active substance: 1 hard capsule prolonged action contains diclofenac sodium 100 mg
auxiliary substances: sucrose, corn starch, talc, shellac, ammonium methacrylate copolymer (type a), gelatin, titanium dioxide (E 171).
Capsule prolonged action solid.
The main physical and chemical properties: hard gelatin capsules from white to cream color (color is not more intense than 9001 RAL) (capsule size 2). Contents: globular granules from white to ivory (color is not more intense than 1014 RAL).
Nonsteroidal anti-inflammatory drugs.
Code ATH M01A B05.
Diclofenac is an active ingredient Dikloberl Retard, are non-steroidal compound with pronounced Antirheumatic, antipyretic, analgesic and anti-inflammatory properties. The major mechanism of action of diclofenac prescribed in the conditions of the experiment, is considered to be the inhibition of biosynthesis of prostaglandins. Prostaglandins play an important role in the Genesis of inflammation, pain and fever.
In vitro sodium diclofenac in concentrations equivalent to those achieved in the treatment of patients does not inhibit the biosynthesis of cartilaginous tissue proteoglycans.
In rheumatic diseases, the anti-inflammatory and analgesic effect of Dicloberl Retard leads to a significant reduction in the severity of pain (both at rest and during movement), morning stiffness, swelling of the joints and thereby to an improvement in the functional state of the patient.
In the presence of inflammation caused by trauma or surgery, Dicloberl Retard quickly eliminates both spontaneous pain and pain when moving, as well as reduces inflammatory swelling of tissues and swelling in the surgical wound. When combined with opioids to eliminate postoperative pain Dicloberl Retard significantly reduces the need for opioids.
In clinical studies, it was found that diclofenac also shows a pronounced analgesic effect in moderate and severe pain of non-rheumatic origin.
Analysis of urine output in unchanged diclofenac and its hydroxylated metabolites showed that the amount of released and absorbed diclofenac is the same as in the case of an equivalent dose of diclofenac sodium in the form of tablets with intestinal coating. However, the systemic bioavailability of diclofenac (released from Dicloberl Retard) is an average of 82% of the corresponding figure after oral intestinal-soluble tablets Dicloberl in the same dose. Due to the slow release of the active substance from Dicloberl Retard, the maximum concentrations of the drug, which are achieved in blood plasma, are lower than after the use of tablets covered with intestinal coating. The average peak concentration of 0.4 µg/ml or 0.5 µg/ml (1.25 or 1.6 µmol/l) is achieved on average within 5-6 hours after the use of 75 mg tablets or 100 mg.meal clinically does not affect the absorption and systemic bioavailability of Dicloberl Retard. On the other hand, the average concentration in the blood plasma 13 ng/ml (40 nmol/l) can be observed after 24 hours (16 hours) after zastosuvannya of sodium in the form of prolonged 75 mg. Kilkist absorbed active substance is in linear dependence on the dose of the drug. Since about half of diclofenac is metabolized during the first pass through the liver ("first pass effect"), the area under the concentration/time curve (AUC) after The application of dicloberl Retard capsule is almost twice less than in the case of parenteral administration of the equivalent dose of the drug. After repeated use Dicloberl Retard pharmacokinetics indicators do not change. In compliance with the recommended intervals between doses of individual drug cumulation is not noted. The corresponding concentrations are 22 ng/ml or 25 ng/ml (70 nmol/l or 80 nmol/l) when diclofenac is applied in prolonged form 75 mg twice a day.
99.7% of diclofenac binds to plasma proteins, mainly albumin (99.4%). The volume of distribution is 0.12-0.17 l/kg. Diclofenac penetrates into synovial fluid, where maximum concentrations observed 2-4 hours later than in plasma. The imaginary half - life period of synovial fluid is 3-6 hours. After 2:00 after reaching the maximum concentration in the blood plasma, the concentration of the active substance in the synovial fluid is higher than in the blood plasma, and remains higher for 12:00.
Biotransformatsiyadiklofenaku is carried out partly by glucuronization of the unchanged molecule, but mainly-by single and multiple hydroxylation and methoxylation, which leads to the formation of several phenolic metabolites (3' - hydroxy -, 4'-hydroxy -, 5 '- hydroxy -, 4' 5-dihydroxy-and 3'-hydroxy-4 ' -methoxy-diclofenac), most of which is conjugated with glucurone acid. Two of these phenolic metabolites are pharmacologically active, but to a much lesser extent than diclofenac.
Total systemic clearance of diclofenac from plasma is 263 + 56 ml/min. Final half-life from plasma is 1-2 hours. The half-life of 4 metabolites, including 2 pharmacologically active, is also short and is 1-3 hours. One of the metabolites, 3'-hydroxy-4'-methoxycyclohexyl, has a longer half-life in plasma. However, this metabolite is completely inactive in the pharmacological relation.
About 60% of the dose is excreted in the urine as glucuronic conjugates of the intact molecule of the active substance and as metabolites, most of which also turns into glucuronic conjugates. Less than 1% of diclofenac is displayed unchanged. The remaining doses of the drug is excreted as metabolites through bile, feces.
Pharmacokinetics in certain groups of patients.
The influence of the patient's age on the absorption, metabolism and excretion of the drug is not determined.
In patients with impaired renal function treated with therapeutic doses, there were no accumulation of the unchanged active substance. In patients with creatinine clearance less than 10 ml/min, the calculated equilibrium concentrations of hydroxylated metabolites in blood plasma were approximately 4 times higher than in healthy patients. However, eventually all metabolites were excreted with bile.
In patients with chronic hepatitis or compensated cirrhosis, the pharmacokinetics and metabolism of diclofenac are similar to those in patients without liver disease.
Pain relief and reduce inflammation of varying degrees in different conditions, including:
joint pathology: rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, acute gout attacks
acute musculo-skeletal disorders such as periarthritis (for example frozen shoulder), tendinitis, tenosynovitis, bursitis,
other pathological conditions caused by injuries, including fractures, lower back pain, sprains, dislocations, orthopedic, dental and other minor surgical interventions.
Hypersensitivity to the active substance or to any other component of the drug;
acute gastric or intestinal ulcer; gastrointenstinal bleeding or perforation;
high risk of postoperative bleeding, blood clotting, hemostasis disorders, hematopoietic disorders or cerebrovascular bleeding;
bleeding or perforation of the gastrointestinal tract in history associated with previous treatment with nonsteroidal anti-inflammatory drugs (NSAIDs)
active form of peptic ulcer disease/bleeding or recurrent ulcer disease/history of bleeding (two or more separate episodes of diagnosed ulcer or bleeding)
inflammatory bowel disease (e.g. ulcerative colitis chlorobornane);
the last trimester of pregnancy;
congestive heart failure (NYHAII-IV);
ischemic heart disease in patients with angina, myocardial infarction
cerebrovascular disease in patients who have had a stroke, or have episodes of transient ischemic attacks;
peripheral arterial disease
treatment of PERIOPERATIVE pain in coronary artery bypass grafting (or use a heart-lung machine)
like other NSAIDs, diclofenac is also contraindicated in patients who use ibuprofen, acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs to provoke attacks of bronchial asthma, angioedema, urticaria or acute rhinitis.
Interaction with other medicinal products and other forms of interaction
The following interaction, which was observed with use of diclofenac in the form of enteric tablets and/or other dosage forms.
Lithium. Provided the simultaneous use of diclofenac can increase the concentration of lithium in plasma. Recommended monitoring of lithium level in blood serum.
Digoxin. Provided the simultaneous use of diclofenac can increase the concentration of digoxin in blood plasma. It is recommended to monitor the level of digoxin in serum.
Diuretics and antihypertensive agents. Like other NSAIDs, use of diclofenac with diuretics and antihypertensive agents (eg, ?-blockers, ACE inhibitors (ACE)) can lead to a decrease in their antihypertensive effect by inhibiting the synthesis of vasodilating prostaglandins. Thus, such a combination is used with a reservation, and patients, especially the elderly, should be under close supervision regarding blood pressure. Patients should receive adequate hydration, it is recommended that monitoring of renal function after initiation of concomitant therapy and a regular basis thereafter, particularly for diuretics and ACE inhibitors, in Association with an increased risk of nephrotoxicity.
Drugs are known to cause hyperkalemia. Simultaneous treatment with potassium-sparing diuretics, cyclosporine, tacrolimus or trimethoprim may be associated with an increase in serum potassium levels, so patient monitoring should be carried out more frequently.
Anticoagulants and antithrombotic agent. Simultaneous use can increase the risk of bleeding, so it is recommended to take precautions. Although clinical studies do not indicate the effect of diclofenac on the activity of anticoagulants, there is some evidence of an increase in the risk of bleeding in patients taking both diclofenac and anticoagulants. So to be sure, sonicspin in the dosage of the anticoagulants are not needed, recommended careful monitoring of these patients. Like other nonsteroidal anti-inflammatory drugs, diclofenac in high doses can temporarily suppress platelet aggregation.
Other NSAIDs, including selective COX-2 inhibitors, and corticosteroids. Simultaneous use of diclofenac and other NSAIDs or GCS may increase the risk of gastrointestinal bleeding or ulcers. Simultaneous use of two or more NSAIDs should be avoided.
Selective inhibitors of serotonin reuptake (SSRIs).
The simultaneous use of NSAIDs and SSRIs may increase the risk of gastrointestinal bleeding.
Antidiabetic drugs. Clinical studies have shown that diclofenac can be used with oral hypoglycemic agents and do not change their therapeutic effect. However, there are some reports of the development in such cases as hypoglycemia and hyperglycemia, which led to the need to change the dose of antidiabetic agents during the application of diclofenac. For this reason, as a precaution it is recommended during combined therapy to control the level of glucose in the blood.
Methotrexate. Diclofenac can suppress the clearance of methotrexate in the renal tubules, resulting in increased levels of methotrexate. Caution should be exercised in appointing NSAIDs, including diclofenac, less than 24 hours before the use of methotrexate, as in such cases may increase the concentration of methotrexate in the blood and increase its toxic effect. There have been cases of serious toxicity when the interval between use of methotrexate and NSAIDs, including diclofenac, were within 24 hours. This interaction is mediated through the accumulation of methotrexate as a result of impaired renal excretion in the presence of NSAIDs.
Cyclosporine. The influence of diclofenac, as well as other NSAIDs on prostaglandin synthesis in the kidneys can increase the nephrotoxicity of cyclosporin, therefore diclofenac should be used at lower doses than for patients, cyclosporin is not used.
Tacrolimus. With the use of NSAIDs with tacrolimus may increase the risk of nephrotoxicity, which may be mediated via renal antiprostaglandin effects NSAID and calcineurin inhibitor.
Antibacterial quinolones. It is possible to develop seizures in patients, simultaneously taking quinolone derivatives and NSAIDs. This can be observed in patients with both epilepsy and history of seizures, and without them. Thus, caution should be exercised when deciding on applications inaloo patients who are already receiving NSAIDs.
Phenytoin. When using phenytoin simultaneously with diclofenac it is recommended to monitor the concentration of phenytoin in the blood plasma due to the expected increase in the influence of phenytoin.
Probenecid. Drugs containing probenecid may inhibit the excretion of diclofenac sodium.
Cholesterol and cholesterol. These drugs can delay or reduce the absorption of diclofenac. Thus, it is recommended to appoint diclofenac at least 1:00 before or after 4-6 hours after use of cholestipol/colestiramine.
Cardiac glycoside. The simultaneous use of cardiac glycosides and NSAIDs may increase heart failure, reduce glomerular filtration rate and increase the level of glycosides in plasma.
Mifepristone. NSAIDs should not be used for 8-12 days after use of mifepristone, as NSAIDs can reduce the effect of mifepristone.
Strong inhibitors of CYP2C9. Caution is advised when administered together diclofenac with potent CYP2C9 inhibitors (e.g. voriconazole), which can lead to a significant increase in maximum concentration in blood plasma and exposure of diclofenac due to inhibition of metabolism of diclofenac.
To minimize side effects, treatment should begin with the lowest effective dose for the shortest period of time necessary to control symptoms.
Simultaneous use of Dicloberl Retard with systemic NSAIDs, such as selective cyclooxygenase-2 inhibitors, should be avoided due to the lack of any evidence of synergistic effects and potential additive side effects. Caution is required regarding elderly patients. In particular, it is recommended to use the lowest effective dose for debilitated elderly patients with low body weight.
That the use of other NSAIDs may experience allergic reactions, including anaphylactic/anaphylactoid reactions, even without prior exposure to diclofenac.
Due to its pharmacodynamic properties, Dicloberl Retard, other NSAIDs, can mask the signs are the symptoms of infection.
The effect on the digestive tract (TT).
With all NSAIDs, including diclofenac, there have been cases of gastrointestinal bleeding (vomiting blood, melena), ulceration or perforation which can be fatal and occur anytime during treatment with or without warning symptoms or a previous history of serious events from the gastrointestinal tract. These phenomena are usually serious consequences in elderly patients. If patients receiving diclofenac, the phenomena of gastro-enteric bleeding or formation of ulcers, the drug should be discontinued.
As with the use of other NSAIDs, including diclofenac, for patients with symptoms that indicate a violation of the digestive tract (TT), be sure to medical supervision and special caution. The risk of bleeding, ulcers or perforation of TT increases with increased doses of NSAIDs, including diclofenac.
Elderly patients have an increased frequency of adverse reactions to NSAID use, especially in relation to gastrointestinal bleeding and perforation which may be fatal.
To reduce the risk of such toxic effects on TT, treatment is initiated and maintained by low effective doses.For such patients, as well as those in need of concomitant use of medicinal products containing low dose acetylsalicylic acid (ASA/aspirin) or other drugs that are likely to increase the risk of undesirable effects on the TT, you should consider the use of combination therapy with protective agents (e.g. proton pump inhibitors or misoprostol) to Patients with gastrointestinal toxicity in history, particularly the elderly, should report any unusual abdominal symptoms (especially bleeding in the TT). Caution is also needed in patients receiving both drugs, which can increase the risk of ulceration or bleeding, such as systemic corticosteroids, anticoagulants (warfarin), antithrombotic agent (e.g., ASA) or selective inhibitors of serotonin reuptake.
The effect on the liver.
Careful medical supervision is necessary in the case when Dicloberl Retard is prescribed to patients with impaired liver function, because their condition may deteriorate. As when using other NSAIDs, including diclofenac, the level of one or more liver enzymes may increase.
In the course of long-term treatment Dicloberl Retard is prescribed regular monitoring of liver function and liver enzyme levels as a precaution. If liver dysfunction persists or deteriorates and if clinical signs or symptoms may be associated with progressive liver disease or if there are other manifestations (eg, eosinophilia, rash), the use of The drug dicloberl Retard should be discontinued. For diseases such as hepatitis can occur without prodromal symptoms. Caution is necessary if Dicloberl Retard is used in patients with hepatic porphyria, due to the likelihood of provoking an attack.
The effect on the kidney.
Because treatment with NSAIDs, including diclofenac, there have been cases of fluid retention and swelling, particular attention should be paid to patients with impaired heart or kidneys, hypertension in the anamnesis, elderly patients, patients receiving therapy with diuretics or medications that can significantly affect renal function, patients with a substantial decrease in extracellular fluid volume from any cause, e.g. before or after major surgery. In such cases, as a precaution it is recommended to monitor renal function. Discontinuation of therapy usually leads to a return to the condition that preceded treatment.
Effect on skin.
In connection with the use of NSAIDs, including drug Dikloberl Retard, in very rare cases have been reported serious reactions of the skin (some of them were fatal, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis. In patients, a high risk of these reactions is observed at the beginning of the course of therapy: the appearance of the reaction is observed in most cases during the first month of treatment. The use of the drug Dicloberl Retard should be discontinued when the first appearance of skin rashes, lesions of the mucous membrane or the appearance of any other signs of hypersensitivity.
SLE and mixed connective tissue disease.
In patients with systemic lupus erythematosus (SLE) and mixed connective tissue diseases, there may be an increased risk of aseptic meningitis.
Cardiovascular and cerebrovascular effects.
For patients with a history of hypertension and/or congestive heart failure of mild to moderate severity, appropriate monitoring and recommendations are required, as there have been reported cases of fluid retention and edema due to the use of NSAIDs, including diclofenac.
Data from clinical trials and epidemiological data suggest that use of diclofenac, particularly at high doses (150 mg/day) and long-term treatment may be associated with a slight increased risk of developing arterial thrombotic events (for example myocardial infarction or stroke).
Patients with uncontrolled hypertension, congestive heart failure, stable coronary artery disease, peripheral artery disease and/or cerebrovascular disease and to appoint diclofenac is Not recommended, if necessary use only after a careful evaluation of the risk-use only in a dosage of not more than 100 mg per day. Such an assessment should be carried out before long-term treatment of patients with risk factors for cardiovascular events (for example, hypertension, hyperlipidemia, diabetes mellitus and patients who smoke).
Patients should be informed of the possibility of serious antithrombotic cases (chest pain, shortness of breath, weakness, speech impairment) that may occur at any time. In this case, you should immediately consult a doctor.
Influence on hematological parameters.
Long-term use of this drug, like other NSAIDs, it is recommended to monitor complete blood count.
Dikloberl Retard may temporarily inhibit platelet aggregation. Patients with hemostasis disorders, hemorrhagic diathesis or haematological disorders should be carefully monitored.
History of asthma.
In patients with asthma, seasonal allergic rhinitis, swelling of the nasal mucosa (i.e. nasal polyps), chronic obstructive pulmonary disease or chronic respiratory infections (especially those associated with allergic-like rhinitis, symptoms) more likely to have reactions on NSAIDs like asthma exacerbations (so called intolerance to analgesics/analgesic asthma), Quincke's edema, urticaria. In this regard, special measures (readiness for emergency medical care) are recommended for such patients. This also applies to patients with allergic reactions to other substances such as rash, itching, urticaria.
As with other drugs that suppress the activity of prostaglandinsynthase, diclofenac sodium and other NSAIDs can precipitate bronchospasm if administered to a patients suffering from bronchial asthma, or patients with bronchial asthma in history.
Fertility in women.
Regarding female fertility (see section"use during pregnancy or breastfeeding").
Acute hypersensitivity reactions (e.g. anaphylactic shock) are rare. At the first sign of hypersensitivity reaction after Dicloberl Retard therapy should be stopped.
With prolonged use of painkillers, headache may occur, do not treat an increase in the dose of the drug.
With the simultaneous use of alcohol adverse reactions associated with the action of the active substances, especially those that affect the gastrointestinal tract or the Central nervous system may be aggravated by the use of NSAIDs.
Application during pregnancy and lactation
In the I and II trimesters of pregnancy, Dicloberl Retard can be prescribed only when the expected benefit to the mother exceeds the potential risk to the fetus and only in the minimum effective dose, and the duration of treatment should be as short as possible. As in the case of other NSAIDs, the drug is contraindicated in the last 3 months of pregnancy (possible suppression of uterine contractility and premature closure of the arterial duct in the fetus).
Inhibition of prostaglandin synthesis may adversely affect the course of pregnancy and/or embryo/fetus development. Data of epidemiological studies indicate an increased risk of miscarriages and/or the risk of heart defects and gastroschisis after the use of prostaglandin synthesis inhibitor in early pregnancy. The absolute risk of cardiovascular disease was increased from less than 1% to 1.5%.
It is possible that the risk increases with the dose and duration of treatment. It was shown that the introduction of prostaglandin synthesis inhibitor in animals leads to an increase in pre - and post-implantation loss and mortality of the embryo/fetus.
In addition, in animals treated with the inhibitor of prostaglandin synthesis during the period of organogenesis, the bull was a higher incidence of various malformations, including those of the cardiovascular system. If Dicloberl Retard is used by a woman who seeks to become pregnant, or in the first trimester of pregnancy, the dose should be as low as possible, and the duration of treatment-as short as possible.
In the III trimester of pregnancy, all inhibitors of prostaglandin synthesis may affect pletaci way:
cardio-pulmonary toxicity (with premature closure of the marterial Strait and pulmonary hypertension)
the impairment of renal function may progress to renal failure with oligohydramnios.
The mother and newborn, and akonadicontact:
polivitaminny bleeding time, antiagregantnoe, anymoresometimes at very low doses
galloanseres of the uterus that leads to strikebloomberg.
So, Dikloberl Retard is contraindicated on the third trimester of pregnancy.
Like other NSAIDs, diclofenac penetrates into breast milk in small quantities. In this regard, Dicloberl Retard should not be used by women during breastfeeding to avoid unwanted effects on the baby.
Fertility in women.
Like other NSAIDs, Dicloberl Retard can adversely affect female fertility, so it is not recommended to prescribe the drug to women who plan pregnancy. For women who have problems with conception or are tested for infertility, it is necessary to consider the feasibility of abolishing the drug Dicloberl Retard.
The ability to influence the reaction rate when driving motor transport or operating other mechanisms
Patients who have in the course of drug therapy Dikloberl Richardinkatu blurred vision, vertigo, drowsiness, disturbances of the Central nervous system, lethargy or fatigue, you should not drive vehicles or operate machinery.
Method of application and doses
The dose should be selected individually, starting with the lowest effective dose and should zastosovuyutsya a short period of time.
The recommended initial dose of diclofenac for adults is 75-150 mg per day (1 capsule of Dicloberl Retard 100 mg) depending on the severity of the symptoms. With long-term therapy, as a rule, it is enough to use 1 capsule Dikloberl Retard100 mg per day. If the symptoms are most pronounced during the night or in the morning, Dicloberl Retard should be used in the evening. Daily dose should not exceed 150 mg. Capsules should be swallowed whole without chewing, with some liquid, preferably during meals.
Children: Dicloberl Retard is not recommended for use in children.
Elderly patients were not observed clinically significant changes in pharmacokinetics when applying Dicloberl Retard elderly patients. But for elderly patients, NSAIDs should be used with extreme caution, as they are more prone to adverse reactions. It is recommended to use a minimum effective dose in elderly patients or patients with low weight, as well as in patients in need of constant monitoring to detect possible gastrointestinal bleeding in the application of NSAIDs.
DikloberlRetard not to apply to children-for its high content of active substance.
There is no typical clinical picture of diclofenac overdose. Overdose can cause symptoms such as headache, nausea, vomiting, epigastric pain, gastrointestinal bleeding, diarrhea, dizziness, disorientation, excitement, coma, drowsiness, tinnitus or convulsions. Acute renal failure and liver damage are possible in case of severe intoxication.
Treatment of acute poisoning with NSAIDs, including diclofenac, consists in carrying out supportive and symptomatic therapy. This applies to the treatment of manifestations such as arterial hypotension, renal failure, convulsions, gastrointestinal disorders, respiratory depression. It is unlikely that such specific therapeutic measures as forced diuresis, dialysis or hemoperfusion will be effective for the elimination of NSAIDs, including diclofenac, since the active substances of these drugs are largely associated with blood proteins and subjected to intensive metabolism. After applying potencyerection doses may be applied activated carbon, and after the application of potentially life-DOZ - carry out disinfection of the stomach (e.g., causing vomiting, gastric lavage).
The following side effects include phenomena that have been reported in short-term or long-term use of the drug.
From the blood and lymphatic systems: thrombocytopenia, pancytopenia, agranulocytosis, leukopenia, anemia (hemolytic anemia, aplastic anemia). The first signs can be fever, sore throat, superficial wounds in the mouth, flu-like symptoms, severe fatigue, nosebleeds, skin bleeding.
The immune system: hypersensitivity reactions such as skin rash and itching, hives anaphylactic and anaphylactoid reactions (including narrowing of the Airways, respiratory arrest, tachycardia, hypotension, and shock), angioedema, including swelling of the face, tongue, inner throat swelling, allergic vasculitis and pneumonia.
Mental disorders: disorientation, depression, insomnia, irritability, nightmares, psychotic disorders, other mental disorders.
From the nervous system: headache, dizziness, excitation or drowsiness, anxiety, occasional dizziness, drowsiness, fatigue, paresthesia, memory impairment, convulsions, anxiety, tremor, aseptic meningitis, taste disorders, stroke, confusion, hallucinations, sensitivity, and General malaise.
From the side of organs of vision : visual disturbances, blurred Asaru, diplopia, optic neuritis.
On the part of hearing and labyrinth : vertigo, tinnitus, hearing.
From the side of cardiovascular system : palpitations, chest pain, heart failure, myocardial infarction, hypertension, hypotension, vasculitis.
From the respiratory system, chest and mediastinal organs: asthma (including shortness of breath), pneumonitis.
The gastro-intestinal tract : nausea, vomiting, diarrhea, dyspepsia, abdominal pain, flatulence, anorexia, gastritis, gastrointestinal bleeding (hematemesis, melena, diarrhea mixed with blood), ulcers of the stomach or intestines with or without bleeding or perforation (sometimes fatal, especially in elderly patients), colitis (including hemorrhagic colitis and exacerbation of ulcerative colitis or Crohn's disease), constipation, stomatitis (including ulcerative stomatitis), glossitis, impaired function of the esophagus, diaphragmatic stenosis of the intestine, pancreatitis.
From the digestive system: increased transaminases, hepatitis, jaundice, liver disorders, lightning hepatitis, hepatonecrosis, liver failure.
Infections and infections: reported an exacerbation of inflammation associated with infections (eg, the development of necrotic fasciitis), with systemic use of non-steroidal anti-inflammatory drugs. This may be due to the mechanism of action of nonsteroidal anti-inflammatory drugs. If you use Dicloberl Retard, signs of infection have arisen or deteriorate, the patient is recommended to seek medical advice immediately.