Read carefully before use
Tablets 30 mg: white round biconvex film-coated tablets debossed with “E9OX” on one side and “30” on the other side.
Tablets 60 mg: white round biconvex film-coated tablets debossed with “E9OX” on one side and “60” on the other side.
Tablets 90 mg: white round biconvex film-coated tablets debossed with “E9OX” on one side and “90” on the other side.
Tablets 120 mg: white round biconvex film-coated tablets debossed with “E9OX” on one side and “120” on the other side.
One tablet contains:
Active substance: etoricoxib 30 mg, 60 mg, 90 mg or 120 mg;
Auxiliary substances: microcrystalline cellulose, croscarmellose sodium, magnesium stearate, anhydrous calcium hydrophosphate; coating composition: hypromellose, titanium dioxide (E171), triacetin, lactose monohydrate.
Antiinflammatory and antirheumatic agents, non-steroids. Coxibs.
Etoricoxib is a medicinal product for oral administration. It is a selective cyclooxygenase-2 inhibitor (COX-2) when used within the clinical dose range.
In the course of clinical pharmacological studies, the medicinal product inhibited COX-2 dose-dependently without inhibiting COX-1 when used at a dose up to 150 mg per day. Etoricoxib does not inhibit the synthesis of gastric prostaglandins and does not affect platelets function.
Cyclooxygenase is responsible for prostaglandins formation. Two isoforms have been identified – COX-1 and COX-2. COX-2 is an isoform of the enzyme which is induced by pro-inflammatory impulses and is considered as the main factor responsible for the synthesis of prostanoid mediators of pain, inflammation and fever. COX-2 is also involved in the processes of ovulation, implantation and closure of arterial duct as well as regulation of kidney function and the central nervous system (induction of fever, sense of pain, cognitive function). It can also participate in ulcer healing. COX-2 has been identified in the tissue around a human gastric ulcer but the value for ulcer healing has not been established.
For relief of osteoarthritis (OA), rheumatoid arthritis (RA), ankylosing spondylitis, and the pain and signs of inflammation associated with acute gouty arthritis.
For short-term treatment of moderate intensity pain associated with dental surgery.
The decision to prescribe a selective COX-2 inhibitor shall rest on the assessment of all individual risks to the patient.
Artroxib medicinal product is taken orally with or without meal. The effect takes place faster if the medication is taken before meals, keep it in mind if symptoms need to be quickly relieved.
Since the risk of cardiovascular complications due to use of etoricoxib may increase as the dose and duration of use increase, minimum effective doses should be used for the shortest possible period of time. The patient’s need for symptomatic relief and response to therapy should be re-evaluated periodically, especially in patients with osteoarthritis.
The recommended dose is 30 mg once a day. In case of insufficient relief from symptoms, an increased dose of 60 mg once a day may increase efficacy. In the absence of an increase in therapeutic benefit, other therapeutic options should be considered.
Rheumatoid arthritis (RA)
The recommended dose is 60 mg once a day. In some patients with insufficient treatment effectiveness increasing the dose to 90 mg once a day may enhance the therapeutic effect. When clinical stabilization is achieved, it makes sense to reduce the dose to 60 mg once a day. If there is no improvement other possible methods of treatment should be considered.
Ankylosing spondylitis (AS)
The recommended dose is 60 mg once a day. In some patients with insufficient treatment effectiveness increasing the dose to 90 mg once a day may enhance the therapeutic effect. When clinical stabilization is achieved, it makes sense to reduce the dose to 60 mg once a day. If there is no improvement, other possible methods of treatment should be considered.
Conditions accompanied by acute pain
In conditions accompanied by acute pain use etoricoxib only during the period of acute symptomatology.
Acute gouty arthritis
The recommended dose is 120 mg once a day. In clinical trials for acute gouty arthritis, etoricoxib was given for 8 days.
Postoperative dental surgery pain
The recommended dose is 90 mg once a day over a period of max. 3 days. Additional postoperative anesthesia may be necessary for some patients.
Doses greater than those recommended for each indication have either not demonstrated additional efficacy or have not been studied. Therefore:
- The dose in case of OA should not exceed 60 mg per day.
- The dose in case of PA and ankylosing spondylitis should not exceed 90 mg per day.
- The dose in case of acute gout should not exceed 120 mg per day, and the treatment goes on over a period of max. 8 days.
- The dose in case of acute pain after dental surgery should not exceed 90 mg per day, and the treatment goes on over a period of max. 3 days.
No dosage adjustment is necessary for elderly patients. As with other drugs, caution should be exercised in elderly patients.
Regardless of indication, in patients with mild hepatic dysfunction (Child-Pugh score 5-6) a dose of 60 mg once a day should not be exceeded. In patients with moderate hepatic dysfunction (Child-Pugh score 7-9), regardless of indication, the dose of 60 mg once in 2 days should not be exceeded. You can also consider taking the medication at a dose of 30 mg once a day.
Clinical experience is limited particularly in patients with moderate hepatic dysfunction and caution is advised. There is no clinical experience in patients with severe hepatic dysfunction (Child-Pugh score ≥10); therefore, its use is contra-indicated in these patients.
No dosage adjustment is necessary for patients with creatinine clearance ≥30 ml/min he use of etoricoxib in patients with creatinine clearance <30 ml/min is contra-indicated.
Etoricoxib is contra-indicated in children and adolescents under 16 years of age.
In clinical trials, etoricoxib was evaluated for safety in 9295 individuals, including 6757 patients with OA, RA, chronic low back pain or ankylosing spondylitis (approximately 600 patients with OA or RA were treated for one year or longer).
In clinical studies, the undesirable effects profile was similar in patients with OA or RA treated with etoricoxib for one year or longer.
Concurrent reactions are presented by classes of organ systems and occurrence rate: very often (≥ 1/10), often (≥ 1/100, but < 1/10), infrequently (≥ 1/1000, but < 1/100), rarely (≥ 1/10000, but < 1/1000), very rarely (< 1/10000), frequency is unknown (cannot be estimated based on available data).
Infections and infestations: often – alveolar ostitis, infrequently – gastroenteritis, upper respiratory tract infections, urinary tract infections.
Hematopoietic and lymphatic system disorders: infrequently – anemia (mainly as a result of gastrointestinal bleeding), leukopenia, thrombocytopenia.
Immune system disorders: infrequently – hypersensitivity reactions, rarely – angioedema, anaphylactic/anaphylactoid reactions including shock.
Metabolism and nutrition disorders: often – edema / fluid retention, infrequently – decreased or increased appetite, body weight gain.
Psychiatric disorders: infrequently – anxiety, depression, deterioration of mental activity, rarely – confusion, hallucinations.
Nervous system disorders: often – dizziness, headache, infrequently – dysgeusia, insomnia, paresthesia/hypesthesia, drowsiness.
Eye disorders: infrequently – blurred vision, conjunctivitis.
Ear and labyrinth disorders: infrequently – tinnitus, vertigo.
Cardiac disorders: often – palpitation, arrhythmia; infrequently – atrial fibrillation, tachycardia, congestive cardiac failure, nonspecific ECG changes, angina pectoris, myocardial infarction*.
Vascular disorders: often – hypertension; infrequently – blood flushes, stroke*, transient ischemic disorders of cerebral circulation, hypertensive crisis, vasculitis.
Respiratory, thoracic and mediastinal disorders: often – bronchospasm; infrequently – cough, dyspnea, nose bleed.
Gastrointestinal disorders: very often – abdominal pain; often – constipation, flatulence, gastritis, heartburn /acid reflux, diarrhea, dyspepsia / discomfort in the epigastric region, nausea, vomiting, esophagitis, oral cavity ulcers; infrequently – bloating, changing nature of intestinal peristalsis, dry mouth, gastroduodenal ulcers, peptic ulcers including gastrointestinal perforation and bleeding, irritable bowel syndrome, pancreatitis.
Hepatobiliary disorders: often – ALT level increase, AST level increase; rarely – hepatitis, hepatic insufficiency, jaundice.
Skin and subcutaneous tissue disorders: often – ecchymosis; infrequently – facial edema, itching, rash, erythema, urticaria; rarely – Stevens-Johnson syndrome, toxic epidermal necrolysis, fixed drug eruption.
Musculoskeletal and connective tissue disorders: infrequently – muscle spasms / cramps, musculoskeletal pain / stiffness.
Renal and urinary disorders: infrequently – proteinuria, increased serum creatinine, impaired renal function including renal insufficiency, which is usually reversible after treatment discontinuation.
General disorders and administration site conditions: often – asthenia / weakness, flu-like symptoms; infrequently – chest pain.
Effects on the results of laboratory and instrumental studies: infrequently – increase in concentration of blood urea nitrogen, increase in concentration of creatine phosphokinase, hyperkalemia, increase in concentration of uric acid; rarely – decrease in concentration of sodium in one’s blood.
* – Based on analyses of long-term placebo and active controlled clinical trials, selective COX-2 inhibitors have been associated with an increased risk of serious thrombotic arterial events, including myocardial infarction and stroke. The absolute risk increase for such events is unlikely to exceed 1% per year based on existing data (uncommon).
The following serious concurrent reactions have been reported when NSAIDs were used, so we cannot exclude the possibility of their occurrence when using etoricoxib: nephrotoxicity including nephritis and nephrotic syndrome.
If any of the undesirable effects listed in the instructions worsen, or you notice any other undesirable effects not listed in the instructions, inform your doctor about it.
- Hypersensitivity to the active substance or other components of the medicinal product.
- Active peptic ulceration or active gastro-intestinal (GI) bleeding.
- Patients who have had bronchospasm, acute rhinitis, nasal polyps, angioedema, urticaria or other allergic reactions after administration of acetylsalicylic acid or NSAIDs including cyclooxygenase-2 inhibitors (COX-2).
- Pregnancy and lactation.
- Severe hepatic dysfunction (serum albumin <25 g/l or Child-Pugh score ≥10).
- Estimated renal creatinine clearance <30 ml/min.
- Children and adolescents under 16 years of age.
- Inflammatory bowel disease.
- Congestive cardiac failure (NYHA II-IV).
- Patients with hypertension whose blood pressure is persistently elevated above 140/90 mm Hg and has not been adequately controlled.
- Estimated ischemic heart disease, peripheral artery disease and/or cardiovascular disease.
If taking a larger dose than prescribed by your doctor, immediately contact specialists to provide timely medical care!
In clinical studies, administration of single doses of etoricoxib up to 500 mg and multiple doses up to 150 mg/day for 21 days did not result in significant toxicity. Acute etoricoxib overdose has been reported although no concurrent reactions have been reported in most cases. The most frequently observed concurrent reactions were consistent with etoricoxib safety profile (for example, gastrointestinal tract reactions, cardiorenal reactions).
In case of overdose, it is advisable to involve common supportive measures, such as removing the unabsorbed medication from the gastrointestinal tract, conduct clinical observation and supportive therapy if necessary. Etoricoxib is not dialyzed during hemodialysis. It is unknown whether the medicinal product is dialyzed during peritoneal dialysis.
Oral anticoagulants: In subjects stabilized on chronic warfarin therapy, the administration of etoricoxib 120 mg daily was associated with an approximate 13% increase in prothrombin time International Normalized Ratio (INR). Therefore, patients receiving oral anticoagulants should be closely monitored for their prothrombin time INR, particularly in the first few days when therapy with etoricoxib is initiated or the dose of etoricoxib is changed.
Diuretics, angiotensin converting enzyme (ACE) inhibitors and angiotensin II antagonists: NSAIDs may reduce the effect of diuretics and other antihypertensive medications. In some patients with compromised renal function (e.g., dehydrated patients or elderly patients with compromised renal function) the co-administration of an ACE inhibitor or Angiotensin II antagonist and agents that inhibit cyclo-oxygenase may result in further deterioration of renal function, including possible acute renal failure, which is usually reversible. Keep in mind the possibility of such interactions in patients who take etoricoxib simultaneously with ACE inhibitors or with angiotensin II antagonists. Therefore, such a combination should be prescribed with caution, especially in elderly patients. Carry out adequate hydration and consider the matter of kidney function monitoring at the beginning of this combination treatment as well as at certain intervals in the future.
Acetylsalicylic acid: During the study involving healthy volunteers at equilibrium state the use of etoricoxib at a dose of 120 mg once a day did not affect the antiplatelet activity of acetylsalicylic acid (81 mg, once a day). Etoricoxib can be prescribed simultaneously with acetylsalicylic acid used in doses for prevention of cardiovascular complications (low doses). However, co-administration of low doses of acetylsalicylic acid with etoricoxib may lead to an increase in occurrence rate of gastrointestinal ulcers or other complications compared with etoricoxib monotherapy. Co-administration of etoricoxib with acetylsalicylic acid in doses exceeding those prescribed for prevention of cardiovascular complications as well as with other NSAIDs is not recommended.
Cyclosporine and tacrolimus: Although the interaction of etoricoxib with these medications has not been studied, the simultaneous use of NSAIDs with cyclosporines and tacrolimus may enhance the nephrotoxic effect of the latter. Renal function should be monitored while using etoricoxib with any of these medicinal products.
The effects of etoricoxib on the pharmacokinetics of other medicinal products
Lithium: NSAIDs decrease lithium renal excretion and therefore increase lithium plasma levels. Carefully monitor the concentration of lithium in blood, if necessary, and adjust the lithium dosage for the period of simultaneous administration of these medications and when the NSAID is withdrawn.
Methotrexate: In the course of two studies the effects of etoricoxib were examined when administered at doses of 60 mg, 90 mg and 120 mg once a day for seven days by patients who received methotrexate once a week at a dose of 7.5 mg to 20 mg for rheumatoid arthritis. Etoricoxib at a dose of 60 mg and 90 mg did not affect plasma concentrations and renal clearance of methotrexate. In the course of one study etoricoxib at a dose of 120 mg did not affect methotrexate indices, but in the course of another study the concentration of methotrexate in blood plasma increased by 28%, and the renal clearance of methotrexate decreased by 13%. When using etoricoxib in combination with methotrexate, appropriate monitoring should be carried out regarding the toxicity of methotrexate.
Oral contraceptives: Etoricoxib 60 mg given concomitantly with an oral contraceptive containing 35 micrograms ethinyl estradiol (EE) and 0.5 to 1 mg norethindrone for 21 days increased the steady state AUC0-24 of EE by 37%. Etoricoxib 120 mg given with the same oral contraceptive concomitantly or separated by 12 hours, increased the steady state AUC0-24 of EE by 50 to 60%. This increase in EE concentration should be considered when selecting an oral contraceptive for use with etoricoxib. Increased ethinyl estradiol exposure may increase the incidence of concurrent reactions associated with the use of oral contraceptives (for example, venous thromboembolism in women at risk).
Hormone replacement therapy: Administration of etoricoxib 120 mg with hormone replacement therapy consisting of conjugated estrogens (0.625 mg PREMARINTM) for 28 days, increased the mean steady state AUC0-24 of unconjugated estrone (41%), equilin (76%), and 17-β-estradiol (22%). The effect of etoricoxib at doses recommended for long-term administration (30, 60 and 90 mg) has not been studied. The effects of etoricoxib 120 mg on the exposure (AUC0-24) to these estrogenic components of Premarin were less than half of those observed when Premarin was administered alone and the dose was increased from 0.625 to 1.25 mg. Clinical significance of such increases is unknown, and higher doses of Premarin in combination with etoricoxib have not been studied. Such increases in concentration of estrogens should be taken into account when choosing a hormonal preparation for administration during postmenopause in combination with etoricoxib, since increased estrogens exposure may increase the risk of concurrent reactions during hormone replacement therapy.
Prednisone/prednisolone: In the course of drug interaction studies etoricoxib had no clinically significant effects on the pharmacokinetics of prednisone/prednisolone.
Digoxin: Etoricoxib 120 mg administered once daily for 10 days to healthy volunteers did not alter the steady-state plasma AUC0-24 or renal elimination of digoxin. There was an increase in digoxin Cmax (approximately 33%). Such an increase is not significant for most patients as a rule. However, patients at high risk of digoxin toxicity should be monitored for this when etoricoxib and digoxin are administered concomitantly.
Effect of etoricoxib on medications metabolized by sulfotransferases
Etoricoxib is an inhibitor of human sulfotransferase activity, in particular SULT1A1, and has been shown to increase the serum concentrations of ethinyl estradiol. While knowledge about effects of multiple sulfotransferases is presently limited and the clinical consequences for many drugs are still being examined, it may be prudent to exercise care when co-administering etoricoxib with other medications primarily metabolized by human sulfotransferases (e.g., oral salbutamol and minoxidil).
Effect of etoricoxib on medications metabolized by CYP isoenzymes
Based on in vitro studies, etoricoxib is not expected to inhibit cytochromes P450 (CYP) 1A2, 2C9, 2C19, 2D6, 2E1 or 3A4. In a study in healthy subjects, daily administration of etoricoxib 120 mg did not alter hepatic CYP3A4 activity as assessed by the erythromycin breath test.
Effects of other medications on the pharmacokinetics of etoricoxib
The main pathway of etoricoxib metabolism is dependent on CYP enzymes. CYP3A4 appears to contribute to the metabolism of etoricoxib in vivo. In vitro studies indicate that CYP2D6, CYP2C9, CYP1A2 and CYP2C19 also can catalyse the main metabolic pathway, but their quantitative roles have not been studied in vivo.
Ketoconazole: Ketoconazole is a potent inhibitor of CYP3A4. Ketoconazole dosed at 400 mg once a day for 11 days to healthy volunteers did not have any clinically important effect on the single-dose pharmacokinetics of 60 mg etoricoxib (43% increase in AUC).
Rifampicin: Co-administration of etoricoxib with rifampicin, a potent inducer of CYP enzymes, produced a 65% decrease in etoricoxib plasma concentrations. This interaction may result in recurrence of symptoms when etoricoxib is co-administered with rifampicin. While this information may suggest an increase in dose, doses of etoricoxib greater than those listed for each indication have not been studied in combination with rifampicin and are therefore not recommended.
Antacids: Antacids do not affect the pharmacokinetics of etoricoxib to a clinically relevant extent.
Inform your doctor about all medications you are taking. Consult your doctor before you start taking any medication during treatment with Artroxib medicinal product.
Upper gastrointestinal complications (perforations, ulcers or bleedings), some of them resulting in fatal outcome, have occurred in patients treated with etoricoxib.
Caution is advised with treatment of patients most at risk of developing a gastrointestinal complication with NSAIDs (patients using any other NSAID or acetylsalicylic acid concomitantly or patients with a prior history of gastrointestinal disease, such as ulceration and GI bleeding).
There is a further increase in the risk of gastrointestinal adverse effects (gastrointestinal ulceration or other gastrointestinal complications) when etoricoxib is taken concomitantly with acetylsalicylic acid (even at low doses). A significant difference in GI safety between selective COX-2 inhibitors + acetylsalicylic acid vs. NSAIDs + acetylsalicylic acid has not been demonstrated in long-term clinical studies.
Clinical trials suggest that the selective COX-2 inhibitor class of medications may be associated with a risk of thrombotic events (especially myocardial infarction and stroke), relative to placebo and some NSAIDs. As the cardiovascular risks of etoricoxib may increase with dose and duration of exposure, the shortest duration possible and the lowest effective daily dose should be used. It is critical to re-evaluate the patient’s need for symptomatic relief and response to the treatment provided at times, especially in patients with osteoarthritis.
Patients with significant risk factors for cardiovascular events (e.g., hypertension, hyperlipidaemia, diabetes mellitus, smoking) should only be treated with etoricoxib after careful consideration.
COX-2 selective inhibitors are not a substitute for acetylsalicylic acid for prophylaxis of cardiovascular thrombo-embolic diseases because of their lack of antiplatelet effect. Therefore, antiplatelet therapies should not be discontinued.
Renal prostaglandins may play a compensatory role in the maintenance of renal perfusion. Therefore, under conditions of compromised renal perfusion, administration of etoricoxib may cause a reduction in prostaglandin formation and, secondarily, in renal blood flow, and thereby impair renal function. Patients at greatest risk of this response are those with pre-existing significantly impaired renal function, uncompensated heart failure, or cirrhosis. Monitoring of renal function in such patients should be considered.
Fluid retention, oedema and hypertension
As with other medicinal products known to inhibit prostaglandin synthesis, fluid retention, oedema and hypertension have been observed in patients taking etoricoxib. All NSAIDs, including etoricoxib, can be associated with new onset or recurrent congestive heart failure. Caution should be exercised in patients with a history of cardiac failure, left ventricular dysfunction, or hypertension and in patients with pre-existing oedema from any other reason. If there is clinical evidence of deterioration in the condition of these patients, appropriate measures including discontinuation of etoricoxib should be taken.
Etoricoxib may be associated with more frequent and severe hypertension than some other NSAIDs and selective COX-2 inhibitors, particularly at high doses. Therefore, hypertension should be controlled before treatment with etoricoxib and special attention should be paid to blood pressure monitoring during treatment with etoricoxib. Arterial blood pressure (ABP) should be monitored within two weeks after initiation of treatment and periodically thereafter. If ABP rises significantly, alternative treatment should be considered.
Elevations of alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) (approximately three or more times the upper limit of normal) have been reported in approximately 1% of patients in clinical trials treated for up to one year with etoricoxib 30, 60 and 90 mg daily.
Any patients with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal liver function test has occurred, should be monitored. If signs of hepatic insufficiency occur, or if persistently abnormal liver function tests (three times the upper limit of normal) are detected, etoricoxib should be discontinued.
If during treatment, patients deteriorate in any of the organ system functions described above, appropriate measures should be taken and discontinuation of etoricoxib therapy should be considered. Medically appropriate supervision should be maintained when using etoricoxib in the elderly and in patients with renal, hepatic, or cardiac dysfunction.
Caution should be used when initiating treatment with etoricoxib in patients with dehydration. It is advisable to rehydrate patients prior to starting therapy with etoricoxib.
Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs and some selective COX-2 inhibitors during post-marketing surveillance. Patients appear to be at highest risk for these reactions early in the course of therapy with the onset of the reaction occurring in the majority of cases within the first month of treatment. Serious hypersensitivity reactions (such as anaphylaxis and angioedema) have been reported in patients receiving etoricoxib. Some selective COX-2 inhibitors have been associated with an increased risk of skin reactions in patients with a history of any drug allergy. Etoricoxib should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.
Etoricoxib may mask fever and other signs of inflammation.
Caution should be exercised when co-administering etoricoxib with warfarin or other oral anticoagulants.
The use of etoricoxib, as with any medicinal product known to inhibit cyclooxygenase / prostaglandin synthesis, is not recommended in women attempting to conceive.
Artroxib medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medication.
If you have one of the diseases or conditions listed above, be sure to consult your doctor before taking the medicinal product.
The use of etoricoxib, as with any medicinal product known to inhibit COX-2, is not recommended in women attempting to conceive. No clinical data on exposed pregnancies are available for etoricoxib. Studies in animals have shown reproductive toxicity. The potential for human risk in pregnancy is unknown. Etoricoxib, as with other medicinal products inhibiting prostaglandin synthesis, may cause uterine inertia and premature closure of the ductus arteriosus during the last trimester. Etoricoxib is contraindicated in pregnancy. If a woman becomes pregnant during treatment, etoricoxib must be discontinued.
It is not known whether etoricoxib is excreted in human milk. Etoricoxib is excreted in the milk of lactating rats. Women who use etoricoxib must not breast feed.
No studies have been conducted on etoricoxib effects on ability to drive and use machines. Patients who experience dizziness, vertigo or somnolence while taking etoricoxib should refrain from driving or operating machinery.
Film-coated tablets 30 mg, 60 mg and 90 mg.
14 or 15 tablets in a blister made of a double-layer PVC/PVDC film (polyvinyl chloride/polyvinylidene chloride) and flexible packing based on aluminum foil. 2 blisters with guidelines for medical use in a carton.
Coated tablets, 120 mg.
14 or 15 tablets in a blister made of a double-layer PVC/PVDC film (polyvinyl chloride/polyvinylidene chloride) and flexible packing based on aluminum foil. 1 blister with guidelines for medical use in a carton.
Protect from light and moisture, at a temperature not above 25°C.
Keep away from children.
2 years. Do not use after the expiration date indicated on the packing.
State enterprise ACADEMPHARM
220141, 5/3 Kuprevicha Street, Minsk, Belarus,
Phone / Fax +375 17 268-63-64
To report adverse reactions use the electronic application form on the manufacturer’s website: https://academpharm.by/en