Instructions Voltaren gastro-resistant tablets 50 mg No. 20
Composition
active ingredient: diclofenac sodium;
1 gastro-resistant tablet contains diclofenac sodium 25 mg or 50 mg;
excipients:
tablet core 25 and 50 mg: colloidal anhydrous silica; microcrystalline cellulose; lactose monohydrate; magnesium stearate; corn starch; povidone K 30; sodium starch glycolate (type A);
Tablet coating (sub-coating and color) 25 mg:
hypromellose (hydroxypropylmethylcellulose); polyethoxylated castor oil, hydrogenated; iron oxide yellow (E 172); talc; titanium dioxide (E 171);
enteric coating: methacrylate copolymer (type A), polyethylene glycol 8000/ macrogol 8000, silicone antifoam emulsion SE 2/ simethicone, talc;
Tablet coating (sub-coating and color) 50 mg:
hypromellose (hydroxypropylmethylcellulose); polyethoxylated castor oil, hydrogenated; iron oxide yellow (E 172); iron oxide red (E 172); talc; titanium dioxide (E 171);
enteric coating: methacrylate copolymer (type A), polyethylene glycol 8000/ macrogol 8000, silicone antifoam emulsion SE 2/ simethicone, talc.
Dosage form
Gastro-resistant tablets.
Main physicochemical properties:
25 mg: yellow, round, biconvex tablets with beveled edges, embossed with “CG” on one side of the tablet, “BZ” on the other;
50 mg: light brown, round, biconvex tablets with beveled edges, embossed with “CG” on one side of the tablet and “GT” on the other.
Pharmacotherapeutic group
Nonsteroidal anti-inflammatory and antirheumatic drugs.
Acetic acid derivatives and related compounds. Diclofenac. ATC code M01A B05.
Pharmacological properties
Pharmacodynamics.
Voltaren® contains diclofenac sodium, a substance with a non-steroidal structure that has a pronounced analgesic and anti-inflammatory effect.
It is an inhibitor of prostaglandin synthetase (cyclooxygenase).
In vitro, diclofenac sodium at concentrations equivalent to those achieved in the treatment of patients does not inhibit the biosynthesis of cartilage proteoglycans.
Pharmacokinetics.
Absorption
Although absorption is complete, the onset of action may be delayed as a result of gastric transit, which may be affected by food, which delays gastric emptying. Mean peak plasma concentrations of 1.48 ± 0.65 μg/ml (1.5 μg/ml ≡ 5 μmol/l) are reached on average 2 hours after administration of a 50 mg tablet.
Bioavailability
About half of the administered diclofenac is metabolized during the first passage through the liver (first-pass effect); the area under the concentration curve (AUC) after oral administration is approximately half of the value obtained with an equivalent parenteral dose.
The pharmacokinetic characteristics of the drug do not change with repeated administration. Accumulation does not occur if the recommended dosage is observed.
Plasma concentrations in children receiving equivalent doses (mg/kg body weight) are similar to those observed in adults (25 mg tablets only).
Distribution
The binding of diclofenac to serum proteins is 99.7%, and to albumin – 99.4%.
Diclofenac penetrates into the synovial fluid, where its maximum concentration is reached 2-4 hours later than in the blood plasma. The half-life from the synovial fluid is 3-6 hours. 2 hours after reaching the maximum concentration in the plasma, the concentration of diclofenac in the synovial fluid remains higher; this phenomenon is observed for 12 hours.
Diclofenac was detected in low concentrations (100 ng/ml) in the breast milk of one woman. The estimated amount of drug reaching the infant through breast milk is equivalent to a dose of 0.03 mg/kg/day.
Metabolism.
Diclofenac is metabolized partly by glucuronidation of the unchanged molecule, but mainly by single and multiple hydroxylation and methoxylation, leading to the formation of several phenolic metabolites, most of which form conjugates with glucuronic acid. Two of these phenolic metabolites are biologically active, but much less so than diclofenac.
Breeding
The total systemic clearance of diclofenac from plasma is 263 ± 56 ml/min (mean ± SD). The terminal half-life from plasma is 1–2 hours. The half-life from plasma of four metabolites, including two pharmacologically active ones, is also short and is 1–3 hours. About 60% of the administered dose of the drug is excreted in the urine as a glucuronide conjugate of the intact molecule and as metabolites, most of which are also converted to glucuronide conjugates. Less than 1% of diclofenac is excreted unchanged. The remainder of the administered dose of the drug is excreted as metabolites in the feces.
Certain patient groups
Patients with renal impairment. In patients with renal impairment receiving therapeutic doses, accumulation of unchanged active substance is not expected, given the kinetics of the drug after a single dose. In patients with creatinine clearance less than 10 ml/min, the estimated steady-state plasma concentrations of hydroxylated metabolites were approximately 4-fold higher than in healthy volunteers. However, all metabolites were ultimately excreted in the bile.
Patients with liver disease. In patients with chronic hepatitis or compensated cirrhosis of the liver, the pharmacokinetics and metabolism of diclofenac are similar to those in patients without liver disease.
Indication
Inflammatory and degenerative forms of rheumatic diseases (rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, spondyloarthritis);
pain syndromes in the spine;
rheumatic diseases of extra-articular soft tissues;
acute attacks of gout;
post-traumatic and postoperative pain syndromes accompanied by inflammation and swelling, for example, after dental and orthopedic interventions;
gynecological diseases accompanied by pain and inflammation, such as primary dysmenorrhea or adnexitis;
as an adjuvant for severe inflammatory diseases of the ENT organs, which are accompanied by pain, for example, with pharyngotonsillitis, otitis.
According to general therapeutic principles, the underlying disease should be treated with basic therapy. Fever alone is not an indication for the use of the drug.
Contraindication
Hypersensitivity to the active substance or to any other component of the drug.
Acute stomach or intestinal ulcer; gastrointestinal bleeding or perforation.
History of gastrointestinal bleeding or perforation related to previous treatment with nonsteroidal anti-inflammatory drugs (NSAIDs).
Active gastric or duodenal peptic ulcer/bleeding or history of recurrent peptic ulcer/bleeding (two or more separate episodes of established ulceration or bleeding).
The last trimester of pregnancy.
Inflammatory bowel diseases (such as Crohn's disease or ulcerative colitis).
Liver failure.
Renal failure (glomerular filtration rate < 15 ml/min/1.73 m2).
Congestive heart failure (NYHA II–IV).
Treatment of perioperative pain in coronary artery bypass grafting (or the use of a cardiopulmonary bypass machine).
Coronary heart disease in patients who have angina or have had a myocardial infarction.
Cerebrovascular disease in patients who have had a stroke or have episodes of transient ischemic attacks.
Peripheral artery disease.
Voltaren®, like other nonsteroidal anti-inflammatory drugs, is contraindicated in patients who develop attacks of bronchial asthma, angioedema, urticaria or acute rhinitis, nasal polyps and other allergic symptoms in response to the use of ibuprofen, acetylsalicylic acid or other NSAIDs.
Interaction with other medicinal products and other types of interactions
The interactions observed with the use of diclofenac in the form of gastro-resistant tablets and/or in other dosage forms are listed below.
CYP2C9 inducers: Caution is advised when diclofenac is co-administered with CYP2C9 inducers (e.g. rifampicin). This may lead to a significant reduction in plasma concentrations and exposure to diclofenac.
CYP2C9 inhibitors: Caution is advised when co-administering diclofenac with CYP2C9 inhibitors (e.g. voriconazole). This may lead to a significant increase in maximum plasma concentrations and exposure to diclofenac.
Lithium: Diclofenac may increase plasma lithium concentrations when used concomitantly. Monitoring of serum lithium levels is recommended.
Digoxin: Diclofenac may increase the plasma concentration of digoxin when used concomitantly. Monitoring of serum digoxin levels is recommended.
Diuretics and antihypertensives. As with other NSAIDs, concomitant use of diclofenac with diuretics and antihypertensives (e.g. β-blockers, angiotensin-converting enzyme (ACE) inhibitors) may lead to a reduction in their antihypertensive effect due to inhibition of the synthesis of vasodilator prostaglandins. Therefore, such a combination should be used with caution and patients, especially the elderly, should be closely monitored for blood pressure. Patients should be adequately hydrated and monitoring of renal function is recommended after initiation of concomitant therapy and regularly thereafter, especially with diuretics and ACE inhibitors, due to the increased risk of nephrotoxicity.
Drugs causing hyperkalemia: Concomitant treatment with potassium-sparing diuretics, cyclosporine, tacrolimus or trimethoprim may be associated with increases in serum potassium, therefore patients should be monitored more frequently.
Quinolone antibacterials. Convulsions may occur in patients receiving concomitant quinolones and NSAIDs. This may occur in patients with or without a history of epilepsy and seizures. Therefore, caution should be exercised when considering the use of a quinolone in patients already receiving NSAIDs.
Other NSAIDs, including selective cyclooxygenase-2 inhibitors, and corticosteroids. Concomitant use of diclofenac and other NSAIDs or systemic corticosteroids may increase the risk of gastrointestinal bleeding or ulceration. The concomitant use of two or more NSAIDs should be avoided.
Anticoagulants and antithrombotic agents. Concomitant use may increase the risk of bleeding, therefore precautions are recommended. Although clinical studies do not indicate an effect of diclofenac on the activity of anticoagulants, there is evidence of an increased risk of bleeding in patients receiving diclofenac and anticoagulants concomitantly. Therefore, careful monitoring of the condition of such patients is recommended to ensure that no changes in the dosage of anticoagulants are necessary. Like other non-steroidal anti-inflammatory drugs, diclofenac in high doses may temporarily inhibit platelet aggregation.
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 in such cases, which necessitated a change in the dose of antidiabetic agents during the use of diclofenac. For this reason, as a precautionary measure, it is recommended to monitor blood glucose levels during combination therapy.
There have also been isolated reports of metabolic acidosis with concomitant use with diclofenac, especially in patients with pre-existing renal impairment.
Methotrexate. Diclofenac may inhibit the renal tubular clearance of methotrexate, leading to increased methotrexate levels. Caution should be exercised when NSAIDs, including diclofenac, are administered less than 24 hours before or after methotrexate, as this may increase the blood concentration of methotrexate and increase its toxicity. Serious toxicity has been reported when the interval between administration of methotrexate and NSAIDs, including diclofenac, was within 24 hours. This interaction is mediated by accumulation of methotrexate as a result of impaired renal excretion in the presence of NSAIDs.
Phenytoin: When phenytoin is used concomitantly with diclofenac, monitoring of phenytoin plasma concentrations is recommended due to the expected increase in phenytoin exposure.
Colestipol and cholestyramine. These drugs may delay or reduce the absorption of diclofenac. Therefore, it is recommended that diclofenac be administered at least one hour before or 4–6 hours after colestipol/cholestyramine.
Cardiac glycosides. Concomitant use of cardiac glycosides and NSAIDs may exacerbate heart failure, reduce GFR, and increase plasma glycoside levels.
Mifepristone: NSAIDs should not be used for 8–12 days after mifepristone administration, as NSAIDs may reduce the effect of mifepristone.
Application features
General
To minimize undesirable effects, treatment should be initiated at the lowest effective dose for the shortest period of time necessary to control symptoms.
The concomitant use of Voltaren® 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.
The renal effects of NSAIDs include fluid retention with oedema and/or hypertension. Diclofenac should be used with caution in patients with cardiac disease or other conditions predisposing to fluid retention. This is also recommended in patients receiving concomitant diuretics or ACE inhibitors or who are at increased risk of developing hypovolaemia.
The effects are generally more severe in elderly patients. Caution should be exercised when prescribing the drug to elderly patients. Caution is required in patients over 65 years of age. In particular, it is recommended to use the lowest effective dose in frail elderly patients or those with low body weight.
If patients taking Voltaren® develop gastrointestinal bleeding or ulcers, the drug should be discontinued.
As with other NSAIDs, allergic reactions, including anaphylactic/anaphylactoid reactions, may occur, even without prior exposure to diclofenac.
Due to its pharmacodynamic properties, Voltaren®, like other NSAIDs, may mask the symptoms of infection.
Voltaren® gastro-resistant tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take Voltaren® gastro-resistant tablets.
Hypersensitivity reactions may also progress to Kounis syndrome, a serious allergic reaction that can cause myocardial infarction. Symptoms of such reactions may include chest pain that occurs in conjunction with an allergic reaction to diclofenac.
Effects on the digestive tract
Gastrointestinal bleeding (hemorrhage, melena), ulceration or perforation, which can be fatal and can occur at any time during treatment with or without warning symptoms or a previous history of serious gastrointestinal events, have been reported with all NSAIDs, both COX-2 selective and non-COX-2 selective, including diclofenac. These events are usually more severe in the elderly. If gastrointestinal bleeding or ulceration occurs in patients receiving diclofenac, the drug should be discontinued.
As with other NSAIDs, medical supervision and special caution are required when prescribing diclofenac to patients with symptoms suggestive of gastrointestinal (GI) disorders. The risk of GI bleeding, ulceration or perforation increases with increasing dose of NSAIDs, particularly 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 low-dose acetylsalicylic acid (ASA/aspirin or other medicinal products that may increase the risk of gastrointestinal adverse effects), combination therapy with protective agents (e.g. proton pump inhibitors or misoprostol) should be considered. Patients with a history of gastrointestinal toxicity, particularly the elderly, should report any unusual abdominal symptoms (especially gastrointestinal bleeding). Caution is also required in patients receiving concomitant medicinal products 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.
The use of NSAIDs, including diclofenac, may be associated with an increased risk of gastrointestinal anastomotic leakage. Close medical supervision and caution are recommended when using Voltaren® after gastrointestinal surgery.
Effect on the liver
Careful medical supervision is required when Voltaren® is prescribed to patients with impaired liver function, as their condition may worsen.
As with other NSAIDs, one or more liver enzymes may increase with diclofenac. The increase in enzyme levels was generally reversible after discontinuation of the drug.
During long-term treatment with Voltaren®, regular monitoring of liver function and liver enzyme levels is recommended as a precautionary measure. If liver function abnormalities persist or worsen and if clinical symptoms suggestive of progressive liver disease or if other manifestations (e.g. eosinophilia, rash) occur, Voltaren® should be discontinued.
In addition to elevated liver enzymes, there have been rare reports of severe hepatic reactions, including jaundice and fulminant hepatitis, hepatic necrosis and hepatic failure, which in some cases resulted in death.
Diseases such as hepatitis may occur without prodromal symptoms. Caution is required if Voltaren® is used in patients with hepatic porphyria, due to the possibility of provoking an attack.
Effects on the kidneys
NSAIDs, including diclofenac, reduce levels of prostaglandins, which are important for maintaining renal blood flow.
Since fluid retention, oedema and hypertension have been reported commonly (1-10%) with NSAIDs, particularly diclofenac, special attention should be paid to patients with impaired cardiac or renal function, a history of hypertension, the elderly, patients receiving concomitant therapy with diuretics or drugs that significantly affect renal function, and patients with a significant decrease in extracellular fluid volume for any reason, e.g. before or after major surgery. In such cases, monitoring of renal function is recommended as a precautionary measure. Discontinuation of therapy usually results in a return to pre-treatment status.
Effects on the skin
Serious skin reactions (some of which were fatal, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, Lyell's syndrome, and drug hypersensitivity syndrome with eosinophilia and systemic symptoms (DRESS)) have been reported very rarely in association with the use of NSAIDs, including Voltaren®. Patients are at greatest 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. Voltaren® 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
Treatment with Voltaren® is generally not recommended for patients with diagnosed cardiovascular diseases (heart failure, ischemic heart disease, peripheral artery disease) or uncontrolled arterial hypertension.
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 doses up to 100 mg per day for a course of treatment of more than 4 weeks. Since the cardiovascular risks associated with the use 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, especially if treatment is continued for more than 4 weeks.
For patients with a history of hypertension and/or mild to moderate congestive heart failure, appropriate monitoring and advice is necessary, as fluid retention and oedema have been reported in association with the use of NSAIDs, including diclofenac.
Voltaren® should be used with caution in patients taking concomitant diuretics or ACE inhibitors or who are at increased risk of hypovolemia.
Clinical trial data and epidemiological data suggest that the use of diclofenac, especially at high doses (150 mg/day) and with long-term treatment, may be associated with a small increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke).
Diclofenac is not recommended for use in patients with uncontrolled hypertension, congestive heart failure, stable ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease. If necessary, use is possible only after a careful risk/benefit assessment and only at a dosage of no more than 100 mg per day for no more than 4 weeks.
Patients should be informed of the possibility of serious antithrombotic events (chest pain, shortness of breath, weakness, speech disorders) occurring at any time during treatment. In this case, a doctor should be consulted immediately.
Effect on hematological parameters
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 in patients with bronchial asthma or a history of it.
Use during pregnancy or breastfeeding
Pregnancy
Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonal/fetal development. Epidemiological data suggest an increased risk of miscarriage and/or cardiac malformations and gastroschisis following exposure to a prostaglandin synthesis inhibitor in early pregnancy. This risk is believed to be proportional to the dose administered and the duration of treatment. The absolute risk of cardiovascular malformations increased from less than 1% to approximately 1.5%.
In animals, treatment with a prostaglandin synthesis inhibitor has been shown to increase pre- and post-implantation loss and embryo/fetal death. In addition, an increased incidence of various malformations, including cardiovascular malformations, has been reported in animals treated with a prostaglandin synthesis inhibitor during organogenesis.
First/second trimester
In the first and second trimesters of pregnancy, Voltaren® should only be used if the expected benefit to the woman outweighs the potential risk to the fetus. If Voltaren® is used by a woman attempting to conceive or by a pregnant woman in the first or second trimester of pregnancy, the dose should be kept as low and the duration of treatment as short as possible.
Oligohydramnios/neonatal renal impairment/narrowing of the ductus arteriosus
Use of NSAIDs from the 20th week of pregnancy may lead to impaired renal function in the fetus, which may cause oligohydramnios and, in some cases, renal failure in the newborn. These adverse reactions are observed on average after a few days or weeks of treatment, although in rare cases oligohydramnios has developed as early as 48 hours after the start of NSAID use. Oligohydramnios often, but not always, resolves after discontinuation of NSAID treatment. Complications of prolonged oligohydramnios may include, for example, limb contractures and delayed lung development. In some post-marketing clinical cases, neonatal renal failure has required invasive procedures such as exchange transfusion or dialysis.
In addition, narrowing of the ductus arteriosus has been reported following treatment in the second trimester, which resolves in most cases after discontinuation of treatment.
If treatment with Voltaren® lasts more than 48 hours, ultrasound monitoring of amniotic fluid and fetal heart rate should be considered. In the event of oligohydramnios or narrowing of the ductus arteriosus, Voltaren® should be discontinued and appropriate treatment should be given according to clinical practice.
Third trimester
During the third trimester of pregnancy, the use of Voltaren® is contraindicated.
All prostaglandin synthesis inhibitors can:
expose the fetus to the following risks:
o cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension);
o renal dysfunction, which may progress to renal failure with oligohydramnios;
expose mother and child to the following risks:
o possible prolongation of bleeding time – an effect of inhibition of platelet aggregation, which can be observed even when using very low doses; inhibition of uterine contractions, leading to delayed or prolonged labor.
Breast-feeding
Like other NSAIDs, diclofenac is excreted in small amounts in breast milk. Therefore, Voltaren® is contraindicated in women during breastfeeding to avoid undesirable effects on the infant.
If treatment is necessary, breastfeeding should be discontinued.
Fertility in women
Like other NSAIDs, Voltaren® 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 Voltaren® should be considered.
Based on relevant animal data, impaired male reproductive function cannot be excluded. The relevance of these data to humans has not been established.
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 Voltaren® should not drive or operate complex machinery.
Method of administration and doses
The drug should be used in the lowest effective dose for the shortest period of time, taking into account the goal of treatment in each individual patient.
Adults
It is advisable to take the tablets before meals, with liquid; they should not be divided or chewed.
The initial dose is usually 100–150 mg per day. For mild symptoms and long-term therapy, a dose of 75–100 mg/day is sufficient. The daily dose is divided into 2–3 doses. To avoid night pain or morning stiffness, treatment with Voltaren® gastro-resistant tablets can be supplemented with the administration of Voltaren® rectal suppositories before bedtime. The maximum daily dose of the drug should not exceed 150 mg.
In primary dysmenorrhea, the daily dose is selected individually, usually it is 50-150 mg. The initial dose may be 50-100 mg, but if necessary it can be increased over several menstrual cycles to a maximum of 150 mg per day.
The recommended maximum daily dose of Voltaren® is 150 mg.
Children aged 1–14 years
Voltaren®, gastro-resistant tablets in a dose of 50 mg, are not used in children due to their high content of the active substance. Tablets in a dose of 25 mg can be used in children from the age of 1 year on the prescription of a doctor in a daily dose of 0.5–2 mg/kg of body weight depending on the severity of the symptoms; this dose is divided into 2–3 doses.
If it is impossible to achieve the prescribed dose, other dosage forms of diclofenac with the appropriate dosage are used for children.
Elderly patients (aged 65 years and over)
Although the pharmacokinetics of Voltaren® are not altered to any clinically significant extent in the elderly, NSAIDs should be used with caution in patients who are generally more susceptible to adverse reactions. In particular, the lowest effective dose is recommended for frail elderly patients or patients with low body mass; patients should also be monitored for gastrointestinal bleeding during NSAID therapy.
Existing cardiovascular disease or significant risk factors
Diclofenac should only be prescribed to patients with significant risk factors for cardiovascular events (such as hypertension, hyperlipidemia, diabetes mellitus, smoking) after careful clinical evaluation and, if used for more than 4 weeks, at maximum daily doses of up to 100 mg (see "Special instructions"). 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 periodically reviewed.
Patients with renal impairment
Voltaren® is contraindicated in patients with renal insufficiency (glomerular filtration rate < 15 ml/min/1.73 m2).
No specific studies have been conducted in patients with renal impairment and no dose adjustment recommendations are available. Voltaren® should be used with caution in patients with renal impairment.
Patients with hepatic impairment
Voltaren® is contraindicated in patients with hepatic insufficiency.
No specific studies have been conducted in patients with hepatic impairment and no dose adjustment recommendations are available. Voltaren® should be used with caution in patients with moderate or severe hepatic impairment.
Children.
Voltaren®, gastro-resistant tablets in a dose of 50 mg, are not used in children due to the high content of the active ingredient in them.
