Meloksikam Kanon suppositories

General characteristics. Structure:

Active agent: to meloksika - 7,5 mg or 15 mg
excipient: fatty acids glycerides (Vitepsol H 15) – 992,5 mg or 985 mg.

Description
Suppositories of yellow color, torpedo-shaped form, without impregnations on longitudinal section. On a cut existence of an air core or funneled deepening is allowed.

Pharmacological properties:

Pharmacodynamics. Meloksikam – the non-steroidal anti-inflammatory drug (NPVP) possessing anesthetic, antiinflammatory and febrifugal action. The mechanism of action is connected with inhibition of synthesis of prostaglandins as a result of selective suppression of enzymatic activity of cyclooxygenase-2 (TsOG-2) participating in biosynthesis of prostaglandins in the field of an inflammation. At use in high doses, prolonged use and specific features of an organism of TsOG-2 selectivity decreases. Suppresses synthesis of prostaglandins in the field of an inflammation more than in a mucous membrane of a stomach or kidneys that is connected with rather selective inhibition of TsOG-2. To a lesser extent to meloksika affects cyclooxygenase-1 (TsOG-1) participating in synthesis of the prostaglandins which are protecting a mucous membrane of the digestive tract (DT) and taking part in regulation of a blood-groove in kidneys.

Pharmacokinetics. Absorption
Meloksikam is well soaked up after rectal administration, absolute bioavailability – 89%.
Average maximum concentration in plasma is reached within 5 – 6 hours. At repeated use the steady condition of pharmacokinetics is reached from 3 to 5 days in time.
The maximum concentration of drug in plasma in the period of a steady condition of pharmacokinetics is reached approximately in 5 hours after drug use. Ranges of distinctions between maximum (Cmax) and basal concentration (Cmin) are similar for tablets and suppositories and make after its reception 0,4 – 1,0 mkg/ml once a day – for a dose of 7,5 mg, and 0,8 – 2,0 mkg/ml – for a dose of 15 mg.
Distribution
Linkng with proteins of plasma makes more than 99%. Range of distinctions between the maximum and basal concentration of drug after its reception is rather small once a day and makes when using a dose 7,5 mg 0,4 - 1,0 mkg/ml, and when using a dose of 15 mg – 0,8 – 2,0 mkg/ml, (Cmin and Cmax values are given, respectively). Meloksikam gets through gistogematichesky barriers, concentration in synovial fluid reaches 50% of the maximum concentration of drug in plasma.
Metabolism
Almost it is completely metabolized in a liver with formation of four inactive derivatives in the pharmacological relation. The main metabolite, 5-carboxy-meloksikam (60% of dose size), is formed by oxidation of an intermediate metabolite, a 5-gidroksimetilmeloksikam who is also excreted, but to a lesser extent (9% of dose size). The researches in vitro showed that in this metabolic transformation an important role is played by CYP2C9, additional value has CYPZA4 isoenzyme. Peroxidase which activity probably individually varies takes part in formation of two other metabolites (making, respectively, 16% and 4% of drug dose size).
Removal
It is removed equally through intestines and kidneys, it is preferential in the form of metabolites.
Through intestines in not changed look less than 5% of the size of a daily dose are removed, in urine in not changed look drug is found only in trace quantities. The elimination half-life (T1/2) of a meloksikam makes 15 – 20 hours. The plasma clearance averages 8 ml/min. At elderly people the clearance of drug decreases. Distribution volume low also averages 11 l.
Insufficiency of function of a liver and/or kidneys
Insufficiency of function of a liver, and also moderately expressed renal failure has no significant effect on pharmacokinetics of a meloksikam. At a terminal renal failure increase in volume of distribution can result in higher concentration of a free meloksikam therefore at these patients the daily dose should not exceed 7,5 mg.
Elderly patients
At elderly patients the average plasma clearance in the period of a steady condition of pharmacokinetics is a little lower, than at young patients.

Indications to use:

Symptomatic treatment of an osteoarthrosis;
Symptomatic treatment of a pseudorheumatism;
Symptomatic treatment of an ankylosing spondylitis (Bekhterev's disease), other diseases of the joints which are followed by a pain syndrome.

Route of administration and doses:

Rektalno (previously having exempted a candle from planimetric packaging, enter it deeply into an anus).
The recommended dosing mode:
Pseudorheumatism: 15 mg a day (on 1 candle of 15 mg × 1 time a day or on 1 candle 7,5 mg × 2 times a day). Depending on medical effect the dose can be lowered to 7,5 mg a day.
Osteoarthrosis: 7,5 mg a day (on 1 candle of 7,5 mg × 1 time a day). At inefficiency the dose can be increased to 15 mg a day.
Ankylosing spondylitis (Bekhterev's disease): 15 mg a day (on 1 candle of 15 mg × 1 time a day or on 1 candle 7,5 mg × 2 times a day). The maximum daily dose should not exceed 15 mg.
Patients with the increased risk have development of side effects, and also at the patients with a heavy renal failure who are on a hemodialysis, the dose should not exceed 7,5 mg a day.
The combined use. The total daily dose of drug of the meloksikam used in the form of tablets, candles, suspension for intake and injections should not exceed 15 mg.

Features of use:

It is necessary to be careful at use of drug for patients who have in the anamnesis a peptic ulcer of a stomach and duodenum, and also at the patients who are on anticoagulating therapy. At such patients the risk of emergence of erosive cankers of a GIT is increased. It is necessary to be careful and control indicators of function of kidneys at use of drug for patients of advanced age, patients with chronic heart failure with the circulatory unefficiency phenomena, at patients with cirrhosis, and also at patients with a hypovolemia as a result of surgical interventions.
Correction of the mode of dosing is not required from patients with insignificant or moderate depression of function of kidneys (clearance of creatinine more than 30 ml/min.). The patients accepting at the same time diuretics and to meloksika have to accept enough liquid.
Meloksikam, also as well as other NPVP, can mask symptoms of infectious diseases.
Use of a meloksikam, as well as other drugs blocking synthesis of prostaglandins can influence fertility therefore it is not recommended to the women planning pregnancy.
If in the course of treatment there were allergic reactions (an itch, skin rash, a small tortoiseshell, a photosensitization), and also the patients noting against the background of administration of drug of a vision disorder need to see a doctor for the purpose of the solution of a question of the termination of administration of drug.

Influence on ability to manage vehicles and to perform the works demanding the high speed of psychomotor reactions:
During treatment it is necessary to be careful during the driving of motor transport and occupation other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

Frequency of the side reactions given below was defined according to the following:
- very often
- often
- infrequently
- seldom
- very seldom
From the alimentary system: often – dyspepsia, including nausea, vomiting, abdominal pains, a lock, a meteorism, diarrhea; infrequently – passing increase in activity of "hepatic" transaminases, a hyperbilirubinemia, an eructation, an esophagitis, a gastroduodenal ulcer, bleeding from a GIT (including hidden), stomatitis; seldom – perforation of a GIT, colitis, hepatitis, gastritis.
From bodies of a hemopoiesis: often – anemia; infrequently – change of a blood count, including a leukopenia, thrombocytopenia.
From integuments: often – an itch, skin rash; infrequently – a small tortoiseshell; seldom – a photosensitization, violent rashes, a mnogoformny erythema, including Stephens-Johnson's syndrome, a toxic epidermal necrolysis.
From respiratory system: seldom – a bronchospasm.
From a nervous system: often – dizziness, a headache; infrequently – вертиго, a sonitus, drowsiness; seldom – confusion of consciousness, a disorientation, emotional lability.
From cardiovascular system: often – peripheral hypostases; infrequently – increase in arterial pressure, a heart consciousness, "inflows" of blood to face skin.
From an urinary system: infrequently – a giperkreatininemiya and/or increase in concentration of urea in blood serum; seldom – an acute renal failure; connection with reception of a meloksikam is not established – intersticial nephrite, an albuminuria, a hamaturia.
From sense bodys: seldom – conjunctivitis, a vision disorder, including an illegibility of visual perception.
Allergic reactions: seldom – a Quincke's disease, anaphylactoid / anaphylactic reactions.

Interaction with other medicines:

At simultaneous use with other non-steroidal anti-inflammatory drugs (and also with acetylsalicylic acid) the risk of emergence of erosive cankers and bleedings of a GIT increases.
At simultaneous use with hypotensive drugs decrease in efficiency of action of the last is possible.
At simultaneous use with drugs of lithium development of cumulation of lithium and increase in its toxic action is possible (control of concentration of lithium in blood is recommended).
At simultaneous use with a methotrexate side effect of the last on the hemopoietic system amplifies (danger of developing of anemia and a leukopenia, periodic performing the general blood test is shown).
At simultaneous use with diuretics and with cyclosporine the risk of development of a renal failure increases.
At simultaneous use with intrauterine contraceptive means decrease in efficiency of action of the last is possible.
At simultaneous use with anticoagulants (heparin, тиклопидин, warfarin), and also with thrombolytic drugs (Streptokinasa, fibrinolysin) the risk of development of bleedings increases (periodic control of indicators of coagulability of blood is necessary).
At simultaneous use with Colestyraminum removal of drug from an organism accelerates.
At simultaneous use with selective serotonin reuptake inhibitors the risk of development of gastrointestinal bleedings increases.

Contraindications:

- hypersensitivity to a meloksikam or an auxiliary component of drug;
- a state after performing aortocoronary shunting;
- dekompensirovanny heart failure;
- anamnestic data on an attack of a bronkhoobstruktion, rhinitis;
- a small tortoiseshell after reception of acetylsalicylic acid or other NPVP (a full or incomplete combination of bronchial asthma, the nose recuring a polypose and okolonosovy bosoms and intolerance of acetylsalicylic acid or other non-steroidal anti-inflammatory drugs (including in the anamnesis));
- erosive and ulcer changes of a mucous membrane of a stomach or duodenum, active gastrointestinal bleeding;
- inflammatory diseases of intestines (ulcer colitis, disease Krone);
- cerebrovascular bleeding or other bleedings;
- the expressed liver failure or an active disease of a liver;
- the chronic renal failure (CRF) at the patients who are not exposed to dialysis (clearance of creatinine less than 30 ml/min.), the progressing diseases of kidneys, including the confirmed hyperpotassemia;
- pregnancy, breastfeeding period;
- children's age up to 15 years.
Suppositories should not be applied at patients with any inflammatory diseases of a rectum or an anus, or at patients with recently noted proctorrhagia or an anus.

With care:
Coronary heart disease, cerebrovascular diseases, congestive heart failure, дислипидемия / a lipidemia, a diabetes mellitus, diseases of peripheral arteries, smoking, anamnestic data on development of a canker of a GIT, existence of an infection of Helicobacter pylori, HPN with clearance of creatinine of 30-60 ml/min., advanced age, long use of NPVP, frequent alcohol intake, heavy somatopathies, the accompanying therapy by the following drugs:

- anticoagulants (for example, warfarin);
- antiagregant (for example, acetylsalicylic acid, klopidogret);
- peroral glucocorticosteroids (for example, Prednisolonum);
- selective serotonin reuptake inhibitors (for example, to tsitalopra, fluoxetine, пароксетин, sertraline).
For decrease in risk of development of the undesirable phenomena from a GIT it is necessary to use a minimal effective dose the greatest possible short course.

Use during pregnancy and during breastfeeding:
Drug is not recommended to be used during pregnancy and a lactation.

Overdose:

Overdose symptoms: consciousness disturbance, nausea, vomiting, pains in epigastriums, GIT bleeding, an acute renal failure, a liver failure, an apnoea, an asystolia.
Treatment: there is no specific antidote; at overdose of drug the gastric lavage, reception of absorbent carbon (within the next hour), symptomatic therapy is recommended. The artificial diuresis, urine alkalinization, a hemodialysis – are ineffective.

Storage conditions:

Period of validity: 2 years. Not to apply after a period of validity. To store in the dry, protected from light place at a temperature not above 25 °C. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Suppositories rectal 7,5 mg or 15 mg.
On 6 suppositories place in a blister strip packaging from a film polyvinyl chloride. On 1, 2 blister strip packagings together with the application instruction place in a pack from a cardboard.