Instructions Diclutol film-coated tablets 100 mg blister No. 100
Composition
active ingredient: aceclofenac;
1 tablet contains aceclofenac 100 mg;
excipients: microcrystalline cellulose, croscarmellose sodium, colloidal anhydrous silicon dioxide, stearic acid, Opadry-YS-1-7027 White (hydroxypropylmethylcellulose), titanium dioxide (E 171), triacetin).
Dosage form
Film-coated tablets.
Main physicochemical properties: round biconvex tablets, coated with a white coating.
Pharmacotherapeutic group
Nonsteroidal anti-inflammatory and antirheumatic drugs. Acetic acid derivatives and related substances. ATC code M01A B16.
Pharmacological properties
Pharmacodynamics
Aceclofenac is a nonsteroidal anti-inflammatory and analgesic drug. The mechanism of action of this drug is believed to be based on inhibition of prostaglandin synthesis.
Pharmacokinetics
Absorption
After oral administration, aceclofenac is rapidly absorbed, its bioavailability is almost 100%. Peak plasma concentrations are reached approximately 1.25-3 hours after administration. Food intake slows down absorption, but does not affect its extent.
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.
Breeding
The mean 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 probably metabolized by CYP2C9 to the major metabolite 4-OH-aceclofenac, which is of little clinical significance. Diclofenac and 4-OH-diclofenac have been identified among the many metabolites.
Special patient groups
No changes in the pharmacokinetics of aceclofenac were found in elderly patients.
In patients with reduced liver function, aceclofenac was eliminated more slowly after a single dose. In studies with multiple doses of 100 mg daily, there was no difference in pharmacokinetic parameters between patients with mild to moderate liver cirrhosis and healthy volunteers.
In patients with mild or moderate renal impairment, no clinically significant differences in pharmacokinetics were observed after a single dose.
Indication
Symptomatic treatment of pain and inflammation in osteoarthritis, rheumatoid arthritis and ankylosing spondylitis, as well as other diseases of the musculoskeletal system accompanied by pain (for example, shoulder-scapular periarthritis or extra-articular rheumatism). As an analgesic in conditions accompanied by pain (including low back pain, toothache and primary (functional) dysmenorrhea).
Contraindication
Hypersensitivity to aceclofenac, other non-steroidal anti-inflammatory drugs (NSAIDs) or to any of the excipients of the drug; asthma attacks, acute rhinitis, angioedema or urticaria caused by taking acetylsalicylic acid or other NSAIDs; history of gastrointestinal bleeding or ulcer perforation associated with previous NSAID therapy; peptic ulcer or bleeding, including a history (two or more separate proven episodes of ulceration or bleeding); acute bleeding or diseases accompanied by bleeding (hemophilia or blood clotting disorders); congestive heart failure (functional class II-IV according to NYHA); ischemic heart disease, including angina or previous myocardial infarction; peripheral artery disease; cerebrovascular disorders or diseases; history of stroke or episodes of transient ischemic attacks; coronary artery bypass grafting (to relieve perioperative pain) or use of a cardiopulmonary bypass machine); severe hepatic insufficiency; severe renal insufficiency.
Interaction with other medicinal products and other types of interactions
Due to the lack of pharmacokinetic interaction studies with aceclofenac, the information below is based on data from other NSAIDs.
Other analgesics, NSAIDs, including selective cyclooxygenase-2 inhibitors.
The simultaneous use of two or more NSAIDs (including acetylsalicylic acid) should be avoided, as this increases the incidence of adverse events, including the risk of gastrointestinal bleeding.
NSAIDs may also reduce the effect of antihypertensive drugs. The 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 the necessary amount of fluid and be under appropriate supervision (monitoring of renal function at the beginning of concomitant use and periodically during treatment).
Diuretics.
Reduced 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.
Cardiac glycosides.
NSAIDs can exacerbate heart failure, reduce glomerular filtration rate, and increase plasma glycoside levels.
Lithium and digoxin drugs.
Some NSAIDs inhibit the renal clearance of lithium and digoxin, leading to increased serum concentrations of both substances. Concomitant use should be avoided unless frequent monitoring of lithium and digoxin concentrations is performed.
Methotrexate.
Decreased elimination of methotrexate. Interactions between NSAIDs and methotrexate are possible, 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 drug.
Mifepristone.
NSAIDs should not be taken for 8-12 days after taking mifepristone, as NSAIDs may reduce the effect of mifepristone.
Corticosteroids.
The risk of ulcers and bleeding from the gastrointestinal tract (GI) increases (see section "Special warnings and precautions for use").
Anticoagulants.
NSAIDs may enhance the effects of anticoagulants such as warfarin. Careful monitoring of the condition of patients receiving combined therapy with anticoagulants and Diclotol is required.
Quinoline group 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.
Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs).
The risk of gastrointestinal bleeding increases (see section "Special warnings and precautions for use").
Cyclosporine, 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.
Zidovudine.
The risk of hematological toxicity increases with concomitant use of NSAIDs and zidovudine. There is evidence of an increased risk of hemarthrosis and hematomas in HIV (+) hemophiliac patients receiving zidovudine and ibuprofen.
Hypoglycemic agents.
Clinical studies show that diclofenac can be used together with oral hypoglycemic agents without affecting their clinical effect. However, there are isolated reports of hypoglycemic and hyperglycemic effects of the drug. Therefore, when taking aceclofenac, the doses of drugs that can cause hypoglycemia should be adjusted.
Application features
Undesirable effects can be minimized by short-term use of the lowest effective dose to control symptoms (see GI and cardiovascular risks below). The concomitant use of Diclotol and NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided.
Effects on the gastrointestinal tract
Fatal gastrointestinal bleeding, ulceration, or perforation have been reported with all NSAIDs at any time during treatment, with or without warning symptoms, and regardless of a history of serious acute gastrointestinal disease.
Patients with gastrointestinal diseases, including the elderly, should be informed of any unusual symptoms related to the gastrointestinal tract (especially gastrointestinal bleeding), including at the beginning of treatment. Particular caution should be exercised in patients taking concomitant medications that increase the risk of bleeding or ulceration, such as systemic corticosteroids, anticoagulants (e.g. warfarin), selective serotonin reuptake inhibitors or antiplatelet agents (such as acetylsalicylic acid) (see section "Interaction with other medicinal products and other forms of interaction").
If gastrointestinal bleeding or ulceration occurs in patients taking Diclotol®, treatment should be discontinued.
Cardiovascular and cerebrovascular effects
Appropriate monitoring and special instructions are necessary for patients with arterial hypertension and/or mild to moderate congestive heart failure, as fluid retention and edema have been reported in association with NSAIDs. Clinical trials and epidemiological data suggest that some NSAIDs (especially at high doses and in long-term use) are associated with a small increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke).
Patients with heart failure (NYHA functional class I) and cardiovascular risk factors (e.g. hypertension, hyperlipidemia, diabetes mellitus, and smoking) should be treated with special caution when taking aceclofenac. Since the adverse effects on the cardiovascular system increase with increasing dose and duration of treatment, the minimum effective daily dose should be used for the shortest possible treatment period. The need for further symptomatic treatment of the patient and the effectiveness of 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 suggestive of gastrointestinal disease, including upper and lower gastrointestinal tract; history of gastrointestinal ulceration, bleeding, or perforation; ulcerative colitis; Crohn's disease; bleeding tendency, SLE (systemic lupus erythematosus), porphyria, and disorders of hematopoiesis and hemostasis.
Effects on the liver and kidneys
NSAIDs may cause a dose-dependent reduction in prostaglandin formation and sudden renal failure. The importance of prostaglandins in maintaining renal blood flow should be considered when using the drug in patients with impaired cardiac, renal or hepatic function, in persons receiving diuretics, in patients after surgery, and in elderly patients.
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 may lead to impaired renal function and fluid retention. Caution should also be exercised when using the drug Diclotol® in patients taking diuretics or in individuals at increased risk of hypovolemia. The minimum effective dose and regular medical monitoring of renal function are necessary. Renal phenomena usually resolve after discontinuation of aceclofenac.
Aceclofenac should be discontinued if liver function tests persist or worsen, clinical signs of liver disease develop, or other manifestations occur (eosinophilia, rash). Hepatitis may develop without prodromal symptoms. Use of NSAIDs in patients with hepatic porphyria may precipitate an attack.
Systemic lupus erythematosus and mixed connective tissue disease
Patients with systemic lupus erythematosus and mixed connective tissue diseases are at increased risk of developing aseptic meningitis (see section "Adverse reactions").
Hypersensitivity and skin reactions
Like other NSAIDs, Diclotol® can cause allergic reactions, including anaphylactic/anaphylactoid reactions, even when the drug 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 observed very rarely after taking NSAIDs (see section "Adverse reactions"). The highest risk of these reactions in patients is observed at the beginning of the drug, and the development of these undesirable reactions is observed during the first month of taking the drug. If skin rashes, lesions on the oral mucosa or other signs of hypersensitivity occur, aceclofenac should be discontinued.
In special cases, complications may occur with chickenpox: serious skin and soft tissue infections. At this time, the role of NSAIDs in worsening the course of these infections cannot be ruled out. Therefore, Diclotol® should be avoided in chickenpox.
Hematological disorders
Aceclofenac may cause reversible inhibition of platelet aggregation (see section "Adverse reactions").
Caution should be exercised when administering the drug to patients with bronchial asthma, including those with a history of it, since taking NSAIDs can provoke the development of sudden bronchospasm in such patients.
Elderly patients
Caution should be exercised when using the drug in elderly patients (aged 65 years and over), as they are more likely to experience side effects (especially bleeding, gastrointestinal perforation) when taking NSAIDs. Complications can be fatal. In addition, elderly patients are more likely to suffer from kidney, liver or cardiovascular diseases.
Long-term use
All patients receiving long-term treatment with NSAIDs should be under close medical supervision (complete blood count, liver and kidney function tests).
Ability to influence reaction speed when driving vehicles or other mechanisms
Patients who experience weakness, dizziness, vertigo, or other central nervous system symptoms while taking aceclofenac or other NSAIDs should not drive or operate hazardous machinery.
Use during pregnancy or breastfeeding
Pregnancy
There are no data on the use of aceclofenac during pregnancy.
Inhibition of prostaglandin synthesis may adversely affect 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 embryo-fetal lethality. In addition, animals receiving prostaglandin synthesis inhibitors have an increased incidence of various congenital malformations, including cardiac malformations, during organogenesis.
During the first and second trimesters of pregnancy, drugs containing aceclofenac should not be prescribed unless clearly necessary. If aceclofenac is used by a woman planning a pregnancy or in the first or second trimester of pregnancy, the dose should be kept as low as possible and the duration of treatment as short as possible.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may affect the fetus, causing:
cardiopulmonary toxicity (premature closure of the ductus arteriosus and pulmonary hypertension); renal dysfunction, which may progress to renal failure on the background of oligohydramnios.
The use of aceclofenac at the end of pregnancy may lead to:
increased bleeding duration, decreased platelet aggregation, even when using very low doses of the drug; suppression of uterine contractile function, which may lead to increased duration of labor.
Thus, the use of aceclofenac is contraindicated in the third trimester of pregnancy.
Breastfeeding period
Limited data available indicate that NSAIDs are found in breast milk at very low concentrations. There is no conclusive clinical data on the passage of aceclofenac into breast milk. Therefore, the drug is contraindicated for use in women during breastfeeding in order to avoid undesirable effects on the child.
Fertility
Aceclofenac, like other cyclooxygenase/prostaglandin synthesis inhibitors, may impair fertility and is not recommended in women attempting to conceive. Women who have difficulty conceiving or are undergoing fertility investigation should discontinue use of Diclotol®.
Method of administration and doses
Diclotol® film-coated tablets are intended for oral use and should be taken with at least ½ glass of liquid. Diclotol® should preferably be taken with food.
Adverse events can be minimized if the duration of drug administration is the shortest necessary to control symptoms (see section "Special instructions").
Adults
The maximum recommended dose is 200 mg per day in 2 doses of 100 mg (1 tablet in the morning and 1 tablet in the evening).
Elderly patients
Such patients should be carefully monitored, as they are more likely to have impaired renal and hepatic function, cardiovascular disorders, and 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 the lowest possible doses and for the shortest possible time. As a rule, dose reduction is not required. Patients should be carefully monitored for the timely detection of gastrointestinal bleeding during NSAID therapy, and the recommendations described in the section "Special instructions for use" should be followed.
Liver failure
For patients with mild to moderate hepatic impairment, the dose of aceclofenac should be reduced. The recommended starting dose is 100 mg per day (see section 4.4).
There is no information that patients with mild renal insufficiency require dose adjustment of aceclofenac, however, these patients should be cautious when using the drug (see section "Special warnings and precautions for use").
Children
Diclotol is contraindicated in children.
Overdose
There are no data on overdose with aceclofenac in humans.
Possible symptoms
Headache, nausea, vomiting, stomach pain, dizziness, drowsiness, gastrointestinal irritation, gastrointestinal bleeding, diarrhea, disorientation, agitation, coma, tinnitus, hypotension, respiratory depression, loss of consciousness, convulsions. In cases of severe poisoning, acute renal failure and impaired liver function may occur.
Treatment
Treatment of acute NSAID poisoning consists of the use of antacids (if necessary) and other supportive and symptomatic therapy for complications such as hypotension, renal failure, convulsions, gastrointestinal mucosal irritation, and respiratory depression.
Treatment of acute poisoning with aceclofenac orally consists of preventing absorption of the drug by gastric lavage and administration of activated charcoal (repeated doses) as soon as possible after overdose. Forced diuresis, dialysis or hemoperfusion may not be effective enough to remove NSAIDs due to the high degree of binding of NSAIDs to blood proteins and extensive metabolism.
Adverse reactions
Gastrointestinal: dyspepsia, abdominal pain, nausea, vomiting, hematemesis, gastritis, gastrointestinal ulcers, flatulence, diarrhea, constipation, melena, hemorrhagic diarrhea, gastrointestinal hemorrhage, gastrointestinal bleeding, gastrointestinal perforation, exacerbation of Crohn's disease and ulcerative colitis, stomatitis, pancreatitis.
From the blood and lymphatic system: anemia, hemolytic anemia, bone marrow depression, aplastic anemia, granulocytopenia, agranulocytosis, thrombocytopenia, neutropenia, increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke).
Immune system: hypersensitivity reactions; anaphylactic reactions (including shock); pseudoallergic reactions, manifested as anaphylactic reactions, respiratory tract reactivity, including asthma, worsening of asthma, bronchospasm or dyspnea, various skin reactions, including rashes of various types, itching, urticaria, purpura, angioedema, less often - exfoliative and bullous dermatitis (including epidermal necrolysis and erythema multiforme).
Metabolism and nutrition disorders: hyperkalemia.
On the part of the psyche: depression, unusual dreams, insomnia.
Nervous system: dizziness, paresthesia, tremor, drowsiness, headache, dysgeusia (taste disorders), cases of aseptic meningitis (especially in patients with autoimmune disorders such as systemic lupus erythematosus, mixed connective tissue disease) with symptoms such as numbness (rigidity) of the neck muscles, fever, disorientation, confusion, hallucinations, malaise.
From the organs of vision: visual impairment, optic neuritis.
From the side of the organs of hearing and vestibular apparatus: vertigo, tinnitus.
Cardiovascular system: palpitations, heart failure, hypertension, worsening of hypertension, flushing, hot flashes, vasculitis.
Respiratory, thoracic and mediastinal disorders: dyspnea, bronchospasm, stridor.
Hepatobiliary disorders: liver damage (including hepatitis), jaundice.
Skin and subcutaneous tissue disorders: pruritus, rash, dermatitis, urticaria, angioedema, purpura, eczema, severe skin and mucous membrane reactions (including Stevens-Johnson syndrome and toxic epidermal necrolysis), photosensitivity, skin and soft tissue infections (when using NSAIDs during chickenpox).
Renal and urinary disorders: nephrotic syndrome, renal failure, interstitial nephritis.
General disorders and local reactions: edema, fatigue, muscle cramps (in the legs).
Laboratory test results: increased activity of liver enzymes, increased activity of alkaline phosphatase in the blood, increased concentration of urea in the blood, increased content of creatinine in the blood, increased body weight.
Expiration date
3 years.
Storage conditions
Store at a temperature not exceeding 25 °C in the original packaging.
Keep out of reach of children.
Packaging
10 tablets in a blister, 10 blisters in a cardboard box.
Vacation category
According to the recipe.
Producer
KUSUM HEALTHCARE PVT LTD/ KUSUM HEALTHCARE PVT LTD.
Location of the manufacturer and its business address
SP-289 (A), RIICO Industrial area, Chopanki, Bhiwadi, Dist. Alwar (Rajasthan), India.
