Description
Atorika Tabs Pharmacodynamics
When administered orally at therapeutic concentrations, etoricoxib is a selective inhibitor of cyclooxygenase-2 (COX-2). In clinical pharmacological studies, etoricoxib inhibited COX-2 in a dose-dependent manner, with no effect on COX-1 at a daily dose up to 150 mg. The drug does not inhibit the synthesis of prostaglandins in the gastric mucosa and does not affect platelet function.
Cyclooxygenase is responsible for formation of prostaglandins. Two isoforms of cyclooxygenase, COX-1 and COX-2, have been isolated. COX-2 is an isoenzyme that is induced by various proinflammatory mediators and is considered the main enzyme responsible for the synthesis of prostanoid mediators of pain, inflammation and fever. COX-2 is involved in the processes of ovulation, implantation and closure of the arterial duct, regulation of the nocicular and central nervous system function (induction of fever, sensation of pain, cognitive function), and may also play a role in the process of ulcer healing. COX-2 has been found in the tissues surrounding gastric ulcers in humans, but its importance in ulcer healing has not been established.
Efficacy
In patients with osteoarthritis (OA), etoricoxib, when administered at a dose of 60 mg once daily, provided a significant reduction in pain and improvement in patients’ assessment of their condition. These favorable effects were observed on the second day of treatment and persisted for 52 weeks. Studies of etoricoxib at a dose of 30 mg once daily (using similar evaluation methods) demonstrated efficacy compared to placebo over a treatment period of 12 weeks. In a study conducted to determine the optimal dose, etoricoxib, when used at a dose of 60 mg, demonstrated significantly greater improvement than the 30 mg dose for all three primary endpoints after 6 weeks of treatment. The 30 mg dose has not been studied in osteoarthritis of the hand joints.
In patients with rheumatoid arthritis (RA), etoricoxib, when administered at a dose of 90 mg once daily, provided a significant reduction in pain and inflammation and improved mobility. These favorable effects persisted for a treatment period of 12 weeks.
In patients with acute gouty arthritis, etoricoxib at a dose of 120 mg once daily for a full treatment period of eight days reduced moderate to severe joint pain and inflammation. The efficacy was comparable to that of indomethacin when used in a dose of 50 mg three times a day. Pain reduction was noted as early as four hours after the start of treatment.
In patients with ankylosing spondylitis, etoricoxib at a dose of 90 mg once daily provided a significant reduction in back pain, inflammation, stiffness, and improved function. The clinical efficacy of etoricoxib was observed as early as the second day of treatment and was maintained throughout the entire treatment period of 52 weeks.
In a clinical study of pain after dental surgery, etoricoxib at a dose of 90 mg was administered once a day for three days. In a subgroup of patients with moderate pain (at baseline assessment), etoricoxib had the same analgesic effect as ibuprofen at a dose of 90 mg (16.11 vs. 16.39 P=0.722), and was superior to the paracetamol/codeine combination at a dose of 600 mg/60 mg (11.00, P<0.001) and placebo (6.84, P<0.001), according to the overall first 6-hour pain reduction score (TOPAR6). The proportion of patients who required rapid-acting pain medication within the first 24 hours of taking the study drugs was 40.8% with etoricoxib at 90 mg, 25.5% with ibuprofen at 600 mg every 6 hours, and 46.7% with the paracetamol/codein combination at 600 mg/60 mg every 6 hours, compared with 76.2% in the placebo group. In this study, the median onset of action (perceived pain reduction) with etoricoxib at a dose of 90 mg was 28 minutes after drug administration.
Indications
– Symptomatic therapy of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, pain and inflammation associated with acute gouty arthritis.
– Short-term therapy for moderate acute pain after dental surgery.
Contraindications
– Hypersensitivity to any component of the drug.
– Gastric and 12 duodenal ulcer in the acute stage, active gastrointestinal bleeding.
– Complete or incomplete combination of bronchial asthma, recurrent polyposis of the nose and sinuses, and intolerance to acetylsalicylic acid or other non-steroidal anti-inflammatory drugs (including history).
– Pregnancy, breastfeeding.
– Severe hepatic impairment (serum albumin <25 g/L or >10 points on the Child-Pugh scale).
– Severe renal failure (CKR less than 30 ml/min).
– Childhood under 16 years of age.
– Inflammatory bowel disease.
– Chronic heart failure (NYHA functional class II-1V).
– Uncontrolled arterial hypertension in which BP is persistently above 140/90 mm Hg.
– Confirmed coronary heart disease, peripheral arterial disease and/or cerebrovascular disease.
– Confirmed hyperkalemia.
– Progressive renal disease.
Caution
Caution should be exercised when using the drug in the following groups of patients:
– Patients with an increased risk of gastrointestinal complications due to NSAIDs; elderly patients taking other NSAIDs, including acetylsalicylic acid, simultaneously or patients with a history of gastrointestinal diseases such as peptic ulcer disease and gastrointestinal bleeding;
– patients with a history of cardiovascular risk factors such as dyslipidemia/hyperlipidemia, diabetes mellitus, arterial hypertension, smoking, heart failure, left ventricular dysfunction, edema and fluid retention;
– Patients with mild hepatic impairment (Child-Pugh score 5-6) should not exceed 60 mg once daily, patients with moderate hepatic impairment (Child-Pugh score 7-9) should not exceed 30 mg once daily;
– Patients with dehydration;
– Patients with impaired renal function concomitantly using ACE inhibitors, diuretics, angiotensin II receptor antagonists, especially elderly;
– patients with creatinine clearance <60 ml/min;
– patients with a previous significant decrease in renal function, with impaired renal function, uncompensated heart failure or cirrhosis of the liver, who are at risk for long-term use of NSAIDs.
– concomitant therapy with anticoagulants (e.g., warfarin); antiaggregants (e.g., acetylsalicylic acid, clopidogrel); drugs metabolized by sulfotransferases.
Use in pregnancy and during breastfeeding
Pregnancy
There are no clinical data on the use of etoricoxib during pregnancy. Toxic effects on the reproductive system have been observed in animal studies. The potential risk in women during pregnancy is unknown. The use of etoricoxib, as well as other drugs that inhibit the synthesis of prostaglandins, during the last trimester of pregnancy may lead to suppression of uterine contractions and premature closure of the arterial duct.
Etoricoxib is contraindicated during pregnancy (see section “Contraindications”). If pregnancy occurs during treatment, etoricoxib should be discontinued.
Breastfeeding.
In lactating rats, etoricoxib is excreted with milk. Studies confirming excretion of etoricoxib with breast milk in women have not been conducted. Women who take etoricoxib should stop breastfeeding (see Contraindications),
Fertility .
The use of etoricoxib, as well as other drugs that inhibit COX-2 and prostaglandin synthesis, is not recommended for women who are planning to become pregnant.
Dosage and administration
- Orally, with a small amount of water, regardless of meals.
Atorika® tablets should be used in the lowest effective dose for the shortest possible course. - Osteoarthritis
The recommended dose is 30 mg once a day or 60 mg once a day.
The daily dose in osteoarthritis should not exceed 60 mg.
Rheumatoid arthritis and ankylosing spondylitis - The recommended dose is 90 mg once daily.
The minimum effective daily dose is 60 mg once daily. In some patients, a dose of 90 mg once daily may increase the therapeutic effect. - The daily dose in rheumatoid arthritis and ankylosing spondylitis should not exceed 90 mg.
- Acute gouty arthritis.
The recommended dose in the acute period is 120 mg once a day. - The duration of use of the drug in a dose of 120 mg is not more than 8 days.
- Daily dose in acute gouty arthritis should not exceed 120 mg.
- Acute pain after dental surgery
The recommended dose is 90 mg once daily. In the treatment of acute pain after dental surgery, Atorika® tabs should be used only in the acute period for not more than 3 days.
Daily dose for pain relief after dental surgery should not exceed 90 mg.
Doses higher than those recommended for each indication either have no additional efficacy or have not been studied. - Special patient groups
- Elderly patients.
No dose adjustment is required in elderly patients. As with the use of other drugs in elderly patients, caution should be exercised when using Atorika® tabs (see section “Special Precautions”). - Patients with liver dysfunction
Regardless of the indications for use, patients with mild hepatic impairment (5-6 according to Child-Pugh classification) should not exceed the dose of 60 mg once daily, patients with moderate hepatic impairment (7-9 according to Child-Pugh classification) – 30 mg once daily. - Caution is recommended when administering Atorika® tablets in patients with moderate hepatic impairment, since clinical experience with etoricoxib in this group of patients is limited. Due to the lack of clinical experience of etoricoxib administration in patients with severe hepatic impairment (>10 according to Child-Pugh classification), Atorica® tabs is contraindicated for this group of patients (see section “Pharmacological properties”, subsection “Pharmacokinetics” and sections “Contraindications” and “Cautions”).
- Patients with impaired renal function
No dose adjustment is required in patients with creatinine clearance >30 ml/min (see section “Pharmacological properties”, subsection “Pharmacokinetics”). The use of etoricoxib in patients with creatinine clearance <30 ml/min is contraindicated (see sections “Contraindications” and “Special indications”). - Children
Etricoxib is contraindicated in children and adolescents under 16 years of age (see section “Contraindications”)
