Airtal^® (Tablets, Cream, Powder) Instructions for Use

ATC Code

M01AB16 (Aceclofenac)

Active Substance

Aceclofenac (Rec.INN registered by WHO)

Clinical-Pharmacological Group

NSAID

Pharmacotherapeutic Group

Anti-inflammatory and antirheumatic drugs. Non-steroidal anti-inflammatory and antirheumatic drugs

Pharmacological Action

NSAID, has anti-inflammatory and analgesic effects. The mechanism of action of the drug is based on the inhibition of prostaglandin synthesis, which contributes to the development of inflammation.

In rheumatic diseases, the anti-inflammatory and analgesic effects of aceclofenac contribute to a significant reduction in the severity of pain, morning stiffness, and joint swelling, which improves the patient’s functional state.

Pharmacokinetics

Absorption

After oral administration, Aceclofenac is rapidly absorbed. C_max in plasma is reached approximately 1.25-3 hours after drug administration. Food intake slows the rate of absorption but does not affect the extent of absorption. Bioavailability is almost 100%.

Distribution

Aceclofenac has high protein binding (>99.7%). Aceclofenac penetrates into the synovial fluid, where its concentration reaches 60% of the plasma concentration. V_d is approximately 30 L.

Metabolism

Aceclofenac is believed to be metabolized by the isoenzyme CYP2C9. The main metabolite is 4-OH-Aceclofenac. Among a large number of metabolites, diclofenac and 4-OH-diclofenac have been identified.

Excretion

The mean T_1/2 is 4-4.3 hours. Clearance is approximately 5 L/h. Approximately two-thirds of the administered drug dose is excreted by the kidneys, mainly in the form of conjugated hydroxyl metabolites. Only 1% of a single oral dose is excreted unchanged.

Pharmacokinetics in different patient groups

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

In patients with impaired liver function, a slowdown in the rate of drug elimination was detected after a single dose of aceclofenac. In a study of multiple doses of aceclofenac 100 mg once daily, no differences in pharmacokinetic parameters were found in patients with mild and moderate liver cirrhosis and patients without this disease.

In patients with mild to moderate renal impairment, no clinically significant differences in pharmacokinetic parameters were found after a single dose of the drug.

Preclinical safety data

Studies in rats did not provide evidence of a teratogenic effect, although systemic exposure was low, and in studies in rabbits, administration of aceclofenac (10 mg/kg/day) caused a number of morphological changes in some embryos.

Studies of the carcinogenic effect in mice (systemic exposure to aceclofenac is unknown) and rats (metabolism to diclofenac) did not reveal a carcinogenic effect of the drug. A negative result was also shown in tests for the genotoxicity of aceclofenac.

Indications

Treatment of chronic joint diseases with chronic pain and inflammation, including

• Osteoarthritis;
• Rheumatoid arthritis;
• Ankylosing spondylitis;
• Scapulohumeral periarthritis;
• Non-articular rheumatism.

Treatment of conditions with acute inflammation and pain, including

• Lumbago;
• Toothache;
• Joint pain;
• Algodysmenorrhea.

The drug is intended for symptomatic therapy, reducing pain and inflammation at the time of use, and does not affect the progression of the disease.

ICD codes

Dosage Regimen

Tablets

Orally. The tablets should be swallowed whole with a sufficient amount of water. Airtal^® can be taken with food.

Adults aged 18 years and older

The recommended dose is 1 tablet of 100 mg twice a day (morning and evening). The maximum recommended dose is 200 mg/day.

Special patient groups

Patients with impaired liver function. The dose of aceclofenac should be reduced in patients with mild or moderate hepatic impairment. The recommended starting dose is 100 mg/day.

Patients with impaired renal function. There is no data on the need to reduce the dose of aceclofenac in patients with mild renal impairment, but caution should be exercised when using Airtal^®.

Elderly patients (over 65 years). Generally, there is no need to reduce the dose, but the precautions indicated in the “Special Instructions” section should be observed.

Children and adolescents under 18 years. The use of Airtal^® is contraindicated due to the lack of data on efficacy and safety.

Powder

Orally. The contents of the sachets should be dissolved in 40-60 ml of water and taken immediately.

Patients suffering from gastrointestinal diseases should take Airtal^® preferably with meals. Simultaneous food intake slows the rate of absorption of the active substance but does not reduce the extent of absorption from the gastrointestinal tract.

Adults

The recommended dose is 1 sachet twice a day (1 in the morning and 1 in the evening).

Children

The safety and efficacy of the drug for the treatment of children and adolescents have not been established.

Elderly patients

Usually, dose reduction is not required, but the precautions given in the “Special Instructions” section should be taken into account.

Hepatic impairment

When treating patients with mild to moderate hepatic impairment, lower doses of aceclofenac should be used. The recommended starting dose is 100 mg/day.

Renal impairment

There is no evidence of the need to change the dose of aceclofenac 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 the disease symptoms.

Cream

Airtal^® cream is for external use only. The cream should not be applied under occlusive dressings.

After applying the cream, hands should be washed, except when the hands are the area of application. The drug should not get into the eyes or mouth.

Airtal^® should only be applied to intact skin.

Airtal^® should be applied with light massaging movements to the affected area 3 times a day. The applied dose depends on the size of the affected area: 1.5-2 g of Airtal^® cream (approximately corresponding to a 5-7 cm long strip of cream).

The patient should be advised that when using the drug without a doctor’s prescription for the treatment of muscle and joint injuries (sprains, strains, bruises) or tendonitis, the duration of use should not exceed 2 weeks.

The duration of use of the drug without a doctor’s prescription for the treatment of arthritis should not exceed 3 weeks.

If symptoms worsen or do not decrease after 7 days of use, the patient should consult a doctor for further examination.

Dosage adjustment in elderly patients is not required.

There is no experience with the use of Airtal^® cream in children, therefore Airtal^® cream is contraindicated for use in children.

Adverse Reactions

The following are adverse events that have been reported in clinical trials and during post-marketing surveillance. Adverse events are grouped according to system organ classes according to MedDRA and frequency of occurrence: very common (≥1/10); common (from ≥1/100 to <1/10); uncommon (from ≥1/1000 to <1/100), rare (from ≥1/10,000 to <1/1000), very rare (<1/10,000).

Blood and lymphatic system disorders: rare – anemia; very rare – bone marrow function depression, granulocytopenia, thrombocytopenia, neutropenia, hemolytic anemia.

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

Metabolism and nutrition disorders: very rare – hyperkalemia.

Psychiatric disorders: very rare – depression, abnormal dreams, insomnia.

Nervous system disorders: very common – dizziness; very rare – paresthesia, tremor, somnolence, headache, dysgeusia (taste disturbance).

Eye disorders: rare – visual disturbance.

Ear and labyrinth disorders: very rare – vertigo, tinnitus.

Cardiac disorders: rare – heart failure; very rare – palpitations.

Vascular disorders: rare – increased blood pressure, worsening of arterial hypertension; very rare – hyperemia, “hot flushes”, vasculitis.

Respiratory, thoracic and mediastinal disorders: rare – dyspnea; very rare – bronchospasm.

Gastrointestinal disorders common – dyspepsia, abdominal pain, nausea, diarrhea; uncommon – flatulence, gastritis, constipation, vomiting, ulcerative stomatitis; rare – melena, formation of gastric and intestinal ulcers, hemorrhagic diarrhea, gastrointestinal bleeding; very rare – stomatitis, hematemesis, intestinal perforation, exacerbation of Crohn’s disease and ulcerative colitis, pancreatitis.

Hepatobiliary disorders: common – increased liver enzyme activity; very rare – liver disease (including hepatitis), increased alkaline phosphatase activity.

Skin and subcutaneous tissue disorders: uncommon – pruritus, rash, dermatitis; very rare – purpura, eczema, severe mucocutaneous reactions (including Stevens-Johnson syndrome and toxic epidermal necrolysis).

Allergic reactions uncommon – urticaria; rare – angioedema.

Renal and urinary disorders: uncommon – increased serum urea concentration, increased serum creatinine concentration; very rare – nephrotic syndrome, renal failure.

General disorders and administration site conditions: very rare – edema, asthenia, muscle spasms.

Investigations: very rare – increased body weight.

Contraindications

• Erosive and ulcerative lesions of the gastrointestinal tract in the acute phase (including ulcerative colitis, Crohn’s disease);
• Gastrointestinal bleeding or suspicion of it;
• Complete or incomplete combination of bronchial asthma, recurrent polyposis of the nose and paranasal sinuses and intolerance to acetylsalicylic acid or other NSAIDs (including in history);
• Severe hepatic impairment or active liver disease;
• Hematopoiesis and coagulation disorders;
• Severe renal failure (creatinine clearance <30 ml/min), progressive kidney disease, confirmed hyperkalemia;
• Severe heart failure (NYHA class II-IV);
• Coronary artery disease;
• Peripheral arterial and/or cerebrovascular diseases;
• Period after coronary artery bypass graft surgery;
• Pregnancy;
• Lactation period;
• Children under 18 years of age;
• Sucrase/isomaltase deficiency, fructose intolerance, glucose-galactose malabsorption;
• Phenylketonuria;
• Hypersensitivity to aceclofenac or components of the drug.

With caution

Chronic heart failure, coronary artery disease, arterial hypertension, decreased circulating blood volume (including condition after extensive surgical interventions), cerebrovascular diseases, peripheral arterial diseases, chronic renal failure (creatinine clearance 30-60 ml/min), hepatic impairment, history of liver, kidney and gastrointestinal diseases, history of ulcerative colitis, history of Crohn’s disease, bronchial asthma, dyspeptic symptoms at the time of prescribing the drug, history of gastrointestinal ulcerative lesions, presence of Helicobacter pylori infection, diabetes mellitus, dyslipidemia/hyperlipidemia, elderly age, smoking, long-term use of NSAIDs, use of systemic corticosteroids, anticoagulants, antiplatelet agents, serotonin reuptake inhibitors, diuretics, alcoholism, severe somatic diseases, hematological diseases, blood formation disorders, systemic lupus erythematosus, mixed connective tissue disease, porphyria, chickenpox.

Use in Pregnancy and Lactation

Pregnancy

Airtal^® is contraindicated during pregnancy. There is no information on the use of aceclofenac during pregnancy.

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

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

• Having cardiopulmonary toxicity, can cause premature closure of the ductus arteriosus with the development of pulmonary hypertension;
• May cause impairment of fetal renal function, which may progress to renal failure in combination with oligohydramnios.

In late pregnancy

• The drug may affect bleeding time due to an antiplatelet effect, which may develop even after use in very low doses;
• The drug may suppress uterine contractions, leading to delayed or prolonged labor.

Breastfeeding period

Airtal^® should not be taken during breastfeeding. There are no data on the excretion of aceclofenac into breast milk; when using radioactive ¹⁴C-aceclofenac in preclinical studies, no significant transfer of radioactivity into milk was observed.

Fertility

NSAIDs may affect fertility and are not recommended for women planning pregnancy. In this regard, women who have conception problems and are undergoing examination for infertility are advised to temporarily discontinue Airtal^®.

Use in Hepatic Impairment

The drug is contraindicated in patients with severe hepatic impairment or active liver disease.

When treating patients with mild to moderate hepatic impairment, lower doses of aceclofenac should be used.

Use in Renal Impairment

The drug is contraindicated in patients with severe renal failure (creatinine clearance <30 ml/min), progressive kidney disease, confirmed hyperkalemia.

There is no evidence of the need to change the dose of aceclofenac when treating patients with mild to moderate renal impairment, but caution is recommended.

Pediatric Use

The drug is contraindicated in patients under 18 years of age. The safety and efficacy of the drug for the treatment of children and adolescents have not been established.

Geriatric Use

Caution should be exercised when taking the drug in elderly patients.

Special Precautions

The use of Airtal^® simultaneously with other NSAIDs, including selective COX-2 inhibitors, should be avoided.

Adverse events can be reduced by minimizing the duration of treatment and reducing the drug dose to the minimum necessary to achieve control of the disease symptoms.

Effect on the gastrointestinal tract

Aceclofenac should be prescribed with caution and under close medical supervision to patients with the diseases listed below, as their course may worsen

• Symptoms indicating gastrointestinal diseases, including the upper and lower gastrointestinal tract;
• History of ulcer, bleeding or perforation of gastric or intestinal ulcer in the presence of Helicobacter pylori infection;
• History of ulcerative colitis;
• History of Crohn’s disease;
• Hematological diseases, systemic lupus erythematosus (SLE), porphyria and blood formation disorders.

There are reports of gastrointestinal bleeding, formation of gastric or intestinal ulcers or ulcer perforation, which can be fatal when taking any NSAID at any time during treatment, with or without warning symptoms, regardless of a history of serious gastrointestinal complications.

The risk of gastrointestinal bleeding, ulcer formation or ulcer perforation is higher when treating with high doses of NSAIDs in patients with a history of gastric or intestinal ulcer, especially if complicated by bleeding or perforation, as well as in elderly patients. Treatment of these patients should be started with the lowest effective dose. Also, when treating these groups of patients and patients who require simultaneous 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 (e.g., misoprostol or proton pump inhibitors) should be considered.

Patients with a history of gastrointestinal diseases, primarily the elderly, should report any unusual abdominal symptoms (especially gastrointestinal bleeding), paying maximum attention to symptoms in the early stages of treatment. Caution is required when treating patients receiving concomitant medications that may increase the risk of ulceration or bleeding, such as systemic corticosteroids, anticoagulants, for example, warfarin, selective serotonin reuptake inhibitors, or antiplatelet drugs such as acetylsalicylic acid.

In the event of gastrointestinal bleeding or ulcer formation in patients taking Airtal^®, treatment should be discontinued.

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 provided, as there are reports of fluid retention and edema developing during treatment with NSAIDs.

Aceclofenac is structurally related to diclofenac and has similar metabolism. For diclofenac, there are data indicating an increased risk of thromboembolic complications (e.g., myocardial infarction or stroke, particularly during long-term treatment with high doses). There is also a risk of acute coronary syndrome associated with the intake of aceclofenac. With increasing duration of treatment, the risk of cardiovascular complications increases.

Patients with chronic heart failure (NYHA class I) and patients with risk factors for cardiovascular complications (e.g., arterial hypertension, diabetes mellitus, smoking) should initiate treatment with aceclofenac only after a considered decision by the attending physician. Cardiovascular risks may depend on the dose and duration of treatment; therefore, Airtal^® should be prescribed at the lowest effective dose and for the shortest possible duration.

Caution and thorough medical supervision are also required when prescribing aceclofenac to patients with a history of cerebral hemorrhage.

Effect on the Liver and Kidneys

NSAID treatment can cause a dose-dependent decrease in prostaglandin synthesis and provoke renal failure. The importance of prostaglandins for maintaining renal blood flow should be taken into account in patients with impaired heart or kidney function, liver dysfunction, patients receiving diuretic treatment or recovering from major surgery, as well as elderly patients.

Caution should be exercised when treating patients with impaired liver or kidney function, as well as patients with other conditions predisposing to fluid retention. In these patients, NSAID treatment may lead to impaired kidney function and fluid retention in the body. Caution is also required when using the drug in patients receiving diuretic treatment or, conversely, patients at risk of hypovolemia. The minimum effective dose should be prescribed, and regular monitoring of kidney function should be performed. The effect of the drug on kidney function is usually reversible after discontinuation of aceclofenac.

Aceclofenac treatment should be discontinued if deviations in liver function test results from normal values persist or increase, if clinical symptoms corresponding to the development of liver failure appear, or in the case of other manifestations (e.g., eosinophilia, rash).

Hepatitis may develop without preceding symptoms.

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

Hypersensitivity and Skin Reactions

As with the use of other NSAIDs, allergic reactions, including anaphylactic/anaphylactoid reactions, may occur even in the early stages of drug use. In very rare cases, serious skin reactions, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been observed during the use of NSAIDs; some of these can be fatal. Patients are at the highest risk of developing these reactions at the beginning of the treatment course; in most cases, reactions manifest within the first month of treatment. At the first signs of skin rash, mucosal lesions, or any other symptoms of hypersensitivity, treatment with Airtal^® should be discontinued.

In exceptionally rare cases, varicella can provoke serious infectious complications of the skin and soft tissues. Currently, the role of NSAIDs in worsening the course of these infectious complications cannot be ruled out. Therefore, it is recommended to avoid the use of Airtal^® in cases of varicella.

Effect on Hematological Parameters

Aceclofenac may reversibly inhibit platelet aggregation.

Respiratory System Disorders

Caution is required when prescribing the drug to patients with bronchial asthma or a history of bronchial asthma, as there are reports that NSAIDs can cause bronchospasm in such patients.

Elderly Patients

Caution should be exercised when treating elderly patients, as the frequency of adverse events associated with NSAID treatment is increased in this age group, especially gastrointestinal bleeding and ulcer perforation, which can be fatal. Furthermore, elderly patients are more susceptible to renal, hepatic, or cardiovascular failure.

Long-Term Treatment

All patients receiving long-term NSAID treatment should be carefully monitored, with regular complete blood count, liver, and kidney function tests performed.

Excipients

Each sachet of Airtal^®, powder for oral suspension, 100 mg, contains 2639 mg of sorbitol, which may cause gastrointestinal disturbances and diarrhea. Patients with rare hereditary fructose intolerance should not be prescribed this drug.

Airtal^®, powder for oral suspension, 100 mg, contains aspartame, a source of phenylalanine. Patients with phenylketonuria should be aware that each sachet contains 5.61 mg of phenylalanine.

Airtal^®, powder for oral suspension, contains less than 1 mmol (23 mg) of sodium per sachet, meaning it is essentially sodium-free.

Effect on the Ability to Drive and Operate Machinery

Refrain from driving vehicles and engaging in other potentially hazardous activities requiring increased concentration and speed of psychomotor reactions, as the drug may cause dizziness and other side effects that can affect these abilities.

Overdose

There are no data on aceclofenac overdose in humans.

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

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

Drug Interactions

Drug interaction studies have not been conducted, except for studies of interaction with warfarin.

Aceclofenac is metabolized by the CYP2C9 isoenzyme and, according to in vitro studies, may inhibit this isoenzyme. Therefore, there is a possible risk of pharmacokinetic interaction with phenytoin, cimetidine, tolbutamide, phenylbutazone, amiodarone, miconazole, and sulfaphenazole. As with other NSAIDs, there is also a risk of pharmacokinetic interaction with other drugs actively excreted by the kidneys, such as methotrexate and lithium. Aceclofenac is almost completely bound to plasma proteins; consequently, there is a possibility of a displacement-type interaction with other drugs that have high affinity for plasma proteins, which should be taken into account.

Since pharmacokinetic interaction studies are insufficient, the information below is based on data obtained for other NSAIDs.

Drug Combinations to Avoid

Lithium and Digoxin some NSAIDs inhibit the renal clearance of lithium and digoxin, leading to increased serum concentrations of these drugs. This combination of drugs should be avoided, except in cases where frequent monitoring of lithium and digoxin levels is possible.

Anticoagulants NSAIDs inhibit platelet aggregation and damage the gastrointestinal mucosa, which may lead to increased activity of anticoagulants and increase the risk of gastrointestinal bleeding in patients taking anticoagulants. The combination of aceclofenac and oral coumarin anticoagulants, ticlopidine, thrombolytic drugs, and heparin should be avoided, except in cases where careful monitoring is conducted.

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 adjustment and caution

Methotrexate NSAIDs inhibit the tubular secretion of methotrexate; therefore, possible interaction between NSAIDs and methotrexate should also be considered during treatment with low doses of methotrexate, especially in patients with renal failure. In cases where combined treatment is necessary, kidney function should be monitored. Caution is required in cases where both NSAIDs and methotrexate are administered within 24 hours, as the concentration of methotrexate may increase, leading to increased toxicity.

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

Other NSAIDs simultaneous use of acetylsalicylic acid and other NSAIDs may increase the frequency of adverse events; therefore, caution should be exercised.

Corticosteroids the risk of gastrointestinal ulcers or gastrointestinal bleeding may increase.

Diuretics Aceclofenac, like other NSAIDs, may inhibit the activity of diuretics, reduce the diuretic effect of furosemide, bumetanide, and the antihypertensive effect of thiazides. Simultaneous treatment with potassium-sparing diuretics may be associated with increased potassium levels; therefore, serum potassium should be monitored.

Aceclofenac has been shown not to affect blood pressure control when used concomitantly with bendroflumethiazide, although an interaction with other diuretics cannot be ruled out.

Antihypertensive Drugs NSAIDs may also reduce the effectiveness of certain antihypertensive drugs. ACE inhibitors or angiotensin II receptor antagonists in combination with NSAIDs may lead to impaired kidney function. In some patients with reduced kidney function, for example, elderly patients or patients with dehydration, there may be a risk of developing acute renal failure, which is usually reversible. Therefore, caution is required when combining these drugs with NSAIDs, especially when treating elderly patients or patients with dehydration. Patients should be sufficiently hydrated, and it is also recommended to consider the need for monitoring kidney function after starting combined treatment and periodically during treatment.

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

Hypoglycemic Drugs clinical studies have shown that diclofenac can be used simultaneously with oral hypoglycemic drugs without affecting their clinical efficacy. However, there are isolated reports of hypoglycemic and hyperglycemic effects of this drug. Therefore, for aceclofenac, the possibility of dose adjustment for drugs that can cause hypoglycemia should be considered.

Zidovudine when NSAIDs and zidovudine are used concomitantly, the risk of hematological toxicity increases. There are data on an increased risk of hemarthrosis and hematoma formation in HIV-positive patients with hemophilia receiving concomitant treatment with zidovudine and ibuprofen.

Aceclofenac is structurally related to diclofenac and has similar metabolism; therefore, the possibility of the following interactions cannot be excluded.

Mifepristone NSAIDs should not be used for 8-12 days after taking mifepristone, as its effect may be reduced.

Quinolone Antibiotics: the interaction of NSAIDs and quinolones may lead to the development of convulsions. These can occur in patients both with and without a history of convulsions or epilepsy. Therefore, caution is required when prescribing quinolones to patients already taking NSAIDs.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 30°C (86°F).

Shelf Life

The shelf life is 4 years. Do not use after the expiration date printed on the packaging.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.