Arcoxia, 60 mg 28 pcs

Pharmgroup: NSAIDs. A highly selective COX-2 inhibitor.

Pharmaceutical action: Arcoxia – NSAID. A selective COX-2 inhibitor, in therapeutic concentrations blocks the formation of prostaglandins and has anti-inflammatory, analgesic and antipyretic effects. Selective inhibition of COX-2 is accompanied by a decrease in the severity of clinical symptoms associated with the inflammatory process, with no effect on platelet function and gastrointestinal mucosa.

Etoricoxib has a dose-dependent effect of COX-2 inhibition with no effect on COX-1 when used in daily doses up to 150 mg. Arcoxia® has no effect on the production of prostaglandins in the gastric mucosa and on bleeding time. In the conducted studies, no reduction in arachidonic acid and collagen-induced platelet aggregation was observed.

Pharmacokinetics:

absorption

After oral administration it is quickly absorbed from the GI tract. Bioavailability when taken orally is about 100%. After oral administration in adults on an empty stomach at a dose of 120 mg, Cmax is 3.6 mcg/ml, time to reach Cmax -1 hour after intake.

Eat intake has no significant effect on the intensity and absorption rate of etoricoxib when taken in a dose of 120 mg. At the same time there is a decrease in Cmax values by 36% and increase in Tmax by 2 h.

The administration of antacids does not affect the pharmacokinetics of the drug.

Distribution

The geometric mean AUC0-24 was 37.8 µg × h/mL. The pharmacokinetics of etoricoxib within therapeutic doses is linear.

Binding to plasma proteins exceeds 92%. Vd in equilibrium is about 120 l. Etoricoxib penetrates through the placental and blood-brain barrier.

Metabolism

Intensively metabolized in the liver, with the participation of cytochrome P450 isoenzyme (CYP) and the formation of 6-hydroxymethyl etoricoxib. Five metabolites of etoricoxib have been detected, the main ones being 6-hydroxymethyl-etoricoxib and its derivative, 6-carboxy acetyl-etoricoxib. The main metabolites have no effect on COX-1 and are inactive or inactive against COX-2.

Elimation

Elimation of etoricoxib occurs as metabolites by the kidneys. Less than 1% of the drug is excreted unchanged in the urine.

In a single intravenous administration of a labeled radioactive drug containing etoricoxib at a dose of 25 mg to healthy volunteers, it has been demonstrated that 70% of the drug is excreted through the kidneys, 20% – through the intestine, mostly as metabolites. Less than 2% was found unchanged.

The equilibrium state is reached after 7 days at a daily dose of 120 mg, with a cumulation factor of about 2, which corresponds to a T1/2 of about 22 hours. Plasma clearance is approximately 50 ml/min.

Pharmacokinetics in special clinical cases

There are no pharmacokinetic differences in men and women.

Pharmacokinetics in the elderly (65 years and older) are comparable to those in 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 of etoricoxib.

In patients with mild hepatic impairment (Child-Pugh score 5-6) a single administration of etoricoxib at a dose of 60 mg/day was accompanied by an increase in AUC by 16% compared to healthy subjects.
In patients with moderate hepatic impairment (Child-Pugh score 7-9) who received the drug in a dose of 60 mg every other day, the AUC value was the same as in healthy subjects who took the drug daily in the same dose.

There are no data from clinical and pharmacokinetic studies in patients with severe hepatic impairment (more than 9 points on the Child-Pugh scale).

The pharmacokinetic parameters of a single dose of etoricoxib 120 mg in patients with moderate to severe renal impairment and with end-stage chronic renal disease (CKD) on hemodialysis were not significantly different from those in healthy subjects. Hemodialysis had little effect on excretion (dialysis clearance was about 50 ml/min).

The pharmacokinetic parameters of etoricoxib in children younger than 12 years have not been studied. In comparative pharmacokinetic studies we obtained comparable data when using etoricoxib in the group of adolescents (from 12 to 17 years old) with body weight of 40-60 kg at a dose of 60 mg/day, in a similar age group and with body weight over 60 kg – 90 mg/day, and in adults when taking 90 mg/day.

Indications

Rheumatoid arthritis, Osteoarthritis, Osteoarthritis, Arthritis, Gout

Symptomatic therapy for the following diseases and conditions:

• Osteoarthritis.
• Rheumatoid Arthritis.
• Ankylosing Spondylitis.
• Pain and inflammatory symptoms associated with acute gouty arthritis.
• The treatment of moderate to severe acute pain after dental surgery.

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Active ingredient

Etoricoxib

Composition

1 tablet contains:

Active substance:

Etoricoxib – 60 mg.

Associates:

Calcium hydrophosphate;

Cellulose microcrystalline;

Croscarmellose sodium;

Magnesium stearate.

Coating composition:

Opadray II green 39K11520;

Carnauba wax.

The composition of the film coating:

Lactose monohydrate, hypromellose,

Titanium dioxide, triacetin,

Aluminum varnish based on indigo carmine dye (E132),

Iron oxide yellow dye (E172).

How to take, the dosage

The drug is taken orally, regardless of meals, with a small amount of water.

In osteoarthritis the recommended dose is 60 mg once daily. The daily dose in osteoarthritis should not exceed 60 mg.

In rheumatoid arthritis and ankylosing spondylitis the recommended dose is 90 mg once daily. The daily dose in rheumatoid arthritis and ankylosing spondylitis should not exceed 90 mg.

In acute gouty arthritis, the recommended dose in the acute period is 120 mg once daily. The daily dose in acute gouty arthritis should not exceed 120 mg.

The duration of use of the drug in a dose of 120 mg is not more than 8 days. The minimum effective dose should be used for the shortest possible course.

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

Acute pain after dental surgery: the recommended dose is 90 mg once daily. In treatment of acute pain, Arcoxia® should be used only in acute symptomatic period, limited by duration not more than 8 days. Daily dose for pain relief after dental surgery should not exceed 90 mg.

In patients with hepatic impairment (Child-Pugh score 5-9), it is recommended that the daily dose of 60 mg not be exceeded.

Interaction

Pharmacodynamic interaction

In patients receiving warfarin, Arcoxia® at a dose of 120 mg/day was associated with an increase of approximately 13% in MHO and prothrombin time. In patients receiving warfarin or similar drugs, MHO values should be monitored at the start of therapy or change of the dosing regimen of Arcoxia®, especially in the first few days.

There are reports that non-selective NSAIDs and selective COX-2 inhibitors may weaken the hypotensive effect of ACE inhibitors. This interaction should be taken into account when treating patients taking Arcoxia® simultaneously with ACE inhibitors. In patients with impaired renal function (e.g., in dehydration or elderly patients) this combination may aggravate functional renal failure.

Arcoxia® may be used concomitantly with acetylsalicylic acid at low doses intended for prevention of cardiovascular disease. However, concomitant administration of low-dose acetylsalicylic acid and Arcoxia® may result in an increased incidence of GI ulceration and other complications compared to administration of Arcoxia® alone. After reaching equilibrium, administration of etoricoxib at a dose of 120 mg once daily has no effect on the antiplatelet activity of low-dose acetylsalicylic acid (81 mg/day). The drug does not replace the prophylactic effect of acetylsalicylic acid in cardiovascular diseases.

Cyclosporine and tacrolimus increase the risk of nephrotoxicity with Arcoxia®.

Pharmacokinetic interaction

There is evidence that non-selective NSAIDs and selective COX-2 inhibitors may increase the plasma concentration of lithium. This interaction must be taken into consideration when treating patients who take Arcoxia® concomitantly with lithium.

Two studies investigated the effects of Arcoxia® in doses of 60, 90 and 120 mg once daily for seven days in patients who received once weekly methotrexate in doses of 7.5 to 20 mg for rheumatoid arthritis. Arcoxia® at doses of 60 and 90 mg had no effect on plasma concentrations (AUC) and renal clearance of methotrexate. In one study, Arcoxia® at a dose of 120 mg had no effect on plasma concentrations (AUC) and renal clearance of methotrexate. In another study, Arcoxia® at a dose of 120 mg increased plasma concentration of methotrexate by 28% (by AUC) and decreased renal clearance of methotrexate by 13%. When concomitant administration of Arcoxia® in doses above 90 mg/day and methotrexate, the possible occurrence of toxic effects of methotrexate should be monitored.

Peroral contraceptives: taking Arcoxia® in a dose of 120 mg with oral contraceptives containing 35 mcg of ethinylestradiol and 0.5 to 1 mg of norethindrone for 21 days, simultaneously or 12 hours apart, increases the steady-state AUC0-24 of ethinylestradiol by 50-60%. However, norethisterone concentrations are not usually increased to a clinically significant degree. This increase in ethinylestradiol concentration should be taken into account when choosing an appropriate oral contraceptive for concomitant use with Arcoxia®. Such a fact may lead to an increased incidence of thromboembolism, due to increased exposure to ethinylestradiol. No significant pharmacokinetic interaction with GCS was found.

Etoricoxib has no effect on the AUC0-24 in equilibrium or elimination of digoxin. However, etoricoxib increases Cmax (by an average of 33%), which may be important in the development of digoxin overdose.

The concomitant administration of Arcoxia® and rifampicin (a potent inducer of hepatic metabolism) leads to a 65% reduction of AUC of etoricoxib in plasma. This interaction should be considered when concomitant administration of Ancoxia® with rifampicin.

The antacids and ketoconazole (potent CYP3A4 inhibitor) have no clinically significant effect on the pharmacokinetics of Arcoxia®.

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Special Instructions

Administration of the drug Arcoxia® requires close monitoring of BP. All patients should have their BP monitored during the first two weeks of treatment and periodically thereafter.

Hep and renal function should also be monitored regularly.

The drug should be discontinued if hepatic transaminases increase 3-fold or more relative to HGH.

With increasing risk of adverse effects with increasing duration of use, the need to continue the drug and the possibility of reducing the dose should be periodically assessed.

The drug should not be used concomitantly with other NSAIDs.

The film of Arcoxia® contains a small amount of lactose; this must be considered when prescribing the drug in patients with lactase deficiency.

Impact on driving and operating machinery

At the time of treatment, caution should be exercised while driving motor transport and engaging in other potentially dangerous activities requiring increased concentration and quick psychomotor reactions. Patients who have had episodes of dizziness, drowsiness or weakness should refrain from activities requiring concentration.

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Contraindications

Symptomatic therapy of the following diseases and conditions:

• Osteoarthritis.
• Rheumatoid arthritis.
• Ankylosing spondylitis.
• Pain and inflammatory symptoms associated with acute gouty arthritis.
• The treatment of moderate to severe acute pain after dental surgery.

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Side effects

The frequency of adverse reactions is presented according to the following gradation:

• Very common (≥10%).
• Frequent (1-10%).
• Infrequent (0.1-1%).
• Rarely (0.01-0.1%).
• Very rarely (< 0.01%, including isolated cases).

From the digestive system: often – epigastric pain, heartburn, nausea, diarrhea, dyspepsia, flatulence; infrequent – bloating, belching, increased peristalsis, constipation, dry oral mucosa, gastritis, gastric or duodenal ulcer, irritable bowel syndrome, esophagitis, oral mucosa ulcers, vomiting; very rare – GI ulcers (with bleeding or perforation), hepatitis.

Nervous system disorders:often – headache, dizziness, weakness; infrequently – taste disorders, drowsiness, sleep disorders, sensory disturbances, including paresthesia/hyperesthesia, anxiety, depression, concentration disorders; very rarely – hallucinations, confusion.

Sensory organs: frequently – blurred vision, conjunctivitis, tinnitus, vertigo.

Since the urinary system: infrequent – proteinuria; very rare – renal failure, usually reversible on withdrawal of the drug.

Allergic reactions:very rarely – anaphylactic/anaphylactoid reactions, including marked BP decrease and shock.

Cardiovascular system:often – palpitations, increased BP; infrequently – hot flashes, impaired cerebral circulation, atrial fibrillation, congestive heart failure, non-specific ECG changes; myocardial infarction; very rare – hypertensive crisis.

In the respiratory system: infrequent – cough, dyspnea, nasal bleeding; very rare – bronchospasm.

Dermatological reactions:often – ecchymosis; infrequent – facial swelling, skin itching, rash; very rare – urticaria, Stevens-Johnson syndrome, Lyell syndrome.

Andinfectious complications: infrequent – gastroenteritis, infections of the upper respiratory tract, urinary tract.

Muscular system disorders:infrequent – muscle cramps, arthralgia, myalgia.

Metabolism disorders: frequent – edema, fluid retention; infrequent – changes in appetite, weight gain.

From the side of laboratory tests: often – increased activity of hepatic transaminases; infrequent – increased nitrogen in blood and urine, increased CPK activity, decreased hematocrit, decreased hemoglobin, hyperkalemia, leukopenia, thrombocytopenia, increased serum creatinine, increased uric acid; rare – increased serum sodium.

Others: frequent – flu-like syndrome; infrequent – pain in the chest.

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Overdose

No overdose of Arcoxia® has been reported in clinical trials. In clinical trials, single administration of Arcoxia® in a single dose up to 500 mg or multiple administration up to 150 mg/day over 21 days did not cause significant toxic effects.

Symptoms:In overdose of the drug, adverse effects on the gastrointestinal, cardiovascular and renal system may occur.

Treatment: conduct symptomatic therapy. Etricoxib is not excreted by hemodialysis, excretion of the drug in peritoneal dialysis has not been studied.

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Pregnancy use

The drug is contraindicated during pregnancy and lactation.

The use of the drug may adversely affect female fertility and is not recommended for women planning pregnancy.

Similarities

Kostarox, Atorika tablets, Bixitor, Etoricoxib-Teva