Aertal film-coated tablets 100 mg blister No. 60

Instructions for use Aertal film-coated tablets 100 mg blister No. 60

Composition

active ingredient: aceclofenac;

1 film-coated tablet contains aceclofenac 100 mg;

excipients:

tablet core: glycerol distearate, croscarmellose sodium, povidone, microcrystalline cellulose;

shell: sepifilm 752, white (hypromellose, microcrystalline cellulose, titanium dioxide (E 171), macrogol stearate).

Dosage form

Film-coated tablets.

Main physicochemical properties: round biconvex tablets of white color, film-coated, with a diameter of about 8 mm. On one side of the tablet is engraved "A".

Pharmacotherapeutic group

Nonsteroidal anti-inflammatory and antirheumatic drugs. Acetic acid derivatives and related substances. ATC code M01A B16.

Pharmacological properties

Pharmacodynamics

Aceclofenac is a nonsteroidal anti-inflammatory and analgesic drug. The mechanism of action of this drug is believed to be based on inhibition of prostaglandin synthesis.

Pharmacokinetics

Absorption

After oral administration, aceclofenac is rapidly absorbed, its bioavailability is almost 100%. Peak plasma concentrations are reached approximately 1.25-3 hours after administration. Food intake slows down absorption, but does not affect its extent.

Distribution

Aceclofenac is highly bound to plasma proteins (> 99.7%). Aceclofenac penetrates into the synovial fluid, where the concentration reaches approximately 60% of that in blood plasma. The volume of distribution is approximately 30 l.

Breeding

The mean half-life is 4-4.3 hours. Clearance is 5 liters per hour. Approximately two-thirds of the administered dose is excreted in the urine, mainly as conjugated hydroxymetabolites. Only 1% of a single oral dose is excreted unchanged.

Aceclofenac is probably metabolized by CYP2C9 to the major metabolite 4-OH-aceclofenac, which is of little clinical significance. Diclofenac and 4-OH-diclofenac have been identified among the many metabolites.

Special patient groups

No changes in the pharmacokinetics of aceclofenac were found in elderly patients.

In patients with reduced liver function, aceclofenac was eliminated more slowly after a single dose. In studies with multiple doses of 100 mg daily, there was no difference in pharmacokinetic parameters between patients with mild to moderate liver cirrhosis and healthy volunteers.

In patients with mild or moderate renal impairment, no clinically significant differences in pharmacokinetics were observed after a single dose.

Indication

Osteoarthritis, rheumatoid arthritis, ankylosing spondylitis and other diseases of the musculoskeletal system accompanied by pain (for example, shoulder-scapular periarthritis and other extra-articular manifestations of rheumatism).

For conditions accompanied by pain (including low back pain, toothache, primary dysmenorrhea).

Contraindication

Aceclofenac is contraindicated:

patients with hypersensitivity to aceclofenac or to any auxiliary component of the drug (see section "Composition");

patients in whom acetylsalicylic acid or other non-steroidal anti-inflammatory drugs (NSAIDs) cause asthma attacks, acute rhinitis, angioedema or urticaria, as well as patients with hypersensitivity to these drugs;

patients with a history of gastrointestinal bleeding or ulcer perforation related to previous nonsteroidal anti-inflammatory drug (NSAID) therapy;

patients with concomitant peptic ulcer or bleeding, including a history (two or more separate proven episodes of ulceration or bleeding);

patients with acute bleeding or diseases accompanied by bleeding (hemophilia or blood clotting disorders);

patients with congestive heart failure (NYHA functional class II-IV), ischemic heart disease, peripheral arterial disease or cerebrovascular disorders;

patients with cerebrovascular diseases who have had a stroke or have episodes of transient ischemic attacks;

patients with coronary heart disease who have angina or have had a myocardial infarction;

for the treatment of perioperative pain during coronary artery bypass grafting (or when using a cardiopulmonary bypass machine);

patients with severe hepatic or renal insufficiency;

during breastfeeding;

in the last trimester of pregnancy;

patients under 18 years of age.

Interaction with other medicinal products and other types of interactions

Aceclofenac is metabolised by cytochrome P450 2C9 and in vitro data suggest that aceclofenac may be an inhibitor of this enzyme. Therefore, there is a risk of pharmacokinetic interactions with phenytoin, cimetidine, tolbutamide, phenylbutazone, amiodarone, miconazole and sulfaphenazole. As with other NSAIDs, the risk of pharmacokinetic interactions is increased with other drugs that are excreted by active renal secretion, such as methotrexate and lithium. Aceclofenac is almost completely bound to plasma albumin and therefore displacement interactions with other drugs that are protein bound are possible.

Due to the lack of pharmacokinetic interaction studies with aceclofenac, the information below is based on data from other NSAIDs.

Concomitant use should be avoided.

Methotrexate: NSAIDs inhibit the tubular secretion of methotrexate; in addition, a small metabolic interaction may occur, leading to a decrease in the clearance of methotrexate. Therefore, NSAIDs should be avoided when using high doses of methotrexate.

Cardiac glycosides, digoxin. NSAIDs may exacerbate heart failure, reduce GFR (glomerular filtration rate), and inhibit renal clearance of glycosides, leading to increased plasma glycoside levels. Concomitant use should be avoided unless digoxin concentrations are monitored frequently.

Lithium and digoxin. Some NSAIDs inhibit the renal clearance of lithium and digoxin, leading to increased serum concentrations of both substances. Concomitant use should be avoided unless frequent monitoring of lithium and digoxin concentrations is performed.

Anticoagulants. NSAIDs inhibit platelet aggregation and damage the gastrointestinal mucosa, which may lead to increased anticoagulant effects and an increased risk of gastrointestinal bleeding in patients taking anticoagulants. The concomitant use of aceclofenac and oral coumarin anticoagulants, ticlopidine, and thrombolytics should be avoided unless the patient is closely monitored.

Quinolone antibiotics: Animal studies show that NSAIDs increase the risk of seizures associated with the use of quinolone antibiotics. Patients taking NSAIDs and quinolone antibiotics are at increased risk of developing seizures.

Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs). When used simultaneously with NSAIDs, the risk of gastrointestinal bleeding increases (see section "Special warnings and precautions for use").

Combinations requiring dose selection and caution when used

Methotrexate. The potential for interaction between NSAIDs and methotrexate should be considered, even at low doses of methotrexate, especially in patients with impaired renal function. Renal function should be monitored during concomitant administration. Caution should be exercised if NSAIDs and methotrexate are taken within 24 hours, as methotrexate concentrations may increase, which may increase the toxicity of this drug.

Cyclosporine, tacrolimus. When NSAIDs are used concomitantly with cyclosporine or tacrolimus, the risk of increased nephrotoxicity due to reduced renal prostacyclin formation should be considered. Therefore, renal function should be closely monitored during concomitant use.

Other analgesics, NSAIDs, including selective cyclooxygenase-2 inhibitors. The simultaneous use of two or more NSAIDs (including acetylsalicylic acid) should be avoided, as this increases the frequency of adverse events.

Mifepristone: NSAIDs should not be taken for 8-12 days after taking mifepristone, as NSAIDs may reduce the effect of mifepristone.

Corticosteroids: Increased risk of gastrointestinal ulceration or bleeding (see section "Special warnings and precautions for use").

Diuretics. Aceclofenac, like other NSAIDs, may inhibit the activity of diuretics, may reduce the diuretic effect of furosemide and bumetanide and the antihypertensive effect of thiazides. Concomitant use with potassium-sparing diuretics may lead to an increase in potassium levels; therefore, it is necessary to regularly monitor the potassium content in the blood serum.

Aceclofenac did not affect blood pressure control when co-administered with bendrofluazide, although interactions with other diuretics cannot be excluded.

Hypoglycemic agents. Clinical studies show that diclofenac can be used together with oral hypoglycemic agents without affecting their clinical effect. However, there are isolated reports of hypoglycemic and hyperglycemic effects of the drug. Therefore, when taking aceclofenac, the doses of drugs that can cause hypoglycemia should be adjusted.

Zidovudine: Concomitant administration of NSAIDs and zidovudine increases the risk of hematological toxicity. There is evidence of an increased risk of hemarthrosis and hematoma in HIV (+) hemophiliac patients receiving zidovudine and ibuprofen.

Application features

The simultaneous use of Aertal® and NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided.

Undesirable effects can be minimized by using the lowest effective dose for a short period of time to control symptoms (see section "Dosage and Administration" and below risks related to the gastrointestinal tract and cardiovascular system).

Effects on the gastrointestinal tract (GI)

Fatal gastrointestinal bleeding, ulceration, or perforation have been reported with all NSAIDs at any time during treatment, with or without warning symptoms, and regardless of a history of serious gastrointestinal disease.

The risk of bleeding, ulceration and perforation of the gastrointestinal tract increases with increasing dose of NSAIDs in patients with a history of ulcer, especially if it was accompanied by bleeding or perforation (see section "Contraindications"), and in elderly patients. These patients should take the minimum effective dose of the drug. They need combination therapy with the use of protective drugs (for example, misoprostol or proton pump inhibitors), and similar therapy is also necessary for patients who use low doses of acetylsalicylic acid (aspirin) or other drugs that negatively affect the state of the gastrointestinal tract (see section "Interaction with other drugs and other types of interactions").

Patients with gastrointestinal diseases, including the elderly, should be informed of any unusual symptoms related to the gastrointestinal tract (especially gastrointestinal bleeding), including at the beginning of treatment. Particular caution should be exercised in patients taking concomitant medications that increase the risk of bleeding or ulceration, such as systemic corticosteroids, anticoagulants (e.g. warfarin), selective serotonin reuptake inhibitors or antiplatelet agents (such as acetylsalicylic acid) (see section "Interaction with other medicinal products and other forms of interaction").

If gastrointestinal bleeding or ulceration occurs in patients taking Aertal®, treatment should be discontinued.

Cardiovascular and cerebrovascular effects

Appropriate monitoring and special instructions are necessary for patients with arterial hypertension and/or mild to moderate congestive heart failure, as fluid retention and edema have been reported in association with NSAIDs. Clinical trials and epidemiological data suggest that some NSAIDs (especially at high doses and in long-term use) are associated with a small increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke).

Patients with heart failure (NYHA functional class I) and cardiovascular risk factors (e.g. hypertension, hyperlipidemia, diabetes mellitus, and smoking) should be treated with special caution when taking aceclofenac. Since the adverse effects on the cardiovascular system increase with increasing dose and duration of treatment, the minimum effective daily dose should be used for the shortest possible treatment period. The need for further symptomatic treatment of the patient and the effectiveness of therapy should be reviewed periodically.

Aceclofenac should be used with caution and under close medical supervision in patients with the following conditions (as there is a risk of exacerbation of the disease) (see section "Adverse reactions"):

- symptoms indicating the presence of a disease of the gastrointestinal tract, including its upper and lower sections;

- history of ulcer, bleeding or perforation of the gastrointestinal tract;

- ulcerative colitis;

- Crohn's disease;

- bleeding tendency, SLE (systemic lupus erythematosus), porphyria and disorders of hematopoiesis and hemostasis.

Effects on the liver and kidneys

Caution should be exercised when using the drug in patients with mild to moderate hepatic and renal impairment, as well as in patients with other conditions accompanied by fluid retention in the body. In these patients, the use of NSAIDs may lead to impaired renal function and fluid retention. Caution should also be exercised when using the drug Aertal® in patients taking diuretics or in individuals at increased risk of hypovolemia. The minimum effective dose and regular medical monitoring of renal function are necessary. Renal phenomena usually resolve after discontinuation of aceclofenac.

Aceclofenac should be discontinued if liver function tests persist or worsen, clinical signs of liver disease develop, or other manifestations occur (eosinophilia, rash). Hepatitis may develop without prodromal symptoms. Use of NSAIDs in patients with hepatic porphyria may precipitate an attack.

Systemic lupus erythematosus and mixed connective tissue disease

Patients with systemic lupus erythematosus and mixed connective tissue diseases are at increased risk of developing aseptic meningitis (see section "Adverse reactions").

Hypersensitivity and skin reactions

Like other NSAIDs, Aertal® can cause allergic reactions, including anaphylactic/anaphylactoid reactions, even when the drug is taken for the first time. Severe skin reactions (some of which can be fatal), including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, have been observed very rarely after taking NSAIDs (see section "Adverse reactions"). The highest risk of these reactions in patients is observed at the beginning of the drug, and the development of these undesirable reactions is observed during the first month of taking the drug. If skin rashes, lesions on the oral mucosa or other signs of hypersensitivity occur, aceclofenac should be discontinued.

In special cases, complications may occur with chickenpox: serious skin and soft tissue infections. At this time, the role of NSAIDs in worsening the course of these infections cannot be ruled out. Therefore, Aertal® should be avoided in chickenpox.

Hematological disorders

Aceclofenac may cause reversible inhibition of platelet aggregation (see section "Interaction with other medicinal products and other types of interactions").

Respiratory system disorders

Caution should be exercised when administering the drug to patients with bronchial asthma, including those with a history of it, since taking NSAIDs can provoke the development of sudden bronchospasm in such patients.

Elderly patients

Caution should be exercised when using the drug in elderly patients (aged 65 years and over) because they are more likely to experience side effects (especially bleeding, gastrointestinal perforation) when taking NSAIDs. Complications can be fatal. In addition, elderly patients are more likely to suffer from kidney, liver or cardiovascular diseases.

Long-term use

All patients receiving long-term treatment with nonsteroidal anti-inflammatory drugs should be under close medical supervision (complete blood count, liver and kidney function tests).

Use during pregnancy or breastfeeding

Pregnancy

There are no data on the use of aceclofenac during pregnancy.

Inhibition of prostaglandin synthesis may adversely affect the course of pregnancy and/or embryo/fetal development.

Epidemiological data suggest an increased risk of miscarriage, heart defects and gastroschisis after use of prostaglandin synthesis inhibitors in early pregnancy. The absolute risk of heart defects increases from less than 1% to approximately 1.5%. The risk increases with increasing dose and duration of treatment.

In animals, administration of prostaglandin synthesis inhibitors results in pre- and post-implantation fetal death and embryo-fetal lethality. In addition, there is an increased incidence of various malformations, including cardiac malformations, in animals receiving prostaglandin synthesis inhibitors during organogenesis.

From the 20th week of pregnancy, the use of aceclofenac may cause oligohydramnios due to fetal renal dysfunction. This disorder may occur shortly after the start of treatment and is usually reversible after discontinuation of treatment. In addition, there are reports of narrowing of the ductus arteriosus after treatment in the second trimester of pregnancy, which in most cases disappeared after discontinuation of treatment. Therefore, during the first and second trimesters of pregnancy, Aertal® should not be prescribed unless clearly necessary. If aceclofenac is used by a woman attempting to conceive, or during the first or second trimester of pregnancy, the dose should be kept as low and the duration of treatment as short as possible.

It may be advisable to monitor the fetus for oligohydramnios and narrowing of the ductus arteriosus after exposure to aceclofenac for several days, starting from the 20th week of pregnancy. Use of Aertal® should be discontinued if oligohydramnios or narrowing of the ductus arteriosus is detected.

- may affect the fetus, causing cardiopulmonary toxicity (premature narrowing/closure of the ductus arteriosus and pulmonary hypertension);

- may affect the fetus, causing renal dysfunction, which may progress to renal failure with oligohydramnios (see above).

In women at the end of pregnancy and in the newborn, the drug may affect the duration of bleeding due to an antiaggregatory effect that may develop even after the use of very low doses; the drug may inhibit uterine contractions, leading to delayed labor or prolonged labor.

Therefore, the use of aceclofenac is contraindicated in the third trimester of pregnancy (see sections "Contraindications" and "Special instructions for use").

Breastfeeding period

There is no information on the excretion of aceclofenac in breast milk. However, no significant excretion of radiolabeled (C14) aceclofenac into the milk of rats was observed.

Like other NSAIDs, aceclofenac passes into breast milk in small amounts, so the drug is contraindicated for use by women during breastfeeding to avoid undesirable effects on the infant.

Fertility

Aertal®, like other cyclooxygenase/prostaglandin synthesis inhibitors, may impair fertility and is not recommended in women attempting to conceive. Women who have difficulty conceiving or are undergoing fertility investigation should discontinue Aertal®.

Ability to influence reaction speed when driving vehicles or other mechanisms

Patients who experience symptoms such as weakness, dizziness, vertigo, or other central nervous system symptoms while taking NSAIDs should not drive or operate dangerous machinery.

Method of administration and doses

Aertal® film-coated tablets are intended for oral use and should be swallowed with at least ½ glass of liquid. Aertal® should preferably be taken with food.

Adverse events can be minimized if the duration of drug administration is the shortest necessary to control symptoms (see section "Special instructions").

Adults

The maximum recommended dose is 200 mg per day in two doses of 100 mg (1 tablet in the morning and 1 tablet in the evening).

Elderly patients

Such patients should be carefully monitored, as they are more likely to have impaired renal and hepatic function, cardiovascular disorders, and are also more likely to receive concomitant therapy for other diseases, which increases the risk of developing serious adverse reactions. If NSAIDs are prescribed, they should be used in the lowest possible doses and for the shortest possible time. As a rule, dose reduction is not required. Patients should be carefully monitored for timely detection of gastrointestinal bleeding during NSAID therapy, and the recommendations described in the section "Special instructions for use" should be followed.

Liver failure

For patients with mild to moderate hepatic impairment, the dose of aceclofenac should be reduced. The recommended starting dose is 100 mg per day (see section 4.4).

Kidney failure

There is no information that patients with mild renal insufficiency require dose adjustment of aceclofenac, however, these patients should be cautious when using the drug (see section "Special warnings and precautions for use").

Children

There are no clinical data on the use of Aertal® in children, therefore this drug is not recommended for use in this age group.

Overdose

There are no data on overdose with aceclofenac in humans.

Possible symptoms

Headache, nausea, vomiting, stomach pain, dizziness, drowsiness, gastrointestinal irritation, gastrointestinal bleeding, diarrhea, disorientation, agitation, coma, tinnitus, hypotension, respiratory depression, loss of consciousness, convulsions. In cases of severe poisoning, acute renal failure and impaired liver function may occur.

Treatment

Treatment of acute poisoning with nonsteroidal anti-inflammatory drugs consists of the use of antacids (if necessary) and other supportive and symptomatic therapy for complications such as hypotension, renal failure, convulsions, irritation of the gastrointestinal mucosa, and respiratory depression.

Treatment of acute poisoning with aceclofenac orally consists of preventing absorption of the drug by gastric lavage and administration of activated charcoal (repeated doses) as soon as possible after overdose. Forced diuresis, dialysis or hemoperfusion may not be effective enough to remove NSAIDs due to the high degree of binding of NSAIDs to blood proteins and extensive metabolism.

Adverse reactions

Gastrointestinal: The most common adverse reactions were related to the gastrointestinal tract. Gastrointestinal ulcers, perforations or gastrointestinal bleeding, sometimes fatal, may occur with NSAIDs, particularly in the elderly (see section 4.4). Nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, stomach pain, melena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease have been reported with NSAIDs (see section 4.4). Gastritis has been reported less frequently.

Hypersensitivity and skin reactions: when using NSAIDs, nonspecific allergic reactions may develop, manifested as anaphylactic reactions, respiratory tract reactivity, including asthma, worsening of asthma, bronchospasm or dyspnea, various skin reactions, including rashes of various types, itching, urticaria, purpura, angioedema, less often - exfoliative and bullous dermatitis (including epidermal necrolysis and erythema multiforme).

Neurological and sensory disorders: optic neuritis, cases of aseptic meningitis (especially in patients with autoimmune disorders such as systemic lupus erythematosus, mixed connective tissue disease) with symptoms such as numbness (rigidity) of the neck muscles, fever, disorientation, confusion, hallucinations, malaise.

Hematological disorders: agranulocytosis, aplastic anemia.

Edema, hypertension, and heart failure have been reported in association with the use of NSAIDs.

Clinical trials and epidemiological data suggest that some NSAIDs (especially at high doses and in long-term use) slightly increase the risk of arterial thrombotic events (e.g. myocardial infarction or stroke) (see section 4.4).

The table below lists adverse events reported in clinical trials and with the use of Aertal®, grouped by organ system and frequency of occurrence.

Other side effects observed with the use of NSAIDs

Very rare (<1/10,000):

Renal and urinary disorders: interstitial nephritis.

In exceptional cases, serious skin and soft tissue infections have been observed when NSAIDs were taken during chickenpox (see also sections “Special warnings and precautions for use” and “Interaction with other medicinal products and other types of interactions”).

Expiration date

3 years.

Storage conditions

Store at a temperature not exceeding 25 ° C. Keep the drug out of the reach of children.

Packaging

10 film-coated tablets in a blister; 2 or 6 blisters in a cardboard box.

Vacation category

According to the recipe.

Producer

JSC "Gedeon Richter", Hungary, under license from Almiral A. G., Switzerland.

Location of the manufacturer and its business address

H-1103, Budapest, Demrei Street 19-21, Hungary.