Instructions for use Naklofen Duo capsules 75 mg blister No. 20
Composition
active ingredient: diclofenac;
1 capsule contains 75 mg of diclofenac sodium (25 mg in the form of gastro-resistant granules and 50 mg in the form of prolonged-release granules);
excipients: spherical sugar, hydroxypropyl cellulose, hypromellose, heavy magnesium carbonate, methacrylate copolymer dispersion, triethyl citrate, talc, titanium dioxide (E 171), sodium carboxymethyl cellulose, macrogol 6000, sodium hydroxide, ammonium methacrylate copolymer (type A), ammonium methacrylate copolymer (type B), indigo carmine (E 132), gelatin.
Dosage form
Capsules.
Main physicochemical properties: capsules with a white body and a blue cap, filled with white or cream-colored granules.
Pharmacotherapeutic group
Nonsteroidal anti-inflammatory and antirheumatic drugs. Diclofenac. ATC code M01A B05.
Pharmacological properties
Pharmacodynamics
Diclofenac – the active ingredient of the drug Naklofen Duo, is a non-steroidal compound with pronounced antirheumatic, antipyretic, analgesic and anti-inflammatory properties. The main mechanism of action of diclofenac, established in experimental conditions, is considered to be inhibition of prostaglandin synthesis. Prostaglandins play an important role in the genesis of inflammation, pain and fever.
In vitro, diclofenac sodium at concentrations equivalent to those achieved in the treatment of patients does not inhibit the biosynthesis of cartilage proteoglycans.
In rheumatic diseases, the anti-inflammatory and analgesic effect of Naklofen Duo leads to a significant reduction in the severity of pain (both at rest and during movement), morning stiffness, joint swelling, and thereby an improvement in the patient's functional status.
In the presence of inflammation caused by trauma or surgery, Naklofen Duo quickly eliminates both spontaneous pain and pain during movement, and also reduces inflammatory tissue swelling and edema in the surgical wound area. When used together with opioids to eliminate postoperative pain, Naklofen Duo significantly reduces the need for opioids.
Clinical studies have shown that diclofenac also has a strong analgesic effect in moderate to severe pain of non-rheumatic origin. Clinical studies have shown that diclofenac is able to eliminate pain and reduce blood loss in primary dysmenorrhea.
Pharmacokinetics
Absorption
After oral administration, diclofenac is rapidly absorbed. Absorption exceeds 90%, but due to first-pass metabolism in the liver, bioavailability is 60%. In oral forms, maximum serum concentrations are reached after 1-4 hours, depending on the type of drug.
Since diclofenac is absorbed in the duodenum and small intestine, food slows down the rate of absorption, which leads to a delay and a decrease in peak serum concentrations of the active substance. Although food intake reduces the rate of absorption, it does not reduce its extent. After repeated administration, food has no effect on serum levels of diclofenac.
Distribution
99% of diclofenac binds to blood plasma proteins, mainly albumin.
Diclofenac readily penetrates into the synovial fluid, where its concentration is 60-70% of the serum level. After 3-6 hours, the concentration of the drug and its metabolites in the synovial fluid is higher than the concentration in the serum. Diclofenac is eliminated from the synovial fluid much more slowly than from the serum.
Metabolism and excretion
The biological half-life of diclofenac is 1-2 hours. It does not change in case of minor renal or hepatic insufficiency.
Virtually all diclofenac is metabolized in the liver, mainly by hydroxylation and methoxylation. Approximately 70% of diclofenac is excreted in the urine as pharmacologically inactive metabolites. Only 1% of the drug is excreted in the unmetabolized state. The remaining metabolites are excreted in the bile and feces.
There are no significant changes in the absorption, distribution, metabolism, and excretion of diclofenac in the elderly.
Indication
Inflammatory rheumatic diseases: rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, spondyloarthritis, pain syndrome of various localization, extra-articular rheumatism;
post-traumatic and postoperative pain, inflammation and swelling;
painful and/or inflammatory conditions in gynecology (e.g. primary dysmenorrhea, adnexitis).
Naklofen Duo is also effective for migraine attacks.
Contraindication
Hypersensitivity to diclofenac or to other components of the drug.
Active gastric and/or duodenal ulcer or history of recurrent ulcer/bleeding (two or more separate episodes of established ulceration or bleeding); history of gastrointestinal bleeding or perforation related to previous treatment with nonsteroidal anti-inflammatory drugs (NSAIDs).
Severe renal (creatinine clearance <30 mL/min) or hepatic impairment (Child-Pugh class C, cirrhosis or ascites).
Third trimester of pregnancy and breastfeeding.
Children under 18 years of age.
Congestive heart failure (NYHA II-IV).
Coronary heart disease in patients with angina or previous myocardial infarction.
Cerebrovascular disease in patients who have had a stroke or have episodes of transient ischemic attacks.
Peripheral artery disease.
Uncontrolled arterial hypertension.
Treatment of perioperative pain after coronary artery bypass grafting or the use of a cardiopulmonary bypass machine.
Naklofen Duo, like other NSAIDs, is contraindicated in patients in whom attacks of bronchial asthma, angioedema, urticaria or acute rhinitis, nasal polyps and other allergic symptoms are provoked by taking ibuprofen, acetylsalicylic acid or other drugs that have the ability to inhibit prostaglandin synthetase.
Interaction with other medicinal products and other types of interactions
Below are the interactions observed with the use of Naklofen Duo and/or other pharmaceutical forms of diclofenac.
Lithium: Diclofenac may increase plasma lithium concentrations when used concomitantly. Monitoring of serum lithium levels is recommended.
Digoxin: Diclofenac may increase plasma concentrations of digoxin when used concomitantly. Monitoring of serum digoxin levels is recommended.
Diuretics and antihypertensives. As with other NSAIDs, concomitant use of diclofenac may reduce the antihypertensive effect of diuretics or antihypertensive drugs (e.g. beta-blockers, angiotensin-converting enzyme (ACE) inhibitors) by inhibiting the synthesis of vasodilatory prostaglandins. Therefore, such a combination should be used with caution and patients, especially the elderly, should be closely monitored for blood pressure. Patients should be adequately hydrated and monitoring of renal function is recommended after initiation of concomitant therapy and regularly thereafter, especially with diuretics and ACE inhibitors, due to the increased risk of nephrotoxicity.
Drugs known to cause hyperkalemia: Concomitant treatment with potassium-sparing diuretics, cyclosporine, tacrolimus, or trimethoprim may be associated with increases in serum potassium levels, and patients should be monitored more frequently.
Other NSAIDs, including selective cyclooxygenase-2 inhibitors, and corticosteroids. The concomitant use of diclofenac and other systemic NSAIDs or corticosteroids may increase the risk of gastrointestinal bleeding or ulceration. Therefore, the concomitant use of two or more NSAIDs should be avoided (see section 4.4).
Like other NSAIDs, diclofenac in high doses may temporarily inhibit platelet aggregation.
Anticoagulants and antithrombotic agents: Caution is recommended as concomitant use may increase the risk of bleeding, therefore precautions should be taken (see section "Special warnings and precautions for use").
Although clinical studies have not shown that diclofenac affects the effectiveness of anticoagulants, there is evidence of an increased risk of bleeding in patients receiving diclofenac and anticoagulants concomitantly. Therefore, careful monitoring of patients receiving diclofenac and anticoagulants is recommended and, if necessary, adjustment of the anticoagulant dosage.
Potent CYP2C9 inhibitors: Caution is recommended when administering diclofenac concomitantly with potent CYP2C9 inhibitors (e.g. voriconazole), which may lead to a significant increase in maximum plasma concentrations and exposure to diclofenac due to inhibition of diclofenac metabolism.
Antidiabetic agents. Clinical studies have shown that diclofenac can be administered concomitantly with oral antidiabetic agents without affecting the clinical effect of the latter. However, there have been isolated reports of both hypoglycaemic and hyperglycaemic reactions following the use of diclofenac, necessitating dose adjustment of the antidiabetic agent. For this reason, it is recommended to monitor blood glucose levels as a precautionary measure during combination therapy.
Phenytoin: When phenytoin is used concomitantly with diclofenac, monitoring of phenytoin plasma concentrations is recommended due to the expected increase in phenytoin exposure.
Methotrexate. Diclofenac may inhibit the renal tubular clearance of methotrexate, leading to increased methotrexate levels. NSAIDs, including diclofenac, should be used with caution when administered less than 24 hours before or after treatment with methotrexate, as methotrexate blood levels may increase and methotrexate toxicity may be enhanced. Cases of serious toxicity have been observed when methotrexate and NSAIDs, including diclofenac, were administered within 24 hours of each other. This interaction is mediated by accumulation of methotrexate as a result of impaired renal excretion in the presence of NSAIDs.
Probenecid: Medicines containing probenecid may delay the elimination of diclofenac.
Cyclosporine: Diclofenac, like other NSAIDs, may potentiate the nephrotoxicity of cyclosporine through its effects on renal prostaglandins. Therefore, the drug should be used at lower doses than in patients not receiving cyclosporine.
Tacrolimus: There is a possible increased risk of nephrotoxicity when NSAIDs are administered concomitantly with tacrolimus. This may be mediated through the mechanism of inhibition of renal prostaglandins by both the NSAID and the calcineurin inhibitor.
Quinolone antibiotics. Interactions between quinolone antibiotics and NSAIDs may lead to seizures. This may occur in patients with or without a history of epilepsy or seizures. Therefore, caution should be exercised when considering the use of quinolones in patients already receiving NSAIDs.
Cardiac glycosides. Concomitant use of cardiac glycosides and NSAIDs may exacerbate heart failure, reduce glomerular filtration rate, and increase plasma glycoside levels.
Mifepristone: NSAIDs should not be used for 8-12 days after taking mifepristone, as NSAIDs may reduce its effect.
Selective serotonin reuptake inhibitors (SSRIs).
Concomitant use of NSAIDs, including diclofenac, and SSRIs may increase the risk of gastrointestinal bleeding.
Application features
General
Undesirable effects can be minimized by using Naklofen Duo at the lowest effective dose for the shortest possible period and as needed to control (relieve) symptoms (see gastrointestinal and cardiovascular risks below).
The concomitant use of Naklofen Duo with systemic NSAIDs such as selective cyclooxygenase-2 inhibitors should be avoided due to the lack of any evidence of a synergistic effect and due to potential additive side effects. Caution is required in elderly patients. Use with caution in patients over 65 years of age. In particular, it is recommended to use the lowest effective dose in debilitated elderly patients or those with low body weight.
As with other NSAIDs, allergic reactions, including anaphylactic/anaphylactoid reactions, may occur, even without prior exposure to diclofenac. Hypersensitivity reactions may also progress to Kounis syndrome, a serious allergic reaction that may lead to myocardial infarction. Symptoms of such reactions may include chest pain associated with an allergic reaction to diclofenac.
Due to its pharmacodynamic properties, Naklofen Duo, like other NSAIDs, may mask the signs and symptoms of infection.
As with all analgesics, prolonged use of the drug for the treatment of headache may result in improvement or worsening of the condition (medication overuse headache). If the headache is due to analgesic overuse, the dose of the analgesic should not be increased, and in such cases the treatment should be discontinued. Medication overuse headache should be suspected in patients with frequent or daily attacks of headache that occur despite (or because of) regular analgesic use.
Effects on the digestive tract
Gastrointestinal bleeding, ulceration or perforation, which can be fatal, has been reported with all NSAIDs, including diclofenac, and can occur at any time during treatment with or without warning symptoms or a previous history of serious gastrointestinal events. These events are usually more severe in the elderly. If gastrointestinal bleeding or ulceration occurs in patients receiving diclofenac, the drug should be discontinued.
The risk of gastrointestinal bleeding, ulceration or perforation increases with increasing dose of NSAIDs, including diclofenac. Elderly patients have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which can be fatal. To reduce the risk of such gastrointestinal toxicity, treatment should be initiated and maintained at the lowest effective dose. For such patients, as well as those requiring concomitant use of medicinal products containing low doses of acetylsalicylic acid (ASA)/aspirin or other medicinal products that are likely to increase the risk of gastrointestinal adverse reactions, combination therapy with protective agents (e.g. proton pump inhibitors or misoprostol) should be considered.
Patients with a history of gastrointestinal toxicity, especially the elderly, should report any unusual abdominal symptoms (especially gastrointestinal bleeding). Caution is also required in patients receiving concomitant medications that may increase the risk of ulceration or bleeding, such as systemic corticosteroids, anticoagulants (e.g. warfarin), antithrombotic agents (e.g. ASA) or selective serotonin reuptake inhibitors (see section 4.5).
NSAIDs, including diclofenac, may be associated with an increased risk of gastrointestinal anastomotic leakage. Close medical supervision and caution are recommended when using diclofenac after gastrointestinal surgery.
Effect on the liver
Careful medical supervision is required when Naklofen Duo is prescribed to patients with impaired liver function, as their condition may worsen (see section "Adverse reactions").
As with other NSAIDs, including diclofenac, the level of one or more liver enzymes may increase.
In addition to elevated liver enzymes, severe hepatic reactions, including jaundice and fulminant hepatitis, hepatic necrosis and hepatic failure, some of which were fatal, have been reported rarely.
During long-term treatment with Naklofen Duo, regular monitoring of liver function and liver enzyme levels should be performed as a precautionary measure. If liver function abnormalities persist or worsen, and if clinical signs or symptoms suggestive of progressive liver disease or if other manifestations (e.g. eosinophilia, rash) occur, Naklofen Duo should be discontinued. Diseases such as hepatitis may occur without prodromal symptoms. Caution is advised when Naklofen Duo is used in patients with hepatic porphyria, as it may precipitate an attack.
Effects on the kidneys
Since cases of fluid retention and edema have been reported with NSAIDs, including diclofenac, special attention should be paid to patients with impaired cardiac or renal function, a history of hypertension, elderly patients, patients receiving concomitant therapy with diuretics or drugs that significantly affect renal function, as well as patients with a significant decrease in extracellular fluid volume for any reason, for example before or after major surgery (see section "Contraindications"). In such cases, as a precautionary measure, monitoring of renal function is recommended. Discontinuation of therapy usually leads to a return to the state that existed before treatment.
Effects on the skin
Serious skin reactions (some of which were fatal, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis) have been reported very rarely in association with the use of NSAIDs, including Naklofen Duo. Patients are at highest risk of developing these reactions at the beginning of therapy: the onset of the reaction is noted in most cases within the first month of treatment. Naklofen Duo should be discontinued at the first appearance of skin rashes, mucosal lesions or any other sign of hypersensitivity.
SLE and mixed connective tissue diseases
Patients with systemic lupus erythematosus (SLE) and mixed connective tissue diseases may be at increased risk of developing aseptic meningitis.
Cardiovascular and cerebrovascular effects
Appropriate monitoring and advice is required for patients with a history of hypertension and/or mild to moderate congestive heart failure, as fluid retention and oedema have been reported in association with the use of NSAIDs, including diclofenac.
A small increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke) may be associated with the use of diclofenac, especially at high doses (150 mg/day) and with long-term treatment.
Diclofenac should be prescribed to patients with significant risk factors for cardiovascular events (such as hypertension, hyperlipidemia, diabetes mellitus, smoking) only after careful clinical evaluation and only at a dose of ≤100 mg daily, if treatment lasts no more than four 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 patient's need for diclofenac to relieve symptoms and the response to therapy should be reviewed periodically. Patients should be alert for the appearance of serious signs and symptoms of atherothrombosis (e.g. chest pain, shortness of breath, weakness, speech disorders), which may occur at any time. Patients should be warned that in such cases they should immediately consult a doctor.
Effect on hematological parameters
With prolonged use of this drug, as with other NSAIDs, monitoring of complete blood counts is recommended.
Diclofenac may temporarily inhibit platelet aggregation. Patients with impaired hemostasis, hemorrhagic diathesis or hematological disorders should be carefully monitored.
History of asthma
Patients with asthma, seasonal allergic rhinitis, nasal mucosal edema (i.e. nasal polyps), chronic obstructive pulmonary disease or chronic respiratory tract infections (especially those associated with allergic rhinitis-like symptoms) are more likely to experience reactions to NSAIDs, such as exacerbation of asthma (so-called analgesic intolerance/analgesic asthma), angioedema or urticaria. Therefore, special precautions (emergency medical attention) are recommended for such patients. This also applies to patients with allergic reactions to other substances, such as rash, itching or urticaria.
Like other drugs that inhibit prostaglandin synthetase activity, diclofenac sodium and other NSAIDs can provoke the development of bronchospasm when used in patients suffering from bronchial asthma or in patients with a history of bronchial asthma.
Special precautions for excipients
Since Naklofen Duo contains spherical sugar, it is not recommended for use in patients with diabetes mellitus and patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency.
Use during pregnancy or breastfeeding
Pregnancy
As with other NSAIDs, diclofenac is contraindicated in the third trimester of pregnancy (possible inhibition of uterine contractions and premature closure of the ductus arteriosus). From the 20th week of pregnancy, the use of diclofenac may cause oligohydramnios due to fetal renal dysfunction. This disorder may occur shortly after the start of treatment and is usually reversible after discontinuation of treatment. In addition, there have been reports of narrowing of the ductus arteriosus after treatment in the second trimester, which in most cases disappeared after discontinuation of treatment. Therefore, during the first and second trimesters of pregnancy, diclofenac should not be administered unless clearly necessary. If diclofenac is used in the first or second trimester of pregnancy, the dose should be as low as possible and the duration of treatment as short as possible. Antenatal monitoring for oligohydramnios and narrowing of the ductus arteriosus may be advisable if exposure to diclofenac has occurred for several days from the 20th week of pregnancy. If oligohydramnios or narrowing of the ductus arteriosus is detected, the use of diclofenac should be discontinued.
Inhibition of prostaglandin synthesis may adversely affect the course of pregnancy and/or embryo/foetal development. Epidemiological data suggest an increased risk of miscarriage and/or cardiac malformations and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk of cardiovascular malformations was increased from less than 1% to approximately 1.5%.
It is possible that the risk increases with dose and duration of treatment. In animals, administration of a prostaglandin synthesis inhibitor has been shown to result in increased pre- and post-implantation loss and embryo/fetal lethality.
In addition, in animals treated with a prostaglandin synthesis inhibitor during organogenesis, an increased incidence of various malformations, including those of the cardiovascular system, was recorded. If Naklofen Duo is used by a woman attempting to conceive, or during the first and second trimesters of pregnancy, the dose of the drug should be as low as possible and the duration of treatment as short as possible.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may affect the fetus in the following ways:
cardiopulmonary toxicity (premature narrowing/closure of the ductus arteriosus and pulmonary hypertension);
renal dysfunction, which may progress to renal failure with oligohydramnios (see above);
on the mother at the end of pregnancy and the newborn:
prolongation of bleeding time, antiplatelet effect, which can be observed even at very low doses;
suppression of uterine contractions, leading to delayed or prolonged labor.
Like other NSAIDs, diclofenac passes into breast milk in small amounts. Therefore, to avoid undesirable effects on the infant, diclofenac should not be used during breastfeeding. If the use of diclofenac is absolutely necessary, the child should be transferred to artificial feeding.
Fertility in women
As with other NSAIDs, diclofenac may impair female fertility and is therefore not recommended for use in women attempting to conceive. In women who have difficulty conceiving or are undergoing investigation of infertility, discontinuation of the drug should be considered.
Ability to influence reaction speed when driving vehicles or other mechanisms
Patients who experience visual disturbances, dizziness, vertigo, drowsiness, central nervous system disorders, lethargy or fatigue during therapy with Naklofen Duo should not drive or operate complex machinery.
Method of administration and doses
The recommended initial dose of the drug for adults is 75-150 mg per day (1-2 capsules), depending on the severity of the symptoms of the disease.
For long-term therapy, as a rule, it is sufficient to use 1 capsule of the drug Naklofen Duo.
per day. If the symptoms of the disease are most pronounced during the night or in the morning, the drug Naklofen Duo should be used in the evening.
The capsules should be swallowed whole with a small amount of liquid, during or immediately after a meal.
The drug should be used in the lowest effective doses for the shortest period of time, taking into account the treatment regimen of each individual patient (see section "Special instructions").
Children
Naklofen Duo capsules should not be used in children due to the high content of the active substance in the capsule.
Overdose
Symptoms. 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, agitation, tinnitus, convulsions. In case of significant poisoning, acute renal failure and liver damage are possible.
Treatment. Treatment of acute NSAID poisoning consists of supportive and symptomatic therapy. Supportive and symptomatic treatment is indicated for complications such as hypotension, renal failure, convulsions, gastrointestinal disturbances, and respiratory depression. Forced diuresis, hemodialysis, or hemoperfusion are unlikely to be useful in removing NSAIDs because the active substances of these drugs are highly bound to plasma proteins and are extensively metabolized.
Activated charcoal should be considered within 1 hour of ingestion of a potentially toxic amount of the drug. In addition, gastric lavage should be considered in adults within 1 hour of ingestion of a potentially toxic amount of the drug. Diazepam should be administered intravenously if seizures are frequent or prolonged. Other measures may be indicated depending on the clinical condition of the patient. Treatment is symptomatic.
Side effects
Side effects that may occur when taking diclofenac are classified into the following groups according to their frequency:
very often ≥ 1/10;
common ≥ 1/100, < 1/10;
uncommon ≥ 1/1000, <1/100;
rare ≥ 1/10,000, < 1/1,000;
very rarely < 1/10,000, including isolated cases;
frequency unknown (cannot be estimated from available data).
The following undesirable effects include those reported with short-term or long-term use of the drug.
Blood and lymphatic system disorders: very rarely - thrombocytopenia, leukopenia, anemia (including hemolytic anemia and aplastic anemia), agranulocytosis.
Immune system disorders: Rare: hypersensitivity, anaphylactic and anaphylactoid reactions (including hypotension and shock); very rare: angioedema (including facial edema).
Mental disorders: very rarely - disorientation, depression, insomnia, irritability, nightmares, psychotic disorders.
From the nervous system: often - headache, dizziness; rarely - drowsiness, very rarely - paresthesia, memory impairment, convulsions, anxiety, tremor, aseptic meningitis, taste disorders, stroke; frequency unknown - confusion, hallucinations, sensory disturbances, general malaise.
On the part of the organs of vision: very rarely - visual disturbances, blurred vision, diplopia; frequency unknown - optic neuritis.
From the side of the organs of hearing and labyrinth: often - vertigo; very rarely - tinnitus, hearing disorders.
Cardiovascular system: very rarely - palpitations, chest pain, heart failure, myocardial infarction, hypertension, hypotension, vasculitis, frequency unknown - Kounis syndrome.
Gastrointestinal: often - nausea, vomiting, diarrhea, dyspepsia, abdominal pain, flatulence, anorexia; rarely - gastritis, gastrointestinal bleeding (hemorrhage, melena, diarrhea with blood), gastric and intestinal ulcers, accompanied or not accompanied by bleeding or perforation (sometimes fatal, especially in elderly patients), loss of appetite; very rarely - colitis (including hemorrhagic colitis and exacerbation of ulcerative colitis or Crohn's disease), constipation, stomatitis (including ulcerative stomatitis), glossitis, esophageal dysfunction, membrane strictures, pancreatitis;
From the hepatobiliary system: often - increased transaminase levels; rarely - hepatitis, jaundice, liver disorders; very rarely - fulminant hepatitis, liver necrosis, liver failure.
Skin and subcutaneous tissue disorders: common: rash; rare: urticaria; very rare: blistering rash, eczema, erythema, erythema multiforme, Stevens-Johnson syndrome, Lyell's syndrome (toxic epidermal necrolysis), exfoliative dermatitis, hair loss, photosensitivity reactions, purpura, including allergic, pruritus.
From the kidneys and urinary system: very rarely - acute renal failure, hematuria, proteinuria, interstitial nephritis, nephrotic syndrome, papillary renal necrosis.
General disorders: rarely - edema, fatigue.
From the reproductive system and mammary glands: very rarely - impotence.
Clinical trial data and epidemiological data suggest an increased risk of thrombotic complications (e.g. myocardial infarction or stroke) associated with the use of diclofenac, particularly at high therapeutic doses (150 mg per day) and with long-term use.
If severe side effects occur, treatment should be discontinued.
Expiration date
3 years.
Storage conditions
Store below 30°C in the original packaging to protect from moisture. Keep out of the reach of children.
Packaging
10 capsules in a blister; 2 blisters in a cardboard box.
Vacation category
According to the recipe.
Producer
KRKA, dd, Novo mesto/КРKA, dd, Novo mesto.
Address
Smarjeska cesta 6, 8501 Novo mesto, Slovenia.
