Aertal - instructions for use, dose, side effects, contraindications

Excipients: sorbitol 2,639 g, sodium saccharinate 0.010 g, aspartame 0.010 g, silicon dioxide colloid 0.006 g, hypromellose 0.018 g, titanium dioxide 0.012 g, milk flavor 0.100 g, caramel flavor 0.050 g, cream flavor 0.050 g

Description:

Powder white or white with a cream color shade.

Pharmacotherapeutic group:Non-steroidal anti-inflammatory drug (NSAID).

ATX: & nbsp

M.01.A.B Derivatives of acetic acid

M.01.A.B.16 Aceclofenac

Pharmacodynamics:

Aceclofenac is a non-steroidal anti-inflammatory drug that has an anti-inflammatory and analgesic effect. The mechanism of its action is based on the inhibition of the synthesis of prostaglandins.In rheumatic diseases, the anti-inflammatory and analgesic effect of aceclofenac contributes to a significant reduction in the severity of pain, morning stiffness, swelling of the joints, which improves the functional state of the patient.

Pharmacokinetics:

Suction

After oral administration aceclofenac quickly absorbed, its bioavailability is almost 100%. The maximum concentration in the blood plasma is reached approximately in 1,25 - 3 hours after the administration of the drug. Eating slows the rate of absorption, but does not affect the degree of absorption.

Distribution

Aceclofenac has a high affinity for proteins (> 99.7%). Aceclofenac penetrates into the synovial fluid, where its concentration reaches 60% of the concentration in the blood plasma. The volume of distribution is almost 30 liters.

Metabolism

Maybe, aceclofenac is metabolized by isoenzyme CYP2C9. The main metabolite is 4-OH-aceclofenac, whose role in the clinical activity of the drug appears to be negligible. Among a large number of metabolites were isolated diclofenac and 4-OH-diclofenac.

Excretion

The average half-life is 4 to 4.3 hours. The clearance is approximately 5 l / h.Approximately two-thirds of the administered dose of the drug is excreted by the kidneys, mainly in the form of conjugated hydroxyl metabolites. Only 1% of a single dose taken orally is excreted unchanged.

Pharmacokinetics in different patient groups:

In elderly patients no changes in the pharmacokinetics of aceclofenac were observed.

In patients with reduced liver function after a single dose of aceclofenac, a slowing down of the drug withdrawal rate was detected. In a study of multiple aceclofenac at a dose of 100 mg of the drug once a day, there was no difference in pharmacokinetic parameters in patients with mild to moderate liver cirrhosis and patients not suffering from this disease.

Patients with renal insufficiency of mild and moderate severity of clinically significant differences in pharmacokinetic parameters after a single application of the drug were not identified.

Indications:

Symptomatic treatment of rheumatoid arthritis, osteoarthrosis, ankylosing spondylitis, for the relief of inflammation and pain syndrome with lumbago, toothache, humeropathy periarthritis, rheumatic soft tissue damage.The drug is intended for symptomatic therapy, reducing pain and inflammation at the time of use, the progression of the disease is not affected.

Contraindications:

- erosive and ulcerative lesions of the gastrointestinal tract in the phase of exacerbation (including ulcerative colitis, Crohn's disease);

- gastrointestinal bleeding or suspicion of it;

- complete or incomplete combination of bronchial asthma, recurrent nasal polyposis and paranasal sinuses and intolerance to acetylsalicylic acid or other non-steroidal anti-inflammatory drugs (including in anamnesis);

- hypersensitivity to aceclofenac or drug components;

- severe hepatic insufficiency or active liver disease;

- disorders of hematopoiesis and coagulation;

- severe renal failure (creatinine clearance <30 ml / min), progressive kidney disease, confirmed hyperkalemia;

- severe heart failure;

- period after aorto-coronary bypass surgery;

- pregnancy and lactation;

- children's age till 18 years;

- intolerance to fructose;

- phenylketonuria.

Carefully:

Chronic heart failure, ischemic heart disease, arterial hypertension, decreased circulatory blood volume (including after extensive surgery), cerebrovascular diseases, peripheral arterial disease, chronic renal failure (creatinine clearance less than 60 ml / min), hepatic insufficiency , liver, kidney and gastrointestinal (GI) history in history, history of ulcerative colitis, history of Crohn's disease, bronchial asthma, dyspeptic symptoms at the time of n the prescription of the drug, anamnestic data on the development of gastrointestinal ulceration, the presence of infection Helicobacter pylori, diabetes, dyslipidemia / hyperlipidemia, old age, smoking, long-term use of NSAIDs, taking systemic glucocorticosteroids, anticoagulants, antiaggregants, serotonin reuptake inhibitors, diuretics, alcoholism, severe somatic diseases, hematological diseases, hematopoiesis, systemic lupus erythematosus (SLE) , porphyria, chicken pox.

Pregnancy and lactation:

Pregnancy

Aertal® is contraindicated in pregnancy.Information on the use of aceclofenac in pregnancy is absent.

The inhibition of the synthesis of prostaglandins can adversely affect the course of pregnancy and / or the development of the embryo / fetus.

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

- having cardiopulmonary toxicity, can cause premature closure of the Botallov duct with the development of pulmonary hypertension;

- can cause a violation of the kidney function of the fetus, which can progress to renal failure in combination with anhydrous.

Mothers in late pregnancy and newborns:

- the drug can influence the duration of bleeding due to the antiaggregant effect, which can develop even after the application of very low doses;

- the drug can inhibit uterine contractions, resulting in delayed delivery or prolonged labor.

Lactation

Avital® should not be taken during breastfeeding. Data on the isolation of aceclofenac with human milk are not available; when a radioactive ¹⁴C-aceclofenac to lactating rats of appreciable transfer of radioactivity into milk was not observed.

Fertility

Non-steroidal anti-inflammatory drugs (NSAIDs) can affect fertility and are not recommended for use by women planning a pregnancy.

Dosing and Administration:

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

Adults:

The recommended dose is 1 packet 2 times a day (one morning and one evening).

Children:

The safety and effectiveness of the drug for the treatment of children and adolescents is not established.

Older patients:

Usually, a dose reduction is not required, but the precautionary measures in the "Special instructions" section should be taken into account.

Liver failure:

In treating patients with impaired liver function of mild and moderate severity, lower doses of aceclofenac should be used. The recommended initial dose is 100 mg per day.

Renal insufficiency:

Evidence of the need to change the dose of aceclofenac in the treatment of patients with impaired renal function of mild and moderate severity is not available, but caution is recommended.

Undesirable effects can be minimized by shortening the duration of treatment to the minimum required to achieve control of the symptoms of the disease.

Side effects:

The following are undesirable phenomena, information about which was obtained in clinical studies and during post-marketing surveillance; Undesirable phenomena are grouped according to the classes of systems of organs according to the Medical dictionary for regulatory activities (MedDRA) and frequency of occurrence. Very often (> 1/10); often (from> 1/100 to <1/10); infrequently (from> 1/1000 to <1/100), rarely (from> 1/10000 to <1/1000), very rarely (<1/10000).

List of adverse reactions

Violations of the blood and lymphatic system Rare: anemia. Very rarely: suppression of bone marrow function, granulocytopenia, thrombocytopenia, neutropenia, hemolytic anemia.

Immune system disorders Rarely: anaphylactic reactions (including shock), hypersensitivity.

Disorders from the metabolism and nutrition Very rarely: hyperkalemia.

Disorders of the psyche Very rare: depression, unusual dreams, insomnia.

Disturbances from the nervous system Often: dizziness. Very rarely: paresthesia, tremor, drowsiness, headache, dysgeusia (perversion of taste).

Disturbances on the part of the organ of sight Rarely: a vision disorder.

Hearing disorders and labyrinthine disorders Very rarely: dizziness, ringing in the ears.

Heart Disease Rarely: heart failure. Very rarely: a feeling of palpitations.

Vascular disorders Rarely: increased blood pressure, worsening of the course of arterial hypertension. Very rarely: hyperemia, "hot flashes", vasculitis.

Disturbances from the respiratory system, chest and mediastinal organs Rarely: shortness of breath. Very rarely: bronchospasm.

Disorders from the gastrointestinal tract Often: indigestion, abdominal pain, nausea, diarrhea. Infrequent: flatulence, gastritis, constipation, vomiting, ulcerative stomatitis. Rarely: melena, the formation of ulcers of the stomach and intestines, hemorrhagic diarrhea, gastrointestinal bleeding. Very rarely: stomatitis, vomiting of blood, perforation of the intestine, exacerbation of Crohn's disease and ulcerative colitis, pancreatitis.

Disturbances from the liver and bile ducts Often: increased activity of liver enzymes. Very rarely: liver disease (including hepatitis), increased activity of alkaline phosphatase.

Disorders from the rut and subcutaneous tissues Infrequent: itching, rash, dermatitis, hives. Rarely: edema of Quincke. Very rarely: purpura, eczema, severe mucocutaneous reactions (including Stevens-Johnson syndrome and toxic epidermal necrolysis).

Disorders from the kidneys and urinary tract Infrequent: increased serum urea concentration, increased serum creatinine concentration. Very rarely: nephrotic syndrome, renal failure.

General disorders and disorders at the site of administration Very rarely: swelling, weakness, muscle spasms.

Changes in laboratory and instrumental research Very rarely: weight gain.

Overdose:

There is no evidence of an overdose of aceclofenac in humans.

Possible Symptoms: nausea, vomiting, stomach pain, dizziness, headache, hyperventilation phenomena with increased convulsive readiness.

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

Interaction:

Studies of drug interactions were not conducted, except for studies of interaction with warfarin.

Aceclofenac is metabolized in the cytochrome P450 2C9 system and, according to research data in vitro, can inhibit this isoenzyme. Therefore, there is a risk of pharmacokinetic interaction with phenytoin, cimetidine, tolbutamide, phenylbutazone, amiodarone, miconazole and sulfafenazole. As with other drugs of the NSAID group, there is also a risk of pharmacokinetic interactions with other drugs, actively excreted kidneys, such as methotrexate and lithium. Aceclofenac almost completely binds to blood plasma proteins, therefore, there is a possibility of interaction with other drugs with high affinity for plasma proteins, by the type of substitution that should be taken into account.

Since studies of pharmacokinetic interactions are not sufficient, the information below is based on data obtained for other NSAIDs:

The following combinations should be avoided:

Lithium and digoxin: some NSAIDs inhibit renal clearance of lithium and digoxin, which leads to an increase in the concentrations of these drugs in the blood serum.Avoid this drug combination, except when possible frequent monitoring performance of digoxin and lithium.

Anticoagulants: NSAIDs inhibit platelet aggregation and damage the mucous membrane of the gastrointestinal tract, which can lead to increased anticoagulant activity and increase the risk of gastrointestinal bleeding in patients taking anticoagulants. It should avoid the use of a combination of aceclofenac group and coumarin anticoagulants for ingestion, ticlopidine, thrombolytic agents and heparin, except when a careful control.

Antiaggregant drugs and selective serotonin reuptake inhibitors in combination with NSAIDs may increase the risk of gastrointestinal bleeding.

The following combinations of drugs may require dose adjustment and caution:

Methotrexate: NSAIDs inhibit the tubular secretion of methotrexate, so it should also take into account possible interactions between the NSAID and methotrexate in the treatment of low-dose methotrexate, especially in patients with renal insufficiency.In cases where combined treatment is necessary, renal function should be monitored. Care should be taken in cases where both NSAIDs and methotrexate are administered together within 24 hours, as the concentration of methotrexate may increase, which will lead to an increase in its toxicity.

Cyclosporin, tacrolimus: it is considered that the simultaneous use of NSAIDs and cyclosporine or tacrolimus increases the risk of renal toxicity due to decreased prostacyclin synthesis by the kidneys. Therefore, it is very important to carefully monitor the kidney function during the combined treatment.

DOther NSAIDs: simultaneous use of acetylsalicylic acid and other non-steroidal anti-inflammatory drugs can increase the incidence of adverse events, so caution should be exercised.

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

Diuretics: aceclofenac, like other NSAIDs, can inhibit the activity of diuretics, reduce the diuretic effect of furosemide, bumetanide and the antihypertensive effect of thiazides.Simultaneous treatment with potassium-sparing diuretics can be associated with an increase in the potassium content, therefore, it is necessary to control the potassium content in the blood serum.

It was shown that aceclofenac does not affect the control of blood pressure with simultaneous use with bendrofluazidom, despite the fact that drug interactions with other diuretics can not be ruled out.

Hypotensive drugs: NSAIDs may also decrease the effectiveness of certain antihypertensive drugs. ACE inhibitors or angiotensin II receptor antagonists in combination with NSAIDs can lead to impaired renal function. In some patients with reduced renal function, for example, in elderly patients or patients with dehydration, there may be a risk of developing acute renal failure, which is usually reversible. Therefore, care must be taken when combining these drugs with NSAIDs, especially when treating older patients or patients with dehydration. Patients should be sufficiently hydrated, in addition,it is recommended to take into account the need to monitor kidney function after the initiation of combined treatment, as well as periodically during treatment.

It was shown that aceclofenac does not affect the control of blood pressure with simultaneous administration with bendroflaazide, despite the fact that interactions with other diuretics can not be ruled out.

Hypoglycemic drugs: in clinical studies it was shown that diclofenac can be used simultaneously with hypoglycemic drugs for oral administration, without affecting their clinical effectiveness. However, there are some reports of hypoglycemic and hyperglycemic effects of this drug. Therefore, with respect to aceclofenac, the possibility of dose adjustment of drugs that can cause hypoglycemia should be considered.

Zidovudine: with the simultaneous 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 and concomitant treatment with zidovudine and ibuprofen.

Special instructions:

Avetal® should be avoided concomitantly with other NSAIDs, including selective cyclooxygenase-2 inhibitors.

Undesirable effects can be reduced if the duration of treatment is minimized and the dose is reduced to the minimum necessary to achieve control of the symptoms of the disease.

Effect on the gastrointestinal tract

Aceclofenac should be administered with caution and under close medical supervision to patients with the diseases listed below, as there may be a worsening of their course:

- symptoms that indicate gastrointestinal diseases, including the upper and lower gastrointestinal tract;

- ulcer, bleeding or perforation of a stomach ulcer or intestinal anamnesis in the presence of an infection Helicobacter pylori;

- ulcerative colitis in the anamnesis;

- Crohn's disease in history;

- hematological diseases, systemic lupus erythematosus (SLE), porphyria and hematopoiesis.

There are reports of gastrointestinal bleeding, the formation of a stomach ulcer or intestinal ulcer or perforation of the ulcer, which can lead to death when taking any NSAID at any time against the background of treatment,accompanied or not accompanied by anxiety symptoms, regardless of the history of serious gastrointestinal complications.

The risk of gastrointestinal bleeding, ulcer formation or perforation of ulcers is higher when treated with high doses of NSAIDs in patients with a stomach ulcer or intestinal anamnesis, especially if it is complicated by bleeding or perforation, as well as in elderly patients. Treatment of these patients should start with the lowest effective dose. Also, in the treatment of these groups of patients and patients requiring simultaneous use of low-dose acetylsalicylic acid or other drugs that may increase the risk of developing gastrointestinal complications, consideration should be given to the need for combination therapy with protective agents (eg misoprostol or proton pump inhibitors) .

Patients with a history of gastrointestinal disease, especially the elderly, should report any unusual symptoms in the abdomen (especially gastrointestinal bleeding), paying maximum attention to symptoms in the early stages of treatment.Care must be taken when treating patients receiving concomitant medications that may increase the risk of ulceration or bleeding, such as systemic glucocorticosteroids, anticoagulants, for example, warfarin, selective serotonin reuptake inhibitors or antiplatelet agents, such as acetylsalicylic acid.

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

Influence on the cardiovascular system and cerebral circulation

In the treatment of patients with hypertension and / or chronic heart failure, appropriate monitoring and recommendations should be made, as there are reports of the development of fluid retention and edema during the treatment of NSAIDs.

There are reasons to believe that some NSAIDs (especially in high doses and long-term treatment) can cause an increased risk of developing arterial thrombotic complications (eg, myocardial infarction or stroke). To exclude this risk, the use of aceclofenac is inadequate.

Patients with uncontrolled hypertension, congestive heart failure, established ischemic heart disease, peripheral arterial disease and / or cerebrovascular disease should begin treatment with aceclofenac only after a well-informed decision by the treating physician. Similarly, a careful evaluation of indications for long-term treatment of patients with risk factors for cardiovascular disease (for example, hypertension, hyperlipidemia, diabetes and smoking) is necessary before it begins.

Also, care should be taken and careful medical supervision should be performed when aceclofenac is used in patients with an anamnesis of cerebral hemorrhage.

Effects on the liver and kidneys

Treatment with NSAIDs can cause a dose-dependent reduction in prostaglandin synthesis and provoke renal failure. It is necessary to take into account the importance of prostaglandins for maintaining renal blood flow in patients with cardiac or renal dysfunction, liver dysfunction, patients receiving diuretic treatment or recovering from a cavitary operation, and elderly patients.

Caution should be exercised in the treatment of patients with impaired liver or kidney function, as well as patients with other diseases predisposing to fluid retention. In these patients, treatment with NSAIDs can lead to impaired renal function and to fluid retention in the body. Also, care should be taken when using the drug to patients receiving diuretic treatment, or, on the contrary, to patients at risk of hypovolemia. It is necessary to prescribe a minimum effective dose and to conduct regular monitoring of kidney function. The effect of the drug on kidney function is usually reversible after the abolition of aceclofenac.

It is necessary to cancel the treatment with aceclofenac if the deviations in the functional liver tests from normal values persist or increase with the appearance of clinical symptoms corresponding to the development of hepatic insufficiency, or in the case of other manifestations (eg, eosinophilia, rash).

Hepatitis can develop without previous symptoms.

In patients with hepatic porphyria, the use of NSAIDs may provoke an exacerbation of the disease.

Hypersensitivity and skin reactions

As with other NSAIDs, early allergic reactions, including anaphylactic / anaphylactoid reactions, may occur. In very rare cases, with the use of NSAIDs, serious skin reactions have been observed, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, some of which can lead to death. Patients are at the highest risk of developing these reactions at the beginning of the course of treatment, in most cases the reactions manifest in the first month of treatment. At the first signs of skin rash, damage to the mucous membranes or any other symptoms of hypersensitivity, it is necessary to cancel the treatment with the drug Aertal®.

In extremely rare cases, chicken pox can provoke serious infectious complications from the skin and soft tissues. At the moment, the role of NSAIDs in worsening of the course of these infectious complications can not be ruled out. Therefore, Avertal® should be avoided in case of chicken pox.

Influence on hematologic indices

Aceclofenac can reversibly inhibit the aggregation of platelets.

Disturbances from the respiratory system

Care must be taken when using the drug in patients with bronchial asthma or with an anamnesis of bronchial asthma, since there are reports that NSAIDs can cause bronchospasm in such patients.

Elderly patients

Caution should be exercised in the treatment of elderly patients, since the incidence of adverse events associated with the treatment of NSAIDs, especially gastrointestinal bleeding and perforation of the ulcer, which may lead to death, is increased in this age group. In addition, elderly patients are more susceptible to renal, hepatic or cardiovascular failure.

Long-term treatment

It is necessary to carefully monitor all patients receiving long-term treatment with nonsteroidal anti-inflammatory drugs, regularly performing a general blood test, functional tests of the liver and kidneys.

Each packet of the drug Aertal®, powder for oral suspension, 100 mg, contains 2.64 g of sorbitol, which can cause disturbances in the gastrointestinal tract and diarrhea.Patients with a rare hereditary intolerance to fructose can not be prescribed this drug.

Aertal®, powder for oral suspension, 100 mg, contains aspartame, a source of phenylalanine. Patients with phenylketonuria should take into account that each packet contains 5.61 mg of phenylalanine.

Effect on the ability to drive transp. cf. and fur:

It should refrain from driving and other potentially hazardous activities requiring increased attention and speed of psychomotor reactions, as the drug may cause dizziness and other side effects that may affect these abilities.

Form release / dosage:

Powder for suspension for oral administration, 100 mg.

Packaging:

By 3.0 g of the drug in a three-layer sachet (paper / Al / PE). For 20 bags in a cardboard box together with instructions for use.

Storage conditions:

Store at a temperature not exceeding 30 ° C.

Keep out of the reach of children!

Shelf life:

4 years

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-001886

Date of registration:24.10.2012

The owner of the registration certificate:Almiral S.A.Almiral S.A. Spain

Manufacturer: & nbsp

INDUSTRIAS FARMACEUTICAS ALMIRALL, S.L. Spain

Representation: & nbspGEDEON RICHTER OJSC GEDEON RICHTER OJSC Hungary

Information update date: & nbsphttp://grls.rosminzdrav.ru/Grls_View.aspx?idReg=275464&isOld=1&t=

Illustrated instructions

Instructions

Aertal® (Airtal®)