Diclofenac sodium

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT DICLOFENAC SODIUM (DICLOFENACUM NATRICUM)

Composition:

active substance: diclofenac;

1 suppository contains sodium diclofenac 0.05 g;

excipient: hard fat.

Dosage form. Rectal suppositories.

Main physicochemical properties: white suppositories with a slightly yellowish tint.

Pharmacotherapeutic group. Nonsteroidal anti-inflammatory and antirheumatic agents.

ATC code M01AB05.

Pharmacological properties.

Pharmacodynamics.

Sodium diclofenac exerts anti-inflammatory and analgesic effects by inhibiting the biosynthesis of prostaglandins, kinins, and other mediators of inflammation and pain, reducing capillary permeability, and stabilizing lysosomal membranes.

During continuous treatment of musculoskeletal disorders, the drug actively penetrates into joint cavities, helping to reduce joint pain at rest and during movement, increase range of motion, and decrease morning stiffness and joint swelling. A sustained effect is observed within 1–2 weeks after initiation of treatment. In post-traumatic or postoperative inflammation, it promotes rapid reduction of pain syndrome and decreases inflammation and wound edema.

Pharmacokinetics.

After rectal administration, sodium diclofenac is rapidly absorbed through the mucous membrane of the rectum. Maximum plasma concentration is reached within 1–2 hours. The average half-life is approximately 2 hours. About 70% of the administered dose is excreted by the kidneys as metabolites, less than 1% is excreted unchanged, and the remainder is excreted in the feces.

Clinical characteristics.

Indications.

• Inflammatory and degenerative forms of rheumatism: rheumatoid arthritis, juvenile rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, including spondyloarthritis;
• Spinal pain syndromes;
• Rheumatic diseases of soft tissues surrounding joints;
• Post-traumatic and postoperative pain syndromes accompanied by inflammation and swelling, particularly after dental and orthopedic surgeries;
• Gynecological conditions associated with pain and inflammation, e.g., primary dysmenorrhea and adnexitis;
• Migraine attacks;
• Acute gout attacks;
• As an adjunctive agent in severe inflammatory conditions of ENT organs accompanied by pain, e.g., pharyngotonsillitis, otitis.

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

Contraindications.

• Hypersensitivity to the active substance or to any of the excipients of the drug;
• History of gastrointestinal bleeding or perforation associated with previous treatment with nonsteroidal anti-inflammatory drugs (NSAIDs);
• Active peptic ulcer/hemorrhage or recurrent peptic ulcer/hemorrhage (two or more separate episodes of confirmed ulcer or bleeding);
• Third trimester of pregnancy;
• Inflammatory bowel diseases (e.g., Crohn’s disease or ulcerative colitis);
• Hepatic insufficiency (Child-Pugh class C) (liver cirrhosis and ascites);
• Renal insufficiency (glomerular filtration rate (GFR) <15 mL/min/1.73 m²);
• Severe congestive heart failure (NYHA II–IV);
• Treatment of perioperative pain in coronary artery bypass graft (CABG) surgery (or use of cardiopulmonary bypass);
• Ischemic heart disease in patients with angina pectoris or history of myocardial infarction;
• Cerebrovascular diseases in patients with history of stroke or transient ischemic attacks;
• Peripheral arterial disease;
• Diclofenac sodium, like other NSAIDs, is contraindicated in patients who experience attacks of bronchial asthma, urticaria, angioedema, acute rhinitis, or nasal polyps after taking acetylsalicylic acid or other NSAIDs;
• Proctitis.

Interaction with other medicinal products and other forms of interactions.

The interactions listed below have been observed with diclofenac administered as enteric-coated tablets and/or in other dosage forms.

Lithium. When used concomitantly, diclofenac may increase plasma lithium concentrations. Monitoring of serum lithium levels is recommended.

Digoxin. When used concomitantly, diclofenac may increase plasma digoxin concentrations. Monitoring of serum digoxin levels is recommended. Diuretics and antihypertensive agents. As with other NSAIDs, concomitant use of diclofenac with diuretics and antihypertensive agents (e.g., β-blockers, angiotensin-converting enzyme (ACE) inhibitors) may reduce their antihypertensive effect by inhibiting the synthesis of vasodilatory prostaglandins. Therefore, such combinations should be used with caution, and patients, especially elderly ones, should be closely monitored for blood pressure. Adequate hydration is recommended, and monitoring of renal function is advised after initiation and on a regular basis during concomitant therapy, particularly with diuretics and ACE inhibitors, due to increased risk of nephrotoxicity.

Medicinal products known to cause hyperkalemia. Concomitant treatment with potassium-sparing diuretics, cyclosporine, tacrolimus, or trimethoprim may be associated with increased serum potassium levels; therefore, more frequent monitoring of patients is recommended.

Anticoagulants and antiplatelet agents. Concomitant use may increase the risk of bleeding; therefore, precautionary measures are recommended. Although clinical studies do not indicate an effect of diclofenac on anticoagulant activity, there are individual reports of increased bleeding risk in patients taking diclofenac and anticoagulants simultaneously. Therefore, to ensure no dosage adjustment of anticoagulants is required, careful monitoring of such patients is recommended. Like other NSAIDs, diclofenac at high doses may transiently inhibit platelet aggregation.

Other NSAIDs, including selective cyclooxygenase-2 (COX-2) inhibitors, and corticosteroids. Concomitant use of diclofenac with other NSAIDs or corticosteroids may increase the risk of gastrointestinal bleeding or ulceration. 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 both hypoglycemia and hyperglycemia occurring in such cases, necessitating dosage adjustments of antidiabetic agents during diclofenac treatment. For this reason, blood glucose monitoring is recommended during combination therapy.

There are also isolated reports of metabolic acidosis occurring with concomitant use of diclofenac, particularly in patients with pre-existing renal dysfunction.

Methotrexate. Diclofenac may inhibit renal tubular clearance of methotrexate, leading to elevated methotrexate levels. Caution should be exercised when prescribing NSAIDs, including diclofenac, less than 24 hours before or after methotrexate administration, as this may increase methotrexate plasma concentrations and enhance its toxicity. Serious cases of toxicity have been reported when the interval between methotrexate and NSAID (including diclofenac) administration was within 24 hours. This interaction is mediated by methotrexate accumulation due to impaired renal excretion in the presence of NSAIDs.

Cyclosporine. The effect of diclofenac, like other NSAIDs, on prostaglandin synthesis in the kidneys may potentiate the nephrotoxicity of cyclosporine. Therefore, diclofenac should be used at lower doses than in patients not receiving cyclosporine.

Tacrolimus. When NSAIDs are used with tacrolimus, there may be an increased risk of nephrotoxicity, possibly mediated by the renal anti-prostaglandin effects of NSAIDs and the calcineurin inhibitor, thus requiring lower doses than in patients not receiving cyclosporine.

Quinolone antibiotics. There are isolated reports of seizures in patients who concurrently used quinolone derivatives and NSAIDs. This may occur in patients both with and without a history of epilepsy or seizures. Therefore, caution should be exercised when considering quinolone use in patients already receiving NSAIDs.

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

Colestyramine and cholestyramine. These agents may cause delayed or reduced absorption of diclofenac. Therefore, it is recommended to administer diclofenac at least 1 hour before or 4–6 hours after colestyramine/cholestyramine.

Cardiac glycosides. Concomitant use of cardiac glycosides and NSAIDs in patients may exacerbate heart failure, reduce GFR, and increase plasma glycoside levels.

Mifepristone. NSAIDs should not be used within 8–12 days after mifepristone administration, as NSAIDs may reduce the efficacy of mifepristone.

Strong CYP2C9 inhibitors. Caution is advised when co-administering diclofenac with strong CYP2C9 inhibitors (e.g., voriconazole), as this may lead to a significant increase in diclofenac plasma maximum concentration and exposure due to inhibition of its metabolism.

CYP2C9 inducers. Caution is also required when co-administering diclofenac with CYP2C9 inducers (e.g., rifampicin), as this may lead to a significant decrease in diclofenac plasma concentration and exposure.

Special precautions for use.

General

Gastrointestinal ulcers, bleeding, or perforation may occur at any time during use of NSAIDs, regardless of whether they are COX-2 selective, even in the absence of warning symptoms or predisposition in medical history.

To minimize adverse effects, the lowest effective dose should be used for the shortest possible duration.

Placebo-controlled studies have indicated an increased risk of thrombotic cardiovascular and cerebrovascular complications with certain selective COX-2 inhibitors. Whether this risk is directly correlated with the COX-1/COX-2 selectivity of individual NSAIDs remains unknown.

Concomitant use of sodium diclofenac with systemic NSAIDs, such as selective cyclooxygenase-2 inhibitors, should be avoided due to lack of evidence for synergistic effect and potential for additive adverse effects.

As comparative clinical trial data on long-term treatment with maximum doses of diclofenac are currently lacking, the possibility of such increased risk cannot be excluded. Until such data become available, a careful benefit-risk assessment should be performed before initiating diclofenac therapy in patients with clinically confirmed coronary heart disease, cerebrovascular disorders, peripheral arterial disease, or significant risk factors (e.g., arterial hypertension, hyperlipidemia, diabetes mellitus, smoking). Due to this risk, the lowest effective dose should be used for the shortest possible duration.

Caution is required in elderly patients. In particular, the lowest effective dose is recommended for frail elderly patients or those with low body weight. Rarely, as with other NSAIDs, allergic reactions including anaphylactic/anaphylactoid reactions may occur, even without prior exposure to diclofenac. Due to its pharmacodynamic properties, sodium diclofenac, like other NSAIDs, may mask signs and symptoms of infection.

Effect on the gastrointestinal tract

Cases of gastrointestinal bleeding (hematemesis, melena), ulceration, or perforation have been reported with all NSAIDs, including diclofenac. These events may be fatal and may occur at any time during treatment, with or without warning symptoms or prior history of serious gastrointestinal (GI) events. These events usually have more serious consequences in elderly patients. 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 mandatory for patients with symptoms suggesting GI disturbances. The risk of GI bleeding, ulceration, or perforation increases with higher NSAID doses, including diclofenac, and in patients with a history of peptic ulcer, especially with complications such as bleeding or perforation, and in elderly patients.

Elderly patients have an increased frequency of adverse reactions when using NSAIDs, particularly gastrointestinal bleeding and perforation, which may be fatal. To reduce the risk of such GI toxicity, treatment should be initiated and maintained at the lowest effective doses.

For such patients, as well as for those requiring concomitant use of low-dose acetylsalicylic acid (ASA) or other drugs that may increase the risk of GI adverse effects, consideration should be given to combination therapy with protective agents (e.g., proton pump inhibitors or misoprostol).

Patients with a history of gastrointestinal toxicity, especially elderly patients, should report any unusual abdominal symptoms (particularly GI 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), antiplatelet agents (e.g., ASA), or SSRIs.

Effect on the liver

Close medical monitoring is required when sodium diclofenac is prescribed to patients with hepatic dysfunction, as their condition may worsen. As with other NSAIDs, including diclofenac, levels of one or more liver enzymes may increase.

This occurred very frequently in clinical trials of diclofenac (approximately 15% of patients), but rarely was associated with clinical symptoms. Most of these cases involved borderline elevations. Moderate increases (≥3 to <8 times the upper limit of normal) were observed frequently (in 2.5% of cases), while significant increases (≥8 times the upper limit of normal) remained at about 1%. In the aforementioned clinical trials, elevated liver enzymes were clinically associated with evident liver damage in 0.5% of patients. After discontinuation of the drug, liver enzyme levels returned to baseline.

During long-term treatment with sodium diclofenac, regular monitoring of liver function is recommended as a precaution. If liver function abnormalities persist or worsen, or if clinical signs or symptoms suggest progressive liver disease, or if other manifestations occur (e.g., eosinophilia, rash), sodium diclofenac should be discontinued.

In addition to elevated liver enzymes, isolated reports of severe hepatic reactions have been received, including jaundice and fulminant hepatitis, hepatic necrosis, and hepatic failure, some of which were fatal.

Diseases such as hepatitis may progress without prodromal symptoms. Caution is necessary when prescribing sodium diclofenac to patients with hepatic porphyria due to the potential to provoke an attack.

Effect on the kidneys

Due to the importance of prostaglandins in maintaining renal blood flow, prolonged treatment with high doses of NSAIDs, including diclofenac, often (1–10%) leads to fluid retention and edema.

Since fluid retention and edema have been reported during treatment with NSAIDs, including diclofenac, particular attention should be paid to patients with cardiac or renal dysfunction, hypertension, elderly patients, patients receiving concomitant diuretic therapy or drugs that significantly affect renal function, and patients with significant extracellular fluid volume depletion from any cause, such as before or after major surgery. In such cases, monitoring of renal function is recommended as a precaution. Discontinuation of therapy usually results in return to the pre-treatment state.

Effect on the skin

Serious skin reactions (some of which were fatal), including exfoliative dermatitis, Stevens–Johnson syndrome, toxic epidermal necrolysis, and generalized bullous fixed drug eruption, have been very rarely reported in association with diclofenac use (see section "Adverse reactions"). The risk of these reactions is highest at the beginning of therapy; most cases occur within the first month of treatment. Sodium diclofenac should be discontinued at the first appearance of skin rash, mucosal lesions, or any other signs of hypersensitivity.

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

Systemic lupus erythematosus (SLE) and mixed connective tissue disorders

Patients with SLE and mixed connective tissue disorders may have an increased risk of developing aseptic meningitis.

Cardiovascular and cerebrovascular effects

Sodium diclofenac is generally not recommended for patients with established cardiovascular disease (e.g., heart failure, established ischemic heart disease, peripheral arterial disease) or uncontrolled arterial hypertension.

Patients with a history of arterial hypertension and/or mild to moderate congestive heart failure require appropriate monitoring and counseling, as fluid retention and edema have been reported with NSAID use, including diclofenac. Clinical trial data and epidemiological evidence suggest that diclofenac use, particularly at high doses (150 mg daily) and with prolonged treatment, may be associated with a small increased risk of arterial thrombotic events (e.g., myocardial infarction or stroke).

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

The patient's need for symptom relief and response to therapy should be periodically evaluated, especially if treatment duration exceeds 4 weeks.

Patients should be informed about the need to monitor for signs and symptoms of serious arterial thromboembolic events (e.g., chest pain, dyspnea, weakness, slurred speech), which may occur without warning. If such an event occurs, patients should seek immediate medical attention.

Diclofenac may be prescribed to patients with significant cardiovascular risk factors (e.g., arterial hypertension, hyperlipidemia, diabetes mellitus, smoking) only after careful clinical evaluation and at doses up to 100 mg daily if treatment duration exceeds 4 weeks. Since cardiovascular risks of diclofenac may increase with dose and duration of treatment, it should be used for the shortest possible duration and at the lowest effective dose. The patient's need for diclofenac for symptom relief and response to therapy should be reviewed periodically. Use with caution in patients aged 65 years and older.

Effect on hematological parameters

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

Sodium diclofenac may reversibly inhibit platelet aggregation. Careful monitoring is required in patients with hemostatic disorders, hemorrhagic diathesis, or hematological disorders.

Asthma in medical history

Patients with asthma, seasonal allergic rhinitis, nasal mucosal swelling (i.e., nasal polyps), chronic obstructive pulmonary diseases, or chronic respiratory infections (especially those associated with allergic, rhinitis-like symptoms) more frequently experience reactions to NSAIDs, such as asthma exacerbation (so-called analgesic intolerance/analgesic asthma), Quincke's edema, or urticaria. Therefore, special precautionary measures (readiness for emergency treatment) are recommended for such patients. This also applies to patients with allergic reactions to other substances, such as rash, pruritus, or urticaria.

Like other drugs that inhibit prostaglandin synthetase activity, sodium diclofenac and other NSAIDs may provoke bronchospasm when administered to patients suffering from bronchial asthma or with a history of bronchial asthma.

Use during pregnancy or breastfeeding.

Pregnancy.

Diclofenac should not be used during the first or second trimester of pregnancy unless absolutely necessary. Sodium diclofenac may be prescribed during the first and second trimesters only if the expected benefit to the mother outweighs the potential risk to the fetus and only at the lowest effective dose. Treatment duration should be as short as possible. From the 20th week of pregnancy, diclofenac use may cause oligohydramnios due to fetal renal dysfunction. This may occur soon after initiation of treatment and is usually reversible upon discontinuation.

Like other NSAIDs, the drug is contraindicated in the third trimester of pregnancy (possible inhibition of uterine contractility and premature closure of the ductus arteriosus in the fetus).

Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonic/fetal development. Epidemiological data indicate an increased risk of miscarriage and/or risk of cardiac defects and gastroschisis following use of prostaglandin synthesis inhibitors in early pregnancy. The absolute risk of cardiovascular defects increased from less than 1% to approximately 1.5%.

The risk may increase with dose and duration of treatment. Animal studies have shown that administration of a prostaglandin synthesis inhibitor leads to increased pre- and post-implantation loss and embryonic/fetal mortality.

Furthermore, in animals receiving a prostaglandin synthesis inhibitor during organogenesis, an increased incidence of various developmental abnormalities, including cardiovascular malformations, has been observed. If sodium diclofenac is used by a woman trying to conceive or during the first trimester of pregnancy, the dose should be as low as possible and treatment duration as short as possible. Prenatal monitoring for oligohydramnios should be considered after diclofenac exposure for several days starting from week 20 of pregnancy. Diclofenac use should be discontinued if oligohydramnios is detected.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may affect the fetus as follows:

• cardiopulmonary toxicity with premature closure of the ductus arteriosus and pulmonary hypertension;
• impaired renal function (see above).

Effects on the mother and newborn, particularly near term:

• possible prolonged bleeding time, anti-aggregatory effect, which may occur even at very low doses;
• inhibition of uterine contractions, leading to delayed or prolonged labor.

Therefore, sodium diclofenac is contraindicated during the third trimester of pregnancy.

Breastfeeding period.

Like other NSAIDs, diclofenac is excreted in small amounts in breast milk. Therefore, sodium diclofenac suppositories should not be used during breastfeeding to avoid potential adverse effects on the infant. If treatment is essential, the infant should be switched to artificial feeding.

Female fertility

Like other NSAIDs, sodium diclofenac may negatively affect female fertility and is therefore not recommended for women attempting to conceive. For women experiencing infertility or undergoing fertility investigations, discontinuation of the drug should be considered.

In animals, based on relevant data, impairment of male fertility cannot be excluded. The relevance of these data to humans is unknown.

Ability to affect reaction speed when driving or operating machinery.

Patients who experience visual disturbances, dizziness, vertigo, somnolence, central nervous system disorders, lethargy, or fatigue during treatment with sodium diclofenac should not drive or operate machinery.

Method of Administration and Dosage

The dose of the drug depends on the nature, severity, and clinical course of the disease.

The drug should be used at the lowest effective doses for the shortest duration necessary, taking into account the treatment goals for each individual patient.

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

The usual initial dose for adults is 100–150 mg (2–3 suppositories) per day. For mild symptoms and during long-term therapy, a daily dose of 75*–100 mg is sufficient.

*Use suppositories containing the active substance diclofenac in the appropriate dosage strength.

The daily dose should be divided into 2–3 administrations. To prevent nocturnal pain or morning stiffness, administer sodium diclofenac in the form of rectal suppositories before bedtime (the daily dose of the drug must not exceed 150 mg).

For primary dysmenorrhea, the daily dose should be individually adjusted and usually ranges from 50–150 mg per day (1–3 suppositories). The initial dose may be 50–100 mg per day (1–2 suppositories), but if necessary, it can be increased over several menstrual cycles up to the maximum dose of 150 mg per day (3 suppositories). Treatment should begin after the onset of the first painful symptoms and continue for several days, depending on the symptom regression dynamics.

For the treatment of migraine attacks, initiate therapy with a dose of 100 mg (2 suppositories) at the first signs of an attack. If necessary, an additional 50 mg of diclofenac (1 suppository) may be administered on the same day. If needed, treatment may be continued on subsequent days (the daily dose must not exceed 150 mg [3 suppositories]; the dose should be divided into 3 administrations).

Children aged 14 years and older may be prescribed 50 mg (1 suppository).

Due to the high concentration of the active ingredient sodium diclofenac, 50 mg suppositories are not recommended for children and adolescents under 14 years of age.

Elderly patients: Although the pharmacokinetics of sodium diclofenac are not significantly impaired in elderly patients to a clinically relevant extent, NSAIDs should be used with particular caution, as these patients are generally more susceptible to adverse reactions. In particular, frail elderly patients or those with low body weight should be prescribed the lowest effective doses; patients should also be monitored for gastrointestinal bleeding during NSAID therapy.

Renal Function Impairment

The use of sodium diclofenac is contraindicated in patients with renal impairment (GFR <15 mL/min/1.73 m²; see section "Contraindications").

Specific studies in patients with renal impairment have not been conducted; therefore, dosage adjustment recommendations cannot be provided. Sodium diclofenac should be used with caution in patients with renal function impairment (see section "Special Warnings and Precautions for Use").

Hepatic Function Impairment

The use of sodium diclofenac is contraindicated in patients with hepatic insufficiency (see section "Contraindications").

Specific studies in patients with hepatic impairment have not been conducted; therefore, dosage adjustment recommendations cannot be provided. Sodium diclofenac should be used cautiously in patients with mild to moderate hepatic impairment (see section "Special Warnings and Precautions for Use").

Children

This pharmaceutical form of the drug is indicated for use in children aged 14 years and older.

Overdose

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

Treatment. If necessary, treatment is symptomatic. Supportive measures and symptomatic therapy should be initiated for complications such as arterial hypotension, renal failure, convulsions, gastrointestinal disorders, and respiratory depression.

Specific interventions such as forced diuresis, dialysis, or hemoperfusion are unlikely to be effective in eliminating NSAIDs, including diclofenac, from the body due to their high protein binding and extensive metabolism. Administration of activated charcoal should be considered within 1 hour after ingestion of a potentially toxic amount of the drug. Additionally, in adults, gastric lavage should be considered within 1 hour after ingestion of a potentially toxic amount. In cases of frequent or prolonged convulsions, intravenous diazepam should be administered. Other measures may be indicated based on the patient's clinical condition.

Adverse Reactions.

Gastrointestinal: epigastric pain, nausea, vomiting, diarrhea, dyspepsia, flatulence, anorexia, decreased appetite; gastritis; gastrointestinal bleeding (hematemesis, melena, bloody diarrhea), gastric and intestinal ulcers with or without bleeding, gastrointestinal stenosis or perforation (sometimes fatal, especially in elderly patients), which may lead to peritonitis; proctitis; very rare generalized conditions – colitis (including hemorrhagic colitis, ischemic colitis, and exacerbation of ulcerative colitis or Crohn’s disease), constipation, stomatitis (including ulcerative stomatitis), glossitis, esophageal dysfunction, diaphragm-like intestinal stenosis, pancreatitis, hemorrhoidal flare-ups.

Hepatobiliary system: elevated transaminase levels; hepatitis, jaundice, liver disorders; fulminant hepatitis, liver necrosis, liver failure.

Nervous system: headache, dizziness; somnolence, fatigue; paresthesia, memory impairment, convulsions, restlessness, tremor, aseptic meningitis, taste disturbances, stroke; confusion, hallucinations, sensory disturbances, general malaise.

Psychiatric disorders: disorientation, depression, insomnia, irritability, nightmares, psychotic disorders.

Eye disorders: visual disturbances, blurred vision, diplopia, optic neuritis.

Ear and labyrinth disorders: vertigo; tinnitus, hearing disturbances.

Blood and lymphatic system: thrombocytopenia, leukopenia, hemolytic anemia, aplastic anemia, agranulocytosis.

Immune system: hypersensitivity, anaphylactic and anaphylactoid reactions (including arterial hypotension and shock), angioedema (including facial swelling).

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

Respiratory system: asthma (including dyspnea), bronchospasm, pneumonitis.

Skin and subcutaneous tissue: rash; urticaria; very rare – bullous eruptions, eczema, erythema multiforme, Stevens–Johnson syndrome, Lyell’s syndrome (toxic epidermal necrolysis), exfoliative dermatitis, alopecia, photosensitivity reactions; purpura, including allergic purpura, Schönlein-Henoch purpura, pruritus; frequency unknown – fixed drug eruption, generalized bullous fixed drug eruption.

Renal and urinary system: fluid retention, edema, acute kidney injury, acute renal failure, hematuria, proteinuria, tubulointerstitial nephritis; nephrotic syndrome; renal papillary necrosis.

Reproductive system and breast: very rare – impotence.

General disorders and administration site conditions: irritation at the site of administration, swelling.

Clinical studies and epidemiological data indicate 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 prolonged use.

Visual disturbances. Visual disturbances such as impaired vision, worsening of vision, and diplopia are class effects of NSAIDs and are usually reversible upon discontinuation of the drug. The most likely mechanism of visual disturbances is inhibition of prostaglandin synthesis and other related compounds, which disrupt retinal blood flow regulation and contribute to the development of visual disturbances. If such symptoms occur during treatment with diclofenac, an ophthalmological examination should be performed to rule out other possible causes.

Reporting suspected adverse reactions.

Reporting suspected adverse reactions after drug registration is highly important. It enables ongoing monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy through the automated pharmacovigilance information system at: https://aisf.dec.gov.ua.

Shelf life. 2 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging.

5 suppositories per strip. 2 strips per cardboard box.

Prescription status.

Prescription only.

Manufacturer.

JSC "Monfarm".

Manufacturer's address and location of business activity.

8 Zavodska Street, Avramivka, Uman district, Cherkasy region, 19161, Ukraine.