ARKOKSIA

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Active material: etoricoxib
When ATH: M01AH05
CCF: NSAIDs. Highly selective COX-2 inhibitor
ICD-10 codes (testimony): M05, M07, M15, M45
When CSF: 05.01.01.08.01
Manufacturer: MERCK SHARP & DOHME B.V. (Netherlands)

Pharmaceutical form, composition and packaging

Pills, Film-coated green color, lenticular, apple-shaped, Embossed “ARCOXIA 60” on one side, and embossed “200” – another.

	1 tab.
etoricoxib	60 mg

Excipients: calcium hydrogen phosphate, microcrystalline cellulose, Croscarmellose sodium, magnesium stearate.

The composition of the shell: Opadry II green 39K11520, carnauba wax.
The composition of the coating film: lactose monohydrate, gipromelloza, Titanium dioxide, triacetine, aluminum lake dye indigo carmine (E132), dye iron oxide yellow (E172).

2 PC. – blisters (1) – packs cardboard.
2 PC. – blisters (2) – packs cardboard.
4 PC. – blisters (1) – packs cardboard.
4 PC. – blisters (2) – packs cardboard.
7 PC. – blisters (1) – packs cardboard.
7 PC. – blisters (2) – packs cardboard.
14 PC. – blisters (1) – packs cardboard.
14 PC. – blisters (2) – packs cardboard.

Pills, Film-coated white, lenticular, apple-shaped, Embossed “ARCOXIA 90” on one side, and embossed “202” – another.

	1 tab.
etoricoxib	90 mg

Excipients: calcium hydrogen phosphate, microcrystalline cellulose, Croscarmellose sodium, magnesium stearate.

The composition of the shell: Opadry II White 39K18305, carnauba wax.
The composition of the coating film: lactose monohydrate, gipromelloza, Titanium dioxide, triacetine.

Pills, Film-coated light green, lenticular, apple-shaped, Embossed “ARCOXIA 120” on one side, and embossed “204” – another.

	1 tab.
etoricoxib	120 mg

Excipients: calcium hydrogen phosphate, microcrystalline cellulose, Croscarmellose sodium, magnesium stearate.

The composition of the shell: Opadry II green 39K11529, carnauba wax.
The composition of the coating film: lactose monohydrate, gipromelloza, Titanium dioxide, triacetine, aluminum lake dye indigo carmine (E132), dye iron oxide yellow (E172).

Pharmacological action

NSAIDs. Selective COX-2 inhibitor, At 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 inhibiting COX-2, without affecting the COX-1 for use in a daily dose of up to 150 mg. Arkoksia^® no effect on production of prostaglandins in the gastric mucosa and bleeding time. In studies to date have been observed reduction of arachidonic acid and platelet aggregation, collagen-induced.

Pharmacokinetics

Absorption

After ingestion is rapidly absorbed from the gastrointestinal tract. Oral bioavailability is about 100%. After taking the drug on an empty stomach in the adult dose 120 mg C_max is 3.6 ug / ml, T_max -1 h after administration.

Food intake has no significant effect on the extent and rate of absorption etorikoksiba when receiving a dose 120 mg. However, the C_maxare down 36% and T_max increases by 2 no.

Antacids do not affect the pharmacokinetics of the drug.

Distribution

The geometric mean AUC values_0-24 made 37.8 mcg x h / ml. Pharmacokinetics etorikoksiba within the therapeutic dose is linear.

Plasma protein binding exceeds 92%. V_d at steady state is about 120 l. Etoricoxib crosses the placental and blood-brain barrier.

Metabolism

It is extensively metabolized in the liver, with the participation of cytochrome P450 isoenzyme (CYP) and the formation of 6-hydroxymethyl-etorikoksiba. Detected 5 metabolites etorikoksiba, main – 6-hydroxymethyl derivative thereof and etoricoxib – 6-carboxy-acetyl-эtorikoksib. The main metabolites have no effect on COX-1 and completely inactive or inactive against COX-2.

Deduction

Etorikoksiba Breeding takes place in the form of metabolites through the kidneys. Less 1% the drug is excreted in urine as unchanged.

With a single in / introduction of healthy volunteers labeled radioactive drugs, containing a dose etoricoxib 25 mg, demonstrated, what 70% drug is excreted through the kidneys, 20% – through the intestine, primarily as metabolites. Less 2% It found in unchanged form.

The equilibrium state is achieved after 7 days with a daily intake in a dose of 120 mg, with a coefficient of cumulation of about 2, which corresponds to T_1/2– about 22 no. The plasma clearance is approximately 50 ml / min.

Pharmacokinetics in special clinical situations

Pharmacokinetic differences between men and women are absent.

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

Racial differences do not affect the pharmacokinetic parameters etorikoksiba.

In patients with minor hepatic impairment (5-6 scores on the Child-Pugh) single dose in the dose etorikoksiba 60 mg / day, accompanied by an increase AUC by 16% compared with healthy individuals.

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

These clinical and pharmacokinetic studies in patients with severe hepatic impairment (more 9 scores on the Child-Pugh) no.

Pharmacokinetic parameters for single use at a dose of etorikoksiba 120 mg in patients with moderate to severe renal failure and end-stage renal disease (CRF), hemodialysis, They did not differ significantly from that of healthy individuals. Hemodialysis little effect on the elimination of (Dialysis clearance – about 50 ml / min).

The pharmacokinetic parameters in children under etorikoksiba 12 years have not been studied. In comparative pharmacokinetic studies obtained comparable data in the application etorikoksiba group of teenagers (from 12 to 17 years) body weight 40-60 kg dose 60 mg / day, in the same age group and body weight over 60 kg – 90 mg / day, and adults when receiving 90 mg / day.

Testimony

Symptomatic therapy of the following diseases and conditions:

- Osteoarthritis;

- Rheumatoid arthritis;

- Ankiloziruyushtiy spondylitis;

- Pain and inflammatory symptoms, associated with acute gouty arthritis.

Dosage regimen

The drug is taken orally, regardless of the meal, with a little water.

At osteoarthritis The recommended dose is 60 mg 1 time / day.

At revmatoidnom ARTHRO and ankiloziruyushtem spondylitis The recommended dose is 90 mg 1 time / day.

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

The duration of use of the drug at a dose of 120 mg is not more than 8 days. Use the minimum effective dose as low as possible short course.

The average therapeutic dose pain syndrome is once 60 mg.

Patients with hepatic insufficiency (5-9 points on the Child-Pugh) do not exceed the recommended daily dose 60 mg.

Side effect

Often >10%, often -1-10%; sometimes – 0.1-1%; rarely – 0.01-0.1%; very rare -less 0.01%, including individual cases.

From the digestive system: often – epigastric pain, nausea, diarrhea, dyspepsia, flatulence; sometimes – abdominal distention, belching, increased peristalsis, constipation, dryness of the oral mucosa, gastritis, ulcers of the mucous membrane of the stomach or duodenum, Irritable Bowel Syndrome, esophagitis, ulceration of the oral mucosa, vomiting; rarely – GI ulcers (bleeding or perforation), hepatitis.

From the nervous system: often – headache, dizziness, weakness; sometimes – taste disturbance, drowsiness, sleep disorders, sensory disturbances, incl. paresthesia / giperestezii, alarm, depression, poor concentration; rarely – hallucinations, confusion.

From the senses: sometimes – blurred vision, conjunctivitis, noise in ears, vertigo.

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

Allergic reactions: rarely – anaphylactic / anaphylactoid reaction, including a marked decrease in blood pressure and shock.

Cardio-vascular system: often – heartbeat, increased blood pressure; sometimes – tides, cerebrovascular accident, Atrial fibrillation, congestive heart failure, nonspecific ECG changes; myocardial infarction, rarely – hypertensive crisis.

The respiratory system: sometimes – cough, breathlessness, nose bleed; rarely – bronchospasm.

Dermatological reactions: often – ecchymosis; sometimes – swelling of the face, itching, rash; rarely – hives, 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.

Metabolism: often – swelling, fluid retention; sometimes – changes in appetite, weight gain.

From laboratory studies: often – increase in liver transaminases; sometimes – increasing the nitrogen in the blood and urine, Increase CPK activity, decrease in hematocrit, decrease in hemoglobin, hyperkalemia, leukopenia, thrombocytopenia, increase in serum creatinine, increase in uric acid; rarely – increase in serum sodium.

Other: often – flu-like symptoms; sometimes – chest pain.

Contraindications

- Complete or incomplete combination of bronchial asthma, recurrent nasal polyposis, or paranasal sinuses and intolerance of aspirin and other NSAIDs (incl. 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, nespetsificheskiy yazvennыy colitis) exacerbation;

- Hemophilia and other bleeding disorders;

- Severe heart failure (II-IV NYHA functional class);

- Severe hepatic impairment (more 9 points on the Child-Pugh) active liver disease or;

- Severe renal insufficiency (CC less than 30 ml / min), progressive kidney disease, confirmed hyperkalemia;

- The period after coronary artery bypass grafting; peripheral artery disease, cerebrovascular diseases, symptomatic coronary artery disease;

- To persistent BP values, exceeding 140/90 mm Hg. Article. with uncontrolled hypertension;

- Pregnancy,

- Lactation (breast-feeding);

- Children up to age 16 years;

- Hypersensitivity to any component of the drug.

FROM caution used the drug in the presence of anamnestic data on the development of ulcerative lesions GIT, Helicobacter pylori infections, the elderly, patients, long used the NSAID, frequent drinkers, with severe somatic diseases, dyslipidemia / hyperlipidemia, for patients with diabetes, hypertension, swelling and fluid retention, smoking, in patients with CC less 60 ml / min, with concomitant therapy following medicines: anticoagulants (eg, varfarinom), antiplatelet (eg, acetylsalicylic acid, klopidogrelom), GCS (eg, prednisolone), selective serotonin reuptake inhibitors (eg, tsitalopramom, fluoxetine, paroxetine, sertraline).

Pregnancy and lactation

The drug is contraindicated in pregnancy and lactation.

Use of the drug can impair female fertility and is not recommended for women, planning pregnancy.

Cautions

Taking medication Arcoxia^® It requires careful monitoring of blood pressure. All patients in the appointment of the drug should be monitoring of blood pressure during the first two weeks of treatment and periodically thereafter.

You should also regularly monitor liver function and kidney function.

In the case of elevated liver transaminases 3 times or more with respect to the drug Valium should be abolished.

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

Do not use the drug concurrently with other NSAIDs.

The shell of the drug Arcoxia^® It contains lactose in a minor amount, which should be considered when administering the drug to patients with lactase deficiency.

Effects on ability to drive vehicles and management mechanisms

During the period of treatment must be careful when driving and occupation of other potentially hazardous activities, require high concentration and speed of psychomotor reactions. Patients, who observed episodes of vertigo, drowsiness or weakness, should refrain from activities, requiring concentration of attention.

Overdose

In clinical trials on overdose Arcoxia^® not reported. In clinical trials, a single dose of Arcoxia^® in a single dose to 500 mg or multiple reception of up to 150 mg / day for 21 the day did not cause significant toxic effects.
Symptoms: an overdose of the drug may cause undesirable effects on the gastrointestinal tract, cardiovascular and renal.

Treatment: symptomatic therapy. Etoricoxib does not appear in hemodialysis, excretion of the drug in peritoneal dialysis has not been studied.

Drug Interactions

Pharmacodynamic interactions

Patients, receiving warfarin, reception Arcoxia^® dose 120 mg / day, accompanied by an increase of approximately 13% International normalized ratio (MHO) and prothrombin time. Patients, receiving warfarin or similar drugs, It should be monitored indicators MHO during the start of therapy, or change the dosage Arcoxia^®, particularly 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, taking Arcoxia^® together with an ACE inhibitor. In patients with impaired renal function (eg, or by dehydration in the elderly) this combination could exacerbate the functional renal failure.

Arkoksia^® It can be used in conjunction with acetylsalicylic acid, at low doses, for the prevention of cardiovascular diseases. However, the simultaneous appointment of acetylsalicylic acid in low doses and Arcoxia^® It may lead to an increase in the frequency of gastrointestinal ulceration or other complications compared to taking a Arcoxia^® . After reaching equilibrium etorikoksiba receiving a dose 120 mg 1 times / day did not affect the anti-platelet activity of acetylsalicylic acid in low doses (81 mg / day). The drug does not replace the prophylactic effect of aspirin in cardiovascular diseases. Cyclosporine and tacrolimus increase the risk of nephrotoxicity in patients receiving Arcoxia^®.

Pharmacokinetic interactions

There is evidence, that nonselective NSAIDs and selective COX-2 inhibitors may increase the plasma concentration of lithium. This interaction should be taken into account when treating patients, taking Arcoxia^® simultaneously with lithium.

Two studies investigated the effects of Arcoxia^® dose 60, 90 and 120 mg 1 time / day for seven days in patients, receiving 1 methotrexate once a week at a dose of 7.5 to 20 mg about rheumatoid arthritis. Arkoksia^® dose 60 and 90 mg did not affect the plasma concentration (by AUC) and renal clearance of methotrexate. In one study, Arcoxia^® dose 120 mg did not affect the plasma concentration (by AUC) and renal clearance of methotrexate. In another study Arcoxia^® dose 120 mg increased methotrexate plasma concentrations at 28% (by AUC) and reduced renal clearance of methotrexate on 13%. While appointing Arcoxia^® in doses above 90 mg / day and methotrexate should be monitored for the possible appearance of toxic effects of methotrexate.

Oral contraceptives: reception Arcoxia^® dose 120 mg with oral contraceptives, containing 35 micrograms of ethinyl estradiol and 0,5 to 1 mg norethindrone for 21 day, simultaneously or with a difference in 12 h increases fixed AUC_0-24 эtinilэstradiola of 50-60%. However, the concentration of norethisterone usually do not increase to a 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 Arcoxia^®. 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 found.

Etoricoxib does not affect the AUC_0-24in equilibrium or elimination of digoxin. At the same time, etoricoxib increases C_max (on average 33%), which may be relevant in the development of an overdose of digoxin.

Simultaneous reception Arcoxia^® and rifampicin (a potent inducer of hepatic metabolism) reduces to 65% Etorikoksiba plasma AUC. This interaction should be taken into account while appointing Arcoxia^® rifampicin.

Antacidy and ketoconazole (a strong inhibitor of CYP3A4) no clinically significant effect on the pharmacokinetics Arcoxia^®.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored out of reach of children at or above 30 ° C. Shelf life – 2 year, Do not use beyond the expiration date.

Vladimir Andreevich Didenko

1,120 10 minutes read