Pharmacological properties
NSAID of the oxicam group. Has anti-inflammatory, analgesic, antipyretic effects.
Meloxicam is a highly selective inhibitor of the COX-2 isoenzyme, does not affect platelet aggregation induced by collagen or arachidonic acid, and significantly inhibits the production of thromboxane by platelets.
The anti-inflammatory activity of meloxicam has been proven in classical models of inflammatory processes. Its mechanism of action is associated with inhibition of the synthesis of prostaglandins, which are mediators of inflammatory processes.
The bioavailability of meloxicam when administered orally is on average 89%. Meloxicam is slowly absorbed from the gastrointestinal tract, the maximum concentration in the blood plasma is reached 4-5 hours after administration; the concentration in the synovial fluid is 40-50% of the concentration in the blood plasma.
For doses of 7.5 and 15 mg, the average plasma concentration is proportional to the dose taken and is 0.4-1.0 mg/l for a dose of 7.5 mg and 0.8-2.0 mg/l for a dose of 15 mg (C min and C max at steady state).
Meloxicam is extensively bound to plasma proteins, mainly (99%) to albumin.
Metabolized meloxicam is formed mainly by oxidation of the methyl radical to the thiazolyl ring. 3% of the dose is excreted unchanged. Half of the substance is excreted in the urine, the rest in the feces. The average half-life is approximately 20 hours. A constant concentration of the drug is achieved within 5 days.
The clearance of the drug is on average 8 minutes. Clearance is reduced in elderly patients. The volume of distribution is small, on average - 11 liters. Variability for individual people is 30-40%.
In case of significant renal insufficiency, the volume of distribution increases, therefore it is not recommended to exceed the daily dose, which is 7.5 mg.
Indication
Short-term treatment for symptoms of osteoarthritis exacerbation.
Long-term treatment of rheumatoid arthritis symptoms.
Treatment of ankylosing spondylitis.
Application
Oral. The daily dose should be taken once during a meal, with water or another beverage. The dose should not exceed 15 mg/day.
For children over 15 years old and adults
Exacerbation of osteoarthritis: 7.5 mg/day. If necessary, the dose can be increased to 15 mg/day.
Rheumatoid arthritis: 15 mg/day. For elderly patients with rheumatoid arthritis, the recommended dose is 7.5 mg/day; for patients at increased risk of side effects, a starting dose of 7.5 mg/day should be used.
Ankylosing spondylitis: 15 mg/day.
In patients requiring dialysis (with severe renal failure), the dose should not exceed 7.5 mg/day.
Contraindication
Pregnancy and breast-feeding. Hypersensitivity to meloxicam or to any of the excipients or to drugs with a similar effect, such as other non-steroidal anti-inflammatory drugs. Patients who develop asthma symptoms, nasal polyps, angioedema or urticaria after taking acetylsalicylic acid or other non-steroidal anti-inflammatory drugs. Active or recurrent gastric ulcer in history. Severe liver dysfunction. Severe renal failure in patients requiring dialysis. Gastrointestinal bleeding. Blood clotting disorders. Intracranial hemorrhage, hemorrhagic stroke. Children under 15 years of age.
Side effects
From the gastrointestinal tract: dyspepsia, nausea, vomiting, stomach pain, constipation, flatulence, diarrhea, stomatitis, esophagitis. rarely, ulcers, perforation or bleeding in the digestive tract may occur, sometimes severe, especially in elderly patients. in isolated cases - gastritis.
From the blood system: anemia, leukopenia, thrombocytopenia. In rare cases - agranulocytosis.
Skin: itching, rash, urticaria, photosensitivity. In rare cases - erythema multiforme, Stevens-Johnson syndrome and Lyell's syndrome.
Photosensitivity reactions: anaphylactic/pseudoanaphylactic reactions, rarely - angioedema.
On the part of the respiratory system: some people with hypersensitivity to acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs have asthma attacks.
From the side of the central nervous system: headache, feeling of emptiness in the head, dizziness, tinnitus, drowsiness. Rarely - disorientation, mood swings, insomnia.
On the part of the organs of vision: rarely - visual disorders, blurred vision, conjunctivitis.
On the part of the cardiovascular system: edema, including lower extremities, increased blood pressure, palpitations, periodic redness of the face.
From the hepatobiliary and urinary system: decreased liver function (increased transaminases or bilirubin). In rare cases - hepatitis, changes in kidney function (increased creatinine and/or urea).
Special instructions
A history of esophagitis, gastritis or peptic ulcer disease should be completely resolved before starting meloxicam. The possibility of relapse in patients with these conditions should always be considered when using meloxicam.
As with NSAIDs, gastrointestinal bleeding, ulceration and/or perforation have been reported. These adverse reactions may occur at any time during treatment with meloxicam, regardless of prodromal symptoms or a history of serious gastrointestinal events.
Gastrointestinal bleeding, ulceration/perforation usually have serious consequences in elderly patients. In the event of gastrointestinal bleeding or ulceration, patients taking meloxicam should discontinue the drug.
Treatment should also be discontinued if changes in the mucous membranes and skin occur. Severe skin reactions and hypersensitivity reactions may occur during treatment with NSAIDs, including oxicams.
In rare cases, NSAIDs can cause pyelonephritis, glomerulonephritis, renal medulla necrosis, or nephrotic syndrome.
Sometimes there may be an increase in the level of transaminases in the blood plasma, bilirubin or other indicators of liver function, as well as an increase in the concentration of creatinine and urea nitrogen in the blood plasma and changes in other laboratory parameters. Most of these disorders are transient and of minor intensity. If their intensity increases or if they persist, it is necessary to interrupt the administration of meloxicam and conduct the necessary studies.
Sodium, potassium, and water retention may occur when taking nonsteroidal anti-inflammatory drugs. Since NSAIDs simultaneously inhibit the natriuretic effect of diuretics, patients with heart failure or hypertension may experience exacerbation of the disease.
In patients with impaired renal function, treatment with meloxicam or other NSAIDs may lead to a decrease in renal blood flow, which is due to a decrease in prostaglandin synthesis in the kidneys. In these cases, taking NSAIDs can lead to decompensation of latent renal failure. When treatment is discontinued, renal function is restored. This applies to elderly patients and patients with circulatory disorders, cirrhosis of the liver, nephrotic syndrome or impaired renal function, as well as to people taking diuretics or having undergone surgery that may be accompanied by hypovolemia. In such patients, diuresis and renal function should be monitored during treatment.
Elderly patients with signs of cachexia have difficulty tolerating the side effects of the drug, and therefore require more careful medical supervision. Particular caution should be observed in elderly patients with impaired renal, cardiac, and hepatic function.
In case of insufficient therapeutic effect, the recommended maximum daily dose should not be exceeded, and additional nonsteroidal anti-inflammatory drugs should not be included in the treatment. This may lead to increased side effects and toxic effects of the drug.
The safety and efficacy of meloxicam in children under 15 years of age have not been established.
Pregnancy and breastfeeding. Contraindicated during pregnancy and breastfeeding. Pregnancy should be excluded before starting treatment. NSAIDs pass into breast milk, so the drug should not be prescribed during breastfeeding.
Effects on the ability to drive and use machines. No studies have been conducted. However, in case of visual impairment, drowsiness, dizziness or other CNS disorders, driving or using machines is not recommended.
Interactions
Concomitant use of meloxicam with the following drugs requires careful monitoring of the patient's clinical and laboratory parameters.
not recommended combinations
Oral antithrombotic agents, parenteral heparin, and ticlopidine
Increase the risk of bleeding due to inhibition of platelet aggregation and damage to the gastric and duodenal mucosa. If such a combination of drugs cannot be avoided, it is important to monitor the effect of antithrombotic agents.
Other NSAIDs, including high doses of salicylates
The simultaneous use of several NSAIDs may increase the risk of developing ulcers or bleeding from the gastrointestinal tract due to the combined effect.
lithium
NSAIDs increase the level of lithium in the blood, which may lead to toxic concentrations of the drug (reduced renal excretion of lithium). Therefore, it is necessary to monitor the concentration of lithium at the beginning of treatment, during dose adjustment and after treatment with meloxicam.
Use of high-dose methotrexate (15 mg/week)
Increased bone marrow toxicity of methotrexate due to a general decrease in renal clearance by anti-inflammatory agents. Careful monitoring of blood counts is necessary.
Combinations to be used with caution
cyclosporine
NSAIDs may enhance the nephrotoxicity of cyclosporine, which is caused by renal prostaglandins. During the period of combined treatment, renal function should be monitored.
The use of nonsteroidal anti-inflammatory drugs has been associated with the occurrence of acute renal failure, mainly in patients with reduced glomerular filtration due to reduced prostaglandin synthesis in the kidneys. If meloxicam is prescribed in combination with diuretics, it is necessary to ensure that the patient is adequately hydrated and to examine renal function before starting treatment.
Low-dose methotrexate (15 mg/week)
Increased bone marrow toxicity of methotrexate has been reported due to a general decrease in its renal clearance by anti-inflammatory agents. During the first weeks of this combination of drugs, blood counts should be monitored weekly. Caution should be exercised even in the presence of mild renal impairment.
pentoxifylline
Increases the risk of bleeding. Clinical monitoring and control of blood clotting time should be carried out more frequently.
zidovudine
Risk of erythrocyte toxicity due to effects on reticulocytes. Severe anemia may develop 1 week after starting NSAIDs. Blood tests with complete blood count and reticulogram should be performed within 1-2 weeks of starting NSAIDs.
Combinations to watch out for
Antihypertensive drugs, such as β-blockers, ACE inhibitors, diuretics. Treatment with NSAIDs may reduce their hypotensive effect by inhibiting prostaglandin synthesis.
intrauterine contraceptive
Risk of reduced contraceptive effectiveness.
thrombolytic agents
Increased risk of bleeding.
others
No significant pharmacokinetic interactions have been observed between meloxicam and antacids, cimetidine, β-acetyldigoxin and furosemide. Meloxicam does not alter the pharmacokinetics of digoxin. Cholestyramine accelerates the elimination of meloxicam, which binds it in the gastrointestinal tract.
Interactions with oral agents for the treatment of patients with diabetes cannot be excluded.
Overdose
There is an increase in the severity of side effects. There are no specific antidotes. Treatment is symptomatic. In one clinical case, it was reported that cholestyramine accelerates the elimination of meloxicam. Patients with gastrointestinal ulcers can be prescribed antacids or H2-receptor antagonists. In case of overdose, gastric lavage and the use of sorbents are indicated.
Storage conditions
In a dry, dark place at a temperature not exceeding 25 °C.
