Pharmacological properties
Pharmacodynamics. Meloxicam belongs to the nonsteroidal anti-inflammatory drugs of the oxicam group, a selective COX-2 inhibitor, which contains enolic acid. The drug has a pronounced anti-inflammatory, analgesic and antipyretic effect. The mechanism of action of the drug is the ability to inhibit the biosynthesis of prostaglandins - mediators of inflammation due to the selective inhibition of COX-2. During clinical studies, significantly lower toxicity of meloxicam was found compared to other drugs (for example, naproxen, piroxicam and diclofenac), which, to the same extent inhibiting COX-1 and COX-2, can damage the gastrointestinal tract and kidneys. The selectivity coefficient ic50 COX-1 / COX-2 for meloxicam is 2, due to which the drug exhibits the necessary therapeutic effect and, compared to non-selective COX inhibitors, is less likely to cause adverse reactions from the gastrointestinal tract and kidneys. Meloxicam does not affect platelet aggregation and bleeding time.
Pharmacokinetics. Absorption. Meloxicam is well absorbed in the gastrointestinal tract regardless of food intake. The bioavailability of the drug is 89%, C max in blood plasma is reached after 5-6 hours and is, depending on the dose taken, 0.4-1 mg/ml after taking 7.5 mg and 0.8-2.0 mg/ml after taking 15 mg of the drug. Equivalent concentration is reached on the 3-5th day of treatment. Long-term use of the drug (more than 1 year) does not cause an increase in its concentration in blood plasma compared to the indicators at the beginning of use.
Distribution. About 99.5% of the drug binds to blood plasma proteins. The volume of distribution is on average 11 liters. Meloxicam penetrates into the synovial fluid, where its concentration is approximately 2 times lower than in blood plasma.
Metabolism: Biotransformation occurs in the liver by oxidation of methyl groups with the formation of 4 inactive metabolites.
Elimination. About 43% of the dose is excreted in the urine, the rest in the bile. 5% of the dose is excreted unchanged in the bile. The half-life of the drug is 20 hours.
Hepatic and renal insufficiency do not significantly affect the pharmacokinetics of meloxicam. Plasma clearance is 8 ml/min and is reduced in the elderly.
Indication
Treatment of diseases accompanied by pain syndrome: osteoarthritis, arthrosis, degenerative joint diseases, rheumatoid arthritis, ankylosing spondylitis.
Application
In adults, Melbek is used once a day, washed down with a small amount of liquid.
For osteoarthritis: 5 mg/day; if necessary, the dose can be increased to 15 mg/day.
For rheumatoid arthritis and ankylosing spondylitis: 15 mg once a day; depending on the therapeutic effect, the dose can be reduced to 7.5 mg once a day.
Patients at high risk of side effects and patients on dialysis should start treatment with a dose of 7.5 mg once daily.
The maximum daily dose of meloxicam for adults is 15 mg.
The duration of the treatment course is determined individually.
Contraindication
Hypersensitivity to meloxicam, as well as other nonsteroidal anti-inflammatory drugs, gastric and duodenal ulcers, gastrointestinal bleeding, severe hepatic and renal failure; age up to 12 years; pregnancy and breastfeeding.
Side effects
Possible abdominal pain, constipation, flatulence, diarrhea; anemia, itching, dizziness, headache, peripheral edema.
Rarely, transient increases in liver function tests (increased activity of transferases or concentration of bilirubin in blood plasma), esophagitis, peptic ulcer or gastrointestinal bleeding; leukopenia and thrombocytopenia; stomatitis, urticaria, tinnitus, drowsiness; increased blood pressure, facial erythema with a feeling of heat, tachycardia; changes in kidney function (increased level of creatinine and/or urea in blood plasma). With simultaneous use of a drug with a potential negative effect on bone marrow cells (especially methotrexate), pancytopenia may develop.
Very rare - perforation, hepatitis, photosensitization, Stevens-Johnson syndrome, toxic epidermal necrolysis, asthma attack resulting from taking acetylsalicylic acid, acute renal failure, conjunctivitis, visual impairment, angioedema, anaphylactoid/anaphylactic reactions.
Special instructions
It is necessary to strictly monitor the intake of the drug in patients with a history of BA. The drug should be used with caution in cases of dehydration, debilitated patients, the elderly, patients with heart failure, as well as those taking anticoagulant and antiplatelet drugs.
Like other NSAIDs, meloxicam may occasionally cause interstitial nephritis, glomerulonephritis, renal papillary necrosis or nephrotic syndrome. Such complications may occur in patients with chronic renal failure, after extensive surgery (which caused hypovolemia), and in patients with cirrhosis of the liver.
If symptoms of gastrointestinal bleeding, skin changes, as well as gingivitis or conjunctivitis occur, the drug should be discontinued immediately.
Effects on ability to drive and use machines. There are no data on the effects of the drug on the ability to drive or use machines. In case of dizziness or drowsiness, it is necessary to refrain from activities that require psychomotor activity.
Interactions
Melbek may reduce the effectiveness of antihypertensive agents (β-adrenergic blockers, ACE inhibitors).
In women using an intrauterine device, simultaneous use of Melbek may reduce its contraceptive effect.
Meloxicam and other non-steroidal anti-inflammatory drugs (especially acetylsalicylic acid and ibuprofen) should not be taken simultaneously, as this may increase the risk of ulcerogenic effects and gastrointestinal bleeding.
Meloxicam may enhance the effect of ticlopidine and heparin, which increases the risk of gastrointestinal bleeding.
Combined use with lithium salts is not recommended, given the decrease in renal excretion of lithium under the influence of nonsteroidal anti-inflammatory drugs, which may cause lithium accumulation and manifestations of its toxic effects.
Meloxicam should not be taken simultaneously with methotrexate, given the possibility of increasing the toxic effect of the latter on the hematopoietic system. It is not recommended to use Melbek together with cyclosporine, since the risk of nephrotoxic effects of the latter increases.
Pharmacokinetic interaction of meloxicam with other drugs at the metabolic stage is possible due to their effect on cytochrome P450 2C9 and/or cytochrome P450 3A4. With simultaneous use, no pharmacokinetic interaction of the drug with antacids, digoxin and furosemide was detected. Cholestyramine accelerates the elimination of meloxicam.
Drug interactions with oral hypoglycemic drugs cannot be ruled out.
Overdose
Overdose of meloxicam is manifested mainly in the form of increased side effects. In this case, the stomach is washed and symptomatic treatment is carried out. Cholestyramine increases the excretion of meloxicam from the gastrointestinal tract. There is no specific antidote.
Storage conditions
At a temperature not exceeding 25 °C.
