Aceklagin - instructions for use, dose, side effects, contraindications

Excipients: cellulose microcrystalline 159.5 mg, povidone-K30 19.5 mg, croscarmellose sodium 9.7 mg, sodium stearyl fumarate 15.3 mg; poloxamer 407 4.5 mg, hypromellose 40.5 mg, carbomer 941 2.5 mg.

Shell composition: Deficient white OY-C-7000A 12.0 mg: hypromellose 5cP (E 464) 54.850%, titanium dioxide (E 171) 22.860%, ethylcellulose 10cP 13.720%, diethyl phthalate 8.570%.

Description:Oblong biconvex tablets, covered with a film shell of white or almost white color, engraved "UT" on one side and "CL CR" on the other side.

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

ATX: & nbsp

M.01.A.B Derivatives of acetic acid

M.01.A.B.16 Aceclofenac

Pharmacodynamics:

Aceclofenac has an anti-inflammatory, analgesic, antipyretic effect. Oppresses the synthesis of prostaglandins and, thus, affects the pathogenesis of inflammation, the onset of pain and fever. In rheumatic diseases, the anti-inflammatory and analgesic effect of aceclofenac contributes to a significant reduction in the severity of pain, morning stiffness, swelling of the joints, which improves the functional state of the patient.

Pharmacokinetics:

Suction. After oral administration aceclofenac quickly absorbed. The maximum concentration (C_m_Oh), in the blood plasma is achieved through 1.25-3 hours after ingestion. Eating slows down absorption, but does not affect its extent.

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

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

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

Indications:

- Coping of inflammation and pain syndrome with lumbago, toothache, humerus periarthritis, rheumatic soft tissue damage, for symptomatic treatment of rheumatoid arthritis, osteoarthritis and ankylosing spondylitis.

- Symptomatic therapy, reduction of pain and inflammation at the time of use, the progression of the disease is not affected.

- Dysmenorrhea.

Contraindications:

- Hypersensitivity to aceclofenac or ancillary components of the drug;

- bronchospasm, rhinitis or urticaria after taking acetylsalicylic acid or other NSAIDs in anamnesis (complete or incomplete acetylsalicylic acid intolerance syndrome - rhinosinusitis, urticaria, polyps of the nasal mucosa, bronchial asthma);

- erosive and ulcerative lesions of the mucous membrane of the gastrointestinal tract (GIT) in the phase of exacerbation (including ulcerative colitis, Crohn's disease);

- gastrointestinal bleeding or suspicion of it;

- severe heart failure (II-IV class according to the classification of the New York Heart Association), ischemic heart disease, peripheral arterial and / or cerebral arterial disease;

- period after aortocoronary shunting;

- severe hepatic insufficiency or liver disease in the active stage;

- severe renal failure (creatinine clearance <30 ml / min), progressive kidney disease, confirmed hyperkalemia;

- disorders of hematopoiesis and coagulation;

- pregnancy and the period of breastfeeding;

- children's age till 18 years.

Carefully:

Diseases of the liver, kidney and gastrointestinal tract in history, bronchial asthma, arterial hypertension, decrease in the volume of circulating blood (including after extensive surgical interventions), coronary heart disease, chronic renal and hepatic and cardiac insufficiency, creatinine clearance less than 60 ml / min. ulcerative lesions of the gastrointestinal tract in anamnesis, the presence infection Helicobacter pylori, dyslipidemia / hyperlipidemia, diabetes mellitus, smoking, old age, prolonged use of NSAIDs, severe somatic diseases, alcoholism.

Pregnancy and lactation:

Pregnancy

Use of the drug Aceklagin® is contraindicated in pregnancy. Information on the use of aceclofenac in pregnancy is absent. The inhibition of the synthesis of prostaglandins can adversely affect the course of pregnancy and / or the development of the embryo / fetus.

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

- having cardiopulmonary toxicity, can cause premature closure of the Botallov duct with the development of pulmonary hypertension;

- may cause impaired renal function of the fetus, which can progress to renal failure in combination with polyhydramnios.

On late pregnancy:

- the drug can influence the duration of bleeding due to the antiaggregant effect, which can develop even after the application of very low doses;

- the drug can suppress uterine contractions, leading to delayed labor or prolonged labor.

Breastfeeding period

The drug should not be taken during breastfeeding. Data on the isolation of aceclofenac with human milk are absent. In preclinical studies with the introduction of radioactive ¹⁴C-aceclofenac no noticeable transfer of radioactivity into milk was observed.

Fertility

Non-steroidal anti-inflammatory drugs (NSAIDs) can affect fertility and are not recommended for use by women planning a pregnancy.

Dosing and Administration:

Inside. Tablets should be swallowed whole, with enough water. The recommended daily intake for adults is 200 mg for a single dose (1 tablet per day).

Side effects:

The following are undesirable phenomena, information about which was obtained in clinical studies and during post-marketing surveillance.

The incidence of adverse events is classified as follows: very often (≥ 1/10); often (from ≥ 1/100 to <1/10); infrequently (from ≥ 1/1000 to <1/100), rarely (from ≥ 1/10000 to <1/1000), very rarely (<1/10000).

From the side of the blood and lymphatic system: rarely anemia; very rarely - oppression of bone marrow functions, granulocytopenia, thrombocytopenia, neutropenia, hemolytic anemia.

From the immune system: rarely anaphylactic reactions, including shock, hypersensitivity.

From the side of metabolism and nutrition: very rarely - hyperkalemia, weight gain.

From the side of the psyche: very rarely - depression, unusual (atypical) dreams, insomnia.

From the nervous system: often - dizziness; very rarely - paresthesia, tremor, drowsiness, headache, dysgeusia (perversion of taste).

From the side of the organ of vision: rarely - visual impairment.

From the side of the organ of hearing and labyrinth: very rarely - vertigo, noise in the ears.

From the heart: rarely - heart failure; very rarely - heart palpitations.

From the side of the vessels: rarely - increased blood pressure, worsening of the course of arterial hypertension; very rarely - skin hyperemia, "hot flashes" (short-term fever, accompanied by sweating), vasculitis.

From the respiratory, thoracic and mediastinal organs: rarely shortness of breath; very rarely - bronchospasm.

From the gastrointestinal tract: often - dyspepsia, abdominal pain, nausea, diarrhea; infrequently - flatulence, gastritis, constipation, vomiting, ulceration of the oral mucosa; rarely - melena, ulceration of the mucous membrane of the gastrointestinal tract, hemorrhagic diarrhea, hemorrhage of the mucous membrane of the gastrointestinal tract; very rarely - stomatitis, vomiting of blood, perforation of the intestine, worsening of Crohn's disease and ulcerative colitis, pancreatitis.

From the liver and bile ducts: often - increased activity of "liver" enzymes: very rarely - liver damage (including hepatitis), increased activity of alkaline phosphatase.

From the skin and subcutaneous tissue: infrequently - itching, rash, dermatitis, urticaria; rarely - angioedema; very rarely - purpura, eczema, severe reactions from the skin and mucous membranes (including Stevens-Johnson syndrome and toxic epidermal necrolysis).

In some cases, severe skin infections and soft tissue infections were observed when taking NSAIDs during a disease with chicken pox.

From the side of the kidneys and urinary tract: infrequently - increase in the concentration of urea and creatinine in the blood serum; very rarely - nephrotic syndrome, renal failure.

Systemic disorders and complications at the site of administration: very rarely - edema, fatigue, spasms of the muscles of the lower extremities.

If the patient has noted any worsening of any of the listed adverse events or the occurrence of an undesirable phenomenon not specified in this manual, he should contact the doctor in charge.

Overdose:

There is no evidence of an overdose of aceclofenac in humans.

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

Treatment: gastric lavage, reception of activated charcoal, symptomatic therapy. Forced diuresis, hemodialysis is not effective enough.

Interaction:

Except for the simultaneous use of drug interactions with warfarin, no drug interactions have been performed.

Aceclofenac is metabolized by isoenzyme CYP2C9; data in vitro show that aceclofenac may be an inhibitor of this enzyme. Thus, the risk of pharmacokinetic interaction is possible with simultaneous administration with phenytoin, cimetidine, tolbutamide, phenylbutazone, amiodarone, miconazole and sulfafenazole. As with other NSAIDs, there is an increased risk of pharmacokinetic interaction with other drugs that are excreted from the body through active renal secretion, such as methotrexate and lithium preparations. Aceclofenac almost completely binds to blood plasma albumin and, consequently, there is the possibility of reuptake-type interactions with other drugs that bind to proteins.

Below is the class-specific information for NSAIDs:

Methotrexate. NSAIDs inhibit the tubular secretion of methotrexate; moreover, a small metabolic interaction can occur, which leads to a decrease in the clearance of methotrexate. Therefore, when high doses of methotrexate are used, NSAIDs should be avoided.

Preparations of lithium and digoxin. Some NSAIDs inhibit renal clearance of lithium and digoxin. which leads to an increase in serum concentrations of both substances. Joint use should be avoided if frequent monitoring of lithium and digoxin concentrations is not carried out.

Anticoagulants. NSAIDs inhibit platelet aggregation and damage the gastrointestinal mucosa, which can lead to increased anticoagulant action and increase the risk of gastrointestinal bleeding while taking anticoagulants. Avoid the combined use of aceclofenac and oral anticoagulants coumarin group, ticlopidine and thrombolytics, unless careful monitoring of the patient's condition is performed.

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

Cyclosporin, tacrolimus. With the simultaneous administration of NSAIDs with cyclosporine or tacrolimus, the risk of increased nephrotoxicity due to decreased renal prostacyclin formation should be considered. Therefore, with simultaneous admission, you should carefully monitor the indicators of kidney function.

Other NSAIDs. With the simultaneous use of acetylsalicylic acid or other NSAIDs, the incidence of side effects may increase, so caution should be exercised.

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

Diuretics. AceclofenacLike other NSAIDs, may inhibit the activity of diuretics, may reduce the diuretic effect of furosemide and bumetanide and antihypertensive effect of thiazide. Simultaneous reception with potassium-sparing diuretics can lead to an increase in the potassium content in the blood serum. When used simultaneously with potassium-sparing diuretics, potassium in the blood serum is needed. Aceclofenac did not affect the control of blood pressure when combined with bendrofluazidom, although it is impossible to exclude interactions with other diuretics.

Hypotensive drugs. NSAIDs can also reduce the effect of antihypertensive drugs. Co-administration of angiotensin converting enzyme (ACE) inhibitors or antagonists of angiotensin II receptors and NSAIDs can cause renal dysfunction. The risk of acute renal failure, which usually is reversible, may be increased in some patients with impaired renal function, such as the elderly or dehydrated. Therefore, when combined with NSAIDs, care should be taken. Patients should consume the necessary amount of fluid and be under appropriate supervision (monitoring kidney function at the beginning of the joint application 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, you should correct the dosage 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-positive (human immunodeficiency virus) patients with hemophilia receiving zidovudine and ibuprofen.

Special instructions:

It is necessary to avoid simultaneous administration of the drug Aceklagin® and other NSAIDs, including selective inhibitors of cyclooxygenase-2 (COX-2).

Undesirable effects can be minimized by applying the minimum effective dose and reducing the duration of treatment needed to control symptoms.

Effect on the digestive tract

Bleeding ulcer or perforation GI deaths were observed when receiving any NSAIDs at any time during the treatment, both with the appropriate symptoms, and the presence of serious gastrointestinal diseases in history (gastric ulcer and duodenal ulcer, Crohn's disease, ulcerative colitis, etc.), So and without them. The risk of bleeding, ulceration and perforation of the gastrointestinal tract increases with increasing doses of NSAIDspatients with a history of peptic ulcer, especially if it was accompanied by bleeding or perforation, as well as in elderly patients. These patients should take the minimum effective dose of the drug. Consideration should be given to the use of combination therapy with the use of protective agents (for example, misoprostol or proton pump inhibitors). Such treatment is necessary for patients who take small doses of aspirin or other drugs that adversely affect the condition of the digestive tract.

Patients with gastrointestinal diseases, 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 care should be taken in patients taking drugs simultaneously, which may increase the risk of bleeding or ulcers, such as: systemic SCS, anticoagulants (such as warfarin), selective serotonin reuptake inhibitors or antiplatelet agents (such as acetylsalicylic acid).

If gastrointestinal hemorrhage or ulcers occur in patients taking Aceklagin®, treatment should be discontinued.

Cases of development of drug pancreatitis are rare.Nevertheless, cases of development of pancreatitis have been reported in connection with the administration of NSAIDs.

Influence on the cardiovascular and central nervous system

Patients with arterial hypertension and / or congestive heart failure, mild or moderate need appropriate observation because NSAID associated with fluid retention and edema. Aceclofenac structurally close to diclofenac, has a similar metabolism. With respect to diclofenac, there are data indicating an increased risk of developing thromboembolic complications (for example, myocardial infarction or stroke, in particular, with long-term treatment with high doses). There is also an increased risk of developing acute coronary syndrome associated with the administration of aceclofenac. Patients with chronic heart failure (Class I according to the classification of the New York Heart Association) and patients with risk factors for complications from the cardiovascular system (eg, hypertension, diabetes, smoking) should begin treatment with aceclofenac only after a balanced doctor's decision.Risks from the cardiovascular system may depend on the dose and duration of treatment, so the drug should be given at the lowest effective dose and for as short a period of time as possible.

Effects on the liver and kidneys

Taking NSAIDs can cause a dose-related reduction in the formation of prostaglandins and acute renal failure. The importance of prostaglandins for the maintenance of renal blood flow should be considered when taking the drug Aceklagin® in patients with impaired heart, kidney or liver function, in patients receiving diuretics, or in patients after surgery, as well as in elderly patients. Care should be taken when using the drug Aceklagin® in patients with impaired hepatic and renal function of mild or moderate severity, as well as in patients with other conditions predisposing to fluid retention in the body. In such patients, the use of NSAIDs can lead to impaired renal function and fluid retention. In patients taking diuretics, people with an increased risk of hypovolemia should also be careful when taking the drug Aceklagin®.It is necessary to apply the minimum effective dose and regular medical monitoring of kidney function. Undesirable effects from the kidneys are usually resolved after discontinuation of aceclofenac. Reception of the drug Aceklagin®should be discontinued if changes in the liver function indicators persist or worsen, clinical signs or symptoms of liver disease develop, or other manifestations (eosinophilia, skin rash) occur. Hepatitis can develop without prodromal symptoms.

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

Hypersensitivity and skin reactions

Like other NSAIDs, aceclofenac can cause allergic reactions, including anaphylactic / anaphylactoid reactions, even if aceclofenac is accepted for the first time. Severe skin reactions (some of which can lead to death), including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, were very rare after NSAID administration. The highest risk of these reactions in patients is observed at the beginning of the administration of aceclofenac, and the development of these adverse reactions is observed during the first month of admission aceclofenac. In case of skin rash, damage to the oral mucosa or other signs of hypersensitivity, stop taking Aceklagin®.

In some cases, with chickenpox, skin and soft tissue infections may occur.

At present, the role of NSAIDs in worsening of the course of these infections can not be ruled out. Therefore, the use of Aceklagin® should be avoided in case of chicken pox.

Hematologic disorders

Aceclofenac can cause reversible inhibition of platelet aggregation.

Disturbances from the respiratory system

Caution should be exercised when taking the drug Aceklagin® in patients with bronchial asthma (including in anamnesis), since the use of NSAIDs can provoke the development of sudden bronchospasm in such patients.

Elderly patients

Caution should be exercised when taking the drug Aceklagin® in elderly patients, as they often have side effects (especially bleeding and perforation of HCC) when taking NSAIDs. Complications can lead to death. Also, older patients are more likely to suffer from kidney, liver or cardiovascular disease.

Long-term use

All patients receiving long-term treatment with NSAIDs should be closely monitored (for example, a general blood test, functional hepatic and renal tests).

Due to the anti-prostaglandin properties of NSAIDs, caution should be recommended to women taking mifepristone, because when combined with the NSAID, a decrease in the effectiveness of the drug may theoretically occur. Clinical significance is unknown.

Effect on the ability to drive transp. cf. and fur:

It should refrain from driving and other potentially hazardous activities requiring increased attention and speed of psychomotor reactions, as the drug may cause dizziness and other side effects that may affect these abilities.

Form release / dosage:Tablets with modified release, film-coated 200 mg.

Packaging:

For 10 tablets in a blister of PVDC / aluminum foil.

1, 3 or 10 blisters with instructions for use in a pack of cardboard.

Storage conditions:

Store at a temperature not exceeding 30 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-004818

Date of registration:23.04.2018

Expiration Date:23.04.2023

The owner of the registration certificate:Teva Pharmaceutical Enterprises Co., Ltd.Teva Pharmaceutical Enterprises Co., Ltd. Israel

Manufacturer: & nbsp

Korea United Pharm. Inc. The Republic of Korea

Representation: & nbspTeva Teva Israel

Information update date: & nbsp05.06.2018

Illustrated instructions

Instructions

Atsklagin® (Aceclagin®)