Instructions for Olfen-AF modified-release tablets 200 mg blister No. 10
Composition
active ingredient: aceclofenac;
1 tablet contains aceclofenac 200 mg;
excipients: microcrystalline cellulose, povidone, croscarmellose sodium, sodium stearyl fumarate, poloxamer, hypromellose, carbomer, Opadry White (OY-C-7000A).
Dosage form
Modified-release tablets.
Main physicochemical properties: white, oblong, biconvex modified-release tablets, film-coated, debossed with “UT” on one side and “CL CR” on the other side.
Pharmacotherapeutic group
Nonsteroidal anti-inflammatory and antirheumatic drugs. Acetic acid derivatives and related substances. Aceclofenac. ATX code M01A B16.
Pharmacological properties
Pharmacodynamics
Aceclofenac is an effective non-steroidal drug from the phenylacetic acid group, which has anti-inflammatory, analgesic and antipyretic properties. The mechanism of action is believed to be inhibition of the cyclooxygenase enzyme, which is involved in the synthesis of prostaglandins.
Pharmacokinetics
Absorption. Aceclofenac is well absorbed from the gastrointestinal tract: peak plasma concentrations are reached 1-3 hours after oral administration, its bioavailability is almost 100%. The plasma elimination half-life is approximately 4 hours. About two-thirds of the dose is excreted in the urine, mainly as hydroxymetabolites. The time to maximum concentration (Tmax) is delayed by simultaneous ingestion of food, but the extent of absorption is not affected.
Distribution: Aceclofenac is highly bound to plasma proteins (>99.7%). Aceclofenac penetrates into the synovial fluid, where concentrations reach approximately 60% of those in plasma.
Elimination: The mean elimination half-life is 4-4.3 hours. Clearance is
5 liters per hour. Approximately two-thirds of the administered dose is excreted in the urine, mainly as conjugated hydroxymetabolites. Only 1% of a single oral dose is excreted unchanged.
Aceclofenac is metabolized in hepatocytes and microsomes to form [2-(2,6-dichloro-4-hydroxy-phenylamino)phenyl]acetoxyacetic acid as the major metabolite, which then undergoes further conjugation. Secondary metabolites were [2-(2,6-dichlorophenylamino)-5-hydroxyphenyl]acetoxyacetic acid and [2-(2,6-dichlorophenylamino)phenyl]acetic acid, as well as the hydroxylated derivatives [2-(2,6-dichloro-4-hydroxyphenylamino)phenyl]acetic acid and [2-(2,6-dichlorophenylamino)-5-hydroxyphenyl]acetic acid.
Indication
Pain syndrome in rheumatoid arthritis, ankylosing spondylitis, osteoarthritis and shoulder-scapular periarthritis, lumbago, sciatica, extra-articular rheumatism.
Contraindication
Hypersensitivity to the active substance or to any of the excipients; history of gastrointestinal bleeding or perforation associated with previous treatment with nonsteroidal anti-inflammatory drugs (NSAIDs); like other NSAIDs, aceclofenac is also contraindicated in patients in whom the use of acetylsalicylic acid or other NSAIDs provokes attacks of bronchial asthma, angioedema, urticaria or acute rhinitis; bronchial asthma; active peptic ulcer/bleeding or history of recurrent peptic ulcer/bleeding (two or more separate episodes of established ulceration or bleeding); active bleeding or blood clotting disorders; severe hepatic or renal insufficiency; congestive heart failure (NYHA II-IV); ischemic heart disease; peripheral arterial disease; cerebrovascular disease, including previous stroke or transient ischemic attack episodes; treatment of perioperative pain in coronary artery bypass grafting (or use of a cardiopulmonary bypass machine); inflammatory bowel diseases (e.g. Crohn's disease or ulcerative colitis); third trimester of pregnancy or breastfeeding; children.
Interaction with other medicinal products and other types of interactions
No interaction studies have been conducted, except for the interaction with warfarin.
Aceclofenac is metabolised by cytochrome P450 2C9 and in vitro data suggest that aceclofenac may be an inhibitor of this enzyme. Therefore, there is a risk of pharmacokinetic interactions with phenytoin, cimetidine, tolbutamide, phenylbutazone, amiodarone, miconazole and sulfaphenazole. As with other NSAIDs, the risk of pharmacokinetic interactions is increased with other drugs that are excreted by active renal secretion, such as methotrexate and lithium. Aceclofenac is almost completely bound to plasma albumin and therefore displacement interactions with other drugs that are protein bound are possible.
Pharmacokinetic interaction studies with aceclofenac are insufficient; the information below is based on data with other NSAIDs.
Methotrexate. NSAIDs inhibit the tubular secretion of methotrexate; in addition, a small metabolic interaction is possible, leading to a decrease in the clearance of methotrexate. Caution is required when taking NSAIDs and methotrexate within 24 hours, as NSAIDs may increase the plasma concentration of methotrexate, which leads to increased toxicity. Therefore, NSAIDs should be avoided when using high doses of methotrexate.
Cardiac glycosides: NSAIDs may exacerbate heart failure, reduce glomerular filtration rate, and increase plasma glycoside levels. Concomitant use should be avoided unless digoxin concentrations are monitored frequently.
Diuretics. Decreased diuretic effect. Diuretics may increase the risk of nephrotoxicity when taking NSAIDs. Although concomitant use with bendrofluazide did not affect blood pressure control, interactions with other diuretics cannot be excluded. When used concomitantly with potassium-sparing diuretics, serum potassium should be monitored.
Anticoagulants: NSAIDs may enhance the effects of anticoagulants such as warfarin. Careful monitoring of patients receiving combined anticoagulant therapy with aceclofenac is required.
Antidiabetic drugs. It has been found that diclofenac, when used together with oral antidiabetic drugs, may affect the clinical efficacy of the latter. However, there are isolated reports of hypoglycemic and hyperglycemic effects. Therefore, when prescribing aceclofenac, the dose of hypoglycemic drugs should be adjusted.
Lithium: NSAIDs increase plasma lithium levels and decrease renal clearance of lithium. Therefore, patients should be carefully monitored for signs of lithium toxicity when used concomitantly.
Mifepristone. NSAIDs should not be used for 8-12 days after taking mifepristone, as NSAIDs may reduce the effect of mifepristone. Due to the antiprostaglandin effect of NSAIDs, women should be cautious when using mifepristone, as it may theoretically reduce the effectiveness of NSAIDs. The clinical significance of this interaction is unknown.
Cyclosporine and tacrolimus: Increased risk of nephrotoxicity.
Quinoline antibiotics. Animal studies suggest that NSAIDs may increase the risk of seizures associated with quinolone antibiotics. Patients taking NSAIDs and quinolones may be at increased risk of seizures.
Antihypertensive drugs. Reduced antihypertensive effect. Concomitant use of ACE inhibitors or angiotensin II receptor antagonists and NSAIDs may lead to impaired renal function. The risk of acute renal failure, which is usually reversible, is increased in some patients with impaired renal function, such as elderly or dehydrated patients. Therefore, caution should be exercised when used concomitantly with NSAIDs, especially in elderly patients. Patients should be adequately hydrated and should be monitored (monitor renal function at the beginning of concomitant use and periodically during treatment).
Corticosteroids: Increased risk of gastrointestinal ulcers and bleeding.
Antiplatelet drugs and selective serotonin reuptake inhibitors (SSRIs). Increased risk of gastrointestinal bleeding.
Tacrolimus: Concomitant administration of NSAIDs and tacrolimus may increase the risk of nephrotoxicity.
Zidovudine. The risk of hematological toxicity increases when taken with NSAIDs. An increased risk of hemarthrosis and hematomas has been confirmed in HIV-infected patients with hemophilia when zidovudine is taken with ibuprofen.
Other NSAIDs: Concomitant use with acetylsalicylic acid or other NSAIDs may increase the incidence of adverse reactions, including an increased risk of gastrointestinal bleeding.
Angiotensin II inhibitors. NSAIDs may reduce the effects of antihypertensive drugs, so angiotensin II inhibitors should be used with caution, especially in elderly patients.
Aceclofenac is metabolized by CYP2C9, so it may interact with phenytoin, cimetidine, miconazole, sulfaphenazole, amiodarone, tolbutamide, and phenylbutazone.
Application features
Undesirable effects can be minimized by using the lowest effective dose for the shortest period of time sufficient to control symptoms (see gastrointestinal and cardiovascular risks below).
The concomitant use of aceclofenac and NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided.
Elderly patients
Elderly patients are at increased risk of adverse reactions to NSAIDs, especially gastrointestinal perforations and bleeding, which can be fatal. In addition, elderly patients are more likely to suffer from kidney, liver or cardiovascular disease.
NSAIDs may cause a dose-dependent decrease in prostaglandin production and renal failure. Patients at high risk for this reaction include patients with impaired renal function, heart failure, liver dysfunction, patients taking diuretics, and the elderly. Such patients should be monitored for renal function.
Kidneys
The important role of prostaglandins in maintaining renal blood flow should be considered in patients with heart failure or impaired renal function, who are taking diuretics or recovering from major surgery. The effect on renal function is usually reversible and the situation normalizes after discontinuation of aceclofenac.
Caution should be exercised when using the drug in patients with mild to moderate hepatic and renal impairment, as well as in patients with other conditions accompanied by fluid retention in the body. In these patients, the use of NSAIDs can lead to impaired renal function and fluid retention. Caution should also be exercised when using aceclofenac in patients taking diuretics or in individuals at increased risk of hypovolemia. The minimum effective dose should be used and renal function should be regularly monitored. Renal events usually resolve after discontinuation of aceclofenac.
Liver
If liver function tests remain abnormal or worsen, clinical symptoms/signs of liver disease or other manifestations (eosinophilia, rash) appear, aceclofenac should be discontinued. Careful medical monitoring of patients with mild to moderate liver dysfunction is necessary. Hepatitis may develop without prodromal symptoms. The use of aceclofenac in patients with hepatic porphyria may provoke an exacerbation of the disease.
Cardiovascular and cerebrovascular effects
Appropriate monitoring and appropriate advice are necessary in patients with a history of hypertension and/or mild to moderate congestive heart failure, as NSAID therapy is associated with phenomena such as fluid retention and oedema.
Patients with congestive heart failure (NYHA I) and significant risk factors for cardiovascular disease (such as hypertension, hyperlipidemia, diabetes mellitus, smoking) should be treated with aceclofenac only after careful assessment of the possible risks.
The cardiovascular risk may increase with increasing dose and duration of NSAID use, therefore the lowest effective daily dose should be used for the shortest duration possible. The patient's need for symptomatic treatment and response to therapy should be periodically assessed.
Aceclofenac should be used with caution and under close medical supervision in patients with the following conditions (as there is a risk of exacerbation of the disease) (see section "Adverse reactions"):
symptoms indicating the presence of gastrointestinal disease, including its upper and lower sections; history of ulcer, bleeding or perforation of the gastrointestinal tract; ulcerative colitis; Crohn's disease; bleeding tendency, systemic lupus erythematosus (SLE), porphyria, disorders of hematopoiesis and hemostasis.
Ulcer, perforation and bleeding from the gastrointestinal tract
Gastrointestinal ulceration, perforation and bleeding, which can be fatal, have been reported with all NSAIDs at any time during treatment, with or without warning symptoms, and in patients with a history of serious gastrointestinal disease.
Careful medical observation is extremely important if there is a suspicion of a history of gastrointestinal ulcers, for patients with symptoms of gastrointestinal diseases, ulcerative colitis and Crohn's disease, hemorrhagic diathesis, or hematological disorders.
The risk of gastrointestinal ulceration, perforation and bleeding is increased with high doses of NSAIDs in patients with a history of ulcer disease, especially complicated by bleeding or perforation, and in elderly patients. These patients should start treatment with the lowest dose. The possibility of combination therapy with protective agents (such as misoprostol or proton pump inhibitors) should be considered in such patients, as well as in patients who require concomitant low-dose acetylsalicylic acid or other drugs that may increase the risk of gastrointestinal complications.
Patients with a history of gastrointestinal toxicity, particularly the elderly, should report any unusual gastrointestinal symptoms (especially gastrointestinal bleeding), especially at the beginning of treatment. Particular attention should be paid to patients receiving concomitant medications that may increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors, or antiplatelet agents such as acetylsalicylic acid.
If a patient taking aceclofenac develops gastrointestinal ulceration or bleeding, treatment should be discontinued.
NSAIDs should be prescribed with caution to patients with a history of gastrointestinal diseases (ulcerative colitis, Crohn's disease), as these conditions may be exacerbated.
Patients with SLE and mixed connective tissue disease may be at increased risk of developing aseptic meningitis.
Dermatology
Very rarely, severe skin reactions, including fatal ones, have occurred with NSAIDs. These include exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis. The risk of developing such reactions is highest at the beginning of treatment: in most cases, such reactions occur within the first month of taking the drug. Aceclofenac should be discontinued at the first sign of skin rash, mucous membrane lesions or other manifestations of hypersensitivity.
In special cases, complications may occur with chickenpox: serious skin and soft tissue infections. At present, the role of NSAIDs in worsening the course of these infections cannot be ruled out. Therefore, aceclofenac should be avoided in chickenpox.
Impaired fertility in women
Aceclofenac may impair fertility in women. This medicine is not recommended for women attempting to conceive. Aceclofenac should be discontinued in women who have difficulty conceiving or are undergoing investigation of infertility.
Hypersensitivity reactions
As with other NSAIDs, allergic reactions, including anaphylactic/anaphylactoid reactions, may occur in patients who have not previously taken this drug. Serious skin reactions, sometimes fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, have been reported rarely with NSAIDs. The risk of these reactions is greatest at the beginning of therapy (in the first months). At the first signs of skin reactions (rash, mucosal lesions, hypersensitivity reactions), aceclofenac should be discontinued.
Hematological disorders
Aceclofenac may reversibly inhibit platelet aggregation (see “Anticoagulants” in the “Interaction with other medicinal products and other types of interactions” section).
Respiratory system disorders
Caution should be exercised when using the drug in patients with bronchial asthma, including a history of it, because taking NSAIDs can provoke the development of sudden bronchospasm in such patients.
Long-term treatment
All patients taking NSAIDs should be under medical supervision for timely detection of renal failure, liver dysfunction (increased liver enzyme activity), and changes in blood counts.
Ability to influence reaction speed when driving vehicles or other mechanisms
Undesirable effects such as dizziness, vertigo, drowsiness, fatigue and visual disturbances may occur after taking NSAIDs. If such reactions occur, patients should not drive or operate other machinery.
Use during pregnancy or breastfeeding
Pregnancy
There is no information on the use of aceclofenac during pregnancy. Inhibition of prostaglandin synthesis may have a negative effect on the course of pregnancy/fetal development. Based on the known effects of NSAIDs on the cardiovascular system of the fetus (risk of premature closure of the ductus arteriosus) and the possible risk of persistent pulmonary hypertension of the newborn, the use of the drug in the last trimester of pregnancy is contraindicated. The risk increases with increasing dose and duration of therapy. Regular use of NSAIDs in the last trimester of pregnancy may reduce the tone and contractility of the uterus. As a result, labor may be delayed or prolonged with an increased tendency to bleeding in the mother and child. NSAIDs should not be used in the first two trimesters of pregnancy and during labor, unless the potential benefit to the patient outweighs the potential risk to the fetus, the dose should be as low as possible, and the duration of treatment should be as short as possible.
Breast-feeding
Limited data available suggest that NSAIDs are found in breast milk at very low concentrations. These drugs should be avoided during breastfeeding if possible.
If treatment is necessary, breastfeeding should be discontinued.
Fertility
NSAIDs may impair fertility and are therefore not recommended for use in women attempting to conceive. Women attempting to conceive or undergoing investigation of infertility should temporarily discontinue aceclofenac.
Method of administration and doses
Olfen®-AF tablets should be swallowed whole, without chewing or crushing. Wash down with at least ½ glass of water.
Adverse events can be minimized by using the drug for the minimum period necessary to control symptoms.
Adults
The recommended dose is 200 mg per day once (every 24 hours).
As a rule, dose reduction is not required. However, such patients should be carefully monitored, since they are more likely to have impaired renal function, liver function, cardiovascular disorders, and they are also more likely to receive concomitant therapy for other diseases, which increases the risk of developing serious adverse reactions. If NSAIDs are prescribed, they should be used in minimal doses and for the shortest possible time. Patients should be carefully monitored for timely detection of gastrointestinal bleeding during NSAID therapy.
Liver failure
For patients with mild to moderate hepatic impairment, the dose of aceclofenac should be reduced. The recommended initial dose is 100 mg per day (use aceclofenac in a different dosage form).
Kidney failure
There is no information that patients with mild renal insufficiency require dose adjustment of aceclofenac, however, this category of patients should be cautious when using the drug.
Children
There are no clinical data on the use of aceclofenac in children, therefore this drug is contraindicated for use in this age group of patients.
Overdose
Symptoms
Symptoms include headache, nausea, vomiting, epigastric pain, gastrointestinal irritation and bleeding, rarely diarrhea, disorientation, agitation, coma, drowsiness, dizziness, tinnitus, hypotension, respiratory distress, loss of consciousness, and occasionally convulsions. In severe poisoning, acute renal failure and liver damage may develop.
Treatment methods
Patients should receive symptomatic treatment as needed.
Activated charcoal should be administered within one hour of ingestion of potentially toxic amounts of the drug. Alternatively, gastric lavage should be performed within one hour of life-threatening overdose in adults.
Specific therapeutic agents such as dialysis or hemoperfusion are likely to be ineffective in removing NSAIDs due to their high protein binding and extensive metabolism.
It is necessary to provide forced diuresis.
Close monitoring of renal and hepatic function is required.
Patients should be observed for at least 4 hours after ingestion of potentially toxic amounts of the drug. In case of frequent and prolonged seizures, the patient may require intravenous diazepam.
Treatment is symptomatic and supportive.
Adverse reactions
The most common adverse reactions of aceclofenac include gastrointestinal upset, dizziness, and elevated liver enzyme levels.
Aceclofenac is structurally and metabolically similar to diclofenac, which is a known risk factor for thrombotic events (myocardial infarction, stroke, especially at high doses and long-term use). An increased risk of acute coronary syndrome and myocardial infarction has been reported in association with the use of aceclofenac.
On the part of the digestive system: peptic ulcers, perforations or gastrointestinal bleeding sometimes fatal (especially in elderly patients), nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena, haematemesis, ulcerative stomatitis, exacerbation of nonspecific ulcerative colitis or Crohn's disease, gastritis, pancreatitis, stomatitis.
Hepatobiliary disorders: hepatitis, jaundice, increased activity of liver enzymes, increased concentration of creatinine in the blood.
Immune system disorders: anaphylactic reactions (including shock), hypersensitivity.
Cardiovascular system: arterial hypertension, heart failure, palpitations, flushing, hot flashes.
Renal and urinary disorders: nephrotic syndrome, renal failure, nocturnal enuresis.
Nervous system: visual disturbances, headache, drowsiness, tremor, dysgeusia, paresthesia, occipital rigidity, fever, dysesthesia, agitation, hallucinations, tinnitus, exhaustion, drowsiness, dizziness; aseptic meningitis (especially in systemic lupus erythematosus or mixed connective tissue disease).
Blood and lymphatic system disorders: bone marrow depression, anemia, granulocytopenia, thrombocytopenia, neutropenia, agranulocytosis, aplastic anemia, and hemolytic anemia.
Metabolic disorders: hyperkalemia.
Mental disorders: dizziness, depression, abnormal dreams, insomnia.
Respiratory system: shortness of breath, bronchospasm, stridor.
Skin: itching, rash, dermatitis, urticaria, facial edema, purpura, bullous dermatitis, Stevens-Johnson syndrome or Lyell syndrome, photosensitivity, hair loss, angioedema, acute skin and mucous membrane reactions.
General disorders and local reactions: edema, fatigue, calf muscle cramps.
Laboratory test results: increased urea concentration in the blood, increased alkaline phosphatase activity in the blood, increased body weight.
Expiration date
2 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 30 °C, out of the reach of children.
Packaging
10 tablets in a blister in a cardboard box.
Vacation category
According to the recipe.
Producer
Korea United Pharm., Inc.
Location of the manufacturer and its business address
25-23, Nochangongdan-gil, Jeongdong-myeon, Sejong-si, Republic of Korea.
