Aceclofenac

Package leaflet (information for patients)

Tradename
Aceclofenac

Dosage form
Tablets 100 mg

Description
Round, flat, beveled to the edge white tablets with an imprint in the form of the brand name "V" on one side.

Structure
Active ingredient: Aceclofenac 100 mg.
Excipients: microcrystalline cellulose 102, calcium stearate, aerosil ® 200 (hydrophilic pyrogenic silicon dioxide).

Pharmacotherapeutic group
Non-steroidal anti-inflammatory and antirheumatic drugs

Pharmacological properties
Aceclofenac is a phenylacetic acid derivative that indiscriminately inhibits type I and II cyclooxygenase.
Aceclofenac has anti-inflammatory, analgesic and antipyretic effects. It inhibits the synthesis of prostaglandins and thus influences 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, swelling of the joints, which improves the functional state of the patient.
Pharmacokinetics
Suction
Aceclofenac is rapidly and completely absorbed after oral administration. The time to reach the maximum concentration is 1.25-3 hours.
Distribution
It penetrates into the synovial fluid, where its concentration reaches 57% of the plasma concentration, and the time to reach the maximum concentration is 2-4 hours later than in plasma. The volume of distribution is 30 liters. Communication with plasma proteins (albumin) - 99%.
Metabolism
Aceclofenac is metabolized by the isoenzyme CYP 2 C 9 with the formation of the 4- hydroxyaceclofenac metabolite , whose contribution to the clinical effect of the drug, most likely, is minimal.
Withdrawal
The half-life is 4 hours. The clearance is 5 l / h. It is excreted by the kidneys, mainly in the form of hydroxy derivatives (about 2/3 of the administered dose). Only 1% of the dose after oral administration is excreted unchanged.

Indications for use
Symptomatic treatment of moderate or mild pain syndrome of various origins (headache, toothache, migraine, neuralgia, muscle pain, pain during menstruation) in adults and febrile syndrome with colds and other infectious and inflammatory diseases in adults and children over 15 years old.

Method of administration and dosage
Adverse events can be minimized by reducing the duration of treatment required to control symptoms (see section "Precautions"), Aceclofenac- MIC is intended for oral administration; the capsule should be swallowed with at least half a glass of water. Aceclofenac- MIC can be used with meals.
Adults:
The maximum recommended dose is 200 mg daily in two separate 100 mg doses (one capsule in the morning and one in the evening).
Children:
There is no data on the effectiveness and safety of taking the drug in children.
P lively:
Usually no dose reduction is necessary; however, the precautions listed in the Precautions section must be followed.
Hepatic impairment:
The dose of aceclofenac should be reduced in patients with mild to moderate liver disease. The recommended starting dose is 100 mg per day (see PRECAUTIONS section).
Renal failure:
There is no evidence of the need to reduce the dose of aceclofenac in patients with mild renal impairment, but caution should be exercised when using Aceclofenac- MIC (see section "Precautions").

Side effects
- from the gastrointestinal tract:
often - nausea, vomiting, diarrhea, epigastric pain , intestinal colic, dyspepsia, flatulence, anorexia, constipation; in rare cases, - noted the occurrence of erosive and ulcerative lesions, bleeding or perforation of the gastrointestinal tract (hematemesis, melena), stomatitis (in incl . aphthous ), pancreatitis.
- From the nervous system:
rarely - headache, dizziness, sleep disturbances (insomnia or drowsiness), agitation; in some cases, disturbances in sensitivity, disorientation, memory, vision, hearing, taste, tinnitus, convulsions, irritability, tremors, depression, anxiety, and vertigo were noted . aseptic meningitis, paresthesia.
- Allergic reactions:
infrequent skin rash; rarely - urticaria, bronchospasm , systemic anaphylactic reactions; very rarely - vasculitis, pneumonitis , Stevens -Johnson syndrome and Lyell's syndrome , anaphylactic shock, discoid lupus erythematosus; isolated cases of eczema, polymorphic erythema, erythroderma were noted.
- on the part of the kidneys and urinary tract:
rarely peripheral edema; very rarely - acute renal failure, interstitial nephritis, nephrotic syndrome, hematuria, proteinuria.
- from the liver and biliary tract:
Rarely - hepatitis; very rarely - fulminant hepatitis.
- From the side of the hematopoietic organs:
very rarely - leukopenia; individual cases of thrombocytopenia, agranulocytosis , hemolytic anemia, aplastic anemia, neutropenia are described.
- on the part of the cardiovascular system:
isolated cases of tachycardia, arterial hypertension, congestive heart failure, coronary heart disease (CHD) were noted.
- from the respiratory system:
rarely - shortness of breath, pulmonary edema; very rarely bronchospasm.
- on the part of musculoskeletal and connective tissue:
isolated cases of leg cramps were noted.
Laboratory indicators:
often - a transient increase in the activity of transaminases in the blood; infrequently - an increase in the concentration of urea and creatinine in the blood; very rarely, an increase in the level of alkaline phosphatase in the blood.

Contraindication
Aceclofenac is contraindicated in the following cases:

• Hypersensitivity to the active substance or other excipients listed in the "Composition" section;
• Patients in whom substances with the same effect (for example, acetylsalicylic acid or other NSAIDs) provoked attacks of asthma, bronchospasm, acute rhinitis or urticaria; or if there is a hypersensitivity to these substances;
• Patients who have had cases of bleeding or perforation of the gastrointestinal stroke due to taking NSAIDs. Patients with acute, recurrent, or possible gastric or duodenal ulcer or a history of bleeding (two or more overt and proven episodes of ulcer or bleeding);
• Patients with acute bleeding or bleeding disorders (hemophilia or bleeding disorders);
• Heart failure ( NYHA functional class II -IV), coronary artery disease, peripheral arterial disease or cerebrovascular disease;
• Severe violations of liver and kidney function;
• During pregnancy, especially in the last trimester, except for serious indications for use. In this case, the minimum effective dose should be used (see section "Pregnancy and lactation").

Overdose
There is no evidence of an overdose of aceclofenac in humans.
Symptoms include headache, nausea, vomiting, eligastric pain , gastrointestinal irritation, gastrointestinal bleeding, rarely diarrhea, disorientation, agitation, coma, drowsiness, dizziness, tinnitus, hypotension, respiratory depression, fainting, rarely seizures ... In case of severe poisoning, acute renal failure and liver damage are possible.
Poisoning treatment:
If necessary, symptomatic therapy should be carried out. Activated charcoal should be taken within one hour after taking a toxic amount of the drug. Alternatively, in adult patients, gastric lavage may be considered in the first hour after taking a potentially life-threatening dose.
Specific interventions such as hemodialysis or hemoperfusion are probably ineffective in removing NSAIDs due to their high protein binding and extensive metabolism. A good diuresis should be ensured, and kidney and liver function should be closely monitored. The patient should be monitored for at least 4 hours after taking a potentially toxic dose. If frequent or prolonged seizures develop, intravenous diazepam should be used . Other measures may be required depending on the clinical condition of the patient. Treatment of acute NSAID poisoning is mainly supportive and symptomatic therapy.

Precautions
Avoid the simultaneous use of Aceclofenac- MIC and other NSAIDs, including selective inhibitors of cyclooxygenase-2.
Adverse events can be minimized by using the minimum effective dose and reducing the duration of treatment necessary to control symptoms (see the section "Dosage and Administration" and a description of the risks to the gastrointestinal tract and cardiovascular system below).
Effect on the gastrointestinal tract
Bleeding, ulcer or perforation of the gastrointestinal tract with a fatal outcome was observed with any NSAIDs taken at any period of treatment, both with and without dangerous symptoms, with or without a history of serious pathological conditions of the gastrointestinal tract.
The risk of bleeding, ulceration and perforation of the gastrointestinal tract increases with increasing dose of NSAIDs in patients who have had an ulcer, especially if it was accompanied by hemorrhage or perforation (see section "Contraindications"), and in elderly patients. These patients should take the lowest effective dose of the drug. They need combination therapy with protective drugs (for example, misoprostol , or proton pump inhibitors), and similar therapy is needed for patients who take small doses of aspirin or other drugs that negatively affect the state of the gastrointestinal tract (see the section "Interactions").
Patients with diseases of the gastrointestinal tract, including the elderly, should report any unusual symptoms associated with the gastrointestinal tract (especially bleeding), including when taking the drug for the first time. Particular caution should be exercised in patients concurrently taking medications 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) (see Interactions").
If bleeding occurs from a gastrointestinal ulcer in patients taking Aceclofenac- MIC, treatment should be discontinued.
Effects on the cardiovascular system
For patients with arterial hypertension and / or mild to moderate congestive heart failure, appropriate monitoring and special instructions are necessary, since fluid retention and edema associated with the use of NSAIDs have been reported.
Clinical studies and epidemiological data show that the use of some NSAIDs (in particular, in high doses and with prolonged use) may not significantly increase the risk of arterial thrombotic events (for example, myocardial infarction or stroke). There is no reliable data on the absence of this risk when taking aceclofenac.
Patients with uncontrolled hypertension, heart failure (NYHA functional class I), congestive heart failure, cardiovascular risk factors (eg, hypertension, hyperlipidemia , diabetes mellitus, and smoking), and a history of cerebral hemorrhage , special care should be taken when taking aceclofenac.
Aceclofenac should be taken with caution and under the supervision of a physician in patients with the following conditions, since there is a threat of exacerbation of the disease (see section "Side effects):
- symptoms indicating the presence of a disease of the gastrointestinal tract, including its upper and lower sections;
- a history of ulcers, bleeding or perforation of the gastrointestinal tract;
- ulcerative colitis;
- Crohn's disease;
- a tendency to bleeding, SLE (systemic lupus erythematosus), porphyria , and disorders of hematopoiesis and hemostasis.
Aceclofenac should be used with caution and under medical supervision in patients with a history of hemorrhagic stroke.
Effects on the liver and kidneys
Taking NSAIDs can cause a dose-dependent reduction in prostaglandin production and sudden renal failure. The importance of prostaglandin for ensuring renal blood flow should be considered when taking the drug in patients with impaired heart, kidney or liver function, in those receiving diuretics, or in patients after surgery, as well as in elderly patients.
Care should be taken when taking the drug in patients with mild to moderate liver and kidney dysfunction, as well as in patients with other conditions that predispose to fluid retention in the body. In these patients, the use of NSAIDs can lead to impaired renal function and fluid retention. You should also be careful when taking aceclofenac in patients taking diuretics or in those at increased risk of hypovolemia . A minimum effective dose and regular medical monitoring of renal function are required. Kidney problems usually resolve when aceclofenac is stopped.
Receiving aceclofenac should be discontinued if changes in liver function are stored or worsen, develop clinical signs or symptoms of liver disease or other manifestations occur ( eosinophilia , rash). Hepatitis can develop without prodromal symptoms.
The use of NSAIDs in patients with hepatic porphyria can provoke an attack.
Hypersensitivity and skin reactions
Like other NSAIDs, the drug can cause allergic reactions, including anaphylactic / anaphylactoid reactions, even if 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 the Side Effects section). The highest risk of these reactions in patients is observed at the beginning of taking the drug, and the development of these adverse reactions is observed during the first month of taking the drug. If you experience a skin rash, damage to the oral mucosa, or other signs of hypersensitivity, you should stop taking aceclofenac.
In special cases, with chickenpox complications may occur: serious infections of the skin and soft tissues.
Currently, the role of NSAIDs in the worsening of these infections cannot be ruled out. Therefore, you should avoid taking aceclofenac for chickenpox.
Hematological disorders
Aceclofenac can cause reversible inhibition of platelet aggregation (see the section "Interactions").
Respiratory system disorder
Caution should be exercised when taking the drug in patients with bronchial asthma at the present time or in history, since taking NSAIDs can provoke the development of sudden bronchospasm in such patients.
The elderly
Care should be taken when taking the drug in elderly patients, since they often have side effects (especially bleeding and perforation of the gastrointestinal tract) when taking NSAIDs. Complications can be fatal. In addition, older patients are more likely to suffer from kidney, liver, or cardiovascular disease.
Long-term use
All patients receiving long-term treatment with non-steroidal anti-inflammatory drugs should be closely monitored (for example, complete blood count, liver and kidney function tests).

Interaction with other medicinal products
No drug interaction studies have been conducted, with the exception of warfarin.
Aceclofenac is metabolized by cytochrome P450 2C9, and in vitro data indicate that aceclofenac may be an inhibitor of this enzyme. Thus, the risk of pharmacokinetic interaction is possible when taken simultaneously with phenytoin , cimetidine , tolbutamide , phenylbutazone, amiodarone , miconazole and sulfaphenazole . As with other drugs of the NSAID group, the risk of pharmacokinetic interaction with other drugs that are excreted from the body by active renal secretion, such as methorexate and lithium drugs , also increases . Aceclofenac almost completely binds to plasma albumin and, therefore, there is a possibility of displacement-type interactions with other drugs that bind to proteins.
Due to the paucity of studies on the pharmacokinetic interactions of aceclofenac, the following information is based on data from other NSAIDs:
Simultaneous use should be avoided:
Methotrexate : NSAIDs inhibit the tubular secretion of methotrexate ; moreover, there may be a slight metabolic interaction, which leads to a decrease in the clearance of methotrexate . Therefore, when using high doses of methotrexate , NSAIDs should be avoided.
Lithium and digoxin preparations : Some NSAIDs inhibit the renal clearance of lithium and digoxin , resulting in an increase in serum concentrations of both substances. Concomitant use should be avoided unless frequent monitoring of lithium and digoxin concentrations is performed.
Anticoagulants: NSAIDs inhibit platelet aggregation and damage the lining of the gastrointestinal tract, which can increase the effect of anticoagulants and increase the risk of bleeding from the gastrointestinal tract in patients taking anticoagulants. The combined use of aceclofenac and oral anticoagulants of the coumarin group, ticlopidine and thrombolytics should be avoided unless the patient is closely monitored.
Antiplatelet drugs and selective serotonin reuptake inhibitors (SSRIs), when used together with NSAIDs, may increase the risk of gastrointestinal bleeding (see the PRECAUTIONS section).
The following combinations require dose selection and use with caution:
Methotrexate : the possible interaction of NSAIDs and methotrexate should be borne in mind , even with a low dose of methotrexate, especially in patients with impaired renal function. When taken simultaneously, the indicators of renal function should be monitored. Caution should be exercised if both NSAIDs and methotrexate are taken within 24 hours, as the concentration of methotrexate may increase, increasing the toxicity of the drug.
Cyclosporine, tacrolimus: while taking NSAIDs with cyclosporine or tacrolimus , the risk of increased nephrotoxicity due to a decrease in the formation of renal prostacyclin should be considered . Therefore, when taken simultaneously, the indicators of renal function should be carefully monitored.
Other NSAIDs: while taking acetylsalicylic acid or other NSAIDs, the incidence of side effects may increase, so care should be taken. Corticosteroids: Increases the risk of ulcers or bleeding from the gastrointestinal tract (see PRECAUTIONS section).
Diuretics: aceclofenac , like other NSAIDs, can inhibit the activity of diuretics, can reduce the diuretic effect of furosemide and bumetanide and the antihypertensive effect of thiazides . Co-administration with potassium-sparing diuretics can lead to an increase in potassium; therefore, it is necessary to regularly monitor the serum potassium content.
Aceclofenac did not affect blood pressure control when used together with bendrofluazide , although interaction with other diuretics cannot be ruled out.
Antihypertensive drugs: NSAIDs can also reduce the effect of antihypertensive drugs. Co-administration of ACE inhibitors or angiotensin II receptor antagonists and NSAIDs can lead to impaired renal function. The risk of acute renal failure, which is usually reversible, may increase in some patients with impaired renal function, such as the elderly or dehydrated patients. Therefore, when used together with NSAIDs, caution should be exercised, especially in elderly patients. Patients should consume the required amount of liquid and be under appropriate supervision (monitoring of renal function at the beginning of joint use 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 some reports of hypoglycemic and hyperglycemic effects of the drug. Thus, when taking aceclofenac, it is necessary to adjust the doses of drugs that can cause hypoglycemia.
Zidovudine : With the simultaneous administration of NSAIDs and zidovudine , the risk of hematological toxicity increases. There is evidence of an increased risk of hemarthrosis and hematomas in HIV (+) patients with hemophilia receiving zidovudine and ibuprofen.

Special instructions
During the period of treatment with the drug, systematic monitoring of the picture of peripheral blood, liver and kidney function, examination of feces for the presence of blood should be carried out.
Patients taking the drug should refrain from activities that require increased attention and rapid mental and motor reactions. Drinking alcohol should be avoided during treatment.
If signs of liver damage appear (itching, jaundice, nausea, vomiting, abdominal pain, dark urine, increased activity of 'liver' transaminases), stop taking the drug and consult your doctor. In patients with hepatic insufficiency, kinetics and metabolism differ from those in patients with normal liver function.
The drug should not be used concomitantly with other NSAIDs.
The drug can change the properties of platelets, but does not replace the prophylactic effect of acetylsalicylic acid in cardiovascular diseases.
The use of the drug may adversely affect female fertility and is not recommended for women planning a pregnancy. In infertile patients (including those undergoing examination) it is recommended to cancel the drug.
Due to the important role of prostaglandins in maintaining renal blood flow, special care should be taken when prescribing to patients with heart or renal failure, the elderly taking diuretics, and patients with a reduced volume of circulating blood (for example, after extensive surgery). If a drug is prescribed in such cases, it is recommended that renal function be monitored.
To reduce the risk of developing adverse events from the gastrointestinal tract, the minimum effective dose should be used in the shortest possible short course.

Pregnancy and elbowing
Pregnancy
There is no data on the use of aceclofenac in pregnancy.
Inhibition of prostaglandin synthesis can adversely affect the course of pregnancy and / or the development of the embryo / fetus.
Epidemiological data indicate an increased risk of miscarriage, heart disease and gastroschisis following the use of prostaglandin synthesis inhibitors in the early stages of pregnancy. The absolute risk of developing heart disease increases from less than 1% to about 1.5%. The risk increases with dose and duration of treatment.
In animals, the intake of inhibitors of prostaglandin synthesis results in pre- and post- implantation fetal death and mortality of the embryo and fetus. In addition, the incidence of various defects, including heart disease, is increasing in animals receiving prostaglandin synthesis inhibitors during organogenesis.
During the first and second trimester of pregnancy, drugs containing aceclofenac are not prescribed unless absolutely necessary. If aceclofenac is taken by a woman planning a pregnancy, or is in the first or second trimester of pregnancy, the dose should be as low as possible and the duration of treatment should be as short as possible.
During the third trimester of pregnancy, all inhibitors of prostaglandin synthesis:
• can affect the fetus, with cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension);
• can affect the fetus, causing kidney dysfunction, which can lead to kidney failure and oligohydramnios.
Mothers and newborns at the end of pregnancy:
• the drug can affect the duration of bleeding, due to the antiplatelet effect, which can develop even after very low doses;
• the drug can inhibit uterine contractions, leading to delayed labor or prolonged labor.
Thus, the use of aceclofenac is contraindicated in the third trimester of pregnancy (see sections "Contraindications" and "Precautions").
Lactation: There is no information on the penetration of aceclofenac into breast milk. However, there was no noticeable penetration of the labeled radioisotope (C14) aceclofenac into the milk of lactating rats. The decision to continue / stop breastfeeding or use aceclofenac is made after evaluating the benefits of breastfeeding for the baby and the benefits of taking aceclofenac for the mother.
The use of aceclofenac should be avoided during pregnancy and lactation, unless the potential benefit to the mother outweighs the possible risks to the fetus.
Fertility:
The use of aceclofenac, as well as other inhibitors of cyclooxygenase / prostaglandin synthesis , can reduce fertility and is not recommended for women planning children. Women who have difficulty conceiving or undergoing a fertility test should stop taking aceclofenac .

Influence on the ability to drive vehicles and work with mechanisms
Does not affect.

Storage conditions
Store in a dry, dark place at a temperature not exceeding 25 ° C, out of the reach of children.

Shelf life
3 years. Do not use after the expiration date printed on the package.

Vacation conditions
By prescription.

Packaging
Aceclofenac 100 mg Tablets. There are 25 tablets in a blister. 4 blisters are packed in a cardboard box together with an enclosed leaflet.