Arkoksia

General characteristics. Structure:

Active ingredient: 60 mg, 90 mg or 120 mg of an etorikoksib.

Excipients: calcium hydrophosphate, cellulose microcrystallic, croscarmellose sodium, magnesium stearate.

Structure of a cover: опадрай the II green 39K11520, wax of karnaubskiya.

Structure of a film cover: lactoses monohydrate, a gipromelloz, titanium dioxide, triacetin, an aluminum varnish on the basis of dye of indigo carmine (E132), dye ferrous oxide yellow (E172).

Pharmacological properties:

Pharmacodynamics. NPVS. The selection TsOG-2 inhibitor, in therapeutic concentration blocks formation of prostaglandins and has antiinflammatory, analgeziruyushchy and febrifugal effect. The selection oppression of TsOG-2 is followed by reduction of expressiveness of the clinical symptoms connected with inflammatory process, at the same time is absent influence on function of thrombocytes and a mucous membrane of a GIT.

The Etorikoksib has dozozavisimy effect of inhibition of TsOG-2, without exerting impact on TsOG-1 at use in a daily dose to 150 mg. Аркоксиа® does not exert impact on production of prostaglandins in a mucous membrane of a stomach and on a bleeding time. In the conducted researches decrease in level of the arachidonic acid and aggregation of thrombocytes caused by collagen was not observed.

Pharmacokinetics. Absorption. After intake it is quickly absorbed from a GIT. Bioavailability at intake makes about 100%. After administration of drug by adults on an empty stomach in a dose of 120 mg of Cmax makes 3.6 mkg/ml, time of achievement of Cmax - 1 h after reception.

Meal has no significant effect on expressiveness and speed of absorption of an etorikoksib at reception in a dose of 120 mg. At the same time there is a decrease in Cmax values by 36% and increase in Tmax at 2 h.

Reception of antacids does not influence drug pharmacokinetics.

Distribution. The average geometrical size AUC0-24 made 37.8 мкг×ч/мл. The pharmacokinetics of an etorikoksib within therapeutic doses has linear character.

Linkng with proteins of plasma exceeds 92%. Vd in an equilibrium state makes about 120 l. The Etorikoksib gets through a placental barrier and through GEB.

Metabolism. 6-hydroxymethyl-etorikoksiba is intensively metabolized in a liver, with participation of an isoenzyme of P450 (CYP) cytochrome and education. 5 metabolites of an etorikoksib, the main - 6-hydroxymethyl-etorikoksib and its derivative - 6-carboxy-acetyl-etorikoksib are revealed. The main metabolites do not influence TsOG-1 and are absolutely inactive or maloaktivna concerning TsOG-2.

Removal. Removal of an etorikoksib happens in the form of metabolites kidneys. Less than 1% of drug are removed with urine in not changed look.

At single in introduction to healthy volunteers of the marked radioactive drug containing эторикоксиб in a dose of 25 mg it is shown that 70% of drug are removed by kidneys, 20% - through intestines, are preferential in the form of metabolites. Less than 2% are revealed in not changed look.

The equilibrium state is reached in 7 days at daily reception in a dose of 120 mg, with cumulation coefficient about 2 that corresponds to T1/2 - about 22 h. The plasma clearance makes about 50 ml/min.

Pharmacokinetics in special clinical cases. Pharmacokinetic differences at men and women are absent.

The pharmacokinetics at elderly (65 years are also more senior) is comparable to indicators at young people, and there is no need to adjust a drug dose at elderly people.

Racial differences do not influence pharmacokinetic parameters of an etorikoksib.

At patients with insignificant abnormal liver functions (5-6 points on a scale of Chayld-Pyyu) the single dose of an etorikoksib in a dose of 60 mg/days was followed by increase in AUC by 16% in comparison with healthy faces.

The patients with a moderate abnormal liver function (7-9 points on a scale of Chayld-Pyyu) accepting drug in a dose of 60 mg every other day had the same AUC value, as at the healthy faces accepting drug daily in the same dose.

Data of clinical and pharmacokinetic trials at patients with a heavy abnormal liver function (more than 9 points on a scale of Chayld-Pyyu) are absent.

Pharmacokinetic indicators of single use of an etorikoksib in a dose of 120 mg at patients with a moderate and heavy renal failure and with an end-stage of a chronic renal failure, being on a hemodialysis, did not differ significantly from indicators at healthy faces. The hemodialysis slightly influenced removal (clearance of dialysis - about 50 ml/min.).

Pharmacokinetic parameters of an etorikoksib at children are younger than 12 years were not studied. In comparative pharmacokinetic researches comparable data at use of an etorikoksib in group of teenagers (from 12 to 17 years) with the body weight of 40-60 kg in a dose of 60 mg/days are obtained, in a similar age group and with body weight more than 60 kg - 90 mg/days, and adults at reception have 90 mg/days.

Indications to use:

Symptomatic therapy of the following diseases and states:

— osteoarthrosis;

— pseudorheumatism;

— ankylosing spondylitis;

— the pain and inflammatory symptomatology connected with acute gouty arthritis.

Therapy of the moderated and expressed acute pain after dental operations.

Route of administration and doses:

Drug is accepted inside, irrespective of meal, washing down with a small amount of water.

At an osteoarthrosis the recommended dose makes 60 mg of 1 times/days. The daily dose at an osteoarthrosis should not exceed 60 mg.

At a pseudorheumatism and an ankylosing spondylitis the recommended dose makes 90 mg of 1 times/days. The daily dose at a pseudorheumatism and an ankylosing spondylitis should not exceed 90 mg.

At acute gouty arthritis the dose recommended in the acute period makes 120 mg of 1 times/days. The daily dose at acute gouty arthritis should not exceed 120 mg.

Duration of use of drug in a dose of 120 mg makes no more than 8 days. It is necessary to use a minimal effective dose minimum possible short course.

The average therapeutic dose at a pain syndrome makes once 60 mg.

Acute pain after dental operations: the recommended dose makes 90 mg of 1 times/days. At treatment of an acute pain the drug Arkoksia® should be used only during the acute symptomatic period, limited lasting no more than 8 days. The daily dose for stopping of pain after dental operations should not exceed 90 mg.

At patients with a liver failure (5-9 points on a scale of Chayld-Pyyu) are recommended be not to exceeded a daily dose of 60 mg.

Features of use:

Use at pregnancy and feeding by a breast. Drug is contraindicated at pregnancy and in the period of a lactation.

Use of drug can negatively influence female fertility and is not recommended to the women planning pregnancy.

Use at abnormal liver functions. It is contraindicated at the expressed liver failure (more than 9 points on a scale of Chayld-Pyyu) or an active disease of a liver.

At patients with a liver failure (5-9 points on a scale of Chayld-Pyyu) are recommended be not to exceeded a daily dose of 60 mg.

Use at renal failures. It is contraindicated at a renal failure of heavy degree (KK less than 30 ml/min.), the progressing diseases of kidneys, the confirmed hyperpotassemia.

Use for children. It is contraindicated at children's and teenage age up to 18 years.

Use for elderly patients. With care use drug at elderly people.

Special instructions. Reception of Arkoksia® medicine demands careful control of the ABP. All patients at purpose of drug should carry out monitoring of the ABP within the first two weeks of treatment and periodically further.

Also it is regularly necessary to control indicators of function of a liver and kidneys.

In case of increase in level of hepatic transaminases by 3 times and more concerning VGN drug has to be cancelled.

Considering increase of risk of development of undesirable effects with increase in duration of reception it is necessary to estimate periodically need of continuation of administration of drug and a possibility of a dose decline.

It is not necessary to use drug along with other NPVS.

The cover of the drug Arkoksia® contains lactose in insignificant quantity that should be considered at purpose of drug the patient with a lactose intolerance.

Influence on ability to driving of motor transport and to control of mechanisms. 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. Patients at whom episodes of dizzinesses, drowsiness or weakness were noted have to refrain from the occupations demanding concentration of attention.

Side effects:

Frequency of side reactions is presented according to the following gradation: very often (≥10%), it is frequent (1-10%); infrequently (0.1-1%); seldom (0.01-0.1%); very seldom (<0.01%, including separate cases).

From the alimentary system: often - epigastric pain, heartburn, nausea, diarrhea, dyspepsia, a meteorism; infrequently - abdominal distention, an eructation, strengthening of a vermicular movement, a lock, dryness of a mucous membrane of an oral cavity, gastritis, an ulcer of a mucous membrane of a stomach or duodenum, a syndrome of the angry intestines, an esophagitis, ulcers of a mucous membrane of an oral cavity, vomiting; very seldom - GIT ulcers (with bleeding or perforation), hepatitis.

From a nervous system: often - a headache, dizziness, weakness; infrequently - taste disturbance, drowsiness, sleep disorders, sensitivity disturbances, including paresthesias/hyperesthesias, alarm, a depression, concentration disturbances; very seldom - hallucinations, confusion of consciousness.

From sense bodys: infrequently - a sight illegibility, conjunctivitis, a sonitus, вертиго.

From an urinary system: infrequently - a proteinuria; very seldom - a renal failure, usually reversible at drug withdrawal.

Allergic reactions: very seldom - anaphylactic/anaphylactoid reactions, including the expressed decrease in the ABP and shock.

From cardiovascular system: often - heartbeat, increase in the ABP; infrequently - inflows, disturbance of cerebral circulation, fibrillation of auricles, congestive heart failure, nonspecific changes of an ECG; myocardial infarction; very seldom - hypertensive crisis.

From respiratory system: infrequently - cough, short wind, nasal bleeding; very seldom - a bronchospasm.

Dermatological reactions: often - ecchymomas; infrequently - puffiness of the person, a skin itch, rash; very seldom - a small tortoiseshell, Stephens-Johnson's syndrome, a Lyell's disease.

Infectious complications: infrequently - a gastroenteritis, infections of upper parts of respiratory tracts, an urinary path.

From a musculoskeletal system: infrequently - muscular spasms, an arthralgia, a mialgiya.

From a metabolism: often - hypostases, a liquid delay; infrequently - appetite changes, increase in body weight.

From laboratory researches: often - increase in activity of hepatic transaminases; infrequently - increase in nitrogen in blood and urine, increase in activity of KFK, decrease in a hematocrit, decrease in hemoglobin, a hyperpotassemia, a leukopenia, thrombocytopenia, increase in creatinine of serum, increase in uric acid; seldom - increase in sodium in blood serum.

Others: often - a grippopodobny syndrome; infrequently - thorax pains.

Interaction with other medicines:

Pharmakodinamichesky interaction. At the patients receiving warfarin, reception of Arkoksia® in a dose of 120 mg/days was followed by increase approximately for 13% of MHO and a prothrombin time. At the patients receiving warfarin or similar medicines it is necessary to control MHO indicators during the beginning of therapy or change of the mode of dosing of Arkoksia®, in particular in the first few days.

There are messages that non-selective NPVS and the selection TsOG-2 inhibitors can weaken hypotensive effect of APF inhibitors. This interaction should be taken into account at treatment of the patients accepting Arkoksia® along with APF inhibitors. At patients with renal failures (for example, at dehydration or at advanced age) the similar combination can aggravate functional insufficiency of kidneys.

Аркоксиа® it is possible to apply along with acetylsalicylic acid in the low doses intended for prevention of cardiovascular diseases. However co-administration of acetylsalicylic acid in low doses and Arkoksia® can lead to increase in frequency of a canker of a GIT and other complications in comparison with reception of one Arkoksia®. After achievement of an equilibrium state reception of an etorikoksib in a dose of 120 mg of 1 times/days does not exert impact on antithrombocytic activity of acetylsalicylic acid in low doses (81 mg/days). Drug does not replace preventive effect of acetylsalicylic acid at cardiovascular diseases.

Cyclosporine and такролимус increase risk of development of nephrotoxicity against the background of reception of Arkoksia®.

Pharmacokinetic interaction. There are data that non-selective NPVS and the selection TsOG-2 inhibitors can increase concentration of lithium in plasma. This interaction should be taken into account at treatment of the patients accepting Arkoksia® along with lithium.

In two researches effects of Arkoksia® in a dose of 60, 90 and 120 mg of 1 times/days within seven days at the patients receiving once a week a methotrexate in a dose from 7.5 to 20 mg concerning a pseudorheumatism were studied. Аркоксиа® in a dose of 60 and 90 mg did not exert impact on concentration in plasma (on AUC) and renal clearance of a methotrexate.

In one research Arkoksia® in a dose of 120 mg did not exert impact on concentration in plasma (on AUC) and renal clearance of a methotrexate. In other research Arkoksia® in a dose of 120 mg increased concentration of a methotrexate in plasma for 28% (on AUC) and reduced renal clearance of a methotrexate by 13%. At co-administration of Arkoksia® in doses it is higher than 90 mg/days and a methotrexate it is necessary to observe possible emergence of toxic effects of a methotrexate.

Oral contraceptives: reception of Arkoksia® in a dose of 120 mg with the oral contraceptives containing 35 mkg of ethinylestradiol and from 0.5 to 1 mg of norethindrone within 21 days, at the same time or with a difference in 12 h increases stationary AUC0-24 of ethinylestradiol by 50-60%. However concentration of Norethisteronum usually does not increase to clinically significant degree. This increase in concentration of ethinylestradiol should be taken into account at the choice of the corresponding oral contraceptive for simultaneous use with Arkoksia®. The similar fact can lead to increase in frequency of a thromboembolism, due to increase in exposure of ethinylestradiol. Significant pharmacokinetic interaction with GKS is not revealed.

The Etorikoksib does not influence AUC0-24 in an equilibrium state or digoxin elimination. At the same time, эторикоксиб raises Cmax (on average for 33%) that can matter at digoxin overdose development.

The concomitant use of Arkoksia® and rifampicin (the powerful inductor of hepatic metabolism) leads to decrease by 65% of AUC of an etorikoksib in plasma. This interaction should be considered at co-administration of Arkoksia® with rifampicin.

Antacids and кетоконазол (powerful CYP3A4 inhibitor) have no clinically significant effect on pharmacokinetics of Arkoksia®.

Contraindications:

— a full or incomplete combination of bronchial asthma, the nose recuring a polypose or okolonosovy bosoms and intolerance of acetylsalicylic acid and other NPVS (including in the anamnesis);

— erosive and ulcer changes of a mucous membrane of a stomach or duodenum, active gastrointestinal bleeding, cerebrovascular or other bleeding;

— inflammatory diseases of intestines (a disease Krone, nonspecific ulcer colitis) in an aggravation phase;

— hemophilia and other disturbances of coagulability of blood;

— the expressed heart failure (the II-IV functional classes on NYHA classification);

— the expressed liver failure (more than 9 points on a scale of Chayld-Pyyu) or an active disease of a liver;

— a renal failure of heavy degree (KK less than 30 ml/min.), the progressing diseases of kidneys, the confirmed hyperpotassemia;

— the period after performing aortocoronary shunting; diseases of peripheral arteries, cerebrovascular diseases, clinically expressed ischemic heart disease;

— with firmness the remaining ABP values exceeding 140/90 mm of mercury. at uncontrollable arterial hypertension;

— pregnancy;

— period of a lactation (breastfeeding);

— children's age up to 16 years;

— hypersensitivity to any component of drug.

With care use drug in the presence of anamnestic data on development of a canker of a GIT, Helicobacter pylori infection, at elderly people, at patients, it is long the using NPVS often taking alcohol at heavy somatopathies, дислипидемии / lipidemias, at a diabetes mellitus, arterial hypertension, hypostases and a delay of liquid, smoking, patients with KK have less than 60 ml/min., at the accompanying therapy by the following medicines: anticoagulants (for example, warfarin), antiagregant (for example, acetylsalicylic acid, klopidogrely), GKS (for example, Prednisolonum), selective serotonin reuptake inhibitors (for example, tsitalopramy, fluoxetine, paroksetiny, sertraline).

Overdose:

In clinical tests about overdose of Arkoksia® it was not reported. In clinical tests a single dose of Arkoksia® in a single dose to 500 mg or multiple dose to 150 mg/days within 21 days did not cause essential toxic effects.

Symptoms: at overdose of drug emergence of undesirable effects from a GIT is possible, cardiovascular system and kidneys.

Treatment: carry out symptomatic therapy. The Etorikoksib is not removed at a hemodialysis, removal of drug at peritoneal dialysis was not studied.

Storage conditions:

Drug should be stored in the place, unavailable to children, at a temperature not above 30 °C. A period of validity - 3 years not to use after a period of validity.

Issue conditions:

According to the recipe

Packaging:

7 pieces - blisters (1) - packs cardboard.
7 pieces - blisters (4) - packs cardboard.