Meloflam - instructions for use, doses, side effects, contraindications

Excipients: magnesium stearate, silicon dioxide colloidal anhydrous, povidone, sodium citrate, crospovidone, lactose monohydrate (15 mg in tablets of 7.5 mg and 30 mg in tablets of 15 mg), microcrystalline cellulose.

Description:Round flat pills of a pale yellow color with a facet, with a risk on one side and engraved E 361 (on 7.5 mg tablets) or E 362 (on 15 mg tablets) on the other side, odorless or almost odorless.

Pharmacotherapeutic group:Non-steroidal anti-inflammatory drugs, derivatives of oxycam

ATX: & nbsp

M.01.A.C.06 Meloksikam

M.01.A.C Oksikamy

Pharmacodynamics:

Meloxicam is a non-steroidal anti-inflammatory drug (NSAID) from the oxicam group, which has anti-inflammatory, analgesic and antipyretic effects. The anti-inflammatory activity of meloxicam is proved by experiments with classical models of inflammation. NSAIDs (including meloxicam) have a common mechanism of action: all these substances suppress the activity of cyclooxygenases (COX-1 and COX-2) and, accordingly, reduce the synthesis of prostaglandins.

In vivo experiments meloxicam suppressed the synthesis of prostaglandins more actively in the focus of inflammation than in the mucous membrane of the stomach or kidneys.

This difference is probably due to the fact that meloxicam is a stronger inhibitor of the COX-2 enzyme compared to COX-1. The therapeutic effect of NSAIDs is associated with oppression of COX-2,and the inhibition of constitutive enzyme COX-1 is associated with a side effect on the gastrointestinal tract and kidneys.

Pharmacokinetics:

Suction:

Meloksikam is well absorbed from the gastrointestinal tract. Its bioavailability after oral administration is 89%. After a single pill intake, the maximum concentration in the blood plasma is reached after 5-6 hours. Concentrations of meloxicam in blood plasma are proportional to the dose (7.5 or 15 mg). The equilibrium state is achieved after 3 to 5 days of taking the drug. Prolonged use of the drug for more than one year gives the concentration of the drug in the blood, similar to those measured at the first attainment of the equilibrium state. Taking the drug once a day gives a concentration in the blood plasma with a slight difference between the maximum and minimum: 0.4-1.0 μg / ml at a dose of 7.5 mg and 0.8 - 2.0 μg / ml at a dose of 15 mg . The minimum and maximum plasma concentrations in the equilibrium state in some cases exceed the limits indicated above. Absorption of meloxicam after ingestion does not depend on food intake.

Distribution:

In the systemic circulation meloxicam more than 99% associated with blood proteins, mainly salbumin. Meloksikam well penetrates into the synovial fluid, where its concentrations reach about half the concentration in the blood plasma.

The volume of distribution is small - an average of 11 liters; the difference between different patients is about 30-40%.

Biotransformation:

Meloksikam undergoes intensive biotransformation in the liver. Almost the entire dose of meloxicam is converted into four metabolites, none of which has pharmacodynamic activity. The main metabolite, 5'-carboxymeloxicam (60% dose), is formed by oxidation of the intermediate metabolite 5'-hydroxymeloxicam, which is also released, but in smaller amounts (9% of the dose). In vitro studies have shown that CYP 2C9 plays an important role in the metabolism of meloxicam, and the contribution of the CYP 3A4 enzyme is small. Two other metabolites, representing respectively 16% and 4% of the administered dose, are formed by peroxidase.

Excretion:

Meloksikam is excreted mainly in the form of metabolites and is found in equal amounts in urine and feces. In unchanged form with feces, less than 5% of the injected dose of meloxicam is released, and only traces of the initial substance are detected in the urine.

The pharmacokinetics of meloxicam are not affected by liver failure and mild to moderate renal failure.

The average period of sex at the excretion is about 20 hours. The total clearance of the drug from the blood plasma is an average of 8 ml / min; in elderly people, it is somewhat lower than in young people.

Indications:

- Osteoarthritis;

- rheumatoid arthritis;

- Ankylosing spondylitis (Bekhterev's disease)

and other inflammatory and degenerative diseases of the joints, accompanied by pain syndrome.

Contraindications:

- Known hypersensitivity to meloxicam or other components of the drug;

- history of bronchospasm, urticaria or rhinitis caused by taking acetylsalicylic acid or other NSAIDs (complete or incomplete acetylsalicylic acid intolerance syndrome - rhinosinusitis, urticaria, polyps of the nasal mucosa, asthma);

- erosive and ulcerative changes in the gastric mucosa and / or duodenum;

- active gastrointestinal bleeding, cerebrovascular bleeding or other bleeding;

- exacerbation of inflammatory bowel diseases (ulcerative colitis, Crohn's disease);

severe hepatic insufficiency or active liver disease;

- severe renal impairment (creatinine clearance less than 30 mL / min) unless hemodialysis, progressive renal disease, confirmed hyperkalemia;

Decompensated heart failure;

- Children's age (up to 15 years).

- the drug is contraindicated in the period after coronary artery bypass grafting;

- Pregnancy, lactation.

Carefully:

Ischemic heart disease, cerebrovascular disease, congestive heart failure, dyslipidaemia / hyperlipidemia, diabetes, peripheral arterial diseases, hypertension, smoking, creatinine clearance less than 60 mL / min, immediately after a surgical procedure; in the presence of amnestic data on the development of ulcerative lesions gastrointestinal tract, in the presence of infection Helicobacter pylori, in the elderly, long-term use NGTVP, frequent alcohol consumption, severe somatic diseases, concomitant therapy with the following drugs: anticoagulants (eg. warfarin), antiaggregants (ex. acetylsalicylic acid, clopidogrel), oral glucocorticosteroids (ex. prednisolone), selective serotonin reuptake inhibitors (e.g. citalopram, fluoxetine, paroxetine, sertraline).

Also, care should be taken when prescribing depression, Parkinsonism, and epilepsy to patients with mental disorders.

To reduce the risk of developing adverse events, the minimum effective dose should be used with the minimum possible short course.

Pregnancy and lactation:Contraindicated in pregnancy and lactation.

Dosing and Administration:

Tablets should be taken with water or other liquid while eating.

Osteoarthritis: 7.5 mg / day. If necessary, the dose can be increased to 15 mg. Rheumatoid arthritis: 15 mg / day. Depending on the response to treatment, the daily dose can be reduced to 7.5 mg.

Ankylosing spondylitis: 15 mg / day.

In case of an increased risk of adverse reactions, the drug should be taken at 7.5 mg per day.

For patients with severe renal failure during hemodialysis, the dose should not exceed 7.5 mg per day.

Teens:

The recommended dose for adolescents is 0.25 mg / kg body weight.

The proper dose for children is unknown, so Meloflam can be given only to adults or adolescents.

The maximum daily dose of meloxicam should not exceed 15 mg.

Side effects:

It is impossible to exclude the causal relationship between the administration of meloxicam and the undesirable phenomena listed below. The following frequencies of these phenomena are determined in clinical trials, regardless of the presence or absence of a causal relationship.

Digestive system: dyspepsia, nausea, vomiting, abdominal pain, constipation, bloating, diarrhea; rarely: transient changes in laboratory functional liver samples, belching, esophagitis, stomach and / or duodenal ulcers, latent or macroscopic gastrointestinal bleeding; extremely rare (<0.1%): perforation of the gastrointestinal tract, colitis, hepatitis, gastritis.

Hematopoietic system: anemia; rarely: changes in the cellular composition of the blood (eg, leukopenia or thrombocytopenia). Joint use with potentially myelotoxic drugs (most often with methotrexate) can cause cytopenia.

Skin and subcutaneous tissue: itching and rash; rarely: stomatitis, urticaria; extremely rare (<0.1%): photosensitization reactions. In rare cases, bullous skin changes are described (for example, erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis).

Respiratory system: in some patients (<0.1%) after the injection of aspirin or other NSAIDs (meloxicam), asthma attacks occurred.

central nervous system: dizziness, headache; systemic dizziness, tinnitus, drowsiness; extremely rare: confused state of consciousness, disorientation, mood swings.

The cardiovascular system: development of edema, rarely: increased blood pressure, palpitation, hot flashes.

Genitourinary system: increased levels of creatinine and urea, extremely rare: acute renal failure

Dysfunction of the eye: extremely rare: conjunctivitis, visual impairment, visual acuity reduction

Hypersensitivity reactions: extremely rare: angioedema and immediate-type hypersensitivity reactions (anaphylactic / anaphylactoid).

Overdose:

Symptoms: impaired consciousness, nausea, vomiting, epigastric pain, gastrointestinal bleeding, acute renal failure, hepatic insufficiency, respiratory arrest, asystole.

Treatment: there is no specific antidote; When an overdose of the drug should be washed stomach, taking activated charcoal (within the next hour, symptomatic therapy.Holestyramine accelerates the removal of the drug from the body.Crossed diuresis, alkalization of urine, hemodialysis - ineffective due to the high connection of the drug with blood proteins.

Interaction:

Other NSAIDs (including salicylates): the simultaneous use of several NSAIDs may, due to synergism, increase the risk of ulceration and bleeding from the gastrointestinal tract.

Oral anticoagulants, ticlopidine, parenterally injected heparin, thrombolytic drugs: increased risk of bleeding. If it is impossible to avoid such a combination, careful monitoring of the coagulation factors should be established.

Lithium: It is shown that NSAIDs increase the level of lithium in the blood. Care should be taken to monitor the concentration of lithium in the blood plasma at the beginning of the course of treatment, with a dose change and the elimination of meloxicam.

Methotrexate: Like other NSAIDs, meloxicam can enhance the toxic effect of methotrexate on the hematopoietic organs.With the combined use of these funds, careful monitoring of the leukocyte formula is necessary.

Intrauterine contraceptives: There is evidence of a decrease in the effectiveness of intrauterine contraceptives (IUDs) during the administration of NSAIDs.

Diuretics: The use of NSAIDs in dehydrated patients can lead to acute renal failure. With the simultaneous administration of meloxicam and diuretics, it is necessary to ensure sufficient fluid intake and monitoring of kidney function at the beginning of the course of treatment.

Antihypertensive drugs (beta-blockers, ACE inhibitors, vasodilators, diuretics): it is possible to reduce the antihypertensive effect.

Cholestyramine: he connects meloxicam in the gastrointestinal tract and therefore accelerates its excretion.

Cyclosporin: NSAIDs can enhance the nephrotoxic effect of cyclosporine because of their effect on renal prostaglandins. When combined, the use of these drugs should be monitored for kidney function.

Meloksikam is metabolized almost exclusively in the liver. The metabolism of the drug is approximately 2/3 associated with the activity of the enzymes of the cytochrome (CYP) P-450 system (mainlyg isoenzyme CYP 2C9 and to a lesser extent CYP 3A4), and the remaining 1/3 is metabolized by other routes (for example, by peroxidation). Accordingly, inhibitors of CYP 2C9 and / or CYP 3A4 isoenzymes, as well as drugs metabolized by these isoenzymes, can be sources of drug interactions that should be considered.

With the simultaneous administration of antacids, cimetidine, digoxin and furosemide, clinically significant pharmacokinetic drug interactions have not been detected. It is impossible to exclude the possibility of drug interactions meloxicam and oral hypoglycemic drugs.

Special instructions:

Like other NSAIDs, Meloflam should be used with caution in patients with gastrointestinal illnesses in history, as well as during the use of anticoagulants. If symptoms appear on the part of the gastrointestinal tract, careful monitoring of the patient should be made, and in the event of a peptic ulcer or gastrointestinal bleeding, the drug should be discontinued.

Gastrointestinal bleeding, ulceration or perforation can occur at any stage of treatment,even in the absence of anxiety symptoms or in a patient who previously had no serious diseases of the gastrointestinal tract. Gastrointestinal bleeding, ulceration or perforation have much more severe consequences in elderly patients.

Special care should be taken to determine the need to discontinue meloxicam if side effects are found on mucous membranes or skin.

NSAIDs suppress the synthesis of renal prostaglandins, which play an important role in maintaining renal blood flow. In patients with weak renal blood flow or reduced blood volume, the administration of NSAIDs may cause decompensation of latent renal failure. However, after the drug is discontinued, the kidney function returns to its original state, before the drug is injected. The risk of such a reaction is increased in dehydrated patients and with congestive heart failure, liver cirrhosis, nephrotic syndrome or severe renal failure, as well as in patients taking diuretics or who have recently undergone extensive surgery that led to hypovolemia. Such patients need careful monitoring of diuresis and kidney function at the beginning of the course of treatment.

In rare cases, NSAIDs may cause interstitial nephritis, glomerulonephritis, medullary necrosis of the kidneys, or nephrotic syndrome.

In patients receiving hemodialysis in the final stage of renal failure, the daily dose of meloxicam should not exceed 7.5 mg.

As with the majority of NSAIDs, during the course of treatment with meloxicam, there was a periodic increase in serum transaminase levels or pathological changes in other parameters of liver function. In most cases, these violations were minor and transient. If changes in the parameters of laboratory studies become significant or permanent, the use of meloxicam should be discontinued and proper research performed. With clinically stable cirrhosis of the liver, no dose adjustment is required.

Unwanted reactions are often worse tolerated by elderly and weakened patients, who in this connection need careful monitoring. As with other NSAIDs, special caution is needed when prescribing meloxicam to elderly patients, as the incidence of renal, hepatic and cardiac function impairment increases with age.

Taking NSAIDs can induce sodium, potassium and water retention, and also interact with the natriuretic effect of diuretics. This can lead to heart failure, hypertension or exacerbation of these diseases.

Effect on the ability to drive transp. cf. and fur:During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require an increased concentration of attention and speed of psychomotor reactions (with dizziness and drowsiness).

Form release / dosage:Tablets 7.5 mg and 15 mg.

Packaging:10 tablets in a blister of the combined film "cold" (polyamide / al foil / PVC) / al. foil. 1 or 2 blisters together with instructions for medical use in a cardboard box.

Storage conditions:Store at a temperature of no higher than 25 ° C in a dry place. Keep out of the reach of children.

Shelf life:5 years. Do not use after the date shown on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-005888/08

Date of registration:23.07.2008 / 15.01.2015

Expiration Date:Unlimited

The owner of the registration certificate:EGIS ZAO Pharmaceutical Plant EGIS ZAO Pharmaceutical Plant Hungary

Representation: & nbspEGIS ZAO Pharmaceutical Plant EGIS ZAO Pharmaceutical Plant Hungary

Information update date: & nbsp22.04.2018

Illustrated instructions

Instructions

Meloflam® (Meloflam®)