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

Non-steroidal anti-inflammatory drug, belongs to the class of oxycomas. Has anti-inflammatory, analgesic, antipyretic effect. Anti-inflammatory effect of the drug is associated with inhibition of the enzymatic activity of cyclooxygenase-2 (COX-2), involved in the biosynthesis of prostaglandins in the inflammatory region. Less meloxicam acts on cyclooxygenase-1 (COX-1), involved in the synthesis of prostaglandin, which protects the mucous membrane of the gastrointestinal tract and takes part in the regulation of blood flow in the kidneys.

Meloksikam suppresses the synthesis of prostaglandins in the inflammation region to a greater extent than in the mucous membrane of the stomach or kidneys, which is due to the relatively selective inhibition of COX-2.

Pharmacokinetics:

Suction. Meloksikam well absorbed after rectal administration, absolute bioavailability - 89%.The maximum concentration of the drug in the plasma during the steady state of pharmacokinetics is reached approximately 5-6 hours after application of the drug. The range of difference between the maximum (C_m_Oh) and minimal (C_min) the concentration of the drug after its administration once a day is 0.4-1.0 μg / ml for a dose of 7.5 mg and 0.8-2.0 μg / ml for a dose of 15 mg.

Distribution. Meloksikam binds well to plasma proteins (more than 99%). Passes through the histohematological barriers, the concentration in the synovial fluid reaches 50% of the maximum concentration of the drug in the plasma.

Metabolism. Almost completely metabolized in the liver with the formation of four pharmacologically inactive derivatives. 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). Research in vitro showed that in this metabolic transformation an important role is played by the isoenzyme CYP 2C9, isozyme has an additional value CYP AP4. In the formation of the other two metabolites (constituting 16% and 4% of the dose, respectively), peroxidase,the activity of which, probably, individually varies.

Excretion. It is excreted equally through the intestines and kidneys, mainly in the form of metabolites. Through the intestine, less than 5% of the daily dose is excreted in unchanged form, in the unchanged form of the urine the drug is found only in trace amounts. The half-life (T_1/2) meloxicam is 15-20 hours. Plasma clearance is an average of 8 ml / min.

Insufficiency of liver and / or kidney function. Insufficiency of liver function, as well as renal failure of mild to moderate severity, have no significant effect on the pharmacokinetics of meloxicam. At the terminal stage of renal failure, an increase in the volume of distribution can lead to higher concentrations of free meloxicam, so in these patients the daily dose should not exceed 7.5 mg.

Elderly patients (over 65 years of age). In elderly patients, the average plasma clearance during the steady state of pharmacokinetics is slightly lower than in young patients.

Indications:

Treatment of pain and inflammation with: osteoarthritis, rheumatoid arthritis, ankylosing spondylitis (Bechterew's disease) and other inflammatory and degenerative diseases of the joints.The drug is intended for symptomatic therapy, reducing pain and inflammation at the time of use, the progression of the disease is not affected.

Contraindications:

- Hypersensitivity to meloxicam.

- full or partial combination of asthma, recurrent nasal polyposis and paranasal sinuses and intolerance to acetylsalicylic acid and other non-steroidal anti-inflammatory drugs (including history).

- erosive and ulcerative lesions of the mucous membrane of the stomach and duodenum in the acute phase.

- active gastrointestinal bleeding, recent cerebrovascular bleeding or other bleeding.

- Severe liver failure.

- Severe renal failure in patients not undergoing dialysis (creatinine clearance less than 30 mL / min), progressive renal disease, including confirmed hyperkalemia.

- Inflammatory bowel disease in the phase of exacerbation (ulcerative colitis, Crohn's disease).

- Period after aortocoronary bypass surgery.

- Severe uncontrolled heart failure.

- Hemophilia and other bleeding disorders.

- Anamnestic data on an attack of bronchial obstruction, rhinitis.

- Pregnancy, the period of breastfeeding.

- Children under 12 years.

Suppositories should not be used in patients with any inflammatory diseases of the rectum or anus, or in patients with recent bleeding from the rectum or anus.

Carefully:

Elderly age, ischemic heart disease, chronic heart failure, cerebrovascular disease, dyslipidemia / hyperlipidemia, diabetes mellitus, peripheral arterial disease, smoking, renal failure with creatinine clearance from 30 to 60 ml / min, tuberculosis, severe osteoporosis, anamnestic data on the development of ulcerative lesions of the gastrointestinal tract, infection Helicobacter pylori, long-term use of non-steroidal anti-inflammatory drugs, alcoholism, severe somatic diseases, simultaneous administration of oral glucocorticosteroids (including prednisolone), anticoagulants (including warfarin), antiplatelet agents (including clopidogrel), selective serotonin reuptake inhibitors (citalopram,fluoxetine, paroxetine, sertraline).

Pregnancy and lactation:

The drug is contraindicated during pregnancy. Suppressing the synthesis of prostaglandins can have an undesirable effect on the course of pregnancy and fetal development. It is known that non-steroidal anti-inflammatory drugs penetrate into breast milk, so the drug is not recommended for use during breastfeeding.

Dosing and Administration:

Rectally, releasing the suppository from the contour pack, injected deep into the anus. Before using the suppository it is recommended to empty the intestine.

Suppositories are recommended to be applied at a dose of 7.5 mg once a day. In more severe cases, it is possible to use suppositories at a dose of 15 mg. When combined use of the drug in the form of tablets, suppositories, suspensions and injections, the total dose should not exceed 15 mg per day. The maximum dose in adolescents is 0.25 mg / kg.

Osteoarthritis: 7.5 mg per day. If necessary, this dose can be increased to 15 mg per day.

Rheumatoid arthritis: 15 mg per day. Depending on the therapeutic effect, this dose may be reduced to 7.5 mg per day.

Ankylosing spondylitis (Bekhterev's disease): 15 mg per day. Depending on the therapeutic effect, this dose can be reduced to 7.5 mg per day.

In patients with an increased risk of adverse reactions and with severe renal failure who are on hemodialysis, the dose should not exceed 7.5 mg per day.

The drug should be applied rectally for as short a time as possible, taking into account the summation of the risk of local toxicity and the risk associated with the systemic effect of the drug.

Side effects:

Frequency: very often (more than 10%), often (1-10%), infrequently (0.1-1%), rarely (0.01-0.1%), very rarely (less than 0.01%).

From the digestive system: often - dyspepsia, incl. nausea, vomiting, abdominal pain, constipation, flatulence, diarrhea; infrequent - transient increase in the activity of "liver" transaminases, hyperbilirubinemia, belching, esophagitis, gastroduodenal ulcer, bleeding from the gastrointestinal tract (including latent), stomatitis; rarely - perforation of the gastrointestinal tract, colitis, hepatitis, gastritis.

From the hematopoiesis: often - anemia; infrequently - a change in the blood formula, incl. leukopenia, thrombocytopenia.

From the skin: often - itching, skin rash; infrequently - hives; rarely - photosensitivity, bullous eruptions, erythema multiforme, including Stevens-Johnson syndrome, toxic epidermal necrolysis.

From the respiratory system: rarely - bronchospasm.

From the nervous system: often - dizziness, headache; infrequently - vertigo, noise in the ears, drowsiness; rarely confusion, disorientation, emotional lability.

From the sense organs: impaired vision, including vague visual perception, rarely - conjunctivitis.

From the cardiovascular system: often - peripheral edema; infrequently - increased blood pressure, a feeling of palpitations, "tides" of blood to the skin of the face.

From the side of the urinary system, infrequently - hypercreatininaemia and / or increased urea concentration in blood serum; rarely acute renal failure; albuminuria, hematuria; interstitial nephritis.

Allergic reactions: rarely - angioedema, anaphylactoid / anaphylactic reactions.

Overdose:

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

Treatment: symptomatic therapy. Forced diuresis, alkalization of urine, hemodialysis are ineffective because of the high degree of binding of meloxicam to plasma proteins. There is no specific antidote. Kolestyramine accelerates the removal of the drug from the body.

Interaction:

When used simultaneously with other non-steroidal anti-inflammatory drugs (NSAIDs) (as well as acetylsalicylic acid), glucocorticoids and analgesics increases the risk of erosive ulcerative lesions and bleeding from the gastrointestinal tract; when used simultaneously with antihypertensive drugs, the effectiveness of the latter may be reduced; when used simultaneously with lithium preparations, development of cumulation of lithium and increase of its toxic effect is possible (it is recommended to control the concentration of lithium in the blood); with simultaneous use with methotrexate, the side effect of the latter on the hematopoietic system is increased (the risk of anemia and leukopenia,periodic monitoring of the general blood test is shown); when used simultaneously with diuretics and with cyclosporine, the risk of developing renal failure increases; at simultaneous application with intrauterine contraceptives, the effectiveness of the latter may be reduced; with simultaneous use with anticoagulants (heparin, ticlopidine, warfarin), antiplatelet agents (acetylsalicylic acid, clopidogrel), as well as with fibrinolytic drugs (streptokinase, fibrinolysin) increases the risk of bleeding (periodic monitoring of blood coagulability); when used simultaneously with selective serotonin reuptake inhibitors, the risk of gastrointestinal bleeding increases. With the simultaneous use of meloxicam with hypoglycemic agents for oral administration, it can intensify their action, thereby contributing to the risk of hypoglycemia. Meloksikam can weaken the action of digoxin, cortisone, diuretics.

Special instructions:

In the event of peptic ulcers or gastrointestinal bleeding, the development of side effects from the skin and mucous membranes, the drug should be discarded.

In patients with reduced blood volume and reduced glomerular filtration (dehydration, chronic heart failure, liver cirrhosis, nephrotic syndrome, symptomatic kidney disease, diuretics, dehydration after major surgical operations) may cause clinically significant chronic renal failure, which is fully reversible after drug withdrawal (such patients in the early treatment should be monitored daily diuresis and renal function). When persistent and substantial increase in transaminases and changes in other liver function tests drug should be discontinued and conduct control tests.

Meloxicam, like other NSAIDs, may mask the symptoms of infectious diseases.

Use of meloxicam, as well as other drugs that block the synthesis of prostaglandins, can affect fertility, is not recommended for women planning pregnancy.

Patients taking both diuretics and meloxicam, should take a sufficient amount of fluid.

After a two-week use of the drug, it is necessary to monitor the parameters of liver function (transaminase).

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

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 requiring increased concentration and speed of psychomotor reactions (with dizziness and drowsiness).

Form release / dosage:Suppositories rectal 7.5 mg and 15 mg.

Packaging:

There are 5 suppositories in a contiguous cell package. One or two contour packagings along with the instructions for use are placed in a pack of cardboard.

Storage conditions:

In the dark place at a temperature of no higher than 15 ° C.

Keep out of the reach of children.

Shelf life:

2 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-004134

Date of registration:13.02.2017

Expiration Date:13.02.2022

The owner of the registration certificate:DALHIMFARM, OJSC DALHIMFARM, OJSC Russia

Manufacturer: & nbsp

DALHIMFARM, OJSC Russia

Information update date: & nbsp21.03.2017

Illustrated instructions

Instructions

Meloksikam (Meloxicam)