Dicloberl 100 suppositories 100 mg No. 10

Instructions Dicloberl 100 suppositories 100 mg No. 10

Composition

active ingredient: 1 suppository contains diclofenac sodium 100 mg;

excipients: solid fat.

Dosage form

Suppositories.

Main physicochemical properties: ivory-colored torpedo-shaped suppositories.

Pharmacotherapeutic group

Nonsteroidal anti-inflammatory and antirheumatic drugs.

ATX code M01A B05.

Pharmacological properties

Pharmacodynamics.

Dicloberl® 100 contains diclofenac sodium, a non-steroidal substance that has a pronounced analgesic and anti-inflammatory effect. It is an inhibitor of prostaglandin synthetase (cyclooxygenase).

Pharmacokinetics.

Absorption. Absorption is rapid, but slower than with enteric-coated tablets. After administration of Dicloberl suppositories at a dose of 50 mg, the maximum plasma concentration is reached after approximately 1 hour, but the maximum concentration per unit dose is about two-thirds of the concentration achieved after administration of enteric-coated tablets (1.95 ± 0.8 μg/ml (1.9 μg/ml ≡ 5.9 μmol/l)).

Bioavailability. As with oral dosage forms, the area under the concentration curve (AUC) is approximately half that obtained with parenteral dosing. After repeated administration of the drug, its pharmacokinetics do not change. Cumulation of the drug is not observed when the recommended dosage is observed.

Distribution: The binding of diclofenac to serum proteins is 99.7%, mainly to albumin - 99.4%.

Diclofenac penetrates into the synovial fluid, where its maximum concentration is reached 2-4 hours later than in the blood plasma. The apparent half-life from the synovial fluid is 3-6 hours. 2 hours after reaching maximum plasma concentrations, the concentration of diclofenac in the synovial fluid remains higher than in the blood plasma; this phenomenon is observed for 12 hours.

Diclofenac was detected in low concentrations (100 ng/ml) in the breast milk of one lactating woman. The estimated amount of drug reaching the infant in breast milk is equivalent to a dose of 0.03 mg/kg/day.

Metabolism: Diclofenac is metabolized partly by glucuronidation of the unchanged molecule, but mainly by single and multiple hydroxylation and methoxylation, leading to the formation of several phenolic metabolites, most of which form conjugates with glucuronic acid. Two of these phenolic metabolites are biologically active, but much less so than diclofenac.

Elimination. The total systemic clearance of diclofenac from plasma is 263 ± 56 ml/min (mean ± SD). The terminal plasma half-life is 1-2 hours. The plasma half-life of four metabolites, including two pharmacologically active ones, is also short and is 1-3 hours. About 60% of the administered dose is excreted in the urine as a glucuronide conjugate of the intact molecule and as metabolites, most of which are also converted to glucuronide conjugates. Less than 1% of diclofenac is excreted unchanged. The remainder of the administered dose is excreted as metabolites in the feces.

Pharmacokinetics in specific patient groups. The effect of patient age on the absorption, metabolism and excretion of the drug was not observed, except for the fact that in five elderly patients a 15-minute intravenous infusion resulted in a 50% higher plasma concentration of the drug than expected in young healthy volunteers.

In patients with impaired renal function receiving therapeutic doses, no accumulation of unchanged active substance is expected based on the kinetics of the drug after a single dose. In patients with creatinine clearance less than 10 ml/min, the estimated steady-state plasma concentrations of hydroxylated metabolites were approximately 4-fold higher than in healthy volunteers. However, all metabolites were ultimately excreted in the bile.

Patients with impaired liver function. In patients with chronic hepatitis or compensated cirrhosis, the pharmacokinetics and metabolism of diclofenac are similar to those in patients without liver disease.

Indication

Inflammatory and degenerative forms of rheumatism: rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, including spondyloarthritis;

· pain syndromes in the spine;

· rheumatic diseases of extra-articular soft tissues;

· post-traumatic and postoperative pain syndromes accompanied by inflammation and edema, in particular after dental and orthopedic surgeries;

· gynecological diseases accompanied by pain and inflammation, for example, primary dysmenorrhea and adnexitis;

migraine attacks;

· acute attacks of gout;

· as an adjuvant in severe inflammatory diseases of the ENT organs, which are accompanied by pain, for example, in pharyngotonsillitis, otitis.

According to general therapeutic principles, the underlying disease should be treated with basic therapy. Fever alone is not an indication for the use of the drug.

Contraindication

Hypersensitivity to the active substance or to any other component of the drug;

· acute stomach or intestinal ulcer; gastrointestinal bleeding or perforation;

· high risk of developing postoperative bleeding, blood clotting disorders, hemostasis disorders, hematopoietic disorders or cerebrovascular bleeding;

· history of gastrointestinal bleeding or perforation related to previous treatment with nonsteroidal anti-inflammatory drugs (NSAIDs);

Active peptic ulcer/bleeding or history of recurrent peptic ulcer/bleeding (two or more separate episodes of diagnosed ulcer or bleeding);

Inflammatory bowel disease (e.g. Crohn's disease or ulcerative colitis);

· last trimester of pregnancy;

· liver failure;

· renal failure;

· congestive heart failure (NYHA II-IV);

· ischemic heart disease in patients with angina pectoris or previous myocardial infarction;

· cerebrovascular diseases in patients who have had a stroke or have episodes of transient ischemic attacks;

· peripheral artery disease;

· treatment of perioperative pain during coronary artery bypass grafting (or use of a cardiopulmonary bypass machine);

· like other NSAIDs, diclofenac is also contraindicated in patients in whom the use of ibuprofen, acetylsalicylic acid or other non-steroidal anti-inflammatory drugs provokes attacks of bronchial asthma, angioedema, urticaria or acute rhinitis.

· proctitis.

Interaction with other medicinal products and other types of interactions

The following are interactions that have been observed with the use of diclofenac in the form of enteric-coated tablets and/or in other dosage forms.

Lithium: Diclofenac may increase plasma lithium concentrations when used concomitantly. Monitoring of serum lithium levels is recommended.

Digoxin: Diclofenac may increase the plasma concentration of digoxin when used concomitantly. Monitoring of serum digoxin levels is recommended.

Diuretics and antihypertensives: As with other NSAIDs, concomitant use of diclofenac with diuretics and antihypertensives (e.g. β-blockers, angiotensin-converting enzyme (ACE) inhibitors) may lead to a reduction in their antihypertensive effect by inhibiting the synthesis of vasodilator prostaglandins. Therefore, such a combination should be used with caution and patients, especially the elderly, should be closely monitored for blood pressure. Patients should be adequately hydrated and monitoring of renal function is recommended after initiation of concomitant therapy and regularly thereafter, especially with diuretics and ACE inhibitors, due to the increased risk of nephrotoxicity.

Drugs known to cause hyperkalemia: Concomitant treatment with potassium-sparing diuretics, cyclosporine, tacrolimus, or trimethoprim may be associated with increases in serum potassium, and patients should be monitored more frequently.

Anticoagulants and antithrombotic agents. Concomitant use may increase the risk of bleeding, therefore precautions are recommended. Although clinical studies do not indicate an effect of diclofenac on the activity of anticoagulants, there is some evidence of an increased risk of bleeding in patients receiving diclofenac and anticoagulants concomitantly. Therefore, close monitoring of such patients is recommended to ensure that no changes in the dosage of anticoagulants are necessary. As with other non-steroidal anti-inflammatory drugs, diclofenac in high doses may temporarily inhibit platelet aggregation.

Other NSAIDs, including selective cyclooxygenase-2 inhibitors, and corticosteroids. Concomitant use of diclofenac and other NSAIDs or corticosteroids may increase the risk of gastrointestinal bleeding or ulceration. The concomitant use of two or more NSAIDs should be avoided.

Selective serotonin reuptake inhibitors (SSRIs): Concomitant use of NSAIDs and SSRIs may increase the risk of gastrointestinal bleeding.

Antidiabetic agents. Clinical studies have shown that diclofenac can be used together with oral antidiabetic agents without altering their therapeutic effect. However, there are some reports of the development of both hypoglycemia and hyperglycemia in such cases, which necessitated a change in the dose of antidiabetic agents during the use of diclofenac. For this reason, as a precautionary measure, it is recommended to monitor blood glucose levels during combination therapy.

Cyclosporine. The effect of diclofenac, like other NSAIDs, on prostaglandin synthesis in the kidneys may enhance the nephrotoxicity of cyclosporine, therefore diclofenac should be used in lower doses than for patients not taking cyclosporine.

Tacrolimus: There is a possible increased risk of nephrotoxicity when NSAIDs are used with tacrolimus, which may be mediated through the renal antiprostaglandin effects of the NSAID and the calcineurin inhibitor.

Quinolone antibacterials. Convulsions may occur in patients receiving concomitant quinolones and NSAIDs. This may occur in patients with or without a history of epilepsy and seizures. Therefore, caution should be exercised when considering the use of a quinolone in patients already receiving NSAIDs.

Phenytoin: When phenytoin is used concomitantly with diclofenac, monitoring of phenytoin plasma concentrations is recommended due to the expected increase in phenytoin exposure.

Probenecid: Medicinal products containing probenecid may inhibit the excretion of diclofenac sodium.

Colestipol and cholestyramine. These drugs may delay or reduce the absorption of diclofenac. Therefore, it is recommended to administer diclofenac at least 1 hour before or 4-6 hours after colestipol/cholestyramine.

Cardiac glycosides. Concomitant use of cardiac glycosides and NSAIDs may exacerbate heart failure, reduce glomerular filtration rate, and increase plasma glycoside levels.

Mifepristone: NSAIDs should not be used for 8-12 days after mifepristone administration, as NSAIDs may reduce the effect of mifepristone.

Potent CYP2C9 inhibitors: Caution is advised when co-administering diclofenac with potent CYP2C9 inhibitors (e.g. voriconazole), which may lead to a significant increase in maximum plasma concentrations and exposure to diclofenac due to inhibition of diclofenac metabolism.

Application features

General.

To minimize undesirable effects, treatment should be initiated at the lowest effective dose for the shortest period of time necessary to control symptoms.

The concomitant use of Dicloberl 100 with systemic NSAIDs such as selective cyclooxygenase-2 inhibitors should be avoided due to the lack of any evidence of a synergistic effect and due to potential additive side effects.
Caution is required in elderly patients. In particular, it is recommended to use the lowest effective dose in frail elderly patients or those with low body weight.

As with other NSAIDs, allergic reactions, including anaphylactic/anaphylactoid reactions, may occur, even without prior exposure to diclofenac.

Due to its pharmacodynamic properties, Dicloberl® 100, like other NSAIDs, may mask the signs and symptoms of infection.

Effects on the digestive tract (GT).

Gastrointestinal bleeding (hemorrhage, melena), ulceration or perforation, which can be fatal and can occur at any time during treatment with or without warning symptoms or a previous history of serious gastrointestinal events, have been reported with all NSAIDs, including diclofenac. These events are usually more severe in the elderly. If gastrointestinal bleeding or ulceration occurs in patients receiving diclofenac, the drug should be discontinued.

As with other NSAIDs, including diclofenac, medical supervision and special caution are required in patients presenting with symptoms suggestive of gastrointestinal (GI) disorders. The risk of GI bleeding, ulceration or perforation increases with increasing dose of NSAIDs, including diclofenac, and in patients with a history of ulcer, especially complicated by bleeding or perforation, and in the elderly.

Elderly patients have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which can be fatal.

To reduce the risk of such toxic effects on TT, treatment is initiated and maintained at the lowest effective dose.

For such patients, as well as those requiring concomitant use of low-dose acetylsalicylic acid (ASA/aspirin or other drugs likely to increase the risk of adverse effects on the gastrointestinal tract), combination therapy with protective agents (e.g. proton pump inhibitors or misoprostol) should be considered. Patients with a history of gastrointestinal toxicity, especially the elderly, should be informed of any unusual abdominal symptoms (especially gastrointestinal bleeding). Caution is also required in patients receiving concomitant medications that may increase the risk of ulceration or bleeding, such as systemic corticosteroids, anticoagulants (e.g. warfarin), antithrombotic agents (e.g. ASA), or selective serotonin reuptake inhibitors.

Effect on the liver.

During long-term treatment with Dicloberl® 100, regular monitoring of liver function and liver enzyme levels is recommended as a precautionary measure. If liver function abnormalities persist or worsen and if clinical signs or symptoms suggestive of progressive liver disease or if other manifestations occur (e.g. eosinophilia, rash), Dicloberl® 100 should be discontinued. Diseases such as hepatitis may occur without prodromal symptoms. Caution is advised when Dicloberl® 100 is used in patients with hepatic porphyria, as it may precipitate an attack.

Effect on the kidneys.

Since cases of fluid retention and edema have been reported with NSAIDs, including diclofenac, special attention should be paid to patients with impaired cardiac or renal function, a history of hypertension, elderly patients, patients receiving concomitant therapy with diuretics or drugs that significantly affect renal function, and patients with a significant decrease in extracellular fluid volume for any reason, for example, before or after major surgery. In such cases, monitoring of renal function is recommended as a precautionary measure. Discontinuation of therapy usually leads to a return to the state that existed before treatment.

Effect on the skin.

In connection with the use of NSAIDs, including Dicloberl® 100, serious skin reactions (some of which were fatal) have been reported in very rare cases, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis. Patients are at highest risk of developing these reactions at the beginning of therapy: the onset of the reaction is noted in most cases during the first month of treatment. The use of Dicloberl® 100 should be discontinued at the first appearance of skin rashes, mucosal lesions or any other sign of hypersensitivity.

SLE and mixed connective tissue diseases.

Patients with systemic lupus erythematosus (SLE) and mixed connective tissue diseases may be at increased risk of developing aseptic meningitis.

Cardiovascular and cerebrovascular effects.

For patients with a history of hypertension and/or mild to moderate congestive heart failure, appropriate monitoring and advice is necessary, as fluid retention and oedema have been reported in association with the use of NSAIDs, including diclofenac.

Clinical trial data and epidemiological data suggest that the use of diclofenac, especially at high doses (150 mg/day) and with long-term treatment, may be associated with a small increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke).

Diclofenac is not recommended for use in patients with uncontrolled hypertension, congestive heart failure, stable ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease, and should only be used after careful risk-benefit assessment, at a dose not exceeding 100 mg/day. A similar assessment should be made before initiating long-term treatment in patients with risk factors for cardiovascular events (e.g. hypertension, hyperlipidemia, diabetes mellitus and smokers).

Patients should be informed of the possibility of serious antithrombotic events (chest pain, shortness of breath, weakness, speech disorders) that may occur at any time. In this case, a doctor should be consulted immediately.

Effect on hematological parameters.

With prolonged use of this drug, as with other NSAIDs, monitoring of complete blood counts is recommended.

Dicloberl® 100 may temporarily inhibit platelet aggregation. Patients with impaired hemostasis, hemorrhagic diathesis, or hematological disorders should be carefully monitored.

History of asthma.

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 rhinitis-like symptoms) are more likely to experience reactions to NSAIDs, such as exacerbation of asthma (so-called analgesic intolerance/analgesic asthma), angioedema or urticaria. Therefore, special precautions (emergency medical attention) are recommended for such patients. This also applies to patients with allergic reactions to other substances, such as rash, itching or urticaria.

Like other drugs that inhibit prostaglandin synthetase activity, diclofenac sodium and other NSAIDs can provoke the development of bronchospasm when used in patients suffering from bronchial asthma or in patients with a history of bronchial asthma.

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 signs of a hypersensitivity reaction after using Dicloberl® 100, therapy should be discontinued.

With prolonged use of painkillers, a headache may occur, which should not be treated by increasing the dose of the drug.

With concomitant use of alcohol, adverse reactions associated with the action of the active substance, especially those affecting the gastrointestinal tract or the central nervous system, may be exacerbated by the use of NSAIDs.

Use during pregnancy or breastfeeding

Pregnancy.

In the first and second trimesters of pregnancy, Dicloberl® 100 can be prescribed only when the expected benefit to the mother outweighs 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 with other NSAIDs, the drug is contraindicated in the last 3 months of pregnancy (possible inhibition of uterine contractility and premature closure of the ductus arteriosus in the fetus).

Inhibition of prostaglandin synthesis may adversely affect the course of pregnancy and/or embryo/foetal development. Epidemiological data suggest an increased risk of miscarriage and/or cardiac malformations and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk of cardiovascular malformations was increased from less than 1% to approximately 1.5%.

It is possible that the risk increases with dose and duration of treatment. In animals, administration of a prostaglandin synthesis inhibitor has been shown to result in increased pre- and post-implantation loss and embryo/fetal lethality.

In addition, in animals treated with a prostaglandin synthesis inhibitor during organogenesis, an increased incidence of various malformations, including those of the cardiovascular system, was recorded. If DicloberlÒ 100 is used by a woman attempting to conceive, or in the first trimester of pregnancy, the dose of the drug should be 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 in the following ways:

- cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension);

- impaired renal function, which may progress to renal failure with oligohydramnios.

For the mother and newborn, as well as at the end of pregnancy:

- possible prolongation of bleeding time, antiplatelet effect, which can be observed even at very low doses;

- inhibition of uterine contractions, which leads to delayed or prolonged labor.

Therefore, DicloberlÒ 100 is contraindicated during the third trimester of pregnancy.

Breast-feeding.

Like other NSAIDs, diclofenac passes into breast milk in small amounts. Therefore, Dicloberl® 100 should not be used by women during breastfeeding to avoid undesirable effects on the infant.

Fertility in women.

Like other NSAIDs, Dicloberl® 100 may impair female fertility and is therefore not recommended for use in women attempting to conceive. In women who have difficulty conceiving or are undergoing investigation of infertility, discontinuation of Dicloberl® 100 should be considered.

Ability to influence reaction speed when driving vehicles or other mechanisms

Patients who experience visual disturbances, vertigo, drowsiness, central nervous system disorders, lethargy or fatigue during therapy with DicloberlÒ 100 should not drive or operate complex machinery.

Method of administration and doses

In order to minimize undesirable effects, the minimum effective dose should be used for the shortest possible period of time.

Do not use internally, for rectal administration only.

Suppositories should be inserted into the rectum as deeply as possible, preferably after bowel cleansing.

The initial dose is usually 100-150 mg per day. With mild symptoms, as well as with long-term therapy, a dose of 75-100 mg/day is sufficient.

Divide the daily dose into 2-3 doses. To avoid night pain or morning stiffness, administer DicloberlÒ 100 in the form of rectal suppositories before bedtime before using the drug during the day (the daily dose of the drug should not exceed 150 mg).

In primary dysmenorrhea, the daily dose should be selected individually, usually it is 50-150 mg/day. The initial dose may be 50-100 mg/day, but if necessary it can be increased over several menstrual cycles to a maximum of 200 mg/day. The drug should be started after the first painful symptoms appear and continued for several days, depending on the dynamics of symptom regression.

Elderly patients: Although the pharmacokinetics of Dicloberl 100 are not impaired to any clinically significant extent in elderly patients, NSAIDs should be used with caution in such patients, as they are generally more prone to adverse reactions. In particular, it is recommended that the lowest effective dose be used in debilitated elderly patients or patients with low body mass; patients should also be monitored for gastrointestinal bleeding when treated with NSAIDs.

Children

DicloberlÒ 100 suppositories should not be used in children due to their high content of the active ingredient.

Overdose

Symptoms.

There is no typical clinical picture of diclofenac overdose. Overdose may cause symptoms such as headache, nausea, vomiting, epigastric pain, gastrointestinal bleeding, diarrhea, dizziness, disorientation, agitation, coma, drowsiness, tinnitus, or convulsions. Acute renal failure and liver damage are possible in severe intoxication.

Treatment. If necessary, symptomatic treatment. Activated charcoal should be considered within 1 hour of ingestion of a potentially toxic amount. In addition, gastric lavage should be considered in adults within 1 hour of ingestion of a potentially toxic amount. Diazepam should be administered intravenously if seizures are frequent or prolonged. Other measures may be indicated depending on the clinical condition of the patient.

Adverse reactions

The following undesirable effects include those reported with short-term or long-term use of the drug.

From the blood and lymphatic system: thrombocytopenia, pancytopenia, agranulocytosis, leukopenia, anemia (hemolytic anemia, aplastic anemia). The first signs may be fever, pharyngitis, superficial mouth ulcers, flu-like symptoms, severe apathy, nosebleeds, skin bleeding.

Immune system disorders: hypersensitivity reactions such as skin rash and itching, urticaria, anaphylactic and anaphylactoid reactions (including airway narrowing, respiratory arrest, tachycardia, hypotension and shock), angioedema including facial swelling, tongue swelling, internal laryngeal swelling, allergic vasculitis and pneumonia.

Mental disorders: disorientation, depression, insomnia, irritability, nightmares, psychotic disorders, other mental disorders.

From the nervous system: headache, dizziness, agitation or drowsiness, anxiety, episodic dizziness, drowsiness, fatigue, paresthesia, memory impairment, convulsions, anxiety, tremor, aseptic meningitis, taste disorders, stroke, confusion, hallucinations, sensory disturbances, general malaise.

On the part of the organs of vision: visual disturbance, blurred vision, diplopia, optic neuritis

From the side of the organs of hearing and labyrinth: vertigo, tinnitus, hearing disorders

Cardiovascular system: palpitations, chest pain, heart failure, myocardial infarction, hypertension, hypotension, vasculitis.

Respiratory, thoracic and mediastinal disorders: asthma (including dyspnea)

pneumonitis.

Gastrointestinal: nausea, vomiting, diarrhea, dyspepsia, abdominal pain, flatulence, anorexia, gastritis, gastrointestinal bleeding (hemorrhage, melena, diarrhea with blood), gastric or intestinal ulcers with or without bleeding or with 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, esophageal dysfunction, diaphragmatic stenosis of the intestine, pancreatitis.

From the hepatobiliary system: increased transaminase levels, hepatitis, jaundice, liver disorders, fulminant hepatitis, hepatonecrosis, liver failure.

Infections and infestations: Exacerbation of inflammation associated with infections (e.g. development of necrotizing fasciitis) has been reported with systemic use of NSAIDs. This may be due to the mechanism of action of NSAIDs. If signs of infection develop or worsen during the use of Dicloberl®100, the patient is advised to consult a doctor immediately. It should be investigated whether this condition is a reason for treatment with an anti-infective agent/antibiotic. Very rarely, symptoms of aseptic meningitis with stiff neck, headache, nausea, vomiting, fever or confusion have been associated with the use of diclofenac. Patients with autoimmune diseases (SLE, mixed connective tissue disease) are considered susceptible.

Renal and urinary disorders: edema, especially in patients with arterial hypertension or renal failure, acute renal failure, hematuria, proteinuria, interstitial nephritis, nephrotic syndrome, renal papillary necrosis.

General disorders and administration site conditions: When using the suppository, changes may occur at the injection site, including local irritation, bloody mucus discharge, or painful defecation.

Reproductive system and breast disorders: impotence.

Clinical trial data and epidemiological data suggest an increased risk of thrombotic complications (e.g. myocardial infarction or stroke) associated with the use of diclofenac, particularly at high therapeutic doses (150 mg per day) and with long-term use.

Expiration date

3 years.

Do not use the drug after the expiration date indicated on the package!

Storage conditions

Store at a temperature not exceeding 25 ° C. Keep the medicine out of the reach of children!

Packaging

5 suppositories in a blister; 1 or 2 blisters in a cardboard box.

Vacation category

According to the recipe.

Producer

BERLIN-CHEMI AG.

Location of the manufacturer and its business address

Glienicker Weg 125, 12489 Berlin, Germany.