active ingredient: sodium diclofenac
1 tablet gastroresistent contains diclofenac sodium 25 mg or 50 mg
tablet core 25 and 50 mg silica colloidal anhydrous, cellulose microcrystalline lactose monohydrate magnesium stearate maize starch povidone K 30; sodium starch (type a)
coating of tablets (subpalette and color) 25 mg
gipromelloza (hydroxypropylmethyl cellulose) castor oil polyethoxylated, hydrogenated iron oxide yellow (E172) talc, titanium dioxide (E 171)
enteric coating: methacrylate copolymer (type a), 8000 polyethylene glycol/macrogol 8000, silicone antifoam emulsion SE 2/simethicone, talc
coating of tablets (subpalette and color) 50 mg
gipromelloza (hydroxypropylmethyl cellulose) castor oil polyethoxylated, hydrogenated iron oxide yellow (E172) iron oxide red (E172) talc titanium dioxide (E 171)
enteric coating: methacrylate copolymer (type a), 8000 polyethylene glycol/macrogol 8000, silicone antifoam emulsion SE 2/simethicone, talc.
Basic physico-chemical properties:
25 mg: yellow, round, biconvex, with beveled edges, on the one hand - embossing "CG", on the other- " BZ";
50 mg: light brown, round, biconvex, with beveled edges, on the one hand - stamping "CG", on the other - "GT".
Nonsteroidal anti-inflammatory drugs.
Acetic acid derivatives and related compounds. PBX code M01A V05.
Voltaren contains sodium diclofenac-a substance of nonsteroidal structure, has a pronounced analgesic, anti-inflammatory effect.
It is an inhibitor of prostaglandinsynthase (COX).
In vitro sodium diclofenac in concentrations equivalent to those achieved in the treatment of patients does not inhibit the biosynthesis of cartilaginous tissue proteoglycans.
Only for 25 mg tablets
Experience in the use of diclofenac in clinical trials involving pediatric patients with LEGAL/legal limited. During the randomized double-blind 2-week study with parallel groups with the participation of children 3-15 years with JRA/Jia, the efficacy and safety of diclofenac at a dose of 2-3 mg/kg of body weight per day were compared with those of acetylsalicylic acid (ASA , 50 to 100 mg/kg/day) and placebo (15 patients in each group). During the General evaluation of the data was shown to improve the condition of patients (11 out of 15 of patients who use diclofenac, in 6 of 12 patients from the group of the use of aspirin and in 4 of 15 patients of the control group applying a placebo), with statistically significant difference (p<0, 05). The number of painful joints decreased as a result of the use of diclofenac and ASA, but has been increased by the use of a placebo. During the second randomized, double-blind 6-week study with parallel groups with the participation of children 4-15 years with JRA/Jia, the efficacy of diclofenac (daily dose 2-3 mg/kg of body weight, n = 22) was comparable with the efficacy of indomethacin ( daily dose 2-3 mg/kg of body weight, n = 23).
Although absorption occurs completely, the onset of action can be delayed by passing through the stomach, which can be affected by eating, which slows down the emptying of the stomach. Average peak plasma concentrations of 1.48 ± 0.65 µg/ml (1.5 µg/ml EN 5 µmol/l) are achieved on average at 2: 00 after administration of the tablet at a dose of 50 mg.
About half of the diclofenac used is metabolized during the first pass through the liver (the effect of the first pass), the area under the concentration curve (AUC) after oral administration is about half of the value obtained by applying an equivalent parenteral dose.
Pharmacokinetic characteristics of the drug do not change with repeated use. Accumulation does not occur when the recommended dosage is observed.
Concentration in blood plasma in children treated with equivalent dose (mg/kg of body weight), similar to concentrations that have been observed in adults (only for tablets at a dose of 25 mg).
The binding of diclofenac with plasma proteins is 99.7%, with albumin - 99.4%.
Diclofenac penetrates the synovial fluid, where its maximum concentration is achieved 2-4 hours later than in blood plasma. The half-life of synovial fluid is 3-6 hours. After 2:00 after reaching the maximum concentration in the plasma, the concentration of diclofenac in the synovial fluid remains higher; this phenomenon is observed during 12: 00.
Diclofenac has been detected in low concentrations (100 ng/ml) in breast milk in one lactating woman. The estimated amount of the drug enters the baby's body with breast milk, equivalent to a dose of 0.03 mg/kg/day.
Diclofenac is metabolized partly by glucuronidation of the unchanged molecule, but mainly by single and multiple hydroxylation and methoxylation, which leads to the formation of several phenolic metabolites, most of which form conjugates with glucuronic acid. Two of these phenolic metabolites are biologically active, but significantly less than diclofenac.
The total systemic clearance of diclofenac from plasma is 263 ± 56 ml/min (mean ± CO). The final elimination half-life from plasma is 1-2 hours. The half-life of four metabolites from plasma, including two pharmacologically active, is also short and is 1-3 hours. About 60% of the drug dose is excreted in the urine in the form of conjugates with glucuronic acid intact molecule and metabolites, most of which also turns into glucuronide conjugates. Less than 1% of diclofenac is displayed unchanged. The remaining doses of the drug is excreted in the form of metabolites with feces.
Special groups of patients.
Elderly patient. The influence of the patient's age on the absorption, metabolism and excretion of the drug was not observed, except for the fact that in five elderly patients, 15-minute infusion led to a higher concentration of the drug in the blood plasma by 50% than expected in young healthy volunteers.
Patients with impaired renal function. In patients with impaired renal function, receiving therapeutic doses, one can not expect the accumulation of unchanged active substance, based on the kinetics of the drug after a single application. In patients with creatinine clearance less than 10 ml/min, the calculated equilibrium concentrations of hydroxylated metabolites in blood plasma are approximately 4 times higher than in healthy volunteers. However, eventually all metabolites were excreted with bile.
Patients with liver disease. In patients with chronic hepatitis or compensated cirrhosis, the pharmacokinetics and metabolism of diclofenac are similar to those in patients without liver disease.
Inflammatory and degenerative forms of rheumatic diseases (rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, spondyloarthritis)
pain syndromes of the spinal column;
rheumatic diseases of extra-articular soft tissues;
post-traumatic and postoperative pain syndromes, accompanied by inflammation and edema, for example after dental and orthopedic surgery
gynecological diseases accompanied by pain and inflammation, such as primary dysmenorrhea or adnexitis;
as an adjuvant in severe inflammatory diseases of ENT organs, accompanied by pain, for example, when pharyngotonsillitis, otitis media. In accordance with General therapeutic principles, the underlying disease should be treated by means of basic therapy. Fever itself is not an indication for the drug.
Hypersensitivity to the active substance or to any other component of the drug.
Acute gastric or intestinal ulcer; gastrointenstinal bleeding or perforation.
Bleeding or perforation of the gastrointestinal tract in the history associated with previous treatment with nonsteroidal anti-inflammatory drugs (NSAIDs).
Active form of peptic ulcer disease/bleeding or recurrent ulcer disease/history of bleeding (two or more separate episodes of fixed ulcer or bleeding).
The last trimester of pregnancy.
Inflammatory bowel disease (e.g. Crohn's disease or ulcerative colitis).
Congestive heart failure (NYHA II-IV);
Treatment of PERIOPERATIVE pain in coronary artery bypass grafting (or use a heart-lung machine)
Ischemic heart disease in patients with angina who underwent myocardial infarction
Cerebrovascular diseases in patients who have had a stroke or have episodes of transient ischemic attacks;
Peripheral arterial disease
Voltaren , as well as other nonsteroidal anti-inflammatory drugs, is contraindicated in patients who, in response to the use of ibuprofen, acetylsalicylic acid or other NSAIDs, have bronchial asthma attacks, angioedema, urticaria or acute rhinitis, nasal polyps and other allergic symptoms.
Interaction with other medicinal products and other forms of interaction
Below is indicated the interactions that were observed in the application of diclofenac in the form of gastroresistent tablets and/or other dosage forms.
Lithium. Provided the simultaneous use of diclofenac can increase the concentration of lithium in plasma. Recommended monitoring of lithium level in blood serum.
Digoxin. Provided the simultaneous use of diclofenac can increase the concentration of digoxin in blood plasma. It is recommended to monitor the level of digoxin in serum.
Diuretics and antihypertensive agents. Like other NSAIDs, simultaneous use of diclofenac with diuretics and antihypertensive agents (e.g. ?-blockers, ACE inhibitors (ACE)) can lead to a decrease in their antihypertensive effect by inhibiting the synthesis of vasodilating prostaglandins. Thus, such a combination is used with a reservation, and patients, especially the elderly, should be under close supervision regarding blood pressure. Patients should receive proper hydration, monitoring of renal function after initiation of concomitant therapy and on a regular basis after it, especially on diuretics and ACE inhibitors, is also recommended due to increased risk of nephrotoxicity.
Drugs are known to cause hyperkalemia. Simultaneous treatment with potassium-sparing diuretics, cyclosporine, tacrolimus or trimethoprim may be associated with an increase in serum potassium levels, so patient monitoring should be carried out more frequently.
Anticoagulants and antithrombotic agent. Simultaneous use can increase the risk of bleeding, so it is recommended to take precautions. Although clinical studies do not indicate the effect of diclofenac on the activity of anticoagulants, there is some evidence of an increase in the risk of bleeding in patients taking both diclofenac and anticoagulants. Therefore, to ensure that no changes in the dosage of anticoagulants are needed, careful monitoring of such patients is recommended. Like other nonsteroidal anti-inflammatory drugs, diclofenac in high doses can temporarily suppress platelet aggregation.
Other NSAIDs, including selective COX-2 inhibitors, and corticosteroids. Simultaneous use of diclofenac and other NSAIDs or GCS may increase the risk of gastrointestinal bleeding or ulcers. Simultaneous use of two or more NSAIDs should be avoided.
Selective inhibitors of serotonin reuptake (SSRIs).
The simultaneous use of NSAIDs and SSRIs may increase the risk of gastrointestinal bleeding.
Antidiabetic drugs. Clinical studies have shown that diclofenac can be used with oral hypoglycemic agents and do not change their therapeutic effect. However, there are some reports of the development in such cases as hypoglycemia and hyperglycemia, which caused the need to change the dose of antidiabetic agents in the application of diclofenac. For this reason, as a precaution, it is recommended to monitor blood glucose levels during combination therapy.
Methotrexate. Diclofenac can suppress the clearance of methotrexate in the renal tubules, resulting in increased levels of methotrexate. Caution should be exercised in appointing NSAIDs, including diclofenac, less than 24 hours before the use of methotrexate, as in such cases may increase the concentration of methotrexate in the blood and increase its toxic effect. There have been cases of serious toxicity when the interval between use of methotrexate and NSAIDs, including diclofenac, were within 24 hours. This interaction is mediated through the accumulation of methotrexate as a result of impaired renal excretion in the presence of NSAIDs.
Cyclosporine. The influence of diclofenac, as well as other NSAIDs on prostaglandin synthesis in the kidneys can increase the nephrotoxicity of cyclosporin, therefore diclofenac should be used at lower doses than for patients, cyclosporin is not used.
Tacrolimus. With the use of NSAIDs with tacrolimus may increase the risk of nephrotoxicity, which may be mediated via renal antiprostaglandin effects NSAID and calcineurin inhibitor.
Antibacterial quinolones. It is possible to develop seizures in patients, simultaneously taking quinolone derivatives and NSAIDs. This can be observed in patients with both epilepsy and history of seizures, and without them. Caution should therefore be exercised when deciding whether to use quinolones in patients who are already receiving NSAIDs.
Phenytoin. When using phenytoin simultaneously with diclofenac it is recommended to monitor the concentration of phenytoin in the blood plasma due to the expected increase in the influence of phenytoin.
Cholesterol and cholesterol. These drugs can delay or reduce the absorption of diclofenac. Thus, it is recommended to appoint diclofenac at least an hour before or after 4-6 hours after the application of colestipol/colestiramine.
Cardiac glycoside. The simultaneous use of cardiac glycosides and NSAIDs may increase heart failure, reduce GFR and increase the level of glycosides in plasma.
Mifepristone. NSAIDs should not be used for 8-12 days after use of mifepristone, as NSAIDs can reduce the effect of mifepristone.
Strong inhibitors of CYP2C9. Caution is advised when administered together diclofenac with potent CYP2C9 inhibitors (such as voriconazole), which could lead to a significant increase in maximum concentration in blood plasma and exposure of diclofenac due to inhibition of metabolism of diclofenac.
To minimize side effects, treatment should begin with the lowest effective dose for the shortest period of time necessary to control symptoms.
Simultaneous use of Voltaren with systemic NSAIDs, such as selective cyclooxygenase-2 inhibitors, should be avoided due to the lack of any evidence of synergistic effect and potential additive side effects.
Caution is required for use in patients older than 65 years. In particular, it is recommended to use the lowest effective dose for debilitated elderly patients with low body weight.
As the use of other NSAIDs may experience allergic reactions, including anaphylactic/anaphylactoid reactions, even without prior exposure to diclofenac.
Due to its pharmacodynamic properties, Voltaren , like other NSAIDs, can mask the signs and symptoms of infection.
Voltaren , gastroresistant tablets, containing lactose. Patients with rare hereditary galactose intolerance, severe lactase deficiency or malabsorption of glucose-galactose should not use Voltaren , gastrorezistente pills.
The effect on the digestive tract
With all NSAIDs, including diclofenac, there have been cases of gastrointestinal bleeding (vomiting blood, melena), ulceration or perforation which can be fatal and occur anytime during treatment with or without warning symptoms or a previous history of serious events from the gastrointestinal tract. These phenomena usually have more serious consequences in elderly patients. If patients receiving diclofenac, the phenomena of gastro-enteric bleeding or formation of ulcers, the drug should be discontinued.
As with the use of other NSAIDs, including diclofenac, for patients with symptoms that indicate a violation of the digestive tract (TT), be sure to medical supervision and special caution. The risk of bleeding, ulcers or perforations in TT increases with increased doses of NSAIDs, including diclofenac.
Elderly patients have an increased frequency of adverse reactions to NSAID use, especially in relation to gastrointestinal bleeding and perforation which may be fatal.
To reduce the risk of such toxic effects on TT, treatment is initiated and maintained by low effective doses. For such patients, as well as those in need of concomitant use of medicinal products containing low dose acetylsalicylic acid (ASA/aspirin) or other drugs that are likely to increase the risk of undesirable effects on the TT, you should consider the use of combination therapy with protective agents (e.g. proton pump inhibitors or misoprostol). Patients with a history of gastrointestinal toxicity, especially the elderly, should report any unusual abdominal symptoms (especially bleeding in TT). Caution is also needed in patients receiving both drugs, which can increase the risk of ulceration or bleeding, such as systemic corticosteroids, anticoagulants (e.g. warfarin), antithrombotic agent (e.g. ASA) or selective inhibitors of serotonin reuptake.
The effect on the liver
Careful medical supervision is necessary in the case when Voltaren is prescribed to patients with impaired liver function, because their condition may deteriorate. As when using other NSAIDs, including diclofenac, the level of one or more liver enzymes may increase.
During long-term treatment Voltaren is prescribed regular monitoring of liver function and liver enzyme levels as a precaution. If abnormal liver function persist or worsen, if clinical signs or symptoms may be associated with progressive liver disease or if other manifestations occur (e.g. eosinophilia, rash), the drug Voltaren should be discontinued. For diseases such as hepatitis can occur without prodromal symptoms. Caution is necessary if Voltaren is used in patients with hepatic porphyry, due to the likelihood of provoking an attack.
Effect on the kidney
Because treatment with NSAIDs, including diclofenac, there have been cases of fluid retention and swelling, particular attention should be paid to patients with impaired heart or kidneys, hypertension in the anamnesis, elderly patients, patients receiving therapy with diuretics or medications that can significantly affect renal function, patients with a substantial decrease in extracellular fluid volume from any cause, e.g. before or after major surgery. In such cases, as a precaution it is recommended to monitor renal function. Termination therapy usually leads to a return to the condition that preceded the treatment.
Effect on skin
In connection with the use of NSAIDs, including drug Voltaren , in very rare cases have been reported serious reactions of the skin (some of them were fatal, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis. In patients, a high risk of these reactions is observed at the beginning of the course of therapy: the appearance of the reaction is observed in most cases during the first month of treatment. Use of the drug Voltaren should be stopped at the first appearance of skin rashes, lesions of the mucous membrane or when there are any other signs of hypersensitivity.
SLE and mixed connective tissue disease
In patients with systemic lupus erythematosus (SLE) and mixed connective tissue diseases, there may be an increased risk of aseptic meningitis.
Cardiovascular and cerebrovascular effects
Assign diclofenac patients with significant risk factors for cardiovascular events (such as hypertension, hyperlipidemia, diabetes, Smoking) can only after a thorough clinical evaluation. Since cardiovascular risk of diclofenac may increase with increasing dose and duration of treatment, it should be used as soon as possible and in the most effective dose. You should periodically review the needs of the patient in use of diclofenac for the relief of symptoms and response to therapy.
For patients with a history of hypertension and/or congestive heart failure of mild to moderate severity, appropriate monitoring and recommendations are required, as there have been reported cases of fluid retention and edema due to the use of NSAIDs, including diclofenac.
Data from clinical trials and epidemiological data suggest that use of diclofenac, particularly at high doses (150 mg/day) and long-term treatment may be associated with a slight increased risk of developing arterial thrombotic events (for example myocardial infarction or stroke).
Patients with uncontrolled hypertension, congestive heart failure, stable coronary artery disease, peripheral artery disease and/or cerebrovascular disease should not be prescribed diclofenac if necessary, the use is possible only after a thorough assessment of the risk-benefit only in a dosage of no more than 100 mg per day.
Patients should be informed of the possibility of serious antithrombotic cases (chest pain, shortness of breath, weakness, speech impairment) that may occur at any time. In this case, you should immediately consult a doctor.
Impact on hematological parameters
Long-term use of this drug, like other NSAIDs, it is recommended to monitor complete blood count.
Voltaren can temporarily suppress platelet aggregation. Patients with hemostasis disorders, hemorrhagic diathesis or haematological disorders should be carefully monitored.
History of asthma
In patients with asthma, seasonal allergic rhinitis, swelling of the nasal mucosa (i.e. nasal polyps), chronic obstructive pulmonary disease or chronic respiratory infections (especially those associated with allergic-like rhinitis, symptoms) more likely to have reactions on NSAIDs like asthma exacerbations (so called intolerance to analgesics/analgesic asthma), Quincke's edema, urticaria. In this regard, special measures (emergency preparedness) are recommended for such patients. This also applies to patients with allergic reactions to other substances such as rash, itching, urticaria.
As with other drugs that suppress the activity of prostaglandinsynthase, diclofenac sodium and other NSAIDs can precipitate bronchospasm if administered to a patients suffering from bronchial asthma, or patients with bronchial asthma in history.
Use during pregnancy or breast-feeding.
In the I and II trimesters of pregnancy, the drug Voltaren can be prescribed only when the expected benefit to the mother exceeds the potential risk to the fetus and only in the minimum effective dose, and the duration of treatment should be as short as possible. As in the case of other NSAIDs, the drug is contraindicated in the last 3 months of pregnancy (possible suppression of uterine contractility and premature closure of the arterial duct in the fetus).
Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryo/fetus development. Data of epidemiological studies indicate an increased risk of miscarriages and/or the risk of heart defects and gastroschisis after the use of prostaglandin synthesis inhibitor in early pregnancy. The absolute risk of cardiovascular disease was increased from less than 1% to 1.5%.
It is possible that the risk increases with the dose and duration of treatment. It was shown that the introduction of prostaglandin synthesis inhibitor in animals leads to an increase in pre - and post-implantation loss and mortality of the embryo/fetus.
In addition, in animals treated with the inhibitor of prostaglandin synthesis during the period of organogenesis, was registered a higher incidence of various malformations, including those of the cardiovascular system. If Voltaren is used by a woman who wants to get pregnant, or in the first trimester of pregnancy, the dose should be as low as possible, and the duration of treatment - as short as possible.
During the third trimester of pregnancy, all inhibitors of prostaglandin synthesis can affect the fetus as follows:
cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension)
the impairment of renal function may progress to renal failure with oligohydramnios.
On the mother and newborn, and at the end of pregnancy:
possible lengthening of bleeding time, antiplatelet effect, which can be observed even at very low doses
inhibition of uterine contractions, which leads to delay or extend delivery.
So, Voltaren contraindicated during the third trimester of pregnancy.
Like other NSAIDs, diclofenac in small amounts excreted in breast milk. In this regard, Voltaren should not be used in women during breast-feeding, to avoid undesirable effects on the baby.
Fertility in women.
Like other NSAIDs, Voltaren can adversely affect female fertility, so it is not recommended to prescribe the drug to women who are planning a pregnancy. For women who have problems with conception or are tested for infertility, it is necessary to consider the feasibility of abolishing the drug Voltaren .
The ability to influence the reaction rate when driving motor transport or operating other mechanisms.
Patients who during therapy with Voltaren have visual impairment, dizziness, drowsiness, disorders of the Central nervous system, lethargy or fatigue should not drive vehicles or work with mechanisms.
Method of application and doses
The drug should be used in the most effective doses for a short period of time, taking into account the objectives of treatment in each individual patient.
Tablets should preferably be taken before meals with liquid, they can not be divided or chewed.
The initial dose is usually 100-150 mg per day. With unspoken symptoms, as well as with prolonged therapy, a dose of 75-100 mg/day is sufficient. The daily dose is divided into 2-3 admission. Avoid night pain or morning stiffness treatment gastrorezistente pills Voltaren can be supplemented by the appointment of rectal suppositories Voltaren before bedtime. The daily dose should not exceed 150 mg.
In primary dysmenorrhea the daily dosage is selected individually, usually it is 50-150 mg. Initial dose may be 50-100 mg, but if necessary it can be increased over several menstrual cycles up to a maximum constituting of 200 mg per day. The use of the drug should begin after the first pain symptoms and continue for a few days, depending on the dynamics of regression symptoms.
Voltaren , gastroresistant tablets at a dose of 50 mg, is not used in children due to high content of active substance.
For oral administration.
75-150 mg per day, for two or three doses.
The recommended maximum daily dose of Voltaren is 150 mg.
Children (1-14 years old)
Voltaren , gastroresistant tablets at a dose of 50 mg, is not used in children due to high content of active substance. Tablets at a dose of 25 mg can be used in children aged 1 year or more as directed by a physician at a daily dose of 0.5 - 2 mg/kg body weight, depending on the severity of the symptoms, this dose is divided into 2 - 3 admission. In the treatment of juvenile rheumatoid arthritis the daily dose may be increased to 3 mg/kg per day in divided doses.
For example, for a child weighing 30 kg, the daily dose may range from 15 to 60 mg. Based on this range, the child may appoint 2 tablets of 25 mg 2 times a day.
If it is impossible to reach the prescribed dose, children are used other dosage forms of diclofenac with an appropriate dosage.
Children aged 14 to 18 years, the drug is used from 75 to 150 mg per day in two or three doses.
The daily dose should not exceed 150 mg.
Although elderly patients the pharmacokinetics of the drug Voltaren is not impaired to any clinically relevant extent, non-steroidal anti-inflammatory drugs should be used with caution in such patients who generally are more likely to develop adverse reactions. In particular, for weakened elderly patients or patients with low body weight is recommended to use the lowest effective dose patients should be evaluated for gastrointestinal bleeding in the treatment of NSAIDs.
Voltaren , gastroresistant tablets at a dose of 50 mg, is not used in children due to high content of active substance. Tablets at a dose of 25 mg can be used in children aged 1 year with juvenile chronic arthritis, if possible, to reach the prescribed weight doses.
There is no typical clinical picture of diclofenac overdose. Overdose can cause symptoms such as headache, nausea, vomiting, epigastric pain, gastrointestinal bleeding, diarrhea, dizziness, disorientation, excitement, coma, drowsiness, tinnitus or convulsions. Acute renal failure and liver damage are possible with severe intoxication.
Treatment of acute poisoning with NSAIDs, including diclofenac, consists in carrying out supportive and symptomatic therapy. This applies to the treatment of manifestations such as arterial hypotension, renal failure, convulsions, gastrointestinal disorders, respiratory depression. It is unlikely that such specific therapeutic measures as forced diuresis, dialysis or hemoperfusion will be effective for the elimination of NSAIDs, including diclofenac, since the active substances of these drugs are largely associated with blood proteins and subjected to intensive metabolism. After receiving potentially toxic doses, activated charcoal can be used, and after receiving potentially life - threatening doses-performing disinfection of the stomach (for example, causing vomiting, gastric lavage).
The category of the frequency of adverse reactions, starting with the most frequent is defined as follows: very often (>1/10); often (?1/100,<1/10); infrequently (?1/1000,<1/100) rarely (?1/10000,<1/1000); very rarely (<1/10000); frequency unknown (can not be estimated from available data) .
The following side effects include phenomena that have been reported in short-term or long-term use of the drug.
From the blood and lymphatic system: very rarely - thrombocytopenia, leukopenia, anemia, including hemolytic anemia and aplastic anemia, agranulocytosis.
From the immune system: rarely-hypersensitivity, anaphylactic and anaphylactoid reactions (including hypotension and shock); very rarely - angioedema (including facial edema).
Mental disorders: very rarely-disorientation, depression, insomnia, irritability, nightmares, psychotic disorders.
From the nervous system: often-headache, dizziness, rarely-drowsiness, fatigue; very rarely-paresthesia, memory impairment, convulsions, b