SKRIPTA

INSTRUCTIONS FOR MEDICAL USE OF DICLAC⁺ID (DICLAC⁺ID)

Composition:

Active substance: diclofenac;

1 tablet contains 75 mg or 150 mg of sodium diclofenac;

excipients: lactose monohydrate, hypromellose (hydroxypropylmethylcellulose), microcrystalline cellulose, calcium hydrogen phosphate, corn starch, sodium starch glycolate (type A), colloidal anhydrous silicon dioxide, magnesium stearate, iron oxide red (E 172), purified water.

Pharmaceutical form.

Tablets with modified release.

Main physical and chemical properties:

Two-layer tablets of white-pink color, round, flat, with beveled edges and a smooth surface, the pink layer may contain white specks.

Pharmacotherapeutic group.

Non-steroidal anti-inflammatory and anti-rheumatic agents. ATC code M01AE05.

Pharmacological properties.

Pharmacodynamics.

Diclofenac is a non-steroidal compound with pronounced anti-rheumatic, antipyretic, analgesic, and anti-inflammatory properties. The mechanism of action is due to the inhibition of biosynthesis of prostaglandins, kinins, and other mediators of inflammation and pain, reduction of capillary permeability, and stabilizing effect on lysosomal membranes. It inhibits platelet aggregation induced by adenosine diphosphate and collagen. In vitro, sodium diclofenac at concentrations equivalent to those achieved during treatment of patients does not inhibit the biosynthesis of proteoglycans of cartilage tissue.

In rheumatic diseases, the anti-inflammatory and analgesic effects of diclofenac lead to a significant reduction in the severity of pain (both at rest and during movement), morning stiffness, joint swelling, and thus - to an improvement in the patient's functional state.

In the presence of inflammation caused by trauma or surgical intervention, Diclac⁺ID quickly eliminates both spontaneous pain and pain during movement, as well as reduces inflammatory edema of tissues and swelling in the area of surgical wound. When used in combination with opioids for postoperative pain relief, Diclac⁺ID significantly reduces the need for opioids.

Clinical studies have shown that Diclac⁺ID also has a strong analgesic effect in moderately and severely expressed non-rheumatic pain.

Pharmacokinetics.

Diclac⁺ID tablets are two-layer tablets with a combination of fast (1/6 of the total amount) and prolonged (5/6 of the total amount) release of sodium diclofenac. Such a combination of effects in one tablet allows for both rapid onset of action and prolonged circulation of the active substance in the systemic bloodstream and therapeutic effect throughout the day.

After oral administration of the drug, diclofenac is completely absorbed, and depending on the duration of passage through the stomach, the maximum concentration in plasma is reached within 1-16 hours, on average within 2-3 hours. The amount of absorbed active substance linearly depends on the dose of the drug. About half of diclofenac is metabolized during the first pass through the liver. Only 35-70% of the absorbed active substance reaches posthepatic circulation in an unchanged form. Approximately 30% of the active substance is metabolized and excreted with feces. Approximately 70% is excreted by the kidneys in the form of pharmacologically inactive metabolites. The half-life is about 2 hours, and this indicator does not depend on liver and kidney function. Binding to plasma proteins is approximately 99%.

Clinical characteristics.

Indications.

Relief of pain and reduction of inflammation of various degrees in various conditions, including:

• joint pathology: rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, acute attacks of gout;
• acute musculoskeletal diseases, such as periarthritis (e.g., shoulder periarthritis), tendinitis, tenosynovitis, bursitis;
• other pathological conditions caused by trauma, including fractures, back pain, sprains, dislocations, orthopedic, dental, and other minor surgical interventions.

Contraindications.

- Hypersensitivity to the active substance or to any other component of the drug.

- Acute stomach or intestinal ulcers; gastrointestinal bleeding or perforation, gastrointestinal bleeding or perforation in history after taking non-steroidal anti-inflammatory drugs (NSAIDs), acute or recurrent stomach or intestinal ulcers in history (two or more separate episodes of confirmed ulcers or bleeding in history).

- Diclofenac, like other NSAIDs, is contraindicated in patients who develop angioedema, nasal polyps, bronchial asthma attacks, urticaria, acute rhinitis, and other allergic symptoms in response to the use of acetylsalicylic acid or other NSAIDs.

- Hematopoietic disorders of unknown origin.

- Cerebrovascular bleeding or other types of bleeding.

- Inflammatory diseases of the intestine (Crohn's disease or ulcerative colitis).

- Liver failure.

- Kidney failure.

- Congestive heart failure (NYHA II-IV).

- Ischemic heart disease in patients who have had angina pectoris, myocardial infarction.

- Peripheral artery disease.

- Cerebrovascular diseases in patients who have had a stroke or have had episodes of transient ischemic attacks.

- Treatment of perioperative pain during aortocoronary bypass surgery (or use of a heart-lung machine).

- Treatment of postoperative pain after coronary artery bypass grafting (or use of a heart-lung machine).

Interactions with other medicinal products and other types of interactions.

The following interactions have been observed when using diclofenac tablets coated with a gastro-resistant coating and/or other diclofenac pharmaceutical forms.

Lithium. When used in combination with diclofenac, it may increase lithium levels in the blood plasma. It is recommended to monitor lithium levels in the blood plasma.

Digoxin. The concentration of digoxin in the blood plasma may increase when used in combination with diclofenac. It is recommended to monitor digoxin levels in the blood plasma.

Diuretics and antihypertensive agents. As with the use of other NSAIDs, concomitant use of Diclac⁺ID may weaken the antihypertensive effect of diuretics or antihypertensive agents (e.g., beta-blockers, angiotensin-converting enzyme inhibitors (ACE)) by inhibiting the synthesis of vasodilatory prostaglandins. Therefore, such a combination should be used with caution; patients, especially the elderly, should regularly monitor blood pressure. Patients should receive adequate hydration, and kidney function should be monitored at the beginning of combination therapy and regularly thereafter, particularly due to the increased risk of nephrotoxicity when using diuretics and ACE inhibitors.

Anticoagulants and antithrombotic agents. It is recommended to prescribe with caution, as concomitant use may increase the risk of bleeding.

It is recommended to closely monitor patients who concomitantly use diclofenac and anticoagulants, and, if necessary, adjust the dosage of anticoagulants. Like other NSAIDs, diclofenac can reversibly inhibit platelet aggregation at high doses.

Other NSAIDs, including selective cyclooxygenase-2 (COX-2) inhibitors, and corticosteroids. Concomitant use of diclofenac and other systemic NSAIDs or corticosteroids may increase the risk of gastrointestinal bleeding or ulcers. It is recommended to avoid concomitant use of two or more NSAIDs. Concomitant use of diclofenac and corticosteroids may increase the frequency of adverse reactions.

Antidiabetic agents. There have been isolated reports of both hypoglycemic and hyperglycemic reactions after the use of diclofenac, which requires adjustment of the dose of antidiabetic agents. For this reason, it is recommended to monitor blood glucose levels as a precautionary measure during combination therapy.

Probenecid. Medicinal products containing probenecid may cause delayed excretion of diclofenac.

Methotrexate. Diclofenac may inhibit the tubular renal clearance of methotrexate, increasing the level of methotrexate. It is recommended to use NSAIDs, including diclofenac, with caution when prescribing less than 24 hours before methotrexate treatment, as methotrexate levels in the blood plasma and its toxicity may increase.

Cases of serious toxicity have been observed when methotrexate and NSAIDs, including diclofenac, were used at an interval of less than 24 hours. This interaction is mediated by the accumulation of methotrexate due to impaired renal excretion in the presence of NSAIDs.

Cyclosporine. Diclofenac, like other NSAIDs, may enhance the nephrotoxicity of cyclosporine by affecting renal prostaglandins. In this regard, the drug should be used at lower doses than for patients who do not receive cyclosporine.

Tacrolimus. Possible increased risk of nephrotoxicity if NSAIDs are prescribed concomitantly with tacrolimus.

Quinolone antibiotics. Due to the interaction between quinolone antibiotics and NSAIDs, seizures may occur. This can occur in patients with epilepsy or seizures in history, as well as without such history. In this regard, it is recommended to use quinolone antibiotics with caution in patients who are already taking NSAIDs.

Phenytoin. When used in combination with phenytoin and diclofenac, it is recommended to monitor phenytoin levels in the blood plasma, taking into account the expected increase in phenytoin exposure.

Cholestyramine and colestipol. These drugs may cause delayed or reduced absorption of diclofenac. In view of this, it is recommended to take diclofenac at least 1 hour before or 4-6 hours after the administration of cholestyramine/colestipol.

Cardiac glycosides. Concomitant use of cardiac glycosides and NSAIDs in patients may contribute to the enhancement of heart failure, reduction of glomerular filtration rate, and increased concentration of glycoside in the blood plasma.

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

Potent CYP2C9 inhibitors. It is recommended to prescribe diclofenac with caution in combination with potent CYP2C9 inhibitors (e.g., sulfinpyrazone and voriconazole), which may lead to a significant increase in the maximum concentration in the blood plasma and exposure to diclofenac due to the inhibition of its metabolism.

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

Agents that may cause hyperkalemia. Concomitant treatment with potassium-sparing diuretics, cyclosporine, tacrolimus, or trimethoprim may cause an increase in serum potassium levels, which should be monitored.

Special warnings and precautions for use.

To minimize the risk of adverse reactions, treatment should be started with the lowest effective dose, which should be taken for the shortest period of time to control symptoms, taking into account the treatment goals for each individual patient.

General. It is recommended to avoid concomitant use of diclofenac and other systemic NSAIDs, including selective COX-2 inhibitors, due to the lack of any evidence of a synergistic effect and due to potential additive adverse effects.

It is recommended to prescribe treatment to patients over 65 years of age with caution, according to the recommendations for this group of patients. In particular, it is recommended to use the minimum effective dose in weakened elderly patients or patients with low body weight.

The use of oral forms containing diclofenac with rapid release may increase the gastric intolerance of the drug.

When using diclofenac, as well as other NSAIDs, allergic reactions, including anaphylactic/anaphylactoid reactions, may rarely develop, which can occur even if the drug is used for the first time.

Allergic reactions may progress to the Kounis syndrome - severe allergic reactions that can cause myocardial infarction. Symptoms of such reactions are chest pain in combination with allergic reactions to diclofenac.

Like other NSAIDs, diclofenac may mask signs and symptoms of infection.

When using analgesics for a long time, headaches may occur. They cannot be treated with increased doses of diclofenac.

Consuming alcohol during the use of NSAIDs, including diclofenac, may enhance adverse reactions from the gastrointestinal tract (GI) or central nervous system (CNS).

Since Diclac⁺ID contains lactose, it is not recommended to prescribe it to patients with hereditary conditions associated with galactose intolerance, glucose-galactose malabsorption, and lactase deficiency.

It is recommended to periodically review the patient's need for diclofenac use to relieve symptoms and respond to therapy. It is recommended to use with caution in patients over 65 years of age.

Effect on the gastrointestinal tract.

When using NSAIDs, including diclofenac, gastrointestinal bleeding (hematemesis, melena), ulcers, or perforation have been observed, which can be fatal. They can occur at any time during treatment, with or without symptoms, and serious gastrointestinal diseases in history. In elderly patients, such complications are usually more severe. If gastrointestinal bleeding or ulcers occur, the drug should be discontinued.

Close medical supervision and special caution are required when prescribing diclofenac to patients with symptoms indicating gastrointestinal disorders or suspected ulcers, bleeding, or perforation of the stomach or intestines in history. The risk of these events increases with increasing doses of NSAIDs, as well as in patients with ulcers in history, particularly complicated by bleeding or perforation.

In elderly patients, the frequency of adverse reactions to NSAIDs is increased, especially gastrointestinal bleeding and perforation, which can be fatal.

To reduce the risk of adverse events from the gastrointestinal tract, treatment should be started with the lowest effective dose and adhered to.

It is recommended to consider the possibility of combination therapy with the use of protective agents (e.g., misoprostol or proton pump inhibitors) in such patients, as well as in patients who require concomitant use of low doses of acetylsalicylic acid/aspirin or other drugs that may increase the risk of adverse reactions from the gastrointestinal tract.

Caution should be exercised when concomitantly treating with drugs that may increase the risk of ulcers or bleeding, such as systemic corticosteroids, anticoagulants (e.g., warfarin), SSRIs, antiplatelet agents (e.g., acetylsalicylic acid).

Effect on the liver.

Close medical supervision is required if the drug must be prescribed to patients with liver function disorders, as their condition may worsen.

When using NSAIDs, including diclofenac, the level of one or more liver enzymes may increase. During long-term treatment with diclofenac, regular monitoring of liver function is recommended as a precautionary measure.

If liver function test results persist or worsen, clinical signs or symptoms of liver disease appear, or other manifestations (eosinophilia, rash) are observed, the use of the drug should be discontinued.

During the use of diclofenac, hepatitis without prodromal symptoms may develop.

Diclac⁺ID should be prescribed only after careful evaluation of the risk-benefit ratio in cases of congenital porphyria metabolism disorders, as it may cause exacerbation.

Effect on the kidneys.

Since fluid retention and edema have been observed during the use of NSAIDs, special caution should be exercised in patients with impaired heart or kidney function, a history of arterial hypertension, elderly patients, patients receiving concomitant diuretic therapy or drugs that may significantly affect kidney function, as well as patients with significant reduction of extracellular fluid volume for any reason (e.g., before or after surgical intervention). In such cases, when using diclofenac, it is recommended to monitor kidney function as a precautionary measure. After discontinuation of therapy, the patient's condition usually normalizes.

Generally, the usual use of analgesics, especially in combination with several pain-relieving drugs, can lead to prolonged kidney damage with a risk of developing kidney failure (analgesic nephropathy).

Effect on the skin.

Reports have been received of serious skin reactions (some of which were fatal), including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, which have been observed very rarely during the use of diclofenac. The highest risk of these reactions exists at the beginning of therapy, and their development is observed in most cases within the first month of treatment. Particular close supervision is required for patients with allergic reactions to other substances. The drug should be discontinued at the first signs of hypersensitivity.

Systemic lupus erythematosus and mixed connective tissue disease.

In patients with systemic lupus erythematosus and mixed connective tissue diseases, there is a possible increased risk of aseptic meningitis.

Cardiovascular and cerebrovascular manifestations.

There is an increased risk of thrombotic cardiovascular and cerebrovascular complications (including myocardial infarction and stroke) associated with the use of NSAIDs, including diclofenac, especially during long-term treatment with high doses.

Such patients, as well as those with significant risk factors for cardiovascular events (e.g., hypertension, hyperlipidemia, diabetes, smoking), should be prescribed diclofenac only after careful clinical evaluation at daily doses ≤ 100 mg, if treatment lasts more than 4 weeks.

Since the cardiovascular risks of diclofenac may increase with increasing dose and duration of treatment, it should be used for the shortest possible period and at the lowest effective dose. The dose of the drug should be periodically reviewed, especially if treatment lasts more than 4 weeks.

Treatment with diclofenac is usually not recommended for patients with established cardiovascular diseases (congestive heart failure NYHA II-IV, ischemic heart disease, peripheral artery disease) or with uncontrolled arterial hypertension.

Patients should be informed about the signs and symptoms of serious cardiovascular thrombotic complications (e.g., chest pain, shortness of breath, weakness, speech disorders), which can occur suddenly. In case of such symptoms, it is recommended to seek medical attention immediately.

Appropriate medical supervision and consultation are required for patients with hypertension and/or congestive heart failure of mild or moderate degree in history, as fluid retention and edema have been observed during the use of NSAIDs.

Hematological manifestations.

During long-term treatment with diclofenac, it is recommended to monitor blood counts with determination of formed elements. Diclofenac can reversibly inhibit platelet aggregation. Patients with hemostasis disorders, hemorrhagic diathesis, or hematological abnormalities require close supervision.

Respiratory manifestations.

In patients with asthma, seasonal allergic rhinitis, nasal mucosa swelling (e.g., nasal polyps), chronic obstructive lung diseases, or chronic respiratory tract infections (especially if there is a connection with symptoms similar to allergic rhinitis), reactions to NSAIDs similar to asthma exacerbations (so-called aspirin-induced asthma with analgesic intolerance) occur more frequently than in other patients. In this regard, special precautionary measures are recommended for such patients (readiness to provide emergency care). This also applies to patients who have allergic reactions to other substances on the skin.

Like other agents that inhibit prostaglandin synthetase activity, diclofenac can cause bronchospasm when prescribed to patients with asthma (including in history).

Female fertility.

There is evidence that the use of NSAIDs may have a negative impact on female fertility, and therefore, drugs of this group are not recommended for women who plan to become pregnant or patients who suffer from infertility.

Use during pregnancy or breastfeeding.

Pregnancy

Starting from the 20th week of pregnancy, the use of Diclac⁺ID may cause oligohydramnios due to fetal kidney dysfunction. This can occur soon after the start of treatment and is usually reversible after discontinuation of treatment. In addition, there have been reports of narrowing of the arterial duct after treatment in the second trimester of pregnancy, most of which passed after discontinuation of treatment. Therefore, during the first and second trimesters of pregnancy, Diclac⁺ID should not be prescribed unless necessary. If Diclac⁺ID is used in a woman who is trying to become pregnant or during the first and second trimesters of pregnancy, the dose should be as low as possible, and the duration of treatment should be as short as possible. Prenatal monitoring of oligohydramnios and narrowing of the arterial duct should be considered after exposure to Diclac⁺ID for several days, starting from the 20th week of gestation. The use of the drug Diclac⁺ID should be discontinued if oligohydramnios or narrowing of the arterial duct is detected.

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

Risks to the fetus:

- cardiopulmonary toxicity (with premature narrowing/closure of the arterial duct and pulmonary hypertension);

- renal dysfunction (see above);

Risks to the mother at the end of pregnancy and to the newborn:

- possible prolongation of bleeding time, anti-aggregatory effect, which can occur even at very low doses;

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

Therefore, Diclac⁺ID is contraindicated during the third trimester of pregnancy.

Breastfeeding

Like other NSAIDs, diclofenac passes into breast milk in small amounts, so the drug is contraindicated during breastfeeding.

Female fertility

Like other NSAIDs, diclofenac may affect female fertility, and therefore, it is not recommended for women who plan to become pregnant. It is recommended to consider discontinuing the use of diclofenac in women who cannot become pregnant, as well as in women who are undergoing infertility testing.

Ability to affect the reaction rate when driving vehicles or operating other mechanisms.

Patients who experience dizziness, vertigo, drowsiness, fatigue, or CNS disorders, including vision disorders, during the use of the drug should not drive vehicles or operate other mechanisms.

Method of administration and dosage.

The dose of the drug is selected by the doctor individually, starting from the minimum effective dose. To minimize adverse effects, the lowest effective dose should be used for the shortest period of time to control symptoms, taking into account the treatment goals for each individual patient.

The recommended initial dose of the drug for adults is 75-150 mg per day, depending on the severity of symptoms. During long-term therapy, as a rule, the use of 1 tablet (75 mg) per day is sufficient. If the symptoms of the disease are most pronounced at night or in the morning, Diclac⁺ID should be used in the evening.

The maximum daily dose is 150 mg and should not be exceeded. Diclac⁺ID is intended for short-term use (maximum 2 weeks).

The duration of treatment is determined by the doctor.

Tablets should be swallowed whole, without chewing, with a sufficient amount of liquid, preferably during or after meals.

Children: Diclac⁺ID is not recommended for use in children.

Elderly patients: no clinically significant changes in pharmacokinetics have been observed when using the drug in elderly patients. However, such patients should use NSAIDs with caution, as they are more prone to adverse reactions. It is recommended to take the minimum effective dose in weakened elderly patients or patients with low body weight, as well as patients who require constant monitoring to detect possible gastrointestinal bleeding during the use of NSAIDs.

Patients with established cardiovascular diseases and significant risk of their development. Such patients, as well as those with uncontrolled arterial hypertension, should not be treated with diclofenac as a rule. If necessary, the drug can be prescribed only after careful evaluation of the risk-benefit ratio at a dose of ≤ 100 mg per day and a treatment duration of no more than 4 weeks.

Patients with impaired kidney function. Diclofenac is contraindicated in kidney failure. For the treatment of patients with impaired kidney function of mild or moderate degree, the drug should be used with caution.

Patients with impaired liver function. Diclofenac is contraindicated in liver failure. For the treatment of patients with impaired liver function of mild or moderate degree, the drug should be used with caution.

Children.

Diclac⁺ID is contraindicated for the treatment of children due to the high content of the active substance in the tablet.

Overdose.

There is no typical clinical picture of diclofenac overdose. Symptoms of diclofenac overdose may include headache, nausea, epigastric pain, vomiting, gastrointestinal bleeding, diarrhea, dizziness, disorientation, coma, drowsiness, excitement, tinnitus, seizures. In case of significant poisoning, acute kidney failure and liver damage are possible.

Treatment of acute NSAID poisoning consists of supportive and symptomatic therapy. Symptomatic and supportive measures are indicated for such complications as arterial hypotension, kidney failure, seizure syndrome, gastrointestinal disorders, and respiratory depression. It is unlikely that specific treatments such as forced diuresis, dialysis, or hemoperfusion will be useful for removing NSAIDs, as the active substances of these drugs are largely bound to blood proteins and undergo intensive metabolism. After taking potentially toxic doses, activated charcoal can be used, and after taking potentially life-threatening doses, gastric decontamination (induction of vomiting, gastric lavage) can be performed.

Adverse reactions.

The category of adverse reaction frequency is determined as follows: very common (> 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1000, < 1/100); rare (≥ 1/10000, < 1/1000); very rare (< 1/10000), unknown, including isolated reports.

The following adverse effects include phenomena associated with short-term and long-term use.

From the blood and lymphatic system

Very rare: thrombocytopenia, leukopenia, anemia (including hemolytic and aplastic anemia), pancytopenia, agranulocytosis.

The first signs of blood and lymphatic system disorders may be: increased temperature, sore throat, superficial ulcers in the oral cavity, flu-like symptoms, fatigue, nosebleeds, skin hemorrhages.

From the immune system:

Rare: hypersensitivity reactions, anaphylactic and anaphylactoid reactions (including arterial hypotension and shock).

Very rare: angioedema (including facial edema, tongue edema, laryngeal edema).

Psychiatric disorders

Very rare: disorientation, depression, insomnia, nightmares, irritability, psychotic disorders.

From the nervous system

Common: headache, dizziness

Uncommon: drowsiness, increased fatigue

Very rare: paresthesia, memory impairment, seizures, feelings of anxiety, tremor, aseptic meningitis, taste disorders, cerebrovascular disorders

Unknown: confusion, hallucinations, sensory disturbances, general malaise, apoplexy.

From the organs of vision

Very rare: vision disorders, blurred vision, diplopia

Unknown: optic neuritis

From the organs of hearing and balance

Common: vertigo

Very rare: tinnitus, hearing impairment

From the cardiovascular system

Uncommon: palpitations, chest pain, heart failure, myocardial infarction

Very rare: arterial hypertension, hypotension, vasculitis

Unknown: Kounis syndrome

From the respiratory system

Uncommon: bronchial asthma (including dyspnea)

Very rare: pneumonia

From the gastrointestinal tract

Common: nausea, vomiting, diarrhea, dyspepsia, abdominal pain, abdominal cramps, flatulence, loss of appetite

Uncommon: gastritis, gastrointestinal bleeding, hematemesis, hemorrhagic diarrhea, melena, stomach and intestinal ulcers with or without bleeding or perforation (sometimes with fatal outcomes, especially in elderly patients)

Very rare: colitis (including hemorrhagic colitis and exacerbation of ulcerative colitis or Crohn's disease), constipation, stomatitis (including ulcerative stomatitis), glossitis, esophageal disorders, development of diaphragm-like strictures in the intestine, pancreatitis.

From the hepatobiliary system

Common: increased transaminase activity

Uncommon: hepatitis, jaundice, liver function disorders.

Very rare: fulminant hepatitis, liver necrosis, liver failure.

From the skin and subcutaneous tissue

Common: rash

Uncommon: urticaria

Very rare: bullous rash, eczema, erythema, multiform erythema, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), exfoliative dermatitis, erythroderma, hair loss, photosensitivity reactions, purpura, allergic purpura, itching, inflammatory skin changes

From the kidneys and urinary tract

Very rare: acute kidney failure, hematuria, proteinuria, nephrotic syndrome, tubulointerstitial nephritis, papillary necrosis of the kidneys, fluid retention, edema.

From the reproductive system

Very rare: impotence.

Infectious diseases

Exacerbation of infections associated with the use of the drug (e.g., development of necrotizing fasciitis), symptoms of aseptic meningitis.

Clinical trial data 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/day) and during long-term use.

Shelf life.

3 years.

Storage conditions.

Store at a temperature not exceeding 25 °C.

Store in a place inaccessible to children.

Packaging.

10 tablets in a blister pack; 2 (10 × 2) or 10 (10 × 10) blister packs in a carton box.

Release category.

By prescription.

For tablets of 75 mg:

Manufacturer.

Salutas Pharma GmbH.

Location of the manufacturer and address of the place of business.

Otto-von-Guericke-Allee 1, 39179 Barleben, Germany.

For tablets of 150 mg:

Manufacturer.

Salutas Pharma GmbH.

(bulk production, packaging, batch release).

LEK S.A.

(packaging, batch release).

Location of manufacturers and address of the place of business.

Otto-von-Guericke-Allee 1, 39179 Barleben, Germany.

50 C, Domaniewska Street, 02-672 Warsaw, Poland.