Pharmacological action Arcoxia 60 mg
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 the severity of clinical symptoms associated with inflammation, with no effect on platelet function and gastrointestinal mucosa.
Etoricoxib has a dose-dependent effect of inhibition of COX-2 without affecting COX-1 when used in a daily dose of 150 mg. Arcoxia does not affect the production of prostaglandins in the gastric mucosa and bleeding time. In the studies there was no reduction levels of arachidonic acid and platelet aggregation induced by collagen.
Pharmacokinetics Arcoxia 60 mg
Absorption
After oral administration, rapidly absorbed from the gastrointestinal tract. Oral bioavailability is approximately 100%. After taking the drug on an empty stomach in adults a dose of 120 mg Cmax of 3.6 mcg / ml, Tmax -1 h after administration.
Food intake has no significant effect on the magnitude and rate of absorption Etoricoxib when taking 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
The geometric mean AUC0-24 value was 37.8 ug x hr / ml. Pharmacokinetics Etoricoxib within the therapeutic dose is linear.
Plasma protein binding exceeds 92%. Vd at steady state is about 120 liters. Etoricoxib crosses the placental and blood brain barrier.
Metabolism
Extensively metabolized in the liver, involving cytochrome P450 isoenzyme (CYP) and the formation of 6-hydroxymethyl-etorikoksiba. There are 5 Etoricoxib metabolites, the main – to 6-hydroxymethyl-etoricoxib and its derivative – the 6-carboxy-acetyl-etoricoxib. The main metabolites do not affect COX-1 and completely inactive or inactive against COX-2.
Breeding
Withdrawal Etoricoxib occurs in the form of metabolites via the kidneys. Less than 1% of the drug is excreted in the urine in unchanged form.
For a single / in the introduction to healthy volunteers radiolabelled preparation containing etoricoxib 25 mg, demonstrated that 70% of the drug eliminated via the kidneys, 20% – through the intestines, primarily in the form of metabolites. Less than 2% found in an unmodified form.
The equilibrium state is reached after 7 days at a daily intake of 120 mg, with a coefficient of cumulation of about 2, which corresponds to the T1 / 2 – about 22 h. The 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) 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 Etoricoxib.
In patients with minor liver dysfunction (5-6 points on the scale of Child-Pugh) Etoricoxib single dose of 60 mg / day. 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 people taking the drug daily in the same dose.
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 Etoricoxib a dose of 120 mg in patients with moderate to severe renal insufficiency and end-stage chronic renal failure (CRF) on hemodialysis did not differ significantly from that of healthy individuals. Hemodialysis has little effect on the elimination (dialysis clearance – about 50 ml / min).
Pharmacokinetic parameters Etoricoxib in children younger than 12 years have not been studied. Comparative pharmacokinetic studies obtained comparable data in the application Etoricoxib in a group of teenagers (12 to 17 years) weighing 40-60 kg 60 mg / day. In a similar age group and body weight over 60 kg – 90 mg / day. And adults when taking 90 mg / day.
Indications for use of the drug Arcoxia 60 mg
Symptomatic treatment of diseases and conditions following:
- Osteoarthritis;
- Rheumatoid arthritis;
- Ankylosing spondylitis;
- Pain and inflammatory symptoms associated with acute gouty arthritis.
Dosage regimen Arcoxia 60 mg
The drug is taken orally, regardless of the meal, washed down with sips of water.
Osteoarthritis 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 in the acute period recommended dose is 120 mg 1 time / day.
The duration of use of the drug at a dose of 120 mg is no more than 8 days. You should use the minimum effective dose, short-course low as possible.
The average therapeutic dose of the pain syndrome is a single dose of 60 mg.
In patients with hepatic impairment (5-9 points on the Child-Pugh) do not exceed the recommended daily dose of 60 mg.
Side effect Arcoxia 60 mg
The incidence of adverse reactions is presented in accordance with the following gradation: very common (> 10%), common (1-10%), sometimes (0.1-1%), rare (0.01-0.1%), very rare (
From the digestive system: common – epigastric pain, nausea, diarrhea, dyspepsia, flatulence, and sometimes – bloating, belching, increased peristalsis, constipation, dry oral mucosa, gastritis, ulcers, gastric mucosal or duodenal ulcer, irritable bowel syndrome, esophagitis, ulceration of the mucous membranes of the mouth, vomiting, very rarely – GI ulcers (bleeding or perforation), hepatitis.
The nervous system: common – headache, dizziness, weakness, and sometimes – taste disturbance, drowsiness, sleep disturbances, sensory disturbances, including paresthesia / hyperesthesia, anxiety, depression, poor concentration, very rarely – hallucinations, confusion.
From the senses: sometimes – blurred vision, conjunctivitis, tinnitus, vertigo.
Urinary system: sometimes – proteinuria is very rare – kidney failure, usually reversible remove the drug.
Allergic reactions: very rare – anaphylactic / anaphylactoid reactions, including a marked reduction of blood pressure and shock.
Cardio-vascular system: common – rapid heartbeat, increased blood pressure, and sometimes – flushing, cerebrovascular accident, atrial fibrillation, congestive heart failure, nonspecific ECG changes, myocardial infarction, very rarely – a hypertensive crisis.
The respiratory system: sometimes – cough, shortness of breath, nasal bleeding, and very rarely – bronchospasm.
Dermatological reactions: often – ecchymosis, and sometimes – swelling of the face, itching, rash, very rare – rash, Stevens-Johnson syndrome, Lyell’s syndrome.
Infection: Sometimes – gastroenteritis, infections of upper respiratory tract, urinary tract.
On the part of the musculoskeletal system: sometimes – muscle cramps, arthralgia, myalgia.
From a metabolism: often – edema, fluid retention, and sometimes – changes in appetite, weight gain.
From the laboratory studies: common – elevated liver enzymes, and sometimes – increase of nitrogen in the blood and urine, increased activity of creatine kinase, decreased hematocrit, decreased hemoglobin, hyperkalemia, leukopenia, thrombocytopenia, increased serum creatinine, increase of uric acid, rarely – increased sodium serum.
Other: Frequent – flu-like symptoms, and sometimes – pain in the chest.
Contraindications to the use of the drug Arcoxia 60 mg
- Full or partial combination of asthma, recurrent nasal polyposis or sinusitis and intolerant of aspirin and other NSAIDs (including history);
- Erosive and ulcerative changes in the mucous membrane of the stomach or duodenum, active gastrointestinal bleeding, cerebrovascular bleeding or other;
- Inflammatory bowel disease (Crohn’s disease, ulcerative colitis) in acute phase;
- Hemophilia and other bleeding disorders;
- Severe heart failure (II-IV functional classes according to the classification NYHA);
- Severe hepatic impairment (more than 9 points on the Child-Pugh) or active liver disease;
- Renal failure, severe (creatinine clearance below 30 ml / min), advanced kidney disease, hyperkalemia confirmed;
- The period after coronary artery bypass surgery, peripheral arterial disease, cerebrovascular disease, symptomatic coronary artery disease;
- Steadfastly remaining BP values exceeding 140/90 mm Hg. Art. with uncontrolled hypertension;
- Pregnancy
- Lactation (breastfeeding);
- Children up to age 16 years;
- Hypersensitivity to any component of the drug.
With careful use of the drug in the presence of anamnestic data on the development of ulcerative lesions gastrointestinal infection Helicobacter pylori, the elderly, in patients who have used NSAIDs for a long time, often using alcohol, with severe somatic diseases, dyslipidemia / hyperlipidemia, diabetes, hypertension, edema and fluid retention, smoking, in patients with CC than 60 ml / min, with concomitant therapy following drugs: anticoagulants (eg warfarin), antiplatelet (eg aspirin, clopidogrel), corticosteroids (eg prednisone), selective inhibitors SSRIs (eg citalopram, fluoxetine, paroxetine, sertraline).
Use of the drug Arcoxia 60 mg during pregnancy and lactation
The drug is contraindicated during pregnancy and lactation.
Use of the drug may negatively affect female fertility and is not recommended for women planning pregnancy.
Use in hepatic dysfunction Arcoxia 60 mg
Contraindicated in severe hepatic impairment (more than 9 points on a scale of Child-Pugh) or active liver disease. In patients with liver failure (5-9 scores Child-Pugh) do not exceed the recommended daily dose of 60 mg.
Use in renal impairment Arcoxia 60 mg
Contraindicated in severe renal insufficiency (creatinine clearance below 30 ml / min) and progressive kidney disease. Used with caution in patients with CC than 60 ml / min.
Cautions Arcoxia 60 mg
Taking medication Arcoxia requires careful monitoring 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 the performance of liver and kidney function.
In the case of an increase in liver transaminases 3 times ULN and more about the drug should be discontinued.
Given the increased risk of adverse effects with increasing duration of administration should be periodically assess the need to continue taking the drug and the possibility of reducing the dose.
Do not administer concurrently with other NSAIDs.
The shell of the drug Arcoxia contains lactose in small amounts that should be considered when a drug in patients with lactase deficiency.
Effects on ability to drive and control mechanisms
During the period of treatment must be careful when driving lesson and other potentially hazardous activities that require your full attention and psychomotor speed of reaction. Patients, all of whom had episodes of dizziness, drowsiness or weakness, should refrain from activities that require concentration.
Overdose Arcoxia 60 mg
In clinical trials on overdose Arcoxia have been reported. In clinical trials of single dose Arcoxia in a single dose of 500 mg or multiple reception up to 150 mg / day. for 21 days did not cause significant toxic effects.
Symptoms: When a drug overdose, may cause harmful effects on the gastrointestinal tract, cardiovascular system and kidneys.
Treatment: symptomatic therapy. Etoricoxib does not appear in hemodialysis, elimination of the drug in peritoneal dialysis has not been studied.
Drug Interactions Arcoxia 60 mg
Pharmacodynamic interactions
In patients receiving warfarin, reception Arcoxia at a dose of 120 mg / day. accompanied by an increase of about 13% MHO and prothrombin time. In patients receiving warfarin or similar drugs should be monitored indicators MHO during initiation of therapy or change the dosage Arcoxia particularly in the first few days.
There are reports that non-selective NSAIDs and COX-2 inhibitors may reduce the antihypertensive effect of ACE inhibitors. This interaction should be taken into account when treating patients receiving Arcoxia in conjunction with ACE inhibitors. In patients with impaired renal function (eg, dehydration or in old age) this combination may increase the functional renal insufficiency.
Arcoxia can be used simultaneously with aspirin in low doses for the prevention of cardiovascular disease. However, the concurrent use of aspirin in low doses and Arcoxia may increase the frequency of ulcerative lesions, and other gastrointestinal complications compared with taking one Arcoxia. After reaching the equilibrium state Etoricoxib reception at a dose of 120 mg 1 time / day. does not affect the antiplatelet activity of aspirin in low doses (81 mg / day).. The drug does not replace the preventive action of aspirin in cardiovascular diseases. Cyclosporine and tacrolimus increase the risk of nephrotoxicity in patients receiving Arcoxia.
Pharmacokinetic interactions
There is evidence that non-selective NSAIDs and selective COX-2 inhibitors may increase the concentration of lithium in plasma. This interaction should be taken into account when treating patients receiving Arcoxia simultaneously with lithium.
Two studies examined the effects Arcoxia at a dose of 60, 90 and 120 mg 1 time / day. within seven days in patients receiving a weekly methotrexate at a dose of 7.5 to 20 mg about rheumatoid arthritis. Arcoxia at a dose of 60 and 90 mg had no effect on plasma concentration (for AUC) and renal clearance of methotrexate. In one study Arcoxia at a dose of 120 mg had no effect on plasma concentration (for AUC) and renal clearance of methotrexate. In another study Arcoxia at 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%. While the appointment Arcoxia at doses above 90 mg / day. and methotrexate should be monitored for possible appearance of toxic effects of methotrexate.
Oral contraceptives: Taking Arcoxia 120 mg with oral contraceptives containing 35 mcg ethinyl estradiol and 0.5 to 1 mg norethindrone for 21 days, at the same time or a difference of 12 hours increases the steady-state AUC0-24 of ethinyl estradiol by 50-60% . However, the concentration of norethisterone is usually not increased to a clinically significant degree. This increase in the concentration of ethinyl estradiol to 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.
Etoricoxib does not affect the AUC0-24 at steady state or elimination of digoxin. However, etoricoxib increased Cmax (an average of 33%), which may be relevant to the development of an overdose of digoxin.
Simultaneous reception Arcoxia 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 Arcoxia with rifampicin.
Antacids and ketoconazole (a potent inhibitor of CYP3A4) did not have a clinically significant effect on the pharmacokinetics Arcoxia.
