action of diuretics. As a result, predisposed patients may have increased symptoms of heart failure or hypertension. Therefore, close monitoring of such patients is necessary and they should be kept adequately hydrated. Prior to initiation of treatment renal function investigation is necessary.

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

When using meloxicam (as well as most other NSAIDs), occasional increases in serum transaminase activity or other indicators of liver function have been reported. In most cases, these increases were small and transient. If the changes detected are significant or do not decrease over time meloxicam should be discontinued and the laboratory changes detected should be monitored.

Weakened or debilitated patients may have a worse tolerance to adverse events and therefore these patients should be closely monitored.

Meloxicam as well as other NSAIDs may mask symptoms of infectious diseases.

The use of meloxicam as well as other drugs that inhibit the synthesis of cyclooxygenase/prostaglandin may affect fertility so it is not recommended for women who are planning to become pregnant.

The use of the drug may cause undesirable effects in the form of headache and dizziness, drowsiness. It is necessary to refrain from driving vehicles and engaging in other potentially dangerous activities which require high concentration and quick psychomotor reactions.

Contraindications

– Hypersensitivity to the active substance or excipients (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 anamnesis);

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

– acute ulcerative colitis Crohn’s disease;

– severe hepatic insufficiency or active liver disease;

p> – severe renal impairment (unless hemodialysis is performed with creatinine clearance (CK) less than 30 mL/min and with confirmed hyperkalemia) advanced renal disease;

– acute gastrointestinal bleeding recently experienced cerebrovascular bleeding or established diagnosis of blood clotting disorders;

– Significant uncontrolled heart failure;

– Contraindicated in the period after coronary artery bypass grafting;

– pregnancy;

– period of breastfeeding;

– children under 18 years of age.

. elderly age coronary heart disease chronic heart failure cerebrovascular diseases dyslipidemia/hyperlipidemia diabetes mellitus peripheral artery disease smoking moderate renal insufficiency (CK 30-60 ml/min) gastrointestinal diseases in history (presence of Helicobacter pylori infection) long-term use of NSAIDs frequent use of alcohol severe systemic diseases concomitant use of oral glucocorticosteroids (incl.anticoagulants (including warfarin) antiplatelet agents (including acetylsalicylic acid clopidogrel) selective serotonin reuptake inhibitors (including citalopram fluoxetine paroxetine sertraline); bronchial asthma tuberculosis severe osteoporosis.

In order to reduce the risk of gastrointestinal adverse events, the lowest effective dose should be used for 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 common – more than 1/100 and less than 1/10 infrequent – more than 1/1000 and less than 1,100 rare – more than 1/10000 and less than 1/1000 very rare – less than 1/10000 including individual reports.

Digestive system disorders: frequent – dyspepsia nausea vomiting abdominal pain constipation diarrhea flatulence; infrequent – transient changes in liver function parameters (such as increased transaminase or bilirubin activity) belching esophagitis gastroduodenal ulcer hidden or overt gastrointestinal bleeding stomatitis; rare – gastrointestinal tract perforation colitis hepatitis gastritis.

Hematopoietic organs: often – anemia; infrequent – changes in blood count, including changes in the leukocyte count leukopenia thrombocytopenia.

The skin: frequently – skin itching skin rash; infrequently – urticaria; rarely – Stevens-Johnson syndrome toxic epidermal necrolysis; very rarely – photosensitization bullous rash erythema multiforme.

Respiratory system disorders: very rarely – bronchospasm.

Nervous system: common – headache; infrequent – dizziness drowsiness; very rare – confusion disorientation emotional lability.

Sensory system: infrequent – vertigo; rare – tinnitus conjunctivitis visual disorders including blurred vision.

The cardiovascular system: often – peripheral edema; infrequent – increase of blood pressure – feeling of “rush” of blood to the face; rare – feeling of rapid heartbeat.

Urogenital system disorders: infrequent – changes of renal function parameters (increased serum creatinine and/or urea levels) urinary disorders including acute retention; very rare – acute renal failure.

Allergic reactions: very rare – angioedema and reactions of immediate-type hypersensitivity including anaphylactic/anaphylactoid reactions.

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

Overdose

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

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

Pregnancy use

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

It is known that NSAIDs penetrate into the breast milk, so meloxicam is not recommended during breastfeeding.

Similarities