2010/09/21

Arcoxia

Composition, structure and packing

Tablets, film-coated green, biconvex, yablokovidnaya shape, embossed ARCOXIA 60 on one side and 200 embossed on the other.

1 tab. etorikoksib 60 mg.

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

Composition of tablet: Opadray II Green 39K11520, carnauba wax.

The composition of the shell membrane: lactose monohydrate, gipromelloza, titanium dioxide, triacetin, aluminum paint on the dye indigo (E132), color iron oxide yellow (E172).

Tablets, film-coated white, biconvex, yablokovidnaya shape, embossed ARCOXIA 90 on one side and 202 embossed on the other.

1 tab. etorikoksib 90 mg.

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

Composition of tablet: Opadray II White 39K18305, carnauba wax.

The composition of the shell membrane: lactose monohydrate, gipromelloza, titanium dioxide, triacetin.

Tablets, film-coated light-green, biconvex, yablokovidnaya shape, embossed ARCOXIA 120 on one side and 204 embossed on the other.

1 tab. etorikoksib 120 mg.

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

Composition of tablet: Opadray II Green 39K11529, carnauba wax.

The composition of the shell membrane: lactose monohydrate, gipromelloza, titanium dioxide, triacetin, aluminum paint on the dye indigo (E132), color iron oxide yellow (E172).

Clinico-pharmacological group: NSAID. Highly selective inhibitor of COX-2

Pharmacological action

NSAIDs. Selective COX-2 inhibitor, in therapeutic concentrations blocks the formation of prostaglandins and anti-inflammatory, analgesic and antipyretic effect. Selective inhibition of COX-2 is accompanied by a decrease in severity of clinical symptoms associated with inflammation, with no effect on platelet function and gastrointestinal mucosa.

Etorikoksib has a dose-dependent effect of inhibition of COX-2, not affecting the COX-1 when used in a daily dose to 150 mg. Arkoksia no effect on the production of prostaglandins in the gastric mucosa and bleeding time. Our studies were observed to reduce the level of arachidonic acid and platelet aggregation caused by collagen.

Pharmacokinetics

Absorption

After ingestion is rapidly absorbed from the gastrointestinal tract. Oral bioavailability is approximately 100%.

After taking the drug on an empty stomach in the adult dose of 120 mg Cmax of 3.6 mcg / ml, Tmax -1 h after administration.

Eating no significant effect on the severity and rate of absorption etorikoksiba when receiving a dose of 120 mg. However, the values of Cmax decreased by 36% and Tmax is increased by 2 hours

Acceptance of antacids does not affect the pharmacokinetics of the drug.

Distribution

Geometric mean AUC0-24 was 37.8 mg x hr / ml.

Pharmacokinetics etorikoksiba within the therapeutic dose is linear.

Plasma protein binding exceeds 92%. Vd in the equilibrium state is about 120 liters. Etorikoksib penetrate the placenta and the blood-brain barrier.

Metabolism

Intensively metabolized in the liver, involving cytochrome P450 isoenzyme (CYP) and the formation of 6-hydroxymethyl-etorikoksiba. There are 5 metabolites etorikoksiba, major - 6-hydroxymethyl-etorikoksib and its derivative - 6-carboxy-acetyl-etorikoksib. The main metabolites have no effect on COX-1 and completely inactive or inactive against COX-2.

Withdrawal

For a single in / introduction of healthy volunteers labeled radioactive drugs containing etorikoksib a dose of 25 mg, demonstrated that 70% of the drug eliminated through the kidneys, 20% - through the intestines, primarily in the form of metabolites. Less than 2% found in an unmodified form. Putting etorikoksiba occurs in the form of metabolites through the kidneys. Less than 1% of the drug excreted in the urine in unchanged form. The equilibrium state is reached after 7 days at a daily intake of a dose of 120 mg, with a coefficient of cumulation of about 2, which corresponds to the T1 / 2 - about 22 hours plasma clearance is approximately 50 ml / min.

Pharmacokinetics in special clinical situations

Pharmacokinetic differences between males and females available.

Pharmacokinetics in the elderly (65 years and older) comparable with that of the young, and there is no need to adjust the dose of the drug in the elderly.

Racial differences do not affect the pharmacokinetic parameters etorikoksiba. In patients with minor disorders of liver function (5-6 points on the scale of Child-Pugh) single receive etorikoksiba a dose of 60 mg / accompanied by an increase in AUC by 16% compared with healthy individuals.

In patients with moderate hepatic impairment (7-9 points on the scale of Child-Pugh), taking the drug at a dose of 60 mg every other day, the value of AUC was the same as in healthy individuals taking the drug daily in the same dose.

These clinical and pharmacokinetic studies in patients with severe hepatic impairment (more than 9 points on the scale of Child-Pugh) are absent. Pharmacokinetic parameters for single use etorikoksiba at a dose of 120 mg in patients with moderate and severe renal failure and with end stage chronic renal failure (CRF) who are on hemodialysis did not differ significantly from that of healthy people. Hemodialysis little effect on the elimination (dialysis clearance - about 50 ml / min).

Pharmacokinetic parameters etorikoksiba in children under 12 years have not been studied. In comparative pharmacokinetic studies to obtain comparable data in the application etorikoksiba a group of adolescents (12 to 17 years) with body weight 40-60 kg in a dose of 60 mg / in a similar age group and body weight over 60 kg - 90 mg, and adults when receiving 90 mg /

Statement
symptomatic treatment of respiratory diseases and conditions:
osteoarthritis;
rheumatoid arthritis;
ankylosing spondylitis;
pain and inflammatory symptoms associated with acute gouty arthritis.

Dosage regimen

The drug, taken orally, regardless of the meal, washed down with sips of water.

In osteoarthrosis the recommended dose is 60 mg 1 time / day.

In rheumatoid arthritis and ankylosing spondylitis the recommended dose is 90 mg 1 time / day.

In acute gouty arthritis recommended in acute dose of 120 mg 1 time / day.

Duration of use of the drug in a dose of 120 mg is no more than 8 days. You should use the lowest effective dose of the lowest possible short course.

The average therapeutic dose for pain syndrome is a single dose of 60 mg.

Side effect

Very often,> 10%, often -1-10%, sometimes - 0.1-1%, rare - 0.01-0.1%, very rare-less than 0.01%, including individual cases.

On the part of the digestive system: often - epigastric pain, nausea, diarrhea, dyspepsia, flatulence, and sometimes - bloating, belching, increased peristalsis, constipation, dryness of the oral mucosa, gastritis, ulcer of the gastric mucosa or duodenal ulcer, irritable bowel syndrome, oesophagitis, ulcers of the oral mucosa, vomiting, very rarely - gastrointestinal ulcers (with bleeding or perforation), hepatitis.

On the part of the nervous system: frequent - headache, dizziness, weakness; infrequently - a violation of taste, drowsiness, sleep disturbances, violations of sensitivity, including paresthesia / hyperaesthesia, anxiety, depression, concentration disturbances, and sometimes - hallucinations, confusion.

From the senses: sometimes - blurred vision, conjunctivitis, tinnitus, vertigo.

From the urinary system: sometimes - proteinuria, very rarely - renal failure, usually reversible remove the drug.

Allergic reactions: very rare - anaphylactic / anaphylactoid reactions, including a marked reduction of blood pressure and shock.

Since the cardiovascular system: often - heartbeat, increased blood pressure, sometimes - the tides, cerebrovascular accident, atrial fibrillation, congestive heart failure, nonspecific ECG changes, myocardial infarction, very rarely - hypertensive crisis.

On the part of the respiratory system: sometimes - cough, shortness of breath, epistaxis, very rarely - bronchospasm.

Dermatological reactions: often - ecchymosis, sometimes - swollen face, itching, rash, very rare - rash, Stevens-Johnson syndrome, Lyell's syndrome. Infectious complications: sometimes - gastroenteritis, infections of the upper respiratory tract, urinary tract.

On the part of the musculoskeletal system: sometimes - muscle cramps, arthralgia, myalgia.

From the endocrinological system: often - edema, fluid retention, sometimes - changes in appetite, increase body weight.

From the laboratory tests: often - increase in liver transaminases; sometimes - increase of nitrogen in the blood and urine, increased activity of CK, lower hematocrit, lower hemoglobin, hyperkalemia, leukopenia, thrombocytopenia, increased serum creatinine, increase of uric acid often - increasing the sodium serum.

Other: often - flu-like syndrome, sometimes - pain in the chest.

Contraindications
complete or incomplete combination of bronchial asthma, recurrent nasal polyposis, or paranasal sinuses and intolerance of aspirin and other NSAIDs (including history);
erosive and ulcerative changes in gastric mucosa or duodenal ulcer;
active gastrointestinal bleeding;
cerebrovascular or other bleeding;
inflammatory bowel disease (Crohn's disease, ulcerative colitis) in acute;
haemophilia and other bleeding disorders;
severe heart failure (II-IV functional classes NYHA);
severe hepatic insufficiency (more than 9 points on the scale of Child-Pugh) or active liver disease;
severe renal insufficiency (CC less than 30 ml / min), advanced kidney disease, confirmed by hyperkalaemia;
period after coronary artery bypass grafting, peripheral arterial disease, cerebrovascular disease, symptomatic coronary heart disease;
stubbornly persistent BP values exceeding 140/90 mm Hg. Art. with uncontrolled hypertension;
pregnancy
Lactation (breastfeeding);
Children age 16 years;
Hypersensitivity to any component of the drug.

Precautions used drug in the presence of anamnestic data on the development of ulcerative lesions gastrointestinal infection Helicobacter pylori, in the elderly, patients have used NSAIDs for a long time, often alcohol drinkers, with severe somatic diseases, dyslipidemia / hyperlipidemia, diabetes mellitus, hypertension, swelling and fluid retention, smoking, in patients with CC than 60 ml / min, with concomitant therapy following drugs: anticoagulants (eg warfarin) antiagregantami (eg, acetylsalicylic acid, clopidogrel), GCS (eg, prednisolone), a selective inhibitor serotonin reuptake (eg, citalopram, fluoxetine, paroxetine, sertraline). Patients with hepatic insufficiency (5-9 points on a scale Child-Pugh) do not exceed recommended daily dose of 60 mg.

Pregnancy and lactation

The drug is contraindicated during pregnancy and lactation. Use of the drug may negatively affect women's fertility and is not recommended to women planning a pregnancy.

Application for violations of liver function

Contraindicated in severe hepatic insufficiency (more than 9 points on the scale of Child-Pugh) or active liver disease. Patients with hepatic insufficiency (5-9 points on a scale Child-Pugh) do not exceed recommended daily dose of 60 mg.

Application for violations of renal function

Contraindicated in severe renal insufficiency (CC less than 30 ml / min) and progressive kidney disease. With caution used in patients with CC than 60 ml / min.

Cautions

Dosage Arkoksia requires careful control of blood pressure. All patients in the appointment of the drug should be blood pressure monitoring during the first two weeks of treatment and periodically thereafter.

You should also regularly monitor indicators of liver and kidney.

In the case of increase in liver transaminases 3 times and more on FHG drug should be withdrawn.

Given the increase in the risk of adverse effects with increasing duration of admission is necessary to periodically assess the need to continue taking the drug and the possibility of reducing the dose.

You should not use the drug in conjunction with other NSAIDs.

Оболочка препарата Аркоксиа содержит лактозу в незначительном количестве, что следует учитывать при назначении препарата больным с лактазной недостаточностью.

Effects on ability to drive vehicles and management mechanisms

During the period of treatment must be careful when driving and busy with other potentially hazardous activities that require high concentration and speed of psychomotor reactions. Patients in whom there were episodes of dizziness, drowsiness or weakness, should refrain from classes that require concentration.

Overdose

In clinical trials on overdose Arkoksia not reported. In clinical trials of acute administration Arkoksia a single dose of 500 mg or multiple reception of up to 150 mg for 21 days did not cause significant toxic effects.

Symptoms: an overdose of the drug may cause harmful effects from the gastrointestinal tract, cardiovascular system and kidneys.

Treatment: perform symptomatically. Etorikoksib not appear in hemodialysis, elimination of the drug in peritoneal dialysis has not been studied.

Drug Interactions

Pharmacodynamic interaction

In patients receiving warfarin, reception Arkoksia a dose of 120 mg / accompanied by an increase of approximately 13% of international normalized ratio (MHO) and prothrombin time. In patients receiving warfarin or similar drugs should be monitored indicators MHO during the beginning of therapy or changing dosage regimen Arkoksia, especially in the first few days.

There are reports that nonselective NSAIDs and selective Cox-2 inhibitors may reduce the hypotensive effect of ACE inhibitors. This interaction should be taken into account when treating patients receiving Arokoksia concurrently with ACE inhibitors. In patients with impaired renal function (eg, dehydration, or old age) this combination could exacerbate the functional insufficiency of the kidneys.

Arkoksia can be used simultaneously with acetylsalicylic acid in low doses for prevention of cardiovascular diseases. However, co-administration of acetylsalicylic acid in low doses and Arkoksia may lead to an increase in the frequency of canker and other gastrointestinal complications compared with the reception of one Arkoksia. After reaching the equilibrium state reception etorikoksiba in a dose of 120 mg 1 time / does not affect the antiplatelet activity of aspirin in low doses (81 mg). The drug does not replace the prophylactic effect of aspirin in cardiovascular diseases. Cyclosporine and tacrolimus increase the risk of nephrotoxicity in the background of reception Arkoksia.

Pharmacokinetic interaction

Data are available that nonselective NSAIDs and selective Cox-2 inhibitors can increase the concentration of lithium in plasma. This interaction should be taken into account when treating patients receiving Arkoksia simultaneously with lithium. In two studies examining the effects of Arkoksia at a dose of 60, 90 and 120 mg 1 time / seven days in patients receiving a weekly dose of methotrexate, 7.5 to 20 mg about rheumatoid arthritis. Arkoksia a dose of 60 and 90 mg did not influence the plasma concentration (by AUC) and renal clearance of methotrexate. In one study Arkoksia a dose of 120 mg did not influence the plasma concentration (by AUC) and renal clearance of methotrexate. In another study Arkoksia a dose of 120 mg increased the concentration of methotrexate in plasma by 28% (for AUC) and reduced the renal clearance of methotrexate by 13%. At the same time appointing Arkoksia at doses above 90 mg and methotrexate should be monitored for possible appearance of toxic effects of methotrexate. Oral contraceptives: Arkoksia receive a dose of 120 mg with oral contraceptives containing 35 mcg ethinyl estradiol and from 0.5 to 1 mg noretindrona within 21 days, simultaneously or with a difference of 12 h increases the steady-state AUC0-24 of ethinyl estradiol by 50-60%. However, the concentration of norethisterone usually not increased to clinically significant degree. This increase in the concentration of ethinyl estradiol should be taken into account when selecting an appropriate oral contraceptive for the simultaneous application of Arkoksia. This fact may lead to an increase in the frequency of thromboembolism by increasing the exposure of ethinyl estradiol. Significant pharmacokinetic interaction with SCS were detected.

Etorikoksib no effect on the AUC0-24 in the equilibrium state or elimination of digoxin. However, etorikoksib increases Cmax (an average of 33%), which may be relevant in the development of an overdose of digoxin.

Simultaneous reception Arkoksia and rifampicin (a potent inducer of hepatic metabolism) leads to a decrease of 65% AUC etorikoksiba in plasma. This interaction should be taken into account while appointing Arkoksia with rifampicin.

Antacids and ketoconazole (a potent inhibitor of CYP3A4) did not have a clinically significant effect on the pharmacokinetics Arkoksia.

Terms and Conditions of storage

The drug should be stored out of reach of children at or above 30 ° C.

Shelf life - 2 years, do not use after the expiry date.