Aertal, 3 g 20 pcs.

Pharmgroup:

NSAIDs.

Pharmic action:

Aertal is an NSAID. It has anti-inflammatory, analgesic and antipyretic effects. Inhibits the synthesis of prostaglandins and thus affects the pathogenesis of inflammation, pain and fever.

In rheumatic diseases the anti-inflammatory and analgesic effect of aceclofenac helps to significantly reduce the severity of pain, stiffness in the morning and swollen joints and improves the functional state of the patient.

Pharmacokinetics:

Absorption
Quickly and completely absorbed after oral administration. Cmax in plasma after oral administration is reached after 1.25-3 hours.

Distribution
Binding to plasma albumin is 99%.

It penetrates into the synovial fluid where its concentration reaches 57% of the plasma concentration level and Cmax is reached 2-4 hours later than in plasma. Vd is 25 liters.

Metabolism
It is metabolized to a small extent. Its main metabolite found in plasma is 4′-hydroxyacetylophenac.

Elimation
T1/2 – 4 hours. It is excreted by the kidneys mainly as hydroxy derivatives (about 2/3 of the administered dose).

Indications

Cure inflammation and pain syndrome in:
– lumbago;
– toothache;
– periarthritis of the shoulder blade;
– soft tissue rheumatic fever.
Symptomatic treatment of:
– rheumatoid arthritis;
– osteoarthritis;
– ankylosing spondylitis.

Active ingredient

Composition

1 bag:

– aceclofenac 100 mg

Supplements:

sorbitol – 2.639 g,

sodium saccharinate – 0.01 g,

aspartame – 0.01 g,

silicon dioxide colloid – 0.006 g,

hypromellose – 0.018 g,

titanium dioxide – 0.012 g,

milk flavoring – 0.1 g,

caramel flavoring – 0.05 g,

cream flavoring – 0.05 g.

How to take, the dosage

The contents of the sachets should be dissolved in 40-60 ml of water and taken immediately. Simultaneous intake of food slows the rate of absorption of the active ingredient, but does not reduce the degree of absorption from the gastrointestinal tract.

Adults:
The recommended dose of Aertal is 1 sachet 2 times a day (one in the morning and one in the evening).

Children:
The safety and effectiveness of the drug for the treatment of children and adolescents has not been established.

Elderly patients:
Dose reduction is usually not necessary, but the precautions in the “Special Precautions” section should be considered.

Hepatic impairment:
Lower doses of aceclofenac should be used when treating patients with mild to moderate hepatic impairment. The recommended starting dose is 100 mg per day.

Renal impairment:
There is no evidence that the dose of aceclofenac should be changed when treating patients with mild to moderate renal impairment, but caution is recommended.

Adverse events can be minimized by reducing the duration of treatment to the minimum necessary to achieve control of disease symptoms.

Interaction

There have been no studies of drug interactions, except for studies of interaction with warfarin.
Aceclofenac is metabolized in the cntochrome Р450 2С9 system and, according to in vitro studies, can inhibit this isoenzyme. Therefore, there is a possible risk of pharmacokinetic interaction with phenytoin, cimetidine, tolbutamide, phenylbutazone, amiodarone, miconazole and sulfaphenazole. As in the case of other drugs of the NSAID group, there is also a risk of pharmacokinetic interactions with other drugs that are actively excreted by the kidneys, such as methotrexate and lithium. Aceclofenac binds almost completely to plasma proteins; therefore, there is a possibility of interaction with other drugs with high affinity to plasma proteins by substitution type, which should be taken into account.

As there are not enough studies of pharmacokinetic interactions, the following information is based on data obtained for other NSAIDs:

The following drug combinations should be avoided:
Lithium and digoxin: some NSAIDs inhibit renal clearance of lithium and digoxin, which leads to increased serum concentrations of these drugs. This combination of drugs should be avoided unless frequent monitoring of lithium and digoxin is possible.

Anticoagulants: NSAIDs inhibit platelet aggregation and damage the gastrointestinal mucosa, which may lead to increased anticoagulant activity and increase the risk of gastrointestinal bleeding in patients taking anticoagulants. The combination of acyclofenac and oral coumarin-group anticoagulants, ticlopidine, thrombolytics and heparin should be avoided unless closely monitored.

Antiplatelet drugs and selective serotonin reuptake inhibitors in combination with NSAIDs may increase the risk of gastrointestinal bleeding. The following drug combinations may require dose adjustments and caution:

Methotrexate: NSAIDs inhibit the tubular secretion of methotrexate, so possible interactions between NSAIDs and methotrexate should also be considered when treating with low-dose methotrexate, especially in patients with renal impairment. In cases when it is necessary to use combined treatment, renal function should be monitored. Caution should be exercised in cases when both NSAIDs and methotrexate are administered together for 24 hours, since the concentration of methotrexate may increase, leading to an increase in its toxicity.

Cyclosporine, tacrolimus: Simultaneous use of NSAIDs and cyclosporine or tacrolimus is thought to increase the risk of renal toxicity due to reduced renal synthesis of prostacyclin. Therefore, it is very important to carefully monitor renal function during combination therapy.

Other NSAIDs: Concomitant use of acetylsalicylic acid and other NSAIDs may increase the frequency of adverse events, so caution should be exercised.

Glucocorticosteroids: the risk of gastrointestinal ulcers or gastrointestinal bleeding may increase.

Diuretics: Aceclofenac, as well as other NSAIDs, may inhibit the activity of diuretics, decrease the diuretic effect of furosemide, bumetanide, and the antihypertensive effect of thiazides. Concomitant treatment with potassium-saving diuretics may be associated with an increase in potassium, therefore, serum potassium should be monitored.

Aceclofenac has not been shown to affect BP control when used concomitantly with bendrofluazide, although drug interactions with other diuretics cannot be excluded.

Hypotensive drugs: NSAIDs may also decrease the effectiveness of certain hypotensive drugs. ACE inhibitors or angiotensin II receptor antagonists in combination with NSAIDs may lead to impaired renal function. In some patients with reduced renal function, such as elderly patients or patients with dehydration, there may be a risk of acute renal failure, which is usually reversible. Therefore, caution should be exercised when combining these drugs with NSAIDs, especially when treating elderly patients or patients with dehydration. Patients should be adequately hydrated, and consideration should be given to monitoring renal function after initiation of combination therapy, as well as periodically during treatment.

Aceclofenac has not been shown to affect BP control when administered concomitantly with bendrofluazide, although interactions with other diuretics cannot be ruled out.

Hypoglycemic drugs: In clinical studies it has been shown that diclofenac can be used concomitantly with oral hypoglycemic drugs without affecting their clinical efficacy. However, there are isolated reports of hypoglycemic and hyperglycemic effects of this drug. Consequently, with regard to aceclofenac, the possibility of dose adjustment of drugs that may cause hypoglycemia should be considered.

Zidovudine: concomitant use of NSAIDs and zidovudine increases the risk of hematological toxicity. There is evidence of an increased risk of hemarthrosis and hematoma formation in HIV-positive patients with hemophilia who receive concomitant treatment with zidovudine and ibuprofen.

Special Instructions

Aertal® should be avoided concomitantly with other NSAIDs, including selective cyclooxygenase-2 inhibitors.
Adverse events may be reduced by minimizing the duration of treatment and reducing the dose to the minimum necessary to achieve control of symptoms.

Gastrointestinal effects.
Aceclofenac should be prescribed with caution and under close medical supervision in patients with the conditions listed below, as a worsening of their course may occur:

– symptoms suggestive of gastrointestinal disease, including upper and lower GI;
– a history of peptic ulcer, bleeding, or perforation of gastric or intestinal ulcers in the presence of Helicobacter pylori infection;
– history of ulcerative colitis;
– history of Crohn’s disease;
– hematological diseases, systemic lupus erythematosus (SLE), porphyria and hematopoiesis disorders.

There have been reports of gastrointestinal bleeding, gastric or intestinal ulcer formation or ulcer perforation, which can lead to death when taking any NSAID at any time during treatment, with or without alarming symptoms, regardless of a history of serious gastrointestinal complications.

The risk of gastrointestinal bleeding, ulcer formation or ulcer perforation is higher when treated with high doses of NSAIDs in patients with a history of gastric or intestinal ulcers, especially if complicated by bleeding or perforation, and in older patients. Treatment of these patients should be started with the lowest effective dose. Also when treating these groups of patients and patients who require concomitant use of low-dose acetylsalicylic acid or other drugs that may increase the risk of gastrointestinal complications, the need for combination therapy with protective drugs (such as misoprostol or proton pump inhibitors) should be considered.

Patients with a history of gastrointestinal disease, especially the elderly, should report any unusual abdominal symptoms (especially gastrointestinal bleeding), giving maximum attention to symptoms early in treatment. Caution should be exercised when treating patients receiving concomitant medications that may increase the risk of ulceration or bleeding, such as systemic glucocorticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors, or antiaggregant medications such as acetylsalicylic acid.

In case of gastrointestinal bleeding or ulceration in patients taking Aertal® , treatment should be stopped.

The effect on the cardiovascular system and cerebral circulation.

When treating patients with arterial hypertension and/or chronic heart failure, appropriate monitoring and recommendations should be made, since there have been reports of fluid retention and edema development with NSAID treatment.

There are reasons to believe that some NSAIDs (especially in high doses and with long-term treatment) may cause an increased risk of arterial thrombotic complications (e.g., myocardial infarction or stroke). There is insufficient data to rule out this risk with aceclofenac.

Patients with uncontrolled arterial hypertension, congestive heart failure, established coronary heart disease, peripheral artery disease and/or cerebral vascular disease should begin treatment with aceclofenac only after an informed decision by the treating physician. Similarly, careful evaluation of indications for long-term treatment in patients with cardiovascular risk factors (e.g., arterial hypertension, hyperlipidemia, diabetes mellitus, and smoking) before starting treatment is necessary.

Patients with a history of cerebral hemorrhage should also exercise caution and close medical supervision when using aceclofenac.

Impacts on the liver and kidneys.
Treatment with NSAIDs may cause a dose-dependent decrease in prostaglandin synthesis and induce renal failure. The importance of prostaglandins in maintaining renal blood flow in patients with cardiac or renal dysfunction, liver dysfunction, patients being treated with diuretics or recovering from open surgery, and elderly patients must be considered.

Caution should be exercised when treating patients with hepatic or renal dysfunction or patients with other conditions that predispose to fluid retention. In these patients, treatment with NSAIDs may lead to impaired renal function and fluid retention in the body. Caution should also be exercised when using the drug in patients treated with diuretics or, conversely, in patients at risk of hypovolemia. The minimum effective dose should be prescribed and renal function should be monitored regularly. The effect of the drug on renal function is usually reversible after discontinuation of acyclofenac.

The treatment with aceclofenac should be discontinued if liver function tests deviations from normal values persist or increase with the appearance of clinical symptoms consistent with the development of hepatic failure, or if other manifestations (e.g., eosinophilia, rash) appear.

Hepatitis may develop without previous symptoms.
In patients with hepatic porphyria, use of NSAIDs may provoke exacerbation of the disease.

Hypersensitivity and skin reactions.
As with other NSAIDs, allergic reactions, including aaphylactic/anaphylactoid reactions, may occur in the early stages of use of the drug. In very rare cases, serious skin reactions, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, some of which may lead to death, have been observed during the use of NSAIDs. Patients are at highest risk of developing these reactions at the beginning of treatment, with most reactions manifesting in the first month of treatment. At the first signs of skin rash, mucosal damage or any other symptoms of hypersensitivity, treatment with Aerthal® should be discontinued.

In extremely rare cases, chickenpox may cause serious skin and soft tissue infectious complications. At this time, the role of NSAIDs in worsening the course of these infectious complications cannot be excluded. Consequently, it is recommended to avoid using Aertal® in chickenpox.

The effect on hematologic parameters.
Aceclofenac may reversibly inhibit platelet aggregation.

Respiratory system disorders.
Caution should be exercised when using the drug in patients with bronchial asthma or with a history of bronchial asthma because there are reports that NSAIDs may cause bronchospasm in such patients.

Patients in the elderly.
Caution should be exercised when treating elderly patients because this age group has an increased incidence of adverse events associated with NSAID treatment, particularly gastrointestinal bleeding and ulcer perforations, which can lead to death. In addition, elderly patients are more prone to renal, hepatic or cardiovascular failure.

Long-term treatment.
All patients receiving long-term NSAID treatment should be closely monitored with regular blood counts, liver and kidney function tests.

Each sachet of Aertal®, powder for oral suspension, 100 mg contains 2.64 g sorbitol, which may cause GI disorders and diarrhea. Patients with rare hereditary fructose intolerance should not be prescribed this drug.

Aertal®, powder for oral suspension, 100 mg, contains aspartame, a source of phenylalanine. Patients with phenylketonuria should note that each sachet contains 5.61 mg of phenylalanine.

Impact on ability to drive vehicles and operate machinery.

A refrain from driving and engaging in other potentially hazardous activities that require increased concentration and quick psychomotor reactions, as the drug may cause dizziness and other side effects that may affect the above abilities.

Contraindications

– gastrointestinal erosive and ulcerative lesions in the acute phase (including. Ulcerative colitis, Crohn’s disease);
– gastrointestinal bleeding or suspected bleeding;
– full or partial combination of bronchial asthma, recurrent nasal and paranasal sinus polyposis and intolerance to acetylsalicylic acid or other NSAIDs (including anamnesis history of acetylacetic acid or other NSAIDs;
– hypersensitivity to aceclofenac or Aerthal components;
– severe hepatic insufficiency or active liver disease;
– hematopoiesis and coagulation disorders;
– severe renal insufficiency (creatinine clearance < 30 ml/min), progressive renal disease, confirmed hyperkalemia;
– severe heart failure;
– period after coronary artery bypass grafting;
– pregnancy and lactation;
– children under 18 years:
– fructose intolerance;
– feinlketonuria.

With caution:
Chronic heart failure, coronary heart disease, arterial hypertension, decreased circulating blood volume (including the state after extensive surgical interventions. conditions after major surgical interventions), cerebrovascular diseases, peripheral arterial disease, chronic renal insufficiency (creatinine clearance less than 60 ml/min), liver failure, history of liver, kidney and GI diseases, history of ulcerative colitis, history of Crohn’s disease, bronchial asthma, dyspeptic symptoms at the time of the drug administration, history of GI ulcer development, presence of Helicobacter pylori infection, diabetes mellitus, dyslipidemia/hyperlipidemia, elderly age, smoking, long-term use of NSAIDs, taking glucocorticosteroids of systemic action, anticoagulants, antiaggregants, serotonin reuptake inhibitors, diuretics, alcoholism, severe somatic diseases, hematologic diseases, hematopoiesis disorders, systemic lupus erythematosus (SLE), porphyria, varicella.

Side effects

The following are adverse events reported in clinical trials and post-marketing surveillance; adverse events are grouped according to organ system classes according to the Medical Dictionary for Regulatory Affairs (MedDRA) and frequency of occurrence. Very common (≥1/10); common (≥1/100 to

– Blood and lymphatic system disordersRarely: anemia.
Very rare: suppression of bone marrow function, granulocytopenia, thrombocytopenia, neutropenia, hemolytic anemia.
– Immune system disorders
Rare: anaphylactic reactions (including shock), hypersensitivity.

– Metabolic and nutritional disorders
Very rare: hyperkalemia.

– Mental disorders
Very rare: depression, unusual dreams, insomnia.

– Nervous system disorders
Often: dizziness.
Very rare: paresthesia, tremor, somnolence, headache, dysgeusia (perversion of taste).

– Visual disturbances
Rare: visual disturbances.

– Hearing and labyrinth disorders
Very rare: dizziness, tinnitus.

– Heart disorders
Rarely: heart failure.
Very rare: feeling of palpitations.

– Vascular disorders
Rare: increase in BP, worsening the course of arterial hypertension.
Very rare: hyperemia, “hot flashes”, vasculitis.

– Respiratory system, thoracic and mediastinal organs disorders
Rare: dyspnea.
Very rare: bronchospasm.

– Gastrointestinal disorders
Often: dyspepsia, abdominal pain, nausea, diarrhea.
Infrequent: flatulence, gastritis, constipation, vomiting, ulcerative stomatitis.
Rare: melena, formation of gastric and intestinal ulcers, hemorrhagic diarrhea, gastrointestinal bleeding.
Very rare: stomatitis, vomiting blood, intestinal perforation, exacerbation of Crohn’s disease and ulcerative colitis, pancreatitis.

– Disorders of the liver and biliary tract
Often: increased liver enzyme activity.
Very rare: liver disease (including hepatitis), increased alkaline phosphatase activity.

– Skin and subcutaneous tissue disorders
Infrequent: itching, rash, dermatitis, urticaria.
Rare: Quincke’s edema.
Very rare: purpura, eczema, severe skin-mucosal reactions (including Stevens-Johnson syndrome and toxic epidermal necrolysis).

– Renal and urinary tract disorders
Infrequent: increased concentration of serum urea, increased concentration of serum creatinine.
Very rare: nephrotic syndrome, renal failure.

– General disorders and disorders at the site of administration
Very rare: edema, weakness, muscle cramps.

– Changes in laboratory and instrumental examinations
Very rare: weight gain.

Overdose

There are no data on overdose of aceclofenac in humans.

Possible symptoms: nausea, vomiting, stomach pain, dizziness, headache, hyperventilation with increased seizure activity.

Treatment: gastric lavage, administration of activated charcoal, symptomatic therapy. Forced diuresis and hemodialysis are not sufficiently effective.

Pregnancy use

Pregnancy:
Aertal® is contraindicated in pregnancy. There is no information about the use of aceclofenac in pregnancy.

Inhibition of prostaglandin synthesis may adversely affect the course of pregnancy and/or embryo/fetal development.
During the third trimester of pregnancy all inhibitors of prostaglandin synthesis:
– having cardiopulmonary toxicity, may cause premature closure of the Botall’s duct with the development of pulmonary hypertension;
– may cause impaired fetal renal function, which may progress to renal failure in combination with oligo.

Late pregnancy mothers and newborns:
– The drug may affect the duration of bleeding because of the antiaggregant effect, which may develop even after very low doses;
– The drug may suppress uterine contractions, leading to delayed labor or prolonged labor.

Lactation:
Aerthal® should not be taken during breastfeeding. There are no data on excretion of aceclofenac with female milk; no appreciable transfer of radioactive 14C-aceclofenac to milk was observed when administered to lactating rats.

Fertility:
NSAIDs may affect fertility and are not recommended for women planning to become pregnant.

Similarities