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

Composition:Dosage 7.5 mg
Active substance: meloxicam 7.5 mg
Excipients: lactose monohydrate 63.0 mg, microcrystalline cellulose 33.75 mg, silicon dioxide colloid (Aerosil 200) 0.5 mg, magnesium stearate 1.25 mg, sodium citrate 15.0 mg, crospovidone 4.0 mg.
Dosage of 15 mg
Active substance: meloxicam 15 mg
Excipients: lactose monohydrate 126.0 mg, microcrystalline cellulose 67.5 mg, silicon dioxide colloid (Aerosil 200) 1.0 mg, magnesium stearate 2.5 mg, sodium citrate 30.0 mg, crospovidone 8.0 mg.

Description:Tablets 7.5 mg: rounded tablets, slightly biconcave, pale yellow with an engraving "B 18".
Tablets 15 mg: tablets are round, slightly biconvex, light yellow with a risk and engraving "B" higher risks and engraving "19" lower risks.

Pharmacotherapeutic group:nonsteroidal anti-inflammatory drug.

ATX: & nbsp

M.01.A.C.06 Meloksikam

M.01.A.C Oksikamy

Pharmacodynamics:Meloksikam - Non-steroidal anti-inflammatory drug, which has analgesic, antipyretic and analgesic effect.
Anti-inflammatory effect is associated with inhibition of the enzymatic activity of cyclooxygenase-2 (COX-2), involved in the biosynthesis of prostaglandins in the inflammatory region. It acts less on cyclooxygenase-1 (COX-1) involved in the synthesis of prostaglandin, which protects the mucous membrane of the digestive tract and takes part in the regulation of blood flow in the kidneys.

Pharmacokinetics:Well absorbed from the gastrointestinal tract.Absolute bioavailability of meloxicam is 89%. Simultaneous food intake does not change the intake. When the drug is administered orally at doses of 7.5 and 15 mg, its concentrations are proportional to the doses. The equilibrium concentration is achieved within 3-5 days. With prolonged use of the drug (more than 1 year), the concentrations are similar to those observed after the first achievement of a steady state of pharmacokinetics. Binding to plasma proteins is more than 99%. The range of differences between the maximum and basal concentrations of the drug after its administration once a day is relatively small and amounts to 0.4-1.0 μg / ml when taken in a dose of 7.5 mg, and when taken at a dose of 15 mg - 0.8- 2.0 μg / ml, (Cmin and Stach, respectively). Meloksikam penetrates through the histohematological barriers, the concentration in the synovial fluid reaches 50% of the maximum concentration of the drug in the plasma.
Almost completely metabolized in the liver with the formation of four inactive pharmacologically metabolites. The main metabolite, 5'-carboxymeloxicam (60% of the dose value), is formed by oxidation of the intermediate metabolite, 5'-hydroxymethylmeloxicam, which is also excreted, but to a lesser degree (9% of the dose value).In vitro studies have shown that CYP 2C9 plays an important role in this metabolic transformation, the CYP isoenzyme ZA4 is of additional importance. In the formation of the other two metabolites (which constitute, respectively, 16% and 4% of the dose), peroxidase takes part, the activity of which probably varies individually.
It is excreted equally by the kidneys and through the intestine, mainly in the form of metabolites. Through the intestine unchanged output of less than 5% of the daily dose in the urine as unchanged drug is detected only in trace amounts. The half-life period (T1 / 2) of meloxicam is 15-20 hours. Plasma clearance is an average of 8 ml / min. In elderly people, the clearance of the drug is reduced. The apparent volume of distribution is low and averaged 11 liters. Hepatic or renal insufficiency of moderate severity has no significant effect on the pharmacokinetics of meloxicam.

Indications:- Symptomatic treatment of osteoarthritis;
- Symptomatic treatment of rheumatoid arthritis;
- Symptomatic treatment of ankylosing spondylitis (Bekhterev's disease).

Contraindications:- hypersensitivity to any component of the drug;
- a combination of bronchial asthma, recurrent nasal polyposis and paranasal sinuses and intolerance to acetylsalicylic acid and LS of pyrazolone series; exacerbation of peptic ulcer of the stomach and duodenum;
- severe renal failure in patients not undergoing hemodialysis (creatinine clearance less than 30 ml / min), progressive kidney disease, confirmed hyperkalemia;
- condition after coronary artery bypass grafting;
Decompensated cardiovascular insufficiency;
- active gastrointestinal, cerebrovascular or other bleeding;
severe hepatic insufficiency or active liver disease; inflammatory bowel disease (Crohn's disease, ulcerative colitis) in the phase of exacerbation;
- children under the age of 15; pregnancy;
- lactation period;
- lactose intolerance, lactase deficiency, glucose-galactose malabsorption, lactase deficiency of Lappa.

Carefully:Elderly age, ischemic heart disease, congestive heart failure, cerebrovascular disease,diseases of the peripheral arteries, diabetes mellitus, dyslipidemia, hyperlipidemia, smoking, chronic renal failure with creatinine clearance of 30-60 ml / min, anamnesis of ulcerative lesions of the gastrointestinal tract, presence of Helicobacter pylori, prolonged use of nonsteroidal anti-inflammatory drugs, severe concomitant somatic diseases. Concomitant therapy with corticosteroids (including prednisolone), anticoagulants (including warfarin), antiaggregants (eg, acetylsalicylic acid), selective serotonin reuptake inhibitors (for example, sertraline, paroxetine, citalopram, fluoxetine), frequent use of alcohol.

Pregnancy and lactation:The drug is not recommended for use during pregnancy and lactation.

Dosing and Administration:The drug is taken orally during meals once a day. Recommended dosing regimen:
- Rheumatoid arthritis: 15 mg per day. Depending on the therapeutic effect, the dose can be reduced to 7.5 mg per day.
- Osteoarthritis: 7.5 mg per day. If the dose is ineffective, it can be increased to 15 mg per day.
- Ankylosing spondylitis: 15 mg per day.
The maximum daily dose should not exceed 15 mg.
In patients with an increased risk of side effects, as well as in patients with severe renal failure who undergo hemodialysis, the dose should not exceed 7.5 mg per day.

Side effects:The frequency of occurrence of side effects is characterized as often (> 1/10). infrequently (> 1/1000. <1/10). rarely "1/10001
From the digestive system:
Often: dyspepsia, nausea, vomiting, abdominal pain, constipation, flatulence, diarrhea;
Infrequent: stomatitis, esophagitis, gastrointestinal bleeding, peptic ulcer of the stomach or duodenum;
Rarely: gastritis, perforation of the gastrointestinal tract, colitis, pancreatitis, hepatitis.
From the cardiovascular system:
Often: peripheral edema, including swelling of the lower extremities;
Infrequently: arterial hypertension, arterial hypotension, a feeling of palpitations, "tides" of blood to the skin of the face;
Rarely: angina pectoris, heart failure.
From the respiratory system:
Often: upper respiratory tract infections, flu-like symptoms, pharyngitis;
Rarely: bronchospasm, shortness of breath.
From the nervous system:
Often: headache, dizziness;
Infrequent: noises in the ears, drowsiness;
Rarely: disorientation, confusion, sleep disturbance, increased appetite, nervousness, depression, nightmares.
On the part of the hematopoiesis system:
Often: anemia;
Infrequent: thrombocytopenia, leukopenia, agranulocytosis.
From the side of the kidneys and urinary tract:
Infrequent: hypercreatininaemia, increased urea concentration in blood serum, sodium and water retention, hyperkalemia;
Rarely: acute renal failure in patients with risk factors, urinary infection;
Connection with meloxicam is not established: interstitial nephritis, albuminuria, hematuria.
From the sense organs:
Rarely: conjunctivitis, visual impairment, including blurred vision.
From the skin and subcutaneous fat:
Often: itching, rash;
Infrequently: urticaria;
Rarely: erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), photosensitivity.
Allergic reactions:
Rarely: anaphylactoid reactions (including anaphylactic shock), Quincke's edema.
Metabolic and nutritional disorders:
Rarely: weight loss, weight gain.
General disorders and disorders at the site of administration: Rarely: fever.

Overdose:Symptoms: impaired consciousness, nausea, vomiting, epigastric pain, gastrointestinal bleeding, acute renal failure, hepatic insufficiency, respiratory arrest, asystole.
Treatment: there is no specific antidote; with an overdose of the drug should be washed stomach, taking activated charcoal (within the next hour), prescribe symptomatic therapy. Kolestyramine accelerates the removal of the drug from the body. Forced diuresis, alkalinization of urine, hemodialysis - ineffective because of the high connection of the drug with blood proteins.

Interaction:- Other non-steroidal anti-inflammatory drugs (NSAIDs), including salicylates, acetylsalicylic acid in a dose> 3 g / day).
The use of meloxicam with other drugs from the NSAID group increases the risk of ulceration and bleeding from the gastrointestinal tract due to synergistic action. It is not recommended simultaneous use of meloxicam and other NSAIDs.
- Corticosteroids
Increase the risk of ulcers of the gastrointestinal tract or bleeding.
- Oral anticoagulants
NSAIDs can enhance the effect of oral anticoagulants, such as warfarin and acenocoumarol, so their simultaneous use is not recommended. If the need for simultaneous use of these drugs should strictly control the coagulation.
- Thrombolytic and antiplatelet agents
As a result of inhibition of platelet function and damage to the mucous membrane of the gastrointestinal tract, the risk of bleeding increases.
- Selective serotonin reuptake inhibitors Increased risk of bleeding from the gastrointestinal tract.
- Diuretics, angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists
The use of NSAIDs simultaneously with diuretics and other antihypertensive agents may impair their effectiveness. In some patients with impaired renal function (patients with dehydration, elderly patients), simultaneous use of ACE inhibitors or angiotensin receptor antagonists and angiotensin converting enzyme inhibitors can cause subsequent impairment of kidney function, up to the development of acute renal failure (usually reversible).Such drug combinations should be used cautiously, especially in elderly patients. Before the beginning of such treatment it is necessary to fill a deficiency of a liquid in an organism. It is necessary to regularly monitor the function of the kidneys.
- Other antihypertensive agents (eg, beta-blockers)
It is possible to reduce the antihypertensive effect of beta-blockers.
- Cyclosporin
NSAIDs can enhance the nephrotoxic effect of cyclosporine. During treatment, kidney function should be monitored, especially in the elderly.
- Intrauterine release system
There are cases of a decrease in the effectiveness of the intrauterine release system when using NSAIDs.
Pharmacokinetic interactions - the effect of meloxicam on the pharmacokinetics of other drugs
- Solitude
NSAIDs can cause an increase in the concentration of lithium in the blood down to toxic due to a decrease in its clearance by the kidneys. Application of NSAIDs simultaneously with lithium salts is not recommended. If this combination is necessary, careful monitoring of lithium concentration in plasma, especially at the beginning of treatment,after changing the dosage and after stopping the use of meloxicam.
- Methotrexate
NSAIDs may increase the concentration of methotrexate in the blood plasma.
You can not take meloxicam during treatment with high doses of methotrexate (more than 15 mg per week). If the need for combined treatment requires careful monitoring of the blood formula and kidney function. Particular care should be taken when methotrexate and meloxicam are administered every 3 days or more, as there is a risk of achieving a toxic level of methotrexate concentration. Consider the possibility of increasing the toxicity of methotrexate on the hematopoietic system.
Pharmacokinetic interactions - the effect of other drugs on the pharmacokinetics of meloxicam
- Cholestyramine
Cholestyramine accelerates the excretion of meloxicam, disrupting its intestinal-hepatic circulation and increasing the clearance by 50% and reducing the half-life to 13 hours (± 3 hours). This interaction is clinically significant.
There were no significant pharmacokinetic interactions during the simultaneous use of meloxicam with drugs that reduce the acidity of gastric juice (cytamidine, digoxin and furosemide).It is impossible to exclude interactions with oral antidiabetics.

Special instructions:Care should be taken when using the drug in patients who have a history of peptic ulcer and duodenal ulcer, as well as patients who are on anticoagulation therapy. In such patients, the risk of ulcerative-erosive diseases of the gastrointestinal tract is increased.
Drugs from the group of non-steroidal anti-inflammatory drugs (NSAIDs) inhibit the synthesis of prostaglandins in the kidneys that regulate the renal blood flow and the aggravation of this action depends on the dose. The administration of meloxicam to patients with impaired renal blood flow or a reduced volume of circulating blood may increase the symptoms of impaired renal function. The parameters of the kidney function come to the initial state after stopping the meloxicam. In these patients during treatment with meloxicam, diuresis and other biochemical parameters of kidney function are necessary.
The greatest risk of occurrence of the above-mentioned reactions is observed in the following groups of patients:
- in elderly patients;
- in patients taking ACE inhibitors, angiotensin II receptor antagonists (sartan), or diuretics;
- in patients with hypovolemia (regardless of the cause);
- in patients with congestive heart failure;
- in patients with renal insufficiency;
- in patients with nephrotic syndrome;
- in patients with lupus nephropathy;
- in patients with severe impaired hepatic function (serum albumin concentration <25 g / l or Child-Pugh class C).
In rare cases, drugs from the group of NSAIDs can cause interstitial nephritis, glomerular nephritis, necrosis of the medulla of the kidney or nephrotic syndrome.
- In patients with renal failure, if the creatinine clearance is more than 30 ml / min, dosage adjustment is not required.
- In patients who are on dialysis, the dosage of the drug should not exceed
7.5 mg / day.
Patients taking both diuretics and meloxicam, should take a sufficient amount of fluid.
If allergic reactions (itching, skin rash, urticaria, sensitization to light) occur during treatment, the patient should consult a doctor to decide whether to stop taking the drug.

Effect on the ability to drive transp. cf. and fur:The use of the drug can cause the emergence of unwanted effects in the form of headaches and dizziness, drowsiness. If the above phenomena occur, it is necessary to abandon the management of vehicles and maintenance of machinery and mechanisms.

Form release / dosage:Tablets 7.5 mg: 10 tablets in the blister Alum. / PVC / PVDC.
2 blisters with instructions for use in a cardboard pack.
Tablets 15 mg: 10 tablets in the blister Alum. / PVC / PVDC.
For 1 or 2 blisters with instructions for use in a cardboard bundle.

Packaging:

(10) - blisters (1) - packs of cardboard
(10) - blisters (2) - packs cardboard

Storage conditions:

In dry, dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children!

Shelf life:3 years.
Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LS-000172

Date of registration:09.04.2010

The owner of the registration certificate:Gedeon Richter Poland, Open CompanyGedeon Richter Poland, Open Company Poland

Representation: & nbspGEDEON RICHTER OJSC GEDEON RICHTER OJSC Hungary

Information update date: & nbsp15.08.2015

Illustrated instructions

Instructions

Mirlox® (Mirlox® )