Translation of the instructions can be
ALGESICAM® solution for injection 10 mg/ml
Instructions for use of the medicinal product
Composition
Active ingredient: meloxicam;
1.5 ml of the drug contains 15 mg of meloxicam;
1 ml of the drug contains 10 mg of meloxicam;
Excipients: meglumine, glycofurol, poloxamer 188, sodium chloride, glycine, sodium hydroxide, water for injections.
Dosage form.
Solution for injection.
Main physicochemical properties: transparent, yellow with a green tint solution.
Pharmacological group.
Nonsteroidal anti-inflammatory and antirheumatic drugs.
PBX code M01A C06.
Pharmacological properties.
Pharmacodynamics.
ALGEZIKAM ® is a nonsteroidal anti-inflammatory drug (NSAID) of the enolic acid class, which has anti-inflammatory, analgesic and antipyretic effects.
Meloxicam has shown high anti-inflammatory activity in all standard models of inflammation. As with other NSAIDs, its exact mechanism of action remains unknown. However, there is a common mechanism of development for all NSAIDs (including meloxicam): inhibition of the biosynthesis of prostaglandins, which are mediators of inflammation.
Pharmacokinetics.
Absorption. Meloxicam is completely absorbed after i.m. injection. The relative bioavailability compared to oral administration is almost 100%. Therefore, there is no need to adjust the dose when switching from i.m. to oral administration. After i.m. administration of 15 mg, the maximum plasma concentration is about 1.6-1.8 μg/ml and is reached in 1-6 hours.
Distribution. Meloxicam is very well bound to plasma proteins, mainly albumin (99%). Meloxicam penetrates into the synovial fluid, the concentration in which is 2 times lower than in blood plasma. The volume of distribution is low, on average 11 l after i / m or i / v administration, individual deviations within 7-20% are noted. The volume of distribution after multiple oral doses of meloxicam (7.5-15 mg) is 16 l with a coefficient of variation within 11-32%.
Biotransformation: Meloxicam undergoes extensive biotransformation in the liver.
Four different metabolites of meloxicam have been identified in urine, which are pharmacodynamically inactive. The major metabolite, 5'-carboxymeloxicam (60% of the dose), is formed by oxidation of the intermediate metabolite 5'-hydroxymethylmeloxicam, which is also excreted to a lesser extent (9% of the dose). In vitro studies suggest that CYP 2C9 plays an important role in the metabolism process, while CYP 3A4 isoenzymes contribute to a lesser extent. Peroxidase activity in patients may be responsible for the other two metabolites, which constitute
16% and 4% of the dose taken, respectively.
Elimination. Meloxicam is excreted mainly as metabolites in equal parts with urine and feces. Less than 5% of the daily dose is excreted unchanged in the feces, a small amount is excreted in the urine. The half-life varies from 13 to 25 hours depending on the route of administration (oral, intramuscular or intravenous). Plasma clearance is about 7-12 ml / min after a single oral dose, IV or rectal administration.
Dose linearity. Meloxicam showed linear pharmacokinetics within the therapeutic dose range of 7.5 to 15 mg after oral and IM administration.
Special groups of patients.
Patients with hepatic/renal insufficiency. Mild to moderate hepatic and renal insufficiency do not significantly affect the pharmacokinetics of meloxicam. In patients with moderate renal insufficiency, the total clearance is significantly higher. Reduced binding to plasma proteins has been observed in patients with end-stage renal failure. In end-stage renal failure, an increase in the volume of distribution may lead to an increase in the concentration of free meloxicam. The daily dose of 7.5 mg should not be exceeded (see section "Method of administration and dosage").
Elderly patients. In elderly male patients, mean pharmacokinetic parameters were similar to those in young male volunteers. In elderly female patients, the area under the pharmacokinetic curve (AUC) was higher and the half-life was longer compared to those in young volunteers of both sexes. Mean steady-state plasma clearance in elderly patients was slightly lower than in young volunteers.
Clinical characteristics.
Indication.
Contraindication.
III trimester of pregnancy (see section "Use during pregnancy and breastfeeding"); patient age up to 18 years; hypersensitivity to the active substance or to other components of the drug; hypersensitivity to active substances with a similar effect, such as NSAIDs, acetylsalicylic acid. Meloxicam should not be prescribed to patients who have experienced symptoms of asthma, nasal polyps, angioedema or urticaria after taking acetylsalicylic acid or other non-steroidal anti-inflammatory drugs; gastrointestinal bleeding or perforation associated with previous NSAID therapy in history; active or recurrent ulcer / bleeding in history (2 or more separate confirmed cases of ulcer or bleeding); severe hepatic failure, severe renal failure without dialysis; gastrointestinal bleeding, history of cerebrovascular bleeding or other blood clotting disorders; Violation of hemostasis or simultaneous use of anticoagulants (contraindications related to the route of administration) severe heart failure, not used for the treatment of perioperative pain in coronary artery bypass grafting.
Interactions with other drugs and other types of interactions.
Interaction studies were conducted only with the participation of adults.
Risks associated with hyperkalemia.
Some drugs or therapeutic groups may contribute to hyperkalemia: potassium salts, potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, nonsteroidal anti-inflammatory drugs, low molecular weight or unfractionated heparins, cyclosporine, tacrolimus and trimethoprim.
The onset of hyperkalemia may depend on whether there are associated factors. The risk of developing hyperkalemia is increased when the above-mentioned drugs are used concomitantly with meloxicam.
Pharmacodynamic interactions.
Other NSAIDs and acetylsalicylic acid ≥ 3 g/day.
Combination with other NSAIDs is not recommended (see section "Special warnings and precautions for use"), including acetylsalicylic acid at anti-inflammatory doses (≥ 500 mg single dose or ≥ 3 g total daily dose).
Corticosteroids (e.g., glucocorticoids).
Concomitant use with corticosteroids requires caution due to the risk of bleeding or ulceration in the gastrointestinal tract.
Anticoagulants or heparin.
The risk of bleeding is significantly increased due to inhibition of platelet function and damage to the gastroduodenal mucosa. NSAIDs may enhance the effects of anticoagulants such as warfarin (see section "Special instructions"). The simultaneous use of NSAIDs and anticoagulants or heparin in geriatric practice or in therapeutic doses is not recommended (see section "Special instructions"). Meloxicam solution for i / m administration is contraindicated in patients undergoing treatment with anticoagulants (see sections "Contraindications" and "Special instructions").
In other cases (for example, when using prophylactic doses), the use of heparin requires caution due to the increased risk of bleeding.
Thrombolytic and antiplatelet drugs.
Increased risk of bleeding due to inhibition of platelet function and damage to the gastroduodenal mucosa.
Selective serotonin reuptake inhibitors (SSRIs).
Increased risk of gastrointestinal bleeding.
Diuretics, ACE inhibitors and angiotensin II antagonists.
NSAIDs may reduce the effect of diuretics and other antihypertensive drugs. In some patients with impaired renal function (dehydrated patients or elderly patients with impaired renal function), the simultaneous use of ACE inhibitors or angiotensin II antagonists and drugs that inhibit COX may lead to further deterioration of renal function, including possible acute renal failure, which is usually reversible. Therefore, the combination should be used with caution, especially in elderly patients. Patients should be adequately hydrated and renal function should be monitored after initiation of combination therapy and periodically thereafter (see section 4.4).
Other antihypertensive drugs (e.g., β-adrenergic blockers).
As with the following medicinal products, a reduction in the antihypertensive effect of β-adrenergic blockers may occur (due to inhibition of prostaglandins with vasodilating effects).
Calcineurin inhibitors (e.g. cyclosporine, tacrolimus).
Nephrotoxicity of calcineurin inhibitors may be potentiated by NSAIDs due to mediation of renal prostaglandin effects. Renal function should be monitored during treatment. Close monitoring of renal function is recommended, especially in elderly patients.
Deferasirox.
Concomitant use of meloxicam and deferasirox may increase the risk of gastrointestinal adverse reactions. Caution should be exercised when combining these drugs.
Pharmacokinetic interactions are the effects of meloxicam on the pharmacokinetics of other drugs.
There are reports of NSAIDs increasing plasma lithium concentrations (due to reduced renal lithium excretion), which may reach toxic levels. Concomitant use of lithium and NSAIDs is not recommended (see section "Special warnings and precautions for use"). If combination therapy is necessary, careful monitoring of plasma lithium levels is necessary at the beginning of treatment, during dose adjustment and upon discontinuation of meloxicam treatment.
Methotrexate.
NSAIDs may reduce the tubular secretion of methotrexate, thereby increasing its plasma concentration. For this reason, concomitant use of NSAIDs is not recommended in patients receiving high doses of methotrexate (15 mg/week) (see section "Special warnings and precautions for use"). The risk of interaction between NSAIDs and methotrexate should also be considered in patients receiving low doses of methotrexate, particularly in cases of impaired renal function. If combined treatment is required, blood count and renal function should be monitored. Caution should be exercised if NSAIDs and methotrexate are administered for 3 consecutive days, as plasma levels of methotrexate may increase and toxicity may be increased. Although the pharmacokinetics of methotrexate (15 mg/week) are not altered by concomitant treatment with meloxicam, it should be borne in mind that the haematological toxicity of methotrexate may increase during treatment with NSAIDs (see section "Adverse reactions").
Pemetrexed.
When meloxicam is used concomitantly with pemetrexed in patients with mild to moderate renal impairment (creatinine clearance 45-79 ml/min), meloxicam should be discontinued 5 days before, on the day of, and for 2 days after pemetrexed administration. If the combination of meloxicam and pemetrexed is necessary, patients should be closely monitored, especially for myelosuppression and gastrointestinal adverse reactions. For patients with severe renal impairment (creatinine clearance below 45 ml/min), concomitant use of meloxicam and pemetrexed is not recommended.
In patients with normal renal function (creatinine clearance ≥ 80 ml/min), doses of 15 mg meloxicam may reduce the elimination of pemetrexed, thereby increasing the incidence of adverse reactions associated with pemetrexed. Therefore, caution should be exercised when prescribing 15 mg meloxicam with pemetrexed in patients with normal renal function (creatinine clearance ≥ 80 ml/min).
Pharmacokinetic interactions: the effect of other drugs on the pharmacokinetics of meloxicam.
Cholestyramine accelerates the elimination of meloxicam due to impaired intrahepatic circulation, so the clearance of meloxicam increases by 50% and the half-life decreases to 13 ± 3 hours. This interaction is clinically significant.
No clinically significant pharmacokinetic interaction of meloxicam was found when administered simultaneously with antacids, cimetidine and digoxin.
Application features.
Adverse reactions can be minimized by using the lowest effective dose for the shortest duration of treatment necessary to control symptoms (see section "Method of administration" and information on gastrointestinal and cardiovascular risks below).
The recommended maximum daily dose may be exceeded in case of insufficient therapeutic effect, and additional NSAIDs should not be used, as this may increase toxicity, while the therapeutic benefit has not been proven. The concomitant use of meloxicam with NSAIDs, including selective COX-2 inhibitors, should be avoided.
ALGEZICAM® is not suitable for the treatment of patients who require reduction of acute pain.
If there is no improvement after several days of use of the drug, the clinical benefits of treatment should be re-evaluated.
Attention should be paid to a history of esophagitis, gastritis and/or ulcer in order to ensure that they have fully resolved before starting therapy with meloxicam. Patients who have taken meloxicam and patients with a history of such cases should be regularly monitored for possible recurrence.
Gastrointestinal disorders.
As with other nonsteroidal anti-inflammatory drugs, potentially fatal gastrointestinal bleeding, ulceration or perforation may occur at any time during treatment with or without previous symptoms or a history of serious gastrointestinal disease.
The risk of gastrointestinal bleeding, ulceration or perforation is increased with increasing NSAID doses in patients with a history of ulcer, especially complicated by bleeding or perforation (see section "Contraindications"), and in elderly patients. In such patients, treatment should be started with the lowest effective dose. Combination therapy with protective drugs (such as misoprostol or proton pump inhibitors) should be considered for such patients, as well as for patients who require low-dose acetylsalicylic acid or other drugs that increase gastrointestinal risks (see information below and section "Interaction with other drugs and other types of interactions").
The use of meloxicam is not recommended in patients taking concomitant medications that may increase the risk of ulceration or bleeding, in particular heparin, as a radical therapy or in geriatric practice, anticoagulants such as warfarin or other non-steroidal anti-inflammatory drugs, including acetylsalicylic acid at a dose ≥ 500 mg single dose, or ≥ 3 g total daily dose (see section "Interaction with other medicinal products and other forms of interaction").
If gastrointestinal bleeding or ulceration occurs in patients taking meloxicam, treatment should be discontinued.
NSAIDs should be used with caution in patients with a history of gastrointestinal diseases (ulcerative colitis, Crohn's disease), as these conditions may be exacerbated (see section "Adverse reactions").
Liver disorders.
Up to 15% of patients taking NSAIDs (including meloxicam) may experience elevations in one or more liver function tests. These laboratory abnormalities may progress, remain stable, or be transient with continued treatment. Significant elevations in ALT or AST (approximately 3 or more times the upper limit of normal) have been reported in 1% of patients during clinical trials with NSAIDs. In addition, isolated cases of hepatic reactions, including jaundice and fulminant hepatitis, hepatic necrosis, and hepatic failure, some of which were fatal, have been reported during clinical trials with NSAIDs.
Patients with symptoms and/or suspected hepatic dysfunction or with abnormal liver function tests should be evaluated for the development of more severe hepatic impairment during meloxicam therapy. If clinical signs and symptoms consistent with liver disease develop or if systemic manifestations of the disease occur (e.g. eosinophilia, rash), ALGEZICAM® should be discontinued.
Cardiovascular disorders.
Close observation is recommended in patients with hypertension and/or a history of mild to moderate congestive heart failure, as fluid retention and edema have been reported with NSAID therapy.
Clinical monitoring of blood pressure is recommended in patients with risk factors at the beginning of therapy, especially at the beginning of treatment with meloxicam.
Research and epidemiological data suggest that the use of some NSAIDs (especially at high doses and in long-term treatment) may be associated with a small increased risk of vascular thrombotic events (such as myocardial infarction or stroke). There are insufficient data to exclude such a risk for meloxicam.
Patients with uncontrolled hypertension, congestive heart failure, established ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease should be treated with meloxicam only after careful examination. Such examination is necessary before starting long-term treatment in patients with risk factors for cardiovascular disease (e.g. hypertension, hyperlipidemia, diabetes mellitus, smoking).
NSAIDs may increase the risk of serious cardiovascular thrombotic events, myocardial infarction and stroke, sometimes fatal. The increased risk is related to the duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at increased risk of thrombotic events.
Skin disorders.
Life-threatening severe skin reactions: Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported with meloxicam. Patients should be informed of the signs and symptoms of severe skin reactions and should be closely monitored for skin reactions. The greatest risk of developing Stevens-Johnson syndrome or toxic epidermal necrolysis is during the first weeks of treatment. If a patient develops symptoms or signs of Stevens-Johnson syndrome or toxic epidermal necrolysis (e.g. skin rash, often progressing with blistering or mucosal lesions), meloxicam treatment should be discontinued. It is important to diagnose and discontinue any drugs that may cause severe skin reactions: Stevens-Johnson syndrome or toxic epidermal necrolysis as soon as possible. This is associated with a better prognosis in severe skin reactions. If a patient develops Stevens-Johnson syndrome or toxic epidermal necrolysis while taking meloxicam, the drug should not be used at any time in the future.
Anaphylactic reactions.
As with other NSAIDs, anaphylactic reactions may occur in patients with no known history of reaction to meloxicam. ALGESICAM® should not be used in patients with the aspirin triad. This symptom complex is seen in patients with bronchial asthma who have reported rhinitis with or without nasal polyps or severe, potentially fatal bronchospasm after the use of acetylsalicylic acid or other NSAIDs. Emergency care should be sought if an anaphylactoid reaction occurs.
As with most NSAIDs, isolated cases of increased transaminases, serum bilirubin or other liver function tests, as well as increases in serum creatinine and blood urea nitrogen, and other laboratory abnormalities have been reported with meloxicam. In most cases, these abnormalities were minor and transient. If significant or persistent abnormalities occur, meloxicam should be discontinued and follow-up tests performed.
Functional renal failure.
NSAIDs, due to inhibition of the vasodilatory effect of renal prostaglandins, can induce functional renal failure by reducing glomerular filtration. This side effect is dose-dependent. At the beginning of treatment or after increasing the dose, careful monitoring of diuresis and renal function is recommended in patients with the following risk factors:
advanced age;
simultaneous use with ACE inhibitors, angiotensin II antagonists, sartans, diuretics (see section "Interaction with other medicinal products and other types of interactions");
hypovolemia (of any origin); congestive heart failure; renal failure; nephrotic syndrome; lupus nephropathy; severe hepatic dysfunction (plasma albumin
In rare cases, NSAIDs can lead to interstitial nephritis, glomerulonephritis, renal medullary necrosis, or nephrotic syndrome.
The dose of meloxicam for patients with end-stage renal disease on dialysis should not exceed 7.5 mg. In patients with mild to moderate renal impairment (creatinine clearance >25 ml/min), the dose may not be reduced.
Sodium, potassium and water retention.
NSAIDs may increase sodium, potassium and water retention and influence the natriuretic effect of diuretics. In addition, the antihypertensive effect of antihypertensive drugs may be reduced (see section "Interaction with other medicinal products and other types of interactions"). As a result, in susceptible patients, an increase in the severity or exacerbation of edema, heart failure or arterial hypertension may persist. Therefore, clinical monitoring is recommended in patients at risk of sodium, potassium and water retention (see sections "Method of administration and dosage" and "Contraindications").
Hyperkalemia.
Hyperkalemia may be caused by diabetes mellitus or concomitant use of potassium-sparing medicinal products (see section 4.5). In such cases, potassium levels should be monitored regularly.
Combination with pemetrexed
In patients with mild to moderate renal impairment receiving pemetrexed, meloxicam treatment should be discontinued at least 5 days before, on the day of, and for at least 2 days after pemetrexed administration (see section 4.5).
Other warnings and precautions.
Adverse reactions are often worse tolerated by elderly, frail or debilitated patients who require close monitoring. As with other NSAIDs, caution should be exercised in the elderly, who are more likely to have decreased renal, hepatic and cardiac function. Elderly patients have a higher incidence of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which can be fatal (see section 4.2).
Meloxicam, like any other NSAID, may mask the symptoms of infectious diseases.
As with other nonsteroidal anti-inflammatory drugs, abscess or necrosis may occur at the injection site.
The use of meloxicam may impair reproductive function and is not recommended in women attempting to conceive. Therefore, in women planning pregnancy or undergoing investigation of infertility, discontinuation of meloxicam should be considered (see section "Use during pregnancy and lactation").
This medicinal product contains less than 1 mmol sodium (23 mg) per 1.5 ml ampoule, i.e. essentially sodium-free.
Masking inflammation and fever.
The pharmacological action of meloxicam to reduce fever and inflammation may complicate the diagnosis of suspected non-infectious pain syndrome.
Corticosteroid treatment.
ALGEZICAM® cannot be a likely substitute for corticosteroids in the treatment of corticosteroid insufficiency.
Hematological effects.
Anemia may be observed in patients receiving nonsteroidal anti-inflammatory drugs, including ALGEZICAM®. This may be due to fluid retention, gastrointestinal bleeding of unknown origin, or macroscopic or fully described effects on erythropoiesis. Patients on long-term treatment with NSAIDs, including ALGEZICAM®, should have their hemoglobin or hematocrit monitored if symptoms and signs of anemia are detected.
Use in patients with asthma.
Patients with asthma may experience aspirin-sensitive asthma. The use of acetylsalicylic acid in patients with aspirin-sensitive asthma has been associated with severe bronchospasm, which can be fatal. Given the cross-reactivity, including bronchospasm, between acetylsalicylic acid and other NSAIDs, ALGEZICAM® should not be used in patients sensitive to acetylsalicylic acid and should be prescribed with caution to patients with asthma.
Use during pregnancy and breastfeeding.
Pregnancy. Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonal/fetal development. Epidemiological data suggest an increased risk of miscarriage and of cardiac malformations and gastroschisis following exposure to prostaglandin synthesis inhibitors in early pregnancy. The absolute risk of cardiac malformations has increased from less than 1% to approximately 1.5%. This risk is expected to increase with increasing dose and duration of treatment.
During the first and second trimesters of pregnancy, meloxicam should not be used unless clearly necessary. If a woman attempting to conceive or who is pregnant during the first and second trimesters of pregnancy uses meloxicam, the dosage and duration of treatment should be kept to a minimum.
In the third trimester of pregnancy, all prostaglandin synthesis inhibitors may pose a risk to the fetus:
cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension); renal dysfunction, which may progress to renal failure with oligohydramnios.
Possible risks in the last stages of pregnancy for the mother and newborn:
the possibility of prolonging bleeding time, anti-aggregation effect even at very low doses; suppression of uterine contractions, which leads to a delay or prolongation of labor.
Therefore, meloxicam is contraindicated in the third trimester of pregnancy.
Breastfeeding. Although there are no specific data on the drug ALGEZIKAM ®, it is known that NSAIDs can pass into breast milk. Therefore, the use of the drug is not recommended for women who are breastfeeding.
Fertility. ALGEZICAM®, like other drugs that inhibit cyclooxygenase/prostaglandin synthesis, may have an adverse effect on reproductive function and is not recommended in women attempting to conceive. Therefore, in women attempting to conceive or undergoing investigation of infertility, discontinuation of meloxicam should be considered.
The ability to influence the reaction speed when driving or working with other mechanisms.
There are no specific studies on the effect of the drug on the ability to drive or use machines. However, based on the pharmacodynamic profile and the adverse reactions identified, it can be assumed that meloxicam has no or negligible influence on these activities. However, patients who have experienced visual impairment, including blurred vision, dizziness, drowsiness, vertigo or other central nervous system disorders, are advised to refrain from driving or operating machinery.
Method of administration and doses.
Dosage.
Intramuscular application.
One injection of 15 mg once daily.
Do not exceed the dose of 15 mg/day.
Treatment should be limited to a single injection at the start of therapy with a maximum duration of up to 2-3 days in justified exceptional cases (e.g. when oral and rectal routes of administration are not possible). Adverse reactions can be minimized by using the lowest effective dose for the shortest duration of treatment necessary to achieve control. (See section "Special instructions").
The patient's need for symptomatic relief and response to treatment should be assessed periodically.
Special categories of patients.
Elderly patients and patients at increased risk of developing adverse reactions.
The recommended dose for elderly patients is 7.5 mg per day. Patients at increased risk of adverse reactions should start treatment with 7.5 mg per day (half a 1.5 ml ampoule) (see section "Special instructions").
Kidney failure.
For patients with severe renal insufficiency on dialysis, the dose should not exceed 7.5 mg per day (half a 1.5 ml ampoule).
No dose reduction is required in patients with mild to moderate renal impairment (creatinine clearance 25 ml/min). For patients with severe renal impairment not requiring dialysis, see section "Contraindications".
Liver failure.
No dose reduction is required in patients with mild to moderate hepatic impairment. For patients with severe hepatic impairment, see section "Contraindications".
Method of application.
For intramuscular use.
The drug should be administered slowly, by deep intramuscular injection into the upper outer quadrant of the buttock, observing aseptic conditions. In case of repeated administration, it is recommended to alternate the left and right buttock. Before injection, it is important to check that the needle tip does not enter a vessel.
The injection should be stopped immediately if severe pain occurs during the injection.
In the case of a hip prosthesis, the injection should be given in the other buttock.
Children.
Algesicam®, solution for injection 15 mg/1.5 ml, is contraindicated in children (under 18 years of age) (see section “Contraindications”).
Symptoms.
Symptoms of acute NSAID overdose are usually limited to lethargy, drowsiness, nausea, vomiting, and epigastric pain, which are generally reversible with supportive therapy. Gastrointestinal bleeding may occur. Severe poisoning may result in hypertension, acute renal failure, hepatic dysfunction, respiratory depression, coma, convulsions, cardiovascular failure, and cardiac arrest. Anaphylactoid reactions have been reported with therapeutic use of NSAIDs, which may also occur with overdose.
Therapy.
In case of NSAID overdose, symptomatic and supportive measures are recommended. Studies have shown that the elimination of meloxicam is accelerated by administration of 4 oral doses of cholestyramine 3 times daily.
Adverse reactions.
Research and epidemiological data suggest that the use of some NSAIDs (especially at high doses and with long-term treatment) may be associated with a small increased risk of vascular thrombotic events (such as myocardial infarction or stroke) (see section "Special warnings and precautions for use").
Edema, hypertension, and heart failure have been observed with NSAID treatment.
Most of the side effects are of gastrointestinal origin. Ulceration, perforation or gastrointestinal bleeding may occur, sometimes fatal, especially in elderly patients (see section "Special warnings and precautions for use"). Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease have been observed after use (see section "Special warnings and precautions for use"). Gastritis has been observed less frequently.
Severe skin lesions have been reported: Stevens-Johnson syndrome and toxic epidermal necrolysis (see section "Special warnings and precautions for use").
Criteria for assessing the frequency of adverse drug reactions: very common (≥ 1/10); common (≥ 1/100,
From the blood and lymphatic system:
infrequently - anemia;
rarely - deviation of blood test indicators from the norm (including changes in the number of leukocytes), leukopenia, thrombocytopenia.
Very rare cases of agranulocytosis have been reported (see “Selected serious and/or common adverse reactions”).
On the part of the immune system:
infrequently - allergic reactions, except anaphylactic or anaphylactoid;
frequency unknown - anaphylactic reactions, anaphylactoid reactions, including shock.
Mental disorders:
rarely - mood swings, nightmares;
frequency unknown - confusion, disorientation, insomnia.
From the nervous system:
often - headache;
infrequently - dizziness, drowsiness.
On the part of the organs of vision:
rarely - visual disturbances, including blurred vision; conjunctivitis.
From the side of the organs of hearing and vestibular apparatus:
infrequently - dizziness;
rarely - ringing in the ears.
Cardiac disorders:
rarely - palpitations.
Heart failure has been reported in association with the use of nonsteroidal anti-inflammatory drugs.
From the vascular side:
infrequently - increased blood pressure (see section "Special instructions for use"), hot flashes.
From the respiratory system, chest organs and mediastinum:
rarely - asthma in patients allergic to acetylsalicylic acid and other non-steroidal anti-inflammatory drugs;
frequency unknown - upper respiratory tract infections, cough.
Gastrointestinal tract:
very often - digestive system disorders: dyspepsia, nausea, vomiting, abdominal pain, constipation, flatulence, diarrhea;
infrequently - hidden or macroscopic gastrointestinal bleeding, stomatitis, gastritis, belching;
rarely - colitis, gastroduodenal ulcer, esophagitis;
very rarely - gastrointestinal perforation;
frequency unknown - pancreatitis.
Gastrointestinal bleeding, ulceration or perforation may be severe and potentially fatal, especially in elderly patients (see section "Special warnings and precautions for use").
From the hepatobiliary system:
uncommon - abnormal liver function tests (e.g. increased transaminases or bilirubin)
very rarely - hepatitis;
frequency unknown - jaundice, liver failure.
Skin and subcutaneous tissue disorders:
infrequently - angioedema, itching, rash,
rarely - Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria;
very rarely - bullous dermatitis, mucositis
