MOVALYS (Rectal Suppositories)
Active material: Meloxicam
When ATH: M01AC06
CCF: NSAIDs
ICD-10 codes (testimony): M05, M15, M45
When CSF: 05.01.01.07.01
Manufacturer: BOEHRINGER INGELHEIM INTERNATIONAL GmbH (Germany)
PHARMACEUTICAL FORM, COMPOSITION AND PACKAGING
Rectal Suppositories smooth, yellowish green, with a recess in the base.
| 1 supp. | |
| meloxicam | 7.5 mg |
| -“- | 15 mg |
Excipients: suppository mass (BP suppotsyr), Macrogols glicerilgidroksistearat (polyethylene glycol glitserilgidroksistearat) (cremophor RH40).
6 PC. – package outline (1) – packs cardboard.
6 PC. – package outline (2) – packs cardboard.
Pharmacological action
NSAIDs, It refers to derivatives of enolic acid and has anti-, analgesic and antipyretic effect. Inflammatory action of meloxicam is installed on all standard models of inflammation.
The mechanism of action of meloxicam is its ability to inhibit prostaglandin synthesis – known inflammatory mediators. In vivo meloxicam inhibits prostaglandin synthesis at the site of inflammation to a greater extent, than in the mucosa of the stomach or kidney. These differences are associated with a selective inhibition of COX-2 over COX-1.
It is believed, Inhibition of COX-2 provides therapeutic effects of NSAIDs, whereas inhibition of omnipresent isoenzyme COX-1 can cause side effects in the stomach and kidneys.
Meloxicam selectivity for COX-2 was confirmed in various assay systems, how in vitro, and ex vivo. Selective meloxicam ability to inhibit COX-2 is shown when used as a test system human whole blood in vitro. Ex vivo installed, Chto meloxicam (doses 7.5 mg 15 mg) inhibiting activity of COX-2 (providing a greater inhibitory effect on the production of prostaglandin E2,lipopolysaccharide-stimulated / reaction, Controlled COX-2 /), than the products of thromboxane, involved in blood clotting (reaction, controlled by COX-1). These effects depend on the dose.
Ex vivo shown, meloxicam at recommended doses had no effect on platelet aggregation, and bleeding time, unlike indomethacin, diclofenac, ibuprofen and naproxen, that significantly inhibits platelet aggregation and prolong bleeding time.
In clinical studies, side effects from the gastrointestinal tract as a whole rarely occurred when taking meloxicam 7.5 mg 15 mg, than when taking other NSAIDs, which were compared. This difference in the frequency of side effects from the gastrointestinal tract is mainly due to the fact, When administered meloxicam rarely observed phenomena such as dyspepsia, vomiting, nausea, abdominal pain. The frequency of perforations in the upper gastrointestinal tract, ulcers and bleeding, that have been associated with the use of meloxicam, It was low and was dependent on the dose of the drug.
Pharmacokinetics
Absorption and distribution
Cmax the drug in the plasma during the steady-state pharmacokinetics reached approximately 6 hours after treatment.
Meloxicam is well bound to plasma proteins (albumin – 99%). Meloxicam penetrates into synovial fluid; local concentration is approximately 50% plasma concentrations of. Vd low, averages 11 l. Individual fluctuations – 30-40%.
Metabolism
Meloxicam is almost completely metabolized in the liver to form 4 pharmacologically inactive derivatives. The major metabolite, 5′-karʙoksimeloksikam (60% of the dose), formed by oxidation of an intermediate metabolite, 5′-gidroksimetilmeloksikama, which is also excreted, but less (9% of the dose).
Studies in vitro have shown, that in this metabolic pathway plays an important role CYP2C9 isozyme, additional importance of CYP3A4. The formation of two other metabolites (components, respectively, 16% and 4% the magnitude of the dose) prinimaet participation peroxidase, activity is, probably, individually varies.
Deduction
Is displayed equally in the feces and urine, primarily as metabolites. Unchanged in the feces derived less 5% the magnitude of the daily dose, in the urine as unchanged drug is detected in only trace amounts. Average T1/2 is 20 no. The plasma clearance averages 8 ml / min.
Pharmacokinetics in special clinical situations
Insufficiency of liver function, and mild to moderate renal insufficiency significant effect on the pharmacokinetics of meloxicam does not have. When ESRD magnification Vd It may lead to higher concentrations of free meloxicam, therefore, in these patients the daily dose should not exceed 7.5 mg.
In elderly patients, the mean plasma clearance during steady state pharmacokinetics slightly lower, than in younger patients.
During the study of meloxicam in children has been studied pharmacokinetics doses, applied at the rate of 0.25 mg / kg. When comparing children of different ages (2-6 years, n=7 and 7-14 years, n=11) A tendency toward lower Cmax (decrease 34%) и AUC (decrease 28%) young children, and clearance of the drug (adjusted for body weight) in this group of children was higher. The concentrations of meloxicam in plasma in older children and adults alike. The children of both age groups T1/2 meloxicam in plasma are the same and amounted to 13 no, but somewhat shorter, than in adults – 15-20 no.
Testimony
Symptomatic treatment:
- Osteoarthritis (arthrosis, degenerative joint diseases);
- Rheumatoid arthritis;
- Ankiloziruyushtiy spondylitis.
Dosage regimen
Rectal suppositories is recommended at a dose of 7.5 mg 1 time / day. In more severe cases, you can assign the dose 15 mg.
Unnecessarily. the risk of side reatsky depends on the dose and duration of use of the drug should be taken within the shortest possible time and at the lowest effective dose.
The maximum total daily dose Movalis® suppository, tablets and injections of 15 mg.
Side effect
The following describes adverse events, whose connection with the drug Movalis®, It was regarded as a possible. Adverse events, whose connection with the drug intake was regarded as a possible, registered with the broad use of the drug, marked (*).
From the digestive system: nausea, perforation of the gastrointestinal tract, gastroduodenalynaya ulcer, macroscopically visible or hidden gastrointestinal bleeding, colitis, gastritis *, esophagitis, stomatitis, stomach ache, dyspepsia, diarrhea, vomiting, constipation, flatulence, belching, Hepatitis *, changes in liver function (increase in liver transaminases or bilirubin). Gastrointestinal bleeding, erosive and ulcerative lesions and perforation of the gastrointestinal tract can lead to death.
From the hematopoietic system: changes in leukocyte, leukopenia, thrombocytopenia, anemia.
Predisposing factors for the occurrence of cytopenias is the simultaneous use of potentially myelotoxic drugs, in particular methotrexate.
Dermatological reactions: skin rash, itch, photosensitivity, bullous dermatitis *.
The respiratory system: bronchial asthma (bronchospasm) in patients with hypersensitivity to aspirin and other NSAIDs.
CNS: headache, confusion *, disorientation *, mood changes *.
Cardio-vascular system: heartbeat, swelling, increased blood pressure, feeling a rush of blood to the face.
From the urinary system: Acute renal failure *, changes in renal function (increases in serum creatinine and / or urea in blood). In the application of NSAIDs may impair urination, including acute urinary retention *.
From the senses: dizziness, noise in ears, Conjunctivitis *, visual impairment, incl. blurred vision *.
Allergic reactions: angioedema *, immediate hypersensitivity reactions (incl. anafilakticheskie anafilaktoidnыe * and *), toxic epidermal necrolysis *, Stevens-Johnson syndrome *, erythema multiforme *, hives.
Contraindications
- Patients, have previously after ingestion of aspirin or other NSAIDs reported symptoms of asthma, nasal polyposis, angioedema or urticaria;
- Gastric ulcer and duodenal ulcer in the acute phase, with perforation or recently transferred;
- Acute exacerbation of inflammatory bowel disease (Crohn's disease, yazvennыy colitis);
- Severe impairment of liver function;
- Severe renal insufficiency (CC less than 30 ml / min, without hemodialysis);
- Active gastrointestinal bleeding, recently transferred cerebrovascular bleeding or hemorrhagic disease diagnosed System;
- Severe uncontrolled heart failure;
- Confirmed hyperkalemia;
- Pregnancy;
- Lactation (breast-feeding);
- Childhood and adolescence up 12 years (except for use in establishing the diagnosis – juvenile rheumatoid arthritis);
- Hypersensitivity to the drug (there is a possibility of cross-sensitivity to acetylsalicylic acid and other NSAIDs).
Do not use the drug to eliminate postoperative pain (after coronary bypass surgery).
FROM caution should use the drug in patients with reduced renal blood flow and reduced BCC, especially in elderly patients, patients with dehydration, Congestive heart failure, cirrhosis of the liver, nephrotic syndrome or clinically severe kidney disease; during treatment with diuretics, ACE inhibitors, angiotensin II receptor antagonists, hypovolemia due to major surgery, leading to hypovolemia; in patients with end-stage renal disease, hemodialysis; in patients with renal insufficiency lekgo or moderate (QC more 25 ml / min).
Pregnancy and lactation
Movalys® contraindicated in pregnancy. Suppression of prostaglandin synthesis may have an adverse effect on pregnancy and fetal development. Data from epidemiological studies suggest an increased risk of spontaneous abortion and heart defects in the fetus after administration of prostaglandin synthesis inhibitor during pregnancy. The absolute risk of developing heart diseases increased from less 1% to 1.5%. This risk increases with dose and duration of therapy.
In the III trimester of pregnancy, prostaglandin synthesis inhibitors may lead to the following violations of the fetus:
- Premature closure of the ductus arteriosus and pulmonary hypertension due to toxic effects on the cardiopulmonary system;
- Renal dysfunction, with the further development of renal failure from reducing the amount of amniotic fluid.
The mother during labor can increase the duration of bleeding and to decrease uterine contractility, and as a consequence, increase childbirth.
Known, NSAIDs penetrate into breast milk, therefore Movalis® not recommended for use during breast-feeding.
Use of meloxicam, as well as other drugs, blocking COX / prostaglandin synthesis, It can affect fertility, therefore not recommended for women, wishing to get pregnant. In case of violation of fertility in women or survey for infertility need to consider the abolition of meloxicam.
Cautions
Caution should be exercised when treating patients with a history of gastrointestinal diseases and patients, receiving anticoagulants. Patients, who observed symptoms of the gastrointestinal tract, We should be monitored regularly. In the event of gastrointestinal ulceration or gastrointestinal bleeding Movalis® should be abolished.
Gastrointestinal bleeding, ulceration and perforation, potentially dangerous for the patient's life, may occur during treatment at any time, both in the presence of symptoms or the details of serious gastrointestinal complications history, and in the absence of these signs. The consequences of these complications are generally more severe in the elderly.
While NSAIDs are very rarely reported on the development of a serious allergic reaction (some of them fatal), incl. exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis. The greatest risk for these reactions, apparently, It noted at the beginning of treatment, in most cases they began within the first month of treatment. In the case of the first signs of skin rash, changes in the mucous membranes or any other symptoms of hypersensitivity Movalis® should be abolished.
When using NSAIDs (especially for a long time) may increase the risk of serious thrombotic cardiovascular diseases, myocardial infarction and stroke, that can lead to death. The greatest risk is seen in patients with cardiovascular disease or risk factors for cardiovascular disease, renal failure, patients, hemodialysis.
NSAIDs inhibit prostaglandin synthesis in kidney, are involved in maintaining renal perfusion. The use of NSAIDs in patients with reduced renal blood flow or in the volume of circulating blood can lead to decompensation of latent renal failure. After the cancellation of NSAIDs kidney function is usually restored to the original level. The greatest risk of this reaction is susceptible elderly patients, sick, which marked dehydration, congestive heart failure, cirrhosis of the liver, nephrotic syndrome or kidney disease; Patients, receiving diuretics, ACE inhibitors, angiotensin II receptor antagonists , and patients, had undergone serious surgery, leading to hypovolemia. In these patients, at the beginning of therapy should be carefully monitored diuresis and renal function.
In rare cases, NSAIDs may cause interstitial nephritis, glomerulonephritis, renal medullary necrosis or nephrotic syndrome.
When using the drug Movalis® reported occasional raising of transaminases or other liver function tests in the blood serum. In most cases this increase was slight and transient. If significant changes identified or decrease with time, Movalys® should be abolished and conduct surveillance of the changes revealed by laboratory.
In patients with clinically stable liver cirrhosis reduction in dose is not required.
Loose or malnourished patients may endure worse adverse events, therefore, these patients require close monitoring. Care should be taken in the treatment of elderly patients, in which the higher the probability of renal dysfunction, liver and heart.
NSAIDs together with diuretics may lead to sodium, potassium and water, and influence the natriuretic effect of diuretics. As a result, in predisposed patients may increase heart failure or hypertension. It is recommended to monitor the status of patients, with the risk of such complications.
Meloxicam, Like other NSAIDs, may mask the symptoms of an infectious disease. The drug is intended for the symptomatic treatment, reduce pain and inflammation. Effective treatment Movalis® should be used in combination with drugs for the treatment of infectious diseases.
Suppositories should not be used in patients with any inflammation in the rectum or anus, or in patients with recently celebrated bleeding from the rectum or anus.
Effects on ability to drive vehicles and management mechanisms
Special studies on the impact of the drug on the ability to drive vehicles and machinery has not been. From this activity should avoid patients with visual impairment, patients, marking drowsiness or other disorders of the central nervous system.
Overdose
Symptoms: increased side effects.
Treatment: gastric lavage, symptomatic therapy. Specific antidotes and antagonists there.
Drug Interactions
Other inhibitors of prostaglandin synthesis, incl. Corticosteroids and salicylates (acetylsalicylic acid): while the application increases the risk of gastrointestinal ulcers and gastrointestinal bleeding due to synergistic action. The combined use of meloxicam and other NSAIDs is not recommended. The combined use of acetylsalicylic acid (1 g 3 times / day) and meloxicam in healthy volunteers resulted in an increase in AUC (10%) and Cmax (24%) meloxicam. The clinical significance of this interaction is unknown.
Anticoagulants oral, antiagregantы, Heparin for systemic use, thrombolytic agents, while the use movalis® increase the risk of bleeding. If you can not avoid the simultaneous use of these drugs, careful observation of the effects of anticoagulants.
NSAIDs increase the concentration of lithium in the plasma due to lower renal excretion of lithium. The concentration of lithium in the plasma can reach toxic values. The combined use of lithium and NSAIDs is not recommended. If necessary, such combination therapy should be monitored in a plasma concentration of lithium in the treatment beginning, the selection of doses and the abolition of meloxicam.
NSAIDs can reduce the tubular secretion of methotrexate and thus increase the concentration of methotrexate in plasma. Therefore patients, receiving high doses of methotrexate (more 15 mg per week), concurrent use of NSAIDs is not recommended. The risk of interactions with the concomitant use of methotrexate and NSAIDs is also possible for patients, receiving low-dose methotrexate, especially in patients with impaired renal function. If necessary, the combination therapy should be monitored blood count and renal function. Care must be taken in the event of, if the NSAID and methotrexate are used simultaneously for 3 days, tk. plasma concentrations of methotrexate may rise and, Consequently, there may be toxic effects. The simultaneous use of meloxicam did not affect the pharmacokinetics of methotrexate 15 mg per week, however, should take into account, that the hematological toxicity of methotrexate is enhanced while taking NSAIDs.
Previously reported reducing the effectiveness of intrauterine contraceptive devices when using NSAIDs. This observation requires further confirmation.
The use of NSAIDs increases the risk of acute renal failure in patients with dehydration. Patients, receiving Movalis® and diuretics, Adequate hydration should be maintained. Before treatment is necessary to study renal function.
NSAIDs reduce the effect of antihypertensive drugs (eg, beta-blockers, ACE inhibitors, vasodilators, Diuretic), due to inhibition of prostaglandin, vasodilating properties.
The combined use of NSAIDs and angiotensin II receptor antagonists (as well as inhibitors of ACE) enhances the effect of reduction of glomerular filtration. Patients with impaired renal function which may result in the development of acute renal failure.
Cholestyramine, tying meloxicam in the gastrointestinal tract, It leads to its more rapid removal of.
NSAIDs, exerting effects on renal prostaglandins, may increase the nephrotoxicity of cyclosporine. In the case of combination therapy should monitor renal function.
Meloxicam is eliminated from the body primarily by hepatic metabolism, about 2/3 quantities of preparation, are metabolized in the liver, CYP450 isoenzymes destroyed (the main pathway – isoenzyme CYP2S9, additional – isoenzyme CYP3A4), about 1/3 metabolized by other systems, eg, by peroxidation. When used in conjunction with meloxicam drugs, which have a certain ability to inhibit CYP2C9, and / or CYP3A4 (or metabolized, with the participation of these enzymes), should take into account the possibility of a pharmacokinetic interaction.
With simultaneous use of meloxicam, cimetidine, digoxin or furosemide significant pharmacokinetic interactions have been identified.
We can not exclude the possibility of interaction with oral hypoglycemic agents.
Conditions of supply of pharmacies
The drug is released under the prescription.
Conditions and terms
The drug should be stored out of reach of children at or above 30 ° C. Shelf life – 3 year.
