Aceclagin, 200 mg 30 pcs

Pharmacotherapeutic group: Non-steroidal anti-inflammatory drug (NSAIDs)

ATCode: M01AB16

Pharmacological properties

Pharmacodynamics

Aceclofenac has anti-inflammatory, analgesic, 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 significantly reduces the severity of pain, morning stiffness, joint swelling which improves the functional state of the patient.

Pharmacokinetics

absorption. Acclofenac is rapidly absorbed after oral administration. Maximum concentration (C_max) in blood plasma is reached 1.25-3 hours after oral administration. Food intake slows down absorption, but does not affect its degree.

Distribution Aceclofenac is highly bound to plasma proteins (˃99.7%). Aceclofenac penetrates into the synovial fluid, where its concentration reaches 60% of its concentration in blood plasma. The volume of distribution is 30 liters.

Metabolism It is believed that aceclofenac is metabolized by CYP2C9 isoenzyme to form the metabolite 4-OH-aceclofenac. Diclofenac and 4-OH-diclofenac are among the numerous metabolites of aceclofenac.

Evolution.The average half-life (T_1/2) of modified-release tablets is about 5 hours. Clearance is 5 l/h. Approximately 2/3 of the dose taken is excreted by the kidneys, mainly as conjugated hydroxymetabolites. Only 1% of the dose after oral administration is excreted unchanged.

Indications

Relief of inflammation and pain in lumbago, toothache, glenohumeral periarthritis, rheumatic soft tissue lesions, for the symptomatic treatment of rheumatoid arthritis, osteoarthritis and ankylosing spondylitis.
Symptomatic therapy, reducing pain and inflammation at the time of use, does not affect the progression of the disease.
Dysmenorrhea.

Pharmacological effect

Pharmacotherapeutic group: non-steroidal anti-inflammatory drug (NSAID)

ATX code: M01AB16

Pharmacological properties

Pharmacodynamics

Aceclofenac has anti-inflammatory, analgesic, 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, morning stiffness, and swelling of the joints, which improves the patient’s functional condition.

Pharmacokinetics

Suction. After oral administration, aceclofenac is rapidly absorbed. The maximum concentration (Cmax) in blood plasma is achieved 1.25-3 hours after oral administration. Eating slows down absorption, but does not affect its degree.

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

Metabolism. It is believed that aceclofenac is metabolized by the CYP2C9 isoenzyme to form the metabolite 4-OH-aceclofenac. Diclofenac and 4-OH-diclofenac are among the numerous metabolites of aceclofenac.

Excretion. The average half-life (T1/2) when taking modified-release tablets is about 5 hours. Clearance is 5 l/h. Approximately 2/3 of the dose taken is excreted by the kidneys, mainly in the form of conjugated hydroxymetabolites. Only 1% of the dose after oral administration is excreted unchanged.

Special instructions

The simultaneous use of Aceclagin and other NSAIDs, including selective cyclooxygenase-2 (COX-2) inhibitors, should be avoided.

Adverse events can be minimized by using the lowest effective dose and reducing the duration of treatment needed to control symptoms.

Effect on the gastrointestinal tract

Bleeding, ulcers or perforation of the gastrointestinal tract with a fatal outcome were observed when taking any NSAIDs during any period of treatment, both in the presence of corresponding symptoms and a history of serious gastrointestinal diseases (peptic ulcer of the stomach and duodenum, Crohn’s disease, ulcerative colitis, etc.), and without them. The risk of bleeding, ulceration, and gastrointestinal perforation increases with increasing doses of NSAIDs in patients with a history of peptic ulcers, especially those accompanied by bleeding or perforation, and in elderly patients. These patients should take the minimum effective dose of the drug.

Combination therapy with protective drugs (eg, misoprostol or proton pump inhibitors) should be considered. Such treatment is necessary for patients who take small doses of aspirin or other drugs that negatively affect the gastrointestinal tract.

Patients with gastrointestinal diseases, including the elderly, should report any unusual symptoms associated with the gastrointestinal tract (especially bleeding), including when initially taking the drug. Particular caution should be exercised in patients concomitantly taking drugs that may increase the risk of bleeding or ulceration, such as: systemic corticosteroids, anticoagulants (such as warfarin), selective serotonin reuptake inhibitors or antiplatelet agents (such as acetylsalicylic acid).

If gastrointestinal bleeding or ulcers occur in patients taking Aceclagin®, treatment should be discontinued. Cases of drug-induced pancreatitis are rare. However, cases of pancreatitis have been reported in association with NSAID use.

Effects on the cardiovascular and central nervous system

Patients with arterial hypertension and/or mild or moderate congestive heart failure require appropriate monitoring, since fluid retention and edema are associated with the use of NSAIDs. Aceclofenac is structurally close to diclofenac and has similar metabolism. With respect to diclofenac, there is evidence indicating an increased risk of thromboembolic complications (for example, myocardial infarction or stroke, particularly with long-term treatment with high doses). There is also an increased risk of developing acute coronary syndrome associated with aceclofenac. Patients with chronic heart failure (class I according to the New York Heart Association classification) and patients with risk factors for developing complications from the cardiovascular system (for example, arterial hypertension, diabetes mellitus, smoking) should begin treatment with aceclofenac only after an informed decision by the physician. Cardiovascular risks may depend on the dose and duration of treatment, so the drug should be prescribed at the lowest effective dose and for the shortest possible period of time.

Effect on the liver and kidneys

Taking NSAIDs can cause a dose-dependent decrease in prostaglandin formation and acute renal failure. The importance of prostaglandins in maintaining renal blood flow should be considered when taking Aceclagin in patients with impaired cardiac, renal or hepatic function, in patients receiving diuretics or in patients after surgery, as well as in elderly patients. Caution should be exercised when using the drug Aceclagin in patients with mild or moderate hepatic and renal dysfunction, as well as in patients with other conditions predisposing to fluid retention in the body. In such patients, the use of NSAIDs can lead to impaired renal function and fluid retention. In patients taking diuretics and those at increased risk of hypovolemia, caution should also be exercised when taking Aceclagin. It is necessary to use the minimum effective dose and regular medical monitoring of kidney function. Adverse renal events usually resolve after discontinuation of aceclofenac. Aceklagin should be discontinued if changes in liver function tests persist or worsen, clinical signs or symptoms of liver disease develop, or other manifestations (eosinophilia, skin rash) occur. Hepatitis can develop without prodromal symptoms.

The use of NSAIDs in patients with hepatic porphyria may provoke an attack.

Hypersensitivity and skin reactions

Like other NSAIDs, aceclofenac can cause allergic reactions, including anaphylactic/anaphylactoid reactions, even when aceclofenac 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 very rare after taking NSAIDs. The highest risk of these reactions occurring in patients is observed at the beginning of taking aceclofenac, and the development of these adverse reactions is observed during the first month of taking aceclofenac. If skin rash, damage to the oral mucosa, or other signs of hypersensitivity occur, you should stop taking Aceclagin.

In some cases, chickenpox can cause skin and soft tissue infections.

At present, the role of NSAIDs in worsening the course of these infections cannot be ruled out. Therefore, you should avoid taking the drug Aceclagin for chickenpox.

Hematological disorders

Aceclofenac may cause reversible inhibition of platelet aggregation.

Respiratory system disorders

Caution should be exercised when taking the drug Aceclagin in patients with bronchial asthma (including a history of asthma), since taking NSAIDs can trigger the development of sudden bronchospasm in such patients.

Elderly patients

Caution should be exercised when taking Aceclagin in elderly patients, as they are more likely to experience side effects (especially bleeding and gastrointestinal perforation) when taking NSAIDs. Complications can be fatal. Older patients are also more likely to suffer from kidney, liver, or cardiovascular diseases.

Long-term use

All patients receiving long-term treatment with NSAIDs should be closely monitored (eg, complete blood count, liver function tests, and renal function tests).

Due to the antiprostaglandin properties of NSAIDs. Caution should be advised to women taking mifepristone, as when used together with NSAIDs, a decrease in the effectiveness of the drug could theoretically occur.

Clinical significance unknown.

Impact on the ability to drive vehicles and machinery

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

Active ingredient

Aceclofenac

Composition

1 tablet contains: active ingredient aceclofenac 200.0 mg; excipients: microcrystalline cellulose 159.5 mg, povidone K30 19.5 mg, croscarmellose sodium 9.7 mg, sodium stearyl fumarate 15.3 mg; poloxamer 407 4.5 mg, hypromellose 40.5 mg, carbomer 941 2.5 mg.
Shell composition: Opadry white OY-S-7000 A 12.0 mg: hypromellose 5cP (E 464) 54.850%, titanium dioxide (E 171) 22.860%, ethylcellulose 10cP 13.720%, diethyl phthalate 8.570%.

Pregnancy

Pregnancy

The use of Aceclagin® 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 the development of the embryo/fetus.

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

having cardiopulmonary toxicity, they can cause premature closure of the Botallo duct with the development of pulmonary hypertension;
may cause impaired fetal renal function, which may progress to renal failure in combination with polyhydramnios.

In late pregnancy:

the drug may affect the duration of bleeding due to the antiplatelet effect, which can develop even after using very low doses;
the drug may suppress uterine contractions, causing delayed labor or prolonged labor. Breastfeeding period

The drug should not be taken during breastfeeding. There is no data on the excretion of aceclofenac in human milk. In preclinical studies, no significant transfer of radioactivity into milk was observed when radioactive C-aceclofenac was administered.

Fertility

Nonsteroidal anti-inflammatory drugs (NSAIDs) may affect fertility and are not recommended for use by women planning pregnancy.

Contraindications

Hypersensitivity to aceclofenac or auxiliary components of the drug;
bronchospasm, rhinitis or urticaria after taking acetylsalicylic acid or other NSAIDs in history (complete or incomplete acetylsalicylic acid intolerance syndrome – rhinosinusitis, urticaria, polyps of the nasal mucosa, bronchial asthma);
erosive and ulcerative lesions of the mucous membrane of the gastrointestinal tract (GIT) in the acute phase (including ulcerative colitis, Crohn’s disease);
gastrointestinal bleeding or suspicion of it;
severe heart failure (class II-IV according to the New York Heart Association classification), coronary heart disease, diseases of the peripheral arteries and/or cerebral arteries;
period after coronary artery bypass surgery;
severe liver failure or active liver disease;
severe renal failure (creatinine clearance <30 ml/min), progressive kidney disease, confirmed hyperkalemia; disorders of hematopoiesis and coagulation; pregnancy and breastfeeding; children under 18 years of age.

With caution

History of liver, kidney and gastrointestinal diseases, bronchial asthma, arterial hypertension, decreased circulating blood volume (including after major surgical interventions), coronary heart disease, chronic renal and hepatic and heart failure, creatinine clearance less than 60 ml/min, history of ulcerative lesions of the gastrointestinal tract, presence of Helicobacter pylori infection, dyslipidemia/hyperlipidemia, diabetes mellitus, smoking, old age, long-term use of NSAIDs, severe somatic diseases, alcoholism.

Side Effects

The following are adverse events reported in clinical studies and post-marketing surveillance. The incidence of adverse events is classified as follows: very often (≥ 1/10); often (from ≥ 1/100 to < 1/10); uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10000 to < 1/1000), very rare (< 1/10000).From the blood and lymphatic system: rarely – anemia; very rarely – suppression of bone marrow functions, granulocytopenia, thrombocytopenia, neutropenia, hemolytic anemia.From the immune system: rarely – anaphylactic reactions, including shock, hypersensitivity.Metabolism and nutrition: very rarely – hyperkalemia, weight gain.From the mental side: very rarely – depression, unusual (atypical) dreams, insomnia.From the nervous system: often – dizziness; very rarely – paresthesia, tremor, drowsiness, headache, dysgeusia (taste perversion).From the organ of vision: rarely – visual impairment.From the organ of hearing and labyrinth: very rarely – vertigo, tinnitus.From the heart: rarely – heart failure; very rarely – rapid heartbeat.From the side of blood vessels: rarely – increased blood pressure, worsening of arterial hypertension; very rarely – skin hyperemia, “hot flashes” (short-term sensation of heat accompanied by sweating), vasculitis.From the respiratory system, chest organs and mediastinal organs: rarely – shortness of breath; very rarely – bronchospasm.From the gastrointestinal tract: often – dyspepsia, abdominal pain, nausea, diarrhea; uncommon – flatulence, gastritis, constipation, vomiting, ulceration of the oral mucosa; rarely – melena, ulceration of the gastrointestinal mucosa, hemorrhagic diarrhea, hemorrhages of the gastrointestinal mucosa; very rarely – stomatitis, vomiting blood, intestinal perforation, worsening of Crohn’s disease and ulcerative colitis, pancreatitis.From the liver and biliary tract: often – increased activity of liver enzymes; very rarely – liver damage (including hepatitis), increased alkaline phosphatase activity.From the skin and subcutaneous tissue: infrequently – itching. rash, dermatitis, urticaria; rarely – angioedema; very rarely – purpura, eczema, severe reactions from the skin and mucous membranes (including Stevens-Johnson syndrome and toxic epidermal necrolysis).Serious skin and soft tissue infections have been reported in isolated cases when NSAIDs were taken during chickenpox.From the kidneys and urinary tract: infrequently – increased concentrations of urea and creatinine in the blood serum; very rarely – nephrotic syndrome, renal failure.Systemic disorders and complications at the injection site: very rarely – swelling, increased fatigue, muscle spasms of the lower extremities.If the patient notices a worsening of any of the listed adverse events or the occurrence of an adverse event not listed in this instruction, he should contact his doctor.

Interaction

With the exception of concomitant use with warfarin, no drug interaction studies have been conducted.

Aceclofenac is metabolized by the CYP2C9 isoenzyme; In vitro data indicate that aceclofenac may be an inhibitor of this enzyme. Thus, the risk of pharmacokinetic interaction is possible when taken concomitantly with phenytoin, cimetidine, tolbutamide, phenylbutazone, amiodarone, miconazole and sulfaphenazole. As with other NSAIDs, the risk of pharmacokinetic interaction with other drugs that are eliminated from the body by active renal secretion, such as methotrexate and lithium, increases. Aceclofenac is almost completely bound to plasma albumin and, therefore, there is the possibility of displacement interactions with other protein-binding drugs. Below is class-specific information for NSAIDs:

Methotrexate.

NSAIDs inhibit tubular secretion of methotrexate; Moreover, a slight metabolic interaction may occur, resulting in decreased methotrexate clearance. Therefore, when using high doses of methotrexate, NSAIDs should be avoided.

Lithium preparations and digoxin.

Some NSAIDs inhibit the renal clearance of lithium and digoxin, resulting in increased serum concentrations of both substances. Concomitant use should be avoided unless lithium and digoxin concentrations are monitored frequently.

Anticoagulants.

NSAIDs inhibit platelet aggregation and damage the gastrointestinal mucosa, which can lead to increased effects of anticoagulants and increase the risk of gastrointestinal bleeding while taking anticoagulants. The combined use of aceclofenac and oral coumarin anticoagulants, ticlopidine and thrombolytics should be avoided unless the patient’s condition is carefully monitored.

Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs) when used together with NSAIDs may increase the risk of gastrointestinal bleeding.

Cyclosporine, tacrolimus.

When taking NSAIDs concomitantly with cyclosporine or tacrolimus, the risk of increased nephrotoxicity due to decreased renal prostacyclin formation should be considered. Therefore, renal function should be carefully monitored during concomitant use.

Other NSAIDs.

When taking acetylsalicylic acid or other NSAIDs simultaneously, the incidence of side effects may increase, so caution should be exercised.

Glucocorticosteroids (GCS). The risk of ulcers or gastrointestinal bleeding increases.

Diuretics.

Aceclofenac, like other NSAIDs, can inhibit the activity of diuretics and 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 serum potassium levels. When used simultaneously with potassium-sparing diuretics, monitoring of serum potassium is necessary. Aceclofenac did not affect blood pressure control when used in combination with bendrofluazide, although interactions with other diuretics cannot be excluded.

Antihypertensive drugs.

NSAIDs may also reduce the effect of antihypertensive drugs. Concomitant use of angiotensin-converting enzyme (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, may be increased in some patients with impaired renal function, such as the elderly or those who are dehydrated. Therefore, caution should be exercised when used together with NSAIDs. Patients should consume adequate fluid intake and be monitored appropriately (monitor renal function at the start of co-administration and periodically during treatment).

Hypoglycemic agents.

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

Zidovudine.

When NSAIDs and zidovudine are taken concomitantly, the risk of hematological toxicity increases. There is evidence of an increased risk of hemarthrosis and hematomas in HIV-positive (human immunodeficiency virus) patients with hemophilia receiving zidovudine and ibuprofen.

Overdose

There is no evidence of aceclofenac overdose in humans.

Possible symptoms: nausea, vomiting, pain in the stomach, dizziness, headache, hyperventilation with increased convulsive readiness.

Treatment: gastric lavage, taking activated carbon, symptomatic therapy. Forced diuresis, hemodialysis is not effective enough

Storage conditions

Store at a temperature not exceeding 30 °C.

Keep out of the reach of children.

Shelf life

2 years.

Manufacturer

Korea United Pharm. Inc., Republic of Korea