Inflammatory action of meloxicam is installed on all standard models of inflammation. Meloxicam mechanism of action is its ability to inhibit prostaglandin synthesis -.-Known mediators of inflammation In vivo meloxicam inhibits prostaglandin synthesis at the site of inflammation to a greater extent than in the gastric mucosa and kidney. It is believed that COX-2 inhibition provides a therapeutic effect of NSAIDs, while constantly present isoenzyme inhibition of COX-1 can cause side effects in the stomach and kidney. The selectivity of meloxicam for COX-2 was confirmed in various test systems as testosterone propionate 100mg in vitro, and ex vivo. Meloxicam selective ability to inhibit COX-2 is shown when used as a test system in vitro human whole blood. Ex vivo established that meloxicam (at doses of 7.5 and 15 mg) actively inhibited COX-2 by providing a greater inhibitory effect on the production of prostaglandin E 2 , stimulated with lipopolysaccharide (reaction controlled by COX-2) than on production of thromboxane involved in clotting process (reaction controlled by COX-1). These effects depend on the dose. Ex vivo demonstrated that meloxicam at recommended doses had no effect on platelet aggregation, and bleeding time, unlike indomethacin. diclofenac. ibuprofen and naproxen. that significantly inhibited platelet aggregation, and bleeding time was increased. In clinical studies, side effects from the gastrointestinal tract (GIT) is generally less likely to arise when receiving meloxicam 7.5 mg and 15 than the reception of other NSAIDs, which were compared. This difference in the frequency of side effects from the gastrointestinal tract is mainly due to the fact that when taking meloxicam rarely observed phenomena such as dyspepsia, vomiting, nausea, abdominal pain. The frequency of the perforations in the upper gastrointestinal ulceration and bleeding, are contacted with meloxicam, was low and was dependent on the dose of the drug.Pharmacokinetics Meloxicam is well absorbed from the gastrointestinal tract as evidenced by high absolute oral bioavailability (89%). in single dose of the drug in the form of tablets mean maximum concentration is reached within 5-6 hour plasma. Repeated use of the steady state pharmacokinetics is achieved in 3 to 5 days. The range of differences between the maximum (C max ) and basal concentrations (the C min ) of the drug during the steady-state pharmacokinetics after administration once a day is relatively small and is 0.4 -1.0 g / mL – 7.5 mg for the dose and 0.8-2.0 ug / ml – a dose of 15 mg. The maximum plasma concentration during steady state pharmacokinetics is achieved within 5-6 hours when receiving tablets. Concentrations of the drug after ingestion constant for more than 6 months, similar to the concentrations that have been observed after 2 weeks of oral administration of 15 mg per day. When receiving more than 6 months, these differences are unlikely. Simultaneous food intake does not affect absorption of the drug. Distribution Meloxicam is well bound to plasma proteins (albumin – 99%). Meloxicam penetrates into synovial fluid: the local concentration is approximately 50% of plasma concentrations. Low volume of distribution, an average of 11 liters. Individual oscillations -. 30-40% Metabolism Meloxicam is almost completely metabolized in the liver to form 4 pharmacologically inactive derivatives defined in urine. The main metabolite, 5′-karboksimeloksikam (60% of the dose), formed by oxidation of an intermediate metabolite 5′-gidroksimetilmeloksikama which is also excreted, but to a lesser extent (9% of the dose). Studies in vitro have shown that the metabolic conversion plays an important role CYP 2C9, additional importance ZA4 CYP isozyme. The formation of two other metabolites (components, respectively, 16% and 4% of the dose) participates peroxidase. whose activity is likely to vary individually. deduced equally with feces and urine, mainly as metabolites. Unchanged in the feces appears less than 5% of the daily dose in the urine as unchanged drug is found only in trace amounts. The average half-life of meloxicam is 20 hours. Plasma clearance averages of 8 ml / min. Meloxicam demonstrates linear pharmacokinetics at doses of 7.5 -. 15 mg when administered deficiency of the liver and / or kidney disease . The lack of liver function, as well as mild to moderate renal insufficiency significant effect on the pharmacokinetics of meloxicam has no At the terminal renal insufficiency an increase in volume of distribution may result in higher concentrations of free meloxicam, so these patients the daily dose should not exceed 7.5 mg. elderly patients are elderly patients average plasma clearance during steady-state pharmacokinetics is slightly lower than in younger patients. During the study, children meloxicam It was studied pharmacokinetics of the drug in doses applied at the rate of 0.25 mg / kg. When comparing the performance of different age children (2-6 years old, n = 7 and 7-14 years, n = 11) is set to a lower tendency to maximum plasma concentration (C max , -34%) and AUC 0 ∞- (- 28%) in young children, and the clearance of the drug (adjusted for body weight) in this group of children was higher testosterone propionate 100mg price. The concentrations of meloxicam in plasma in older children and adults alike. In children of both age groups of meloxicam half-lives testosterone propionate 100mg were similar to plasma (13 hours) and several shorter than adults (15-20 hours).
Symptomatic treatment of:
– osteoarthritis (arthrosis, degenerative joint disease),
– rheumatoid arthritis
– ankylosing spondylitis.
– Hypersensitivity to the active ingredient or auxiliary ingredients. There is a possibility of cross-sensitivity to acetylsalicylic acid and other NSAIDs;
– The symptoms of asthma, nasal polyps, angioneurotic edema or urticaria after taking aspirin or other NSAIDs in history;
– Peptic ulcer / perforation of the stomach and duodenum in the acute stage or recently transferred;
– Crohn’s disease or ulcerative colitis in the acute stage,
– Severe hepatic insufficiency,
– severe renal insufficiency (unless hemodialysis);
– Acute gastrointestinal bleeding, recently transferred cerebrovascular bleeding or established diagnosis of diseases of the blood coagulation system;
– Severe uncontrolled heart failure;
– Children under the age of 12 years, except for use in juvenile rheumatoid arthritis (in the case of registration of the indications);
– Treatment of perioperative pain during coronary artery bypass (CABG) Precautions: – gastro-intestinal tract in history; – congestive heart failure; – renal failure – coronary heart disease; – cerebrovascular disease; – dyslipidemia / hyperlipidemia; – diabetes; – peripheral arterial disease, – old age, – long-term use of NSAIDs; – smoking; – frequent alcohol consumption.
In patients with increased risk of adverse reactions, it is recommended to begin treatment with a dose of 7.5 mg per day.
In patients with severe renal impairment on hemodialysis dose should not exceed 7.5 mg per day. Adolescents: The maximum dose in adolescents is 0, . 25 mg / kg As a rule, the drug should only be used in adolescents and adults (see contraindications.). The maximum recommended daily dose -. 15 mg tablets should be taken with water or other liquid and taken with food testosterone propionate buy.
Since the risk of adverse reactions is dependent on the dose and duration of application should use the drug within the shortest possible period with the lowest possible effective dose. The combined use. The overall daily dose testosterone propionate 100mg, used in the form of tablets, suppositories, suspensions for oral use and injection should not exceed 15 mg testosterone propionate 100mg price.
The side effects
are described below the side effects whose connection with Movalis drug ® , regarded as possible.
Side effects, whose connection with the drug intake was regarded as possible, and that have been registered with the widespread use of the drug, are marked with *. From the side of hematopoiesis: Changes the number of blood cells, including changes in leukocyte counts, leucopenia, thrombocytopenia, anemia. immune system: anaphylactoid / anaphylactic reaction *, other immediate hypersensitivity reactions such as *. On the part of the central nervous system: headache, dizziness, tinnitus, drowsiness, confusion *, disorientation *, mood changes. * from the gastrointestinal tract: perforation of the gastrointestinal tract, hidden or obvious gastrointestinal bleeding, possibly fatal, gastroduodenal ulcers, colitis, gastritis *, esophagitis, stomatitis, pain abdominal pain, dyspepsia, diarrhea, nausea, vomiting, constipation, bloating, belching, transient changes in liver function parameters (eg, increase in transaminases or bilirubin), hepatitis. * skin and skin appendages: toxic epidermal necrolysis * Stevens -Dzhonsona *, * angioedema, bullous dermatitis *, erythema multiforme *, pruritus, rash, urticaria, photosensitivity. On the part of the respiratory system: asthma. cardio-vascular system: Increase in blood pressure, palpitations, flushing . From the urogenital system: acute renal failure * changes in indicators of kidney function (increased serum creatinine and / or urea in blood serum), urination disorders, including acute urinary retention *, interstitial nephritis, glomerulonephritis, renal medullary necrosis, nephrotic syndrome *. On the part of the organs of vision: conjunctivitis *, visual disturbances including blurred vision *.General disorders: Edema.
Antidote is not known, in the case of overdose should be carried out: the evacuation of the stomach contents and general supportive therapy. Cholestyramine accelerates the elimination of meloxicam.
Interactions with other drugs
– other inhibitors of prostaglandin synthesis, including glucocorticoids and salicylates
-Simultaneous reception with meloxicam increases the risk of ulcers in the gastrointestinal tract and gastrointestinal bleeding (due to synergy of action) and is therefore not recommended. Simultaneous treatment with other NSAIDs is not recommended.
– Selective serotonin reuptake inhibitors – increase the risk of gastrointestinal bleeding.
– Sodium polystyrene sulfonate – due to the presence of sorbitol in the composition testosterone propionate 100mg-administration may cause the risk of developing colon necrosis, with possible fatal outcome.
– Anticoagulants oral, antitrombotsitranye drugs heparin for systemic use, thrombolytic agents, serotonin reuptake inhibitors – simultaneous with meloxicam increases the risk of bleeding due to inhibition of platelet function.
– lithium drugs – NSAIDs increase the level of lithium in the plasma, by reducing the elimination of his kidneys. It is recommended to monitor the lithium level in the period of appointment when changing the dose of drugs lithium and their cancellation.
– Methotrexate – NSAIDs reduce the tubular secretion of methotrexate thereby increasing its concentration in the plasma and hematologic toxicity, pharmacokinetics of methotrexate is not changed. In this connection, simultaneous reception and methotrexate at a dose greater than 15 mg / week is not recommended.
The risk of interaction between NSAIDs and methotrexate may occur in patients treated with methotrexate in low doses, especially in patients with impaired renal function. Therefore, a continuous monitoring of the number of blood cells and kidney function.
When the joint application of meloxicam and methotrexate within 3 days increases the risk of increased toxicity of the latter.
– Contraception – NSAIDs reduce the effectiveness of intrauterine contraceptive devices.
– Diuretics – The use of NSAIDs in the case of patients dehydration accompanied by the risk of acute renal failure.
– Antihypertensive drugs (beta-blockers, angiotensin converting enzyme inhibitors, vasodilators, diuretics). NSAIDs reduce the effect of antihypertensive drugs, due to inhibition of prostaglandins that have vasodilating properties.
– Angiotensin-II receptor with a joint appointment with NSAIDs increase the reduction in glomerular filtration rate, thus, can lead to acute renal failure, especially in patients with impaired renal function.
– cholestyramine tying meloxicam in the gastrointestinal tract, leading to its more rapid removal.
-. NSAIDs, exerting effects on renal prostaglandin may enhance cyclosporine nephrotoxicity
when used with meloxicam drugs which have a certain ability to inhibit CYP 2C9 and / or CYP ZA4 (or are metabolized with the participation of these enzymes), should take into account the possibility of a pharmacokinetic interaction.
We can not exclude the possibility of interaction with antidiabetic drugs for oral administration. With simultaneous use of antacids, cimetidine, digoxin and furosemide, significant pharmacokinetic interactions have been identified.
Patients suffering from diseases of the gastrointestinal tract should be monitored regularly. When an ulcerative lesions of the gastrointestinal tract or gastrointestinal bleeding Movalis ® to cancel.
Ulcers in the digestive tract, perforation or bleeding may occur during treatment at any time, as if warning signs or information about the serious gastrointestinal complications a history, and in the absence of these features. The consequences of these complications are generally more severe in the elderly.
Particular attention should be given to patients reporting of adverse events by the skin and mucous membranes, as well as the reactions of hypersensitivity to the drug, especially if such reactions were observed during the previous courses of treatment. The development of such reactions occur usually within the first month of treatment. In such cases, should be considered the question of terminating the application of testosterone propionate 100mg .
As with other NSAIDs, may increase the risk of serious cardiovascular thrombosis, myocardial infarction, angina, possibly fatal. This increases the risk of long-term use of the drug as well as in patients with the above diseases in history and predisposed to such diseases.
NSAIDs inhibit prostaglandin synthesis in the kidney that are involved in maintaining renal perfusion. The use of NSAIDs in patients with reduced renal blood flow or decreased volume of circulating blood can lead to decompensation of latent renal failure. After the abolition of NSAIDs kidney function is usually restored to the original level. The greatest risk of this reaction are subject to elderly patients, patients who have marked dehydration, congestive heart failure, liver cirrhosis, nephrotic syndrome and acute renal dysfunction, patients concurrently receiving diuretics, and patients who have undergone major surgical procedures, which lead to hypovolemia. In these patients, at the beginning of therapy should be carefully monitored diuresis and kidney function.
The use of NSAID in conjunction with diuretics may lead to sodium retention, potassium and water, as well as to reduce the action of natriuretic diuretics. As a result, in predisposed patients may increase symptoms of heart failure or hypertension. Therefore, careful monitoring state of patients, as well as their adequate hydration should be maintained.
Before treatment is necessary to study renal function.
In the case of combination therapy should also monitor renal function.
When using (as well as most other NSAIDs) may occasional increase in serum transaminases or other parameters of liver function. In most cases, this increase was slight and transient.
If the identified changes are significant or not decrease with time, should be lifted, and to conduct monitoring of the identified laboratory changes.
Loose or depleted patients can worse endure adverse events in connection with which such patients should be monitored closely.
Like other may mask the symptoms of major infectious diseases.
As a drug that inhibits the synthesis of cyclooxygenase / prostaglandin may affect fertility, and is therefore not recommended for women planning pregnancy. In this regard, in women undergoing examination about such problems, it is recommended abolition receiving .
The maximum recommended daily dose of 7.5 and 15 tablets contains 47 mg and 20 mg of lactose respectively. Patients with rare hereditary intolerance to galactose, with Lapp-lactase deficiency or impaired glucose / galactose should not take this drug adsorption.
In the case of simultaneous use of anticoagulants for oral, ticlopidine, heparin for systemic use, thrombolytic agents should be closely monitored for the effects of anticoagulants . Effects on ability to drive vehicles and mechanisms for Advanced studies on the impact of the drug on the ability to drive vehicles and machinery was carried out. However, from this activity should refrain patients with visual impairment, patients noted sleepiness or other disorders of the central nervous system.