Aertal powder for oral suspension 100 mg package No. 20

Instructions for use Aertal powder for oral suspension 100 mg, package No. 20

Composition

active ingredient: aceclofenac;

1 packet of powder for oral suspension contains aceclofenac 100 mg;

excipients: sorbitol (E 420), sodium saccharin, aspartame (E 951), colloidal anhydrous silicon dioxide, hypromellose, titanium dioxide (E 171), milk flavor, caramel flavor, cream flavor.

Dosage form

Powder for oral suspension.

Main physicochemical properties: white or almost white powder.

Pharmacotherapeutic group

Nonsteroidal anti-inflammatory and antirheumatic drugs. Acetic acid derivatives and related substances. ATX 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%. The maximum concentration in the blood plasma is 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). In conditions accompanied by pain (including low back pain, toothache, primary dysmenorrhea).

Contraindication

Aceclofenac is contraindicated:

patients with hypersensitivity to aceclofenac or to any of the excipients of the drug (see section "Composition"); patients in whom acetylsalicylic acid or other non-steroidal anti-inflammatory drugs (NSAIDs) cause asthma attacks, bronchospasm, acute rhinitis, angioedema or urticaria, as well as patients with hypersensitivity to these drugs; patients with a history of gastrointestinal bleeding or ulcer perforation associated with previous NSAID therapy; patients with concomitant peptic ulcer or bleeding, including a history (two or more separate proven episodes of ulcer development 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 artery disease or cerebrovascular disorders; patients with cerebrovascular disease who have had a stroke or have episodes of transient ischemic attacks; patients with ischemic heart disease who have angina or have had a myocardial infarction; for the treatment of perioperative pain in coronary artery bypass grafting (or when using an artificial blood circulation device); 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

No interaction studies have been conducted, except for the interaction with warfarin.

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

The simultaneous use of:

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

Cardiac glycosides, digoxin. NSAIDs may exacerbate heart failure, reduce glomerular filtration rate (GFR), 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 (GI) mucosa, which may potentiate the effects of anticoagulants and increase the risk of gastrointestinal bleeding in patients taking anticoagulants. The concomitant use of aceclofenac with oral coumarin anticoagulants, ticlopidine, and thrombolytics and heparin 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 using:

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 they 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.

Antihypertensive drugs. NSAIDs may also reduce the effect of antihypertensive drugs. Concomitant use of ACE inhibitors or angiotensin II receptor antagonists and NSAIDs may lead to impaired renal function. The risk of acute renal failure, which is usually reversible, is increased in some patients with impaired renal function, such as elderly or dehydrated patients. Therefore, caution should be exercised when using NSAIDs simultaneously, especially in elderly patients. Patients should consume adequate fluids and be under appropriate supervision (monitoring of renal function at the beginning of concomitant use and periodically during treatment).

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 hematologic toxicity. There is evidence of an increased risk of hemarthrosis and hematoma in HIV (+) hemophiliac patients receiving zidovudine and ibuprofen.

Application features

Undesirable effects can be minimized by using the lowest effective dose for short periods to control symptoms (see section “Dosage and Administration” and below for gastrointestinal and cardiovascular risks).

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 hemorrhage 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 taking low doses of acetylsalicylic acid or other drugs that negatively affect the gastrointestinal tract (see section "Interaction with other drugs and other types of interactions").

Patients with gastrointestinal diseases, including elderly patients, should report 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 ulcers, 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 hypertension and/or mild to moderate congestive heart failure, as fluid retention and edema have been reported in association with NSAIDs.

There is insufficient data to exclude this risk when taking aceclofenac.

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

Patients with congestive heart failure (NYHA functional class I) with 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 periodically reviewed.

Aceclofenac should be used with caution and under close medical supervision in patients with a history of cerebrovascular hemorrhage.

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 suggestive of gastrointestinal disease, including upper and lower gastrointestinal tract; history of gastrointestinal ulceration, bleeding, or perforation; ulcerative colitis; Crohn's disease; bleeding tendency, systemic lupus erythematosus (SLE), porphyria, and disorders of hematopoiesis and hemostasis.

Effects on the liver and kidneys

NSAIDs may cause a dose-dependent reduction in prostaglandin formation and sudden renal failure. The importance of prostaglandins in maintaining renal blood flow should be considered when using the drug in patients with impaired cardiac, renal or hepatic function, in persons receiving diuretics, in patients after surgery, and in elderly patients.

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.

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 mainly during the first month of taking the drug. If skin rashes, lesions of 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.

Systemic lupus erythematosus (SLE) and mixed connective tissue disease

Patients with SLE and mixed connective tissue diseases are at increased risk of developing aseptic meningitis (see section 4.8).

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 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), as they are more likely to experience side effects (especially bleeding, gastrointestinal perforation) when taking NSAIDs. Complications can be fatal. Also, elderly patients are more likely to suffer from kidney, liver or cardiovascular diseases.

Long-term use

All patients taking NSAIDs for a long time should be under close medical supervision (complete blood count, liver and kidney function tests).

Excipients

One packet of Aertal®, powder for oral suspension, contains 2.64 g of sorbitol, which may cause gastrointestinal discomfort and diarrhea. Patients with rare hereditary problems of fructose intolerance should not be prescribed this medicine.

Aertal®, powder for oral suspension, contains aspartame, which is a source of phenylalanine. Patients with phenylketonuria should take into account that one sachet contains 5.61 mg of phenylalanine.

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.

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 mortality. There is also an increased incidence of various malformations, including heart defects, in animals receiving prostaglandin synthesis inhibitors during organogenesis.

During the first and second trimesters of pregnancy, drugs containing aceclofenac should not be prescribed unless clearly necessary. If aceclofenac is used by a woman planning a pregnancy or in the first or second trimester of pregnancy, the dose should be kept as low and the duration of treatment as short as possible.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors:

may affect the fetus, causing cardiopulmonary toxicity (premature closure of the ductus arteriosus and pulmonary hypertension); may affect the fetus, causing renal dysfunction, which may progress to renal failure with oligohydramnios.

In a woman (at the end of pregnancy) and a newborn, the drug may affect:

on the duration of bleeding due to the antiplatelet effect, which 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 warnings and precautions for use").

Breastfeeding period

Like other NSAIDs, aceclofenac is excreted in small amounts into breast milk, 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 therefore not recommended in women attempting to conceive. Women who have difficulty conceiving or are undergoing fertility investigation should discontinue Aertal®.

Method of administration and doses

Method of application

Aertal®, powder for oral suspension, is intended for internal use. Dissolve the contents of one sachet in 40-60 ml of water and take immediately.

Simultaneous intake of food slows down the rate of absorption of the active substance, but does not reduce the degree of absorption from the gastrointestinal tract.

Dosage

Adverse reactions can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms (see section "Special warnings and precautions for use").

Adults: The recommended dose is one sachet twice daily (one sachet in the morning and one in the evening).

Elderly patients: Usually no dose reduction is required, however, the precautions mentioned in the section "Special warnings and precautions for use" should be observed.

Such patients should be carefully monitored, as they are more likely to have impaired renal function, liver 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 minimal doses and for the shortest possible time. Usually, 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.

Hepatic impairment: The dose of aceclofenac should be reduced in patients with mild to moderate hepatic impairment. The recommended starting dose is 100 mg daily (see section 4.4).

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

Children

The safety and efficacy of Aertal® in children and adolescents have not been established, 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 NSAID poisoning consists of the use of antacids (if necessary) and other supportive symptomatic therapy for complications such as arterial hypotension, renal failure, convulsions, irritation of the gastrointestinal mucosa, and respiratory depression.

Treatment of acute poisoning with oral aceclofenac 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 protein binding of NSAIDs and extensive metabolism.

Adverse reactions

Gastrointestinal: The most common adverse reactions were gastrointestinal. 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.

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

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 SLE, mixed connective tissue disease) with symptoms such as numbness (rigidity) of the neck muscles, fever, disorientation, confusion, hallucinations, malaise.

Hematological disorders: agranulocytosis, aplastic anemia.

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

In the table below, adverse reactions reported in clinical trials, as well as during the use of the drug Aertal®, are grouped by organ system and by frequency of occurrence: very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1000, <1/100), isolated (≥1/10000, <1/1000), rare (<1/10000).

Other side effects observed with the use of NSAIDs

Rare:

Renal and urinary disorders: interstitial nephritis.

Skin and subcutaneous tissue disorders: bullous reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis (very rare), photosensitivity.

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”).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions during post-marketing surveillance is very important. This allows monitoring of the benefit-risk balance of medicinal products. Healthcare professionals should report suspected adverse reactions.

Expiration date

4 years.

Storage conditions

The medicine does not require any special storage conditions.

Keep out of reach of children.

20 bags of powder in a cardboard box.

Vacation category

According to the recipe.

Producer

Gedeon Richter OJSC, Hungary.

Location of the manufacturer and its business address

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