Instructions for Olfen AF tablets 200 mg No. 30
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. ATC code M01A B16.
Pharmacological properties
Pharmacodynamics.
Aceclofenac is an effective nonsteroidal 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 (GI): peak plasma concentrations are reached 1–3 hours after oral administration, and its bioavailability is almost 100%. The time to maximum concentration (Tmax) is delayed by 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 the concentration reaches approximately 60% of that in blood plasma. The volume of distribution is approximately 30 l.
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 of the medicinal product;
history of gastrointestinal bleeding or perforation related to 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, bronchospasm, angioedema, urticaria or acute rhinitis, as well as in patients with hypersensitivity to these drugs;
bronchial asthma;
active ulcer/bleeding or history of recurrent ulcer/bleeding (two or more separate episodes of established ulceration or bleeding);
active bleeding or a disease accompanied by bleeding (hemophilia, blood clotting disorder);
severe liver or kidney failure;
congestive heart failure [NYHA functional class II–IV];
ischemic heart disease (angina pectoris or previous myocardial infarction);
peripheral artery disease;
cerebrovascular diseases, including previous stroke or episodes of transient ischemic attack;
do not use for the treatment of perioperative pain during coronary artery bypass grafting (or when using a cardiopulmonary bypass machine);
inflammatory bowel diseases (such as Crohn's disease or ulcerative colitis);
III trimester of pregnancy or breastfeeding period;
childhood.
Interaction with other medicinal products and other types of interactions
No interaction studies have been conducted, except for the interaction with warfarin.
Aceclofenac is metabolized by cytochrome P450 2C9, and in vitro data suggest that aceclofenac may be an inhibitor of this enzyme. Thus, pharmacokinetic interactions are possible with concomitant administration of 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. Therefore, NSAIDs should be avoided when using high doses of methotrexate.
Cardiac glycosides, digoxin. NSAIDs may exacerbate heart failure, reduce glomerular filtration rate, and inhibit renal clearance of glycosides, leading to increased plasma levels. Concomitant use should be avoided unless digoxin concentrations are monitored.
Anticoagulants. NSAIDs inhibit platelet aggregation and damage the gastrointestinal mucosa, which may potentiate the effects of anticoagulants and increase the risk of gastrointestinal bleeding in patients taking anticoagulants. The concomitant use of aceclofenac with oral coumarin anticoagulants, ticlopidine, and thrombolytics and heparin should be avoided unless the patient is closely monitored. NSAIDs may potentiate the effects of anticoagulants such as warfarin. Careful monitoring of patients receiving combined anticoagulant therapy with aceclofenac is required.
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. Concomitant use should be avoided unless lithium concentrations are monitored.
Quinolone antibiotics: Animal studies suggest that NSAIDs increase the risk of seizures associated with quinolone antibiotics. Patients taking NSAIDs and quinolones may be at increased risk of seizures.
Antiplatelet drugs and selective serotonin reuptake inhibitors (SSRIs): Increased risk of gastrointestinal bleeding.
Combinations requiring dose selection and caution when used.
Methotrexate. The potential for interaction between NSAIDs and methotrexate should be considered, even at low doses of methotrexate, especially in patients with impaired renal function. Renal function should be monitored during concomitant administration. Caution should be exercised if NSAIDs and methotrexate are taken within 24 hours, as methotrexate concentrations may increase, which may increase the toxicity of this medicinal product.
Cyclosporine and tacrolimus: When NSAIDs are used concomitantly with cyclosporine or tacrolimus, the risk of increased nephrotoxicity due to reduced renal prostacyclin formation should be considered. Therefore, renal function should be closely monitored during concomitant use.
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 efficacy of NSAIDs. The clinical significance of this interaction is unknown.
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.
Antihypertensive drugs. NSAIDs may also reduce the effect of antihypertensive drugs. 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 using NSAIDs simultaneously, especially in elderly patients. Patients should consume adequate fluids and be under appropriate supervision (monitoring of renal function at the beginning of concomitant use and periodically during treatment).
Corticosteroids: Increased risk of gastrointestinal ulcers and bleeding.
Diuretics. Aceclofenac, like other NSAIDs, may reduce the effect of diuretics, reduce the diuretic effect of furosemide and bumetanide and the antihypertensive effect of thiazides. Diuretics 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. Concomitant use with potassium-sparing diuretics may lead to an increase in potassium - serum potassium levels should be monitored.
Antidiabetic drugs. Diclofenac has been shown to have no effect on the clinical efficacy of oral antidiabetic drugs when administered concomitantly. However, there have been isolated reports of hypoglycaemic and hyperglycaemic effects. Therefore, the dose of hypoglycaemic drugs should be adjusted when aceclofenac is administered.
Other analgesics, NSAIDs, including selective cyclooxygenase-2 (COX-2) inhibitors. Concomitant administration with acetylsalicylic acid or NSAIDs should be avoided as this may increase the incidence of adverse reactions, including an increased risk of gastrointestinal bleeding.
Application features
Undesirable effects can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms (see below for gastrointestinal and cardiovascular risks).
The concomitant use of aceclofenac and NSAIDs, including selective COX-2 inhibitors, should be avoided.
Cardiovascular, renal and hepatic disorders
The use of NSAIDs can cause a dose-dependent decrease in prostaglandin production and renal failure. Patients with impaired renal function, heart failure, liver dysfunction, patients taking diuretics, and elderly patients are at high risk of this reaction. Such patients require monitoring of renal function.
Effects on the kidneys
The important role of prostaglandins in maintaining renal blood flow should be taken into account when using the drug in patients with heart failure or impaired renal function, who are taking diuretics or recovering from major surgery, as well as in elderly patients. NSAIDs can cause a dose-dependent reduction in prostaglandin formation and sudden renal failure. The effect on renal function is usually reversible, and the condition 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.
Effect on the liver
Close medical supervision of patients with mild to moderate hepatic impairment is necessary. If liver function test abnormalities persist or worsen, clinical symptoms/signs of liver disease or other manifestations (eosinophilia, rash) appear, aceclofenac should be discontinued. 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 hypertension and/or a history of mild to moderate congestive heart failure, as NSAID therapy is associated with events such as fluid retention and oedema. Clinical trials and epidemiological data suggest that some NSAIDs (especially at high doses and in long-term use) are associated with a small increase in the risk of arterial thrombotic events (e.g. myocardial infarction or stroke).
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 and with special caution.
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 reviewed periodically.
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 gastrointestinal ulcer, bleeding or perforation;
ulcerative colitis;
Crohn's disease;
bleeding tendency, systemic lupus erythematosus, porphyria, disorders of hematopoiesis and hemostasis.
Effects on the gastrointestinal tract
Ulceration, perforation, and fatal gastrointestinal bleeding have been reported with all NSAIDs at any time during treatment, with or without warning symptoms, and regardless of a history of serious gastrointestinal disease.
Careful medical observation is extremely important in cases of suspected history of gastrointestinal ulcers, for patients with symptoms of gastrointestinal diseases, ulcerative colitis and Crohn's disease, hemorrhagic diathesis, or hematological disorders.
Patients with a history of gastrointestinal toxicity, particularly the elderly, should report any unusual abdominal symptoms (especially gastrointestinal bleeding), including at the start of treatment. Particular caution is required in patients receiving concomitant medications that increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants (warfarin), SSRIs or antiplatelet agents (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.
Systemic lupus erythematosus (SLE) and mixed connective tissue disease
Patients with SLE and mixed connective tissue disease are at increased risk of developing aseptic meningitis.
Hypersensitivity reactions and skin reactions
As with other NSAIDs, allergic reactions, including anaphylactic/anaphylactoid reactions, may occur in patients who have not previously taken this drug.
Severe skin reactions, sometimes fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported very rarely with NSAIDs. The risk of these reactions is highest at the beginning of therapy (in the first month).
At the first signs of skin reactions (rash, mucosal lesions, hypersensitivity reactions), the use of aceclofenac should be discontinued.
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, so 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 for infertility.
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, especially in history, because taking NSAIDs can provoke the development of sudden bronchospasm in such patients.
Elderly patients
In elderly patients (aged 65 years and over), NSAIDs are associated with an increased incidence of adverse reactions, especially gastrointestinal perforations and bleeding, which can be fatal. In addition, elderly patients are more likely to suffer from kidney, liver or cardiovascular diseases.
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.
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 and/or embryo/fetal development.
Epidemiological data suggest an increased risk of miscarriage, heart defects and gastroschisis after use of prostaglandin synthesis inhibitors in early pregnancy. The absolute risk of heart defects increases from less than 1% to approximately 1.5%. The risk increases with increasing dose and duration of treatment.
In animals, administration of prostaglandin synthesis inhibitors results in pre- and post-implantation fetal death and increased embryo-fetal lethality. In addition, there is an increased incidence of various malformations, including cardiac malformations, in animals receiving prostaglandin synthesis inhibitors during organogenesis.
From the 20th week of pregnancy, the use of aceclofenac may cause oligohydramnios due to fetal renal dysfunction. This may occur shortly after the start of treatment and is usually reversible after discontinuation of treatment. In addition, there are reports of narrowing of the ductus arteriosus after treatment in the second trimester of pregnancy, most of which resolved after discontinuation of treatment. Therefore, during the first and second trimesters of pregnancy, medicinal products containing aceclofenac should not be prescribed unless clearly necessary. If aceclofenac is used by a woman planning a pregnancy or during the first or second trimester of pregnancy, the dose should be kept as low and the duration of treatment as short as possible.
After use of aceclofenac for several days, starting from the 20th week of pregnancy, antenatal monitoring for oligohydramnios and narrowing of the ductus arteriosus should be considered. Aceclofenac should be discontinued if oligohydramnios or narrowing of the ductus arteriosus is detected.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may cause the following risks:
risks to the fetus:
kidney dysfunction (see above);
Risks for the mother at the end of pregnancy and for the newborn:
possible prolongation of bleeding time, antiplatelet effect, which may develop even after the use of very low doses;
inhibition of uterine contractions, leading to delayed labor or prolonged labor.
Thus, the use of aceclofenac is contraindicated in the third trimester of pregnancy.
Breast-feeding
There is no information on the excretion of aceclofenac in breast milk. However, no significant excretion of radiolabelled (C14) aceclofenac into the milk of rats was observed. Limited available data indicate that NSAIDs are found in breast milk in very low concentrations. The drug is contraindicated for use in women during breastfeeding in order to avoid undesirable effects on the infant. If treatment is necessary, breastfeeding should be discontinued.
Fertility
NSAIDs may impair fertility and are therefore not recommended in women attempting to conceive. Women who have difficulty conceiving or are undergoing investigation for infertility should discontinue aceclofenac.
Ability to influence reaction speed when driving vehicles or other mechanisms
Undesirable effects such as dizziness, vertigo, drowsiness, fatigue and visual disturbances or other CNS symptoms may occur after taking NSAIDs. If such reactions occur, patients should not drive or operate machinery.
Method of administration and doses
Olfen®-AF, modified-release 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/day once (every 24 hours).
Elderly patients
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 or moderate hepatic impairment, the dose of aceclofenac should be reduced. The recommended initial dose is 100 mg/day (use aceclofenac in a different dosage form).
Kidney failure
There is no information that patients with mild renal insufficiency require aceclofenac dose adjustment, 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
There are no data on overdose of aceclofenac in humans.
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 sometimes convulsions. In severe poisoning, acute renal failure and liver damage may develop.
Treatment
Treatment of acute NSAID poisoning consists of the use of antacids as needed and other supportive and symptomatic therapy for complications such as hypotension, renal failure, convulsions, gastrointestinal irritation, and respiratory depression. Activated charcoal should be administered or the stomach should be lavaged within one hour of ingestion of a potentially toxic amount of the drug.
Specific therapeutic agents such as dialysis or hemoperfusion are unlikely to be effective in removing NSAIDs due to their high protein binding and extensive metabolism.
It is necessary to provide forced diuresis and monitor kidney and liver function.
Patients should be observed for at least 4 hours after ingestion of a potentially toxic amount of the drug. In case of frequent and prolonged seizures, the patient requires intravenous diazepam.
Treatment is symptomatic and supportive.
Side effects
The most common adverse reactions of aceclofenac include gastrointestinal upset, dizziness, and elevated liver enzyme levels.
Cardiovascular system: Aceclofenac has a similar structure and metabolism to diclofenac, which is associated with a small increase in the risk of common arterial thrombotic events (myocardial infarction, stroke, especially at high doses or with prolonged use). Epidemiological data also indicate an increased risk of acute coronary syndrome and myocardial infarction associated with the use of aceclofenac. Edema, hypertension and heart failure have been reported with NSAIDs.
Hypersensitivity and skin reactions: when using NSAIDs, allergic reactions may develop, manifested as anaphylactic reactions, respiratory tract reactivity (including asthma, worsening of asthma, bronchospasm, dyspnea), various skin reactions, including rashes of various types, itching, urticaria, purpura, angioedema, less often - exfoliative and bullous dermatitis (in particular epidermal necrolysis and erythema multiforme).
In special cases, with chickenpox, complications may occur: serious infections of the skin and soft tissues.
Neurological and sensory disorders: optic neuritis, cases of aseptic meningitis (especially in patients with autoimmune disorders such as SLE, mixed connective tissue disease) with symptoms such as numbness (rigidity) of the neck muscles, fever, disorientation, confusion, hallucinations, malaise.
Hematological disorders: agranulocytosis, aplastic anemia.
Adverse reactions reported in clinical trials and post-marketing experience
Gastrointestinal: 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, hemorrhagic diarrhea.
Hepatobiliary disorders: hepatitis, jaundice, increased liver enzymes.
Immune system disorders: anaphylactic reactions (including shock), hypersensitivity.
Cardiovascular system: arterial hypertension, heart failure, palpitations, hyperemia, hot flashes, vasculitis.
Renal and urinary disorders: nephrotic syndrome, renal failure, nocturnal enuresis, interstitial nephritis.
Nervous system: visual disturbances, headache, drowsiness, tremor, dysgeusia, paresthesia, occipital rigidity, fever, dysesthesia, agitation, hallucinations, tinnitus, exhaustion, drowsiness, dizziness, aseptic meningitis (especially in SLE 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, eczema, bullous dermatitis, Stevens-Johnson syndrome or Lyell's 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 blood urea concentration, increased blood creatinine concentration, increased blood alkaline phosphatase activity, increased body weight.
Reporting of suspected adverse reactions. All cases of suspected adverse reactions and lack of efficacy of the drug should be reported via the link: https://aisf. dec. gov. ua/.
Expiration date
2 years.
Storage conditions
Store in original packaging at a temperature not exceeding 30 ° C. Keep out of the reach of children.
Packaging
10 tablets in a blister. 1 or 3 or 10 blisters in a cardboard box.
Vacation category
According to the recipe.
Producer
Korea United Pharm., Inc.
Address
25-23, Nochangongdan-gil, Jeongdong-myeon, Sejong-si, Republic of Korea.
