INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT DICLAC®ID

Composition:

Active substance: diclofenac;

1 tablet contains diclofenac sodium 75 mg or 150 mg;

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

Pharmaceutical form. Modified-release tablets.

Main physicochemical properties: bilayer tablets of white-pink color, round, flat, with bevelled edges and smooth surface; the pink layer may contain white specks.

Pharmacotherapeutic group.

Non-steroidal anti-inflammatory and antirheumatic agents. ATC code M01A B05.

Pharmacological properties.

Pharmacodynamics.

Diclofenac is a non-steroidal compound with pronounced anti-rheumatic, antipyretic, analgesic, and anti-inflammatory properties. Its mechanism of action is due to inhibition of the biosynthesis of prostaglandins, kinins, and other mediators of inflammation and pain, reduction of capillary permeability, and stabilizing effects 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 proteoglycan biosynthesis in cartilage tissue.

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

In cases of inflammation caused by injury or surgical intervention, Diclac® ID rapidly relieves both spontaneous pain and pain on movement, as well as reduces inflammatory tissue edema and swelling at the surgical site. When used concomitantly with opioids for postoperative pain relief, Diclac® ID significantly reduces the need for opioids.

Clinical studies have shown that Diclac® ID also exhibits strong analgesic effects in moderate to severe non-rheumatic pain.

Pharmacokinetics.

Diclac® ID tablets are bilayer tablets combining rapid release (1/6 of the total amount) and gradual release (5/6 of the total amount) of sodium diclofenac. This combination of effects in a single tablet ensures both a rapid onset of action and prolonged circulation of the active substance in systemic circulation, providing a therapeutic effect throughout the day.

After oral administration, diclofenac is completely absorbed, and depending on gastric transit time, maximum plasma concentration is reached within 1–16 hours, on average within 2–3 hours. The amount of absorbed active substance is linearly dependent on the dose of the drug. Approximately half of diclofenac undergoes metabolism during its first pass through the liver. Only 35–70% of the absorbed active substance reaches the posthepatic circulation unchanged. About 30% of the active substance is metabolized and excreted in feces. Approximately 70% is eliminated by the kidneys as pharmacologically inactive metabolites. The elimination half-life is approximately 2 hours and is independent of hepatic and renal function. Plasma protein binding is approximately 99%.

Clinical characteristics.

Indications.

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

Joint disorders: rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, acute gout attacks;
Acute musculoskeletal disorders such as periarticular inflammation (e.g., periarthritis of the shoulder), tendinitis, tenosynovitis, bursitis;
Other pathological conditions caused by trauma, including fractures, low back pain, sprains, dislocations, orthopedic, dental, and other minor surgical procedures.

Contraindications.

Hypersensitivity to the active substance or to any other component of the medicinal product.
Active gastric or intestinal ulcer; gastrointestinal bleeding or perforation, gastrointestinal hemorrhage or perforation in history following use of nonsteroidal anti-inflammatory drugs (NSAIDs), active or recurrent gastric or intestinal ulcer in history (two or more distinct episodes of confirmed ulcer or bleeding in history).
Diclofenac, like other NSAIDs, is contraindicated in patients who develop angioedema, nasal polyps, bronchial asthma attacks, urticaria, acute rhinitis, or other allergic symptoms in response to administration of acetylsalicylic acid or other NSAIDs.
Hematopoietic disorders of unknown origin.
Cerebrovascular hemorrhage or hemorrhage of any type.
Inflammatory bowel diseases (Crohn's disease or ulcerative colitis).
Hepatic failure.
Renal failure.
Congestive heart failure (NYHA II–IV).
Ischemic heart disease in patients with angina pectoris or history of myocardial infarction.
Peripheral arterial disease.
Cerebrovascular diseases in patients with history of stroke or transient ischemic attacks.
Treatment of perioperative pain in coronary artery bypass grafting (CABG) (or use of cardiopulmonary bypass).
Postoperative pain treatment following coronary artery bypass surgery (or use of cardiopulmonary bypass equipment).

Interaction with other medicinal products and other forms of interaction.

The interactions listed below have been observed during administration of enteric-coated diclofenac tablets and/or other diclofenac formulations.

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

Digoxin. Plasma digoxin concentrations may increase when used concomitantly with diclofenac. Monitoring of plasma digoxin levels is recommended.

Diuretics and antihypertensive agents. As with other NSAIDs, concomitant use of Diclac® ID may attenuate the antihypertensive effect of diuretics or antihypertensive agents (e.g., beta-blockers, angiotensin-converting enzyme (ACE) inhibitors) due to inhibition of vasodilatory prostaglandin synthesis. Therefore, such combinations should be used with caution; patients, especially elderly, should have regular blood pressure monitoring. Adequate hydration should be ensured, and renal function should be assessed at the start of combined therapy and monitored regularly thereafter, particularly due to the increased risk of nephrotoxicity associated with diuretics and ACE inhibitors.

Anticoagulants and antithrombotic agents. Should be prescribed with caution, as concomitant use may increase the risk of bleeding.

Close monitoring is recommended in patients receiving diclofenac concomitantly with anticoagulants, and dosage adjustment of anticoagulants may be necessary. Like other NSAIDs, diclofenac at high doses may reversibly inhibit platelet aggregation.

Other NSAIDs, including selective cyclooxygenase-2 (COX-2) inhibitors, and corticosteroids. Concomitant use of diclofenac with other systemic NSAIDs or corticosteroids may increase the risk of gastrointestinal ulceration or bleeding. Concomitant use of two or more NSAIDs should be avoided. Concomitant use of diclofenac and corticosteroids may increase the frequency of adverse reactions.

Antidiabetic agents. Isolated reports of both hypoglycemic and hyperglycemic reactions have been reported following diclofenac administration, necessitating dose adjustment of antidiabetic agents. Therefore, blood glucose monitoring is recommended as a precaution during combined therapy.

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

Methotrexate. Diclofenac may inhibit tubular renal clearance of methotrexate, thereby increasing methotrexate levels. NSAIDs, including diclofenac, should be used with caution when administered less than 24 hours before methotrexate treatment, as plasma methotrexate levels and its toxicity may increase.

Serious cases of toxicity have been reported when methotrexate and NSAIDs, including diclofenac, were administered with an interval of less than 24 hours. This interaction is mediated by methotrexate accumulation 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. Therefore, the drug should be administered at lower doses than in patients not receiving cyclosporine.

Tacrolimus. The risk of nephrotoxicity may increase if NSAIDs are administered concomitantly with tacrolimus.

Quinolone antibiotics. Seizures may occur due to interaction between quinolone antibiotics and NSAIDs. This may occur both in patients with epilepsy or history of seizures and in those without such history. Therefore, quinolone antibiotics should be used with caution in patients already receiving NSAIDs.

Phenytoin. Plasma phenytoin concentrations should be monitored when phenytoin and diclofenac are used concomitantly, considering the expected increase in phenytoin exposure.

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

Cardiac glycosides. Concomitant use of cardiac glycosides and NSAIDs in patients may promote worsening of heart failure, reduced glomerular filtration rate, and increased plasma glycoside concentration.

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

Strong CYP2C9 inhibitors. Diclofenac should be used with caution when administered concomitantly with strong CYP2C9 inhibitors (e.g., sulfaphenazole and voriconazole), which may lead to a significant increase in maximum plasma concentration and exposure of diclofenac due to inhibition of its metabolism.

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

Agents whose use may lead to hyperkalemia. Concomitant use of potassium-sparing diuretics, cyclosporine, tacrolimus, or trimethoprim may lead to increased serum potassium levels, which should be monitored.

Special precautions for use.

To reduce the risk of adverse reactions, treatment should be initiated at the lowest effective dose and administered for the shortest duration necessary to control symptoms.

General. Concomitant use of diclofenac and other systemic NSAIDs, including selective COX-2 inhibitors, should be avoided due to lack of evidence for synergistic effect and potential for additive adverse effects.

Treatment should be prescribed with caution in patients over 65 years of age, in accordance with recommendations for this patient group. In particular, the use of the lowest effective dose is recommended in elderly frail patients or those with low body weight.

Oral dosage forms containing rapidly released diclofenac may increase gastrointestinal intolerance to the drug.

Allergic reactions, including anaphylactic/anaphylactoid reactions, may rarely occur during treatment with diclofenac, as with other NSAIDs, even upon first administration.

Hypersensitivity reactions may progress to Kounis syndrome—serious allergic reactions that may lead to myocardial infarction. Symptoms include chest pain in combination with allergic reactions to diclofenac.

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

Prolonged use of analgesics may lead to medication-overuse headache. Such headaches should not be treated with higher doses of diclofenac.

Alcohol consumption during treatment with NSAIDs, including diclofenac, may exacerbate adverse reactions affecting the gastrointestinal tract (GIT) or central nervous system (CNS).

Since Diclac® ID contains lactose, it is not recommended for patients with hereditary conditions associated with galactose intolerance, glucose-galactose malabsorption, or lactase deficiency.

The patient’s need for diclofenac to relieve symptoms and response to therapy should be periodically reviewed. Use with caution in patients aged 65 years and older.

Gastrointestinal effects. Gastrointestinal bleeding (hematemesis, melena), ulceration, or perforation have been reported with NSAIDs, including diclofenac, and may be fatal. These events may occur at any time during treatment, with or without preceding symptoms, and may occur in patients with or without a history of serious gastrointestinal disorders. Such complications are usually more severe in elderly patients. If gastrointestinal bleeding or ulceration occurs, the drug should be discontinued.

Careful medical monitoring and special caution are required when prescribing diclofenac to patients with symptoms suggesting gastrointestinal involvement or suspected ulcer, bleeding, or perforation of the stomach or intestine. The risk of these events increases with higher NSAID doses and in patients with a history of peptic ulcer, particularly if complicated by bleeding or perforation.

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

To reduce the risk of gastrointestinal adverse events, treatment should be initiated at the lowest effective dose, which should be maintained.

Consideration should be given to combination therapy with protective agents (e.g., misoprostol or proton pump inhibitors) in such patients, as well as in those requiring concomitant low-dose acetylsalicylic acid/aspirin or other drugs that may increase gastrointestinal risk.

Caution is advised when co-administering drugs that may increase the risk of ulceration or bleeding, such as systemic corticosteroids, anticoagulants (e.g., warfarin), SSRIs, and antiplatelet agents (e.g., acetylsalicylic acid).

Use of NSAIDs, including diclofenac, may be associated with an increased risk of gastrointestinal anastomotic dehiscence. Close monitoring and caution are recommended when using diclofenac after gastrointestinal surgery.

Hepatic effects. Careful medical monitoring is required when prescribing the drug to patients with hepatic impairment, as their condition may worsen.

During NSAID use, including diclofenac, levels of one or more liver enzymes may increase. As a precaution, regular monitoring of liver function is recommended during long-term diclofenac therapy.

If changes in liver function tests persist or worsen, or if clinical signs or symptoms of liver disease or other manifestations (e.g., eosinophilia, rash) appear, the drug should be discontinued.

Hepatitis without prodromal symptoms may occur during diclofenac treatment.

Diclac® ID should be prescribed only after careful risk-benefit assessment in patients with inherited porphyrin metabolism disorders, as it may trigger an acute attack.

Renal effects. Since fluid retention and edema have been observed during NSAID use, particular caution is required in patients with impaired cardiac or renal function, a history of arterial hypertension, elderly patients, those receiving concomitant diuretic therapy or drugs that may significantly affect renal function, and patients with substantial extracellular fluid volume depletion due to any cause (e.g., before or after surgery). In such cases, monitoring of renal function is recommended as a precautionary measure. After discontinuation of therapy, patients’ condition usually returns to normal.

Generally, chronic use of analgesics, especially in combination with multiple painkillers, may lead to chronic kidney damage with risk of renal failure (analgesic nephropathy).

Skin effects. Serious skin reactions (some with fatal outcomes), including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported rarely during diclofenac use. The highest risk occurs early in therapy, with most cases developing within the first month of treatment. Patients with allergic reactions to other substances require particularly close monitoring. The drug should be discontinued at the first signs of hypersensitivity.

Systemic lupus erythematosus and mixed connective tissue diseases. Patients with systemic lupus erythematosus and mixed connective tissue diseases (collagenoses) may have an increased risk of aseptic meningitis.

Cardiovascular and cerebrovascular effects. There is an increased risk of thrombotic cardiovascular and cerebrovascular complications (including myocardial infarction and stroke) associated with NSAID use, including diclofenac, particularly with long-term, high-dose treatment.

Diclofenac may be prescribed to such patients and to those with significant cardiovascular risk factors (e.g., hypertension, hyperlipidemia, diabetes, smoking) only after careful clinical evaluation at daily doses ≤ 100 mg if treatment lasts longer than 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 dose should be periodically reviewed, especially if treatment exceeds 4 weeks.

Diclofenac therapy is generally not recommended for patients with established cardiovascular disease (NYHA II-IV heart failure, ischemic heart disease, peripheral arterial disease) or uncontrolled arterial hypertension.

Patients should be informed about signs and symptoms of serious cardiovascular thrombotic complications (e.g., chest pain, dyspnea, weakness, speech disturbances), which may occur suddenly. Immediate medical attention should be sought if such symptoms occur.

Appropriate medical monitoring and consultation are required for patients with hypertension and/or mild to moderate heart failure, as fluid retention and edema have been observed during NSAID use.

Hematological effects. Blood parameters, including counts of formed elements, should be monitored during long-term diclofenac therapy. Diclofenac may reversibly inhibit platelet aggregation. Patients with coagulation disorders, hemorrhagic diathesis, or hematological abnormalities require careful monitoring.

Respiratory effects. In patients with asthma, seasonal allergic rhinitis, nasal mucosal edema (e.g., nasal polyps), chronic obstructive lung diseases, or chronic respiratory tract infections (especially if associated with symptoms resembling allergic rhinitis), reactions to NSAIDs resembling asthma exacerbations (so-called aspirin-induced asthma with analgesic intolerance), Quincke’s edema, and urticaria occur more frequently than in other patients. Therefore, special precautionary measures (readiness for emergency intervention) are recommended for such patients. This also applies to patients with allergic skin reactions to other substances.

Like other drugs that inhibit prostaglandin synthetase activity, diclofenac may cause bronchospasm when administered to patients with asthma (including those with a history of asthma).

Female fertility. Data suggest that NSAID use may negatively affect female fertility; therefore, drugs of this class are not recommended for women planning pregnancy or those with infertility.

Use during pregnancy or breastfeeding.

Pregnancy

From the 20th week of pregnancy, use of Diclac® ID may cause oligohydramnios due to fetal renal dysfunction. This may occur soon after starting treatment and is usually reversible upon discontinuation. Additionally, there are reports of arterial duct constriction after second-trimester treatment, most of which resolved after stopping treatment. Therefore, Diclac® ID should not be prescribed during the first and second trimesters unless clearly necessary. If Diclac® ID is used by a woman attempting to conceive or during the first or second trimester of pregnancy, the dose should be as low as possible and the duration of treatment as short as possible. Prenatal monitoring for oligohydramnios and arterial duct constriction should be considered after exposure to Diclac® ID for several days starting from the 20th gestational week. Diclac® ID should be discontinued if oligohydramnios or arterial duct constriction is detected.

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

Risks to the fetus:

cardiopulmonary toxicity (premature constriction/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, antiaggregatory effect, which may 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; therefore, this drug is contraindicated during breastfeeding.

Female fertility

Like other NSAIDs, diclofenac may affect female fertility and is therefore not recommended for women planning pregnancy. Consideration should be given to discontinuing diclofenac in women who are unable to conceive and in those undergoing infertility evaluation.

Ability to influence reaction speed when driving or operating machinery.

Patients who experience dizziness, vertigo, somnolence, lethargy, fatigue, or CNS disturbances, including visual disturbances, while taking the drug should not drive or operate machinery.

Dosage and Administration

The dosage of the drug is individually adjusted by a physician, starting with the lowest effective dose. To minimize adverse effects, the smallest effective dose should be used for the shortest duration necessary to control symptoms, taking into account the individual treatment goals for each patient.

The recommended initial dose for adults is 75–150 mg daily, depending on the severity of disease symptoms. In long-term therapy, usually 1 tablet (75 mg) daily is sufficient. If disease symptoms are most pronounced at night or in the morning, Diclac® ID should be administered in the evening.

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

The duration of treatment is determined by the physician.

Tablets should be swallowed whole, without chewing, with sufficient fluid, 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 the drug is administered to elderly patients. However, NSAIDs should be used with particular caution in this population, as they are more prone to adverse reactions. It is recommended to use the lowest effective dose in elderly patients or those with low body weight, and to ensure close monitoring for possible gastrointestinal bleeding during NSAID therapy.

Patients with established cardiovascular diseases or a high risk of their development: Treatment with diclofenac is generally not recommended in such patients, as well as in patients with uncontrolled arterial hypertension. If necessary, the drug may be prescribed only after careful assessment of the risk-benefit ratio, at a dose of ≤ 100 mg daily and for a treatment duration not exceeding 4 weeks.

Patients with renal impairment: Diclofenac is contraindicated in renal failure. The drug should be used with caution in patients with mild to moderate renal dysfunction.

Patients with hepatic impairment: Diclofenac is contraindicated in hepatic failure. The drug should be used with caution in patients with mild to moderate hepatic dysfunction.

Children

Diclac® ID is contraindicated for use in children due to the high content of active substance per tablet.

Overdose

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

Treatment of acute NSAID poisoning involves supportive and symptomatic therapy. Supportive and symptomatic measures are indicated for complications such as arterial hypotension, renal failure, seizure syndrome, gastrointestinal disturbances, and respiratory depression. Specific interventions such as forced diuresis, dialysis, or hemoperfusion are unlikely to be beneficial in removing NSAIDs due to the high degree of protein binding and extensive metabolism of these drugs. After ingestion of potentially toxic doses, activated charcoal may be administered. After ingestion of potentially life-threatening doses, gastric decontamination (induced emesis, gastric lavage) should be performed.

Adverse Reactions

The frequency category of adverse reactions is defined as follows: very common (> 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1000, < 1/100); rare (≥ 1/10,000, < 1/1000); very rare (< 1/10,000); not known, including isolated case reports.

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

Blood and lymphatic system disorders

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

Initial signs of blood and lymphatic system disorders may include: fever, sore throat, oral ulcers, influenza-like symptoms, fatigue, nosebleeds, skin bruising.

Immune system disorders

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

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

Psychiatric disorders

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

Nervous system disorders

Common: headache, dizziness

Uncommon: somnolence, increased fatigue

Very rare: paraesthesia, memory impairment, convulsions, anxiety, tremor, aseptic meningitis, taste disturbances, cerebral circulation disorders

Not known: confusion, hallucinations, sensory disturbances, malaise, apoplexy.

Eye disorders

Very rare: visual disturbances, blurred vision, diplopia

Not known: optic neuritis

Ear and labyrinth disorders

Common: vertigo

Very rare: tinnitus, hearing impairment

Cardiovascular system disorders

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

Very rare: arterial hypertension, hypotension, vasculitis

Not known: Kounis syndrome

Respiratory system disorders

Uncommon: bronchial asthma (including dyspnea)

Very rare: pneumonitis

Gastrointestinal disorders

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

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

Very rare: colitis (including hemorrhagic colitis, 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.

Hepatobiliary disorders

Common: increased transaminase activity

Uncommon: hepatitis, jaundice, liver function abnormalities

Very rare: fulminant hepatitis, liver necrosis, liver failure

Skin and subcutaneous tissue disorders

Common: rash

Uncommon: urticaria

Very rare: bullous rash, eczema, erythema, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome), exfoliative dermatitis, erythroderma, alopecia, photosensitivity reactions, purpura, allergic purpura, pruritus, inflammatory skin reactions

Renal and urinary disorders

Very rare: acute renal failure, hematuria, proteinuria, nephrotic syndrome, tubulointerstitial nephritis, renal papillary necrosis, fluid retention, edema.

Reproductive system disorders

Very rare: impotence.

Infections and infestations

Exacerbation of infection-related inflammation (e.g., development of necrotizing fasciitis), symptoms of aseptic meningitis.

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/day) and with prolonged use.

Shelf life. 3 years.

Storage conditions.

Store at a temperature not exceeding 25 °C.

Keep out of reach and sight of children.

Packaging.

10 tablets per blister; 2 (10 × 2) or 10 (10 × 10) blisters per cardboard box.

Prescription status. Prescription only.

For 75 mg tablets:

Manufacturer.

Salutas Pharma GmbH.

Manufacturer's address.

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

For 150 mg tablets:

Manufacturer.

Salutas Pharma GmbH.

(bulk production, packaging, batch release).

LEK S.A.

(packaging, batch release).

Manufacturers' addresses.