Instructions Alsocam solution for injection 10 mg/ml ampoule 1.5 ml No. 5
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.
Pharmacotherapeutic group
Nonsteroidal anti-inflammatory and antirheumatic drugs. ATC code M01A C06.
Pharmacological properties
Pharmacodynamics
ALSOKAM is a nonsteroidal anti-inflammatory drug (NSAID) of the enoleic acid class that has anti-inflammatory, analgesic, and antipyretic effects.
Meloxicam has shown high anti-inflammatory activity in all standard models of inflammation. Its exact mechanism of action remains unknown. However, there is a common mechanism of action for all NSAIDs (including meloxicam): inhibition of the biosynthesis of prostaglandins, which are mediators of inflammation.
Pharmacokinetics
Absorption. Meloxicam is completely absorbed after intramuscular injection. The relative bioavailability compared to oral administration is almost 100%. Therefore, dose adjustment is not required when switching from the intramuscular to oral route of administration. After an intramuscular injection 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 highly bound to plasma proteins, mainly albumin (99%). Meloxicam penetrates into the synovial fluid, where its concentration is half that in plasma. The volume of distribution is low, on average 11 l after intramuscular or intravenous administration, with individual deviations in the range of 7-20%. The volume of distribution after multiple oral doses of meloxicam (7.5 to 15 mg) is 16 l with a coefficient of variation in the range of 11% to 32%.
Biotransformation: Meloxicam undergoes extensive biotransformation in the liver.
Four different metabolites of meloxicam have been identified in urine, which are pharmacodynamically inactive. The main 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 play a minor role. Peroxidase activity in patients is probably responsible for the other two metabolites, which account for 16% and 4% of the administered dose, respectively.
Elimination. Meloxicam is excreted mainly in the form of 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 is 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, intravenous or rectal administration.
Dose linearity: Meloxicam exhibits linear pharmacokinetics within the therapeutic dose range of 7.5 mg to 15 mg after oral and intramuscular 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. Patients with moderate renal insufficiency had a significantly higher total clearance. Reduced binding to plasma proteins was 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 (see sections “Method of administration and dosage” and “Contraindications”).
Elderly patients. In elderly male patients, mean pharmacokinetic parameters were similar to those in young male volunteers. In elderly female patients, AUC values were 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 (see section 4.2).
Indication
For short-term symptomatic treatment of acute attacks of rheumatoid arthritis and ankylosing spondylitis when other routes of administration cannot be used.
Contraindication
III trimester of pregnancy (see section "Use during pregnancy or 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, aspirin. Meloxicam should not be prescribed to patients who have developed symptoms of asthma, nasal polyps, angioedema or urticaria after taking aspirin or other NSAIDs; history of gastrointestinal bleeding or perforation associated with previous NSAID therapy; active or recurrent peptic ulcer/bleeding in history (two or more separate confirmed cases of ulceration or bleeding); severe hepatic failure; severe renal failure without dialysis; gastrointestinal bleeding, cerebrovascular bleeding in history or other blood clotting disorders; Hemostasis disorders or concomitant use of anticoagulants (contraindications related to the route of administration); severe heart failure. Do not use for the treatment of perioperative pain in coronary artery bypass grafting (CABG).
Interaction with other medicinal products and other types of interactions
Risks associated with hyperkalemia
Some drugs may contribute to hyperkalemia: potassium salts, potassium-sparing diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, nonsteroidal anti-inflammatory drugs, heparins (low molecular weight or unfractionated), cyclosporine, tacrolimus, and trimethoprim.
The onset of hyperkalemia may depend on whether there are associated factors. The risk of hyperkalemia is increased if the above-mentioned drugs are used concomitantly with meloxicam.
Pharmacodynamic interactions.
Other non-steroidal anti-inflammatory drugs (NSAIDs) and acetylsalicylic acid ≥ 3 g/day. Combination with other NSAIDs (see section "Special warnings and precautions for use"), acetylsalicylic acid in doses ≥ 500 mg per dose or ≥ 3 g total daily dose is not recommended.
Corticosteroids (e.g. glucocorticoids): Concomitant use with corticosteroids requires caution due to increased risk of gastrointestinal bleeding or ulceration.
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 concomitant use of NSAIDs and anticoagulants or heparin is not recommended in geriatric practice or at therapeutic doses. Due to the intramuscular administration, meloxicam solution for injection is contraindicated in patients receiving anticoagulant treatment (see sections "Contraindications" and "Special instructions").
In other cases (e.g., at prophylactic doses), caution is required when using heparin 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 (e.g. dehydrated patients or elderly patients with impaired renal function), the concomitant use of ACE inhibitors or angiotensin II antagonists and drugs that inhibit cyclooxygenase 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 concomitant therapy and periodically thereafter (see section 4.4).
Other antihypertensive drugs (e.g. beta-blockers). Possible reduction of the antihypertensive effect of beta-blockers (due to inhibition of prostaglandins with vasodilating effect).
Calcineurin inhibitors (e.g. cyclosporine, tacrolimus). The nephrotoxicity of calcineurin inhibitors may be potentiated by NSAIDs through mediation of the effects of renal prostaglandins. 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 increases the risk of gastrointestinal adverse reactions. Caution should be exercised when combining these drugs.
Pharmacokinetic interaction: the effect of meloxicam on the pharmacokinetics of other drugs.
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 (more than 15 mg/week) (see section "Special warnings and precautions for use"). The risk of interaction between NSAIDs and methotrexate should also be considered when prescribing to patients receiving low doses of methotrexate, including patients with impaired renal function. If combined treatment is necessary, blood counts and renal function should be monitored. Caution should be exercised when NSAIDs and methotrexate are taken for 3 consecutive days, as plasma levels of methotrexate may increase and toxicity may increase. Although the pharmacokinetics of methotrexate (15 mg/week) were not affected by concomitant treatment with meloxicam, it should be considered that the hematological toxicity of methotrexate may be increased by treatment with NSAIDs (see above and also section "Adverse reactions").
Pemetrexed. When meloxicam is co-administered with pemetrexed in patients with creatinine clearance between 45 and 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. In patients with severe renal impairment (creatinine clearance below 45 ml/min), the co-administration 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 and therefore increase the incidence of adverse reactions associated with pemetrexed. Therefore, caution should be exercised when prescribing 15 mg meloxicam concomitantly with pemetrexed in patients with normal renal function (creatinine clearance ≥ 80 ml/min).
Pharmacokinetic interaction: the effect of other drugs on the pharmacokinetics of meloxicam.
Cholestyramine accelerates the elimination of meloxicam by disrupting intrahepatic circulation, so the clearance of meloxicam increases by 50% and the half-life decreases to 13 ± 3 hours. This interaction is clinically significant.
Pharmacokinetic interaction: effect of the combination of meloxicam and other drugs on pharmacokinetics.
Oral antidiabetic agents (sulfonylureas, nateglinide)
Meloxicam is almost entirely eliminated by hepatic metabolism, approximately two-thirds of which is mediated by cytochrome (CYP) P450 enzymes (primary CYP 2C9 and minor CYP 3A4) and one-third by other pathways, such as peroxidase oxidation. The possibility of pharmacokinetic interactions should be considered when meloxicam is co-administered with medicinal products that are known to inhibit or are metabolised by CYP 2C9 and/or CYP 3A4. Interactions mediated by CYP 2C9 may be expected in combination with medicinal products such as oral antidiabetic agents (sulfonylureas, nateglinide); this interaction may lead to increased plasma levels of these agents and meloxicam. Patients taking meloxicam and a sulfonylurea or nateglinide should be closely monitored for hypoglycaemia.
No clinically significant pharmacokinetic interaction was found when co-administered with antacids, cimetidine, and digoxin.
Children
Interaction studies were conducted only in adults.
Application features
Adverse reactions can be minimized by using the lowest effective dose for the shortest duration (see section “Dosage and Administration” and information on gastrointestinal and cardiovascular risks below).
The recommended maximum daily dose should not be exceeded in case of insufficient therapeutic effect, nor should additional NSAIDs be used, as this may increase toxicity while the therapeutic benefit has not been proven. The concomitant use of meloxicam with NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided.
Meloxicam should not be used to treat patients who require relief of acute pain.
If there is no improvement after several days, the clinical benefit of treatment should be reassessed.
Attention should be paid to a history of esophagitis, gastritis and/or peptic ulcer to ensure that they are completely treated before starting meloxicam therapy. Patients treated with meloxicam and patients with a history of such cases should be regularly monitored for possible recurrence.
Gastrointestinal disorders.
The risk of gastrointestinal bleeding, ulceration or perforation is greater with increasing NSAID doses in patients with a history of ulcer, particularly complicated by bleeding or perforation (see section 4.3), and in the elderly. In such patients, treatment should be initiated at the lowest effective dose. For these patients, as well as for patients requiring concomitant low-dose aspirin or other medicinal products that increase gastrointestinal risks, combination therapy with protective medicinal products (such as misoprostol or proton pump inhibitors) may be required (see information below and section 4.5).
Patients with a history of gastrointestinal toxicity, especially elderly patients, should report any unusual abdominal symptoms (especially gastrointestinal bleeding), especially during the initial stages of treatment.
The use of meloxicam is not recommended in patients taking concomitant medications that increase the risk of ulceration or bleeding, such as heparin, anticoagulants, including warfarin, or other non-steroidal anti-inflammatory drugs, or acetylsalicylic acid at doses ≥ 500 mg per 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 ALSOCAM) may have 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 (alanine aminotransferase) or AST (aspartate aminotransferase) levels (approximately three times or more above normal) have been reported in 1% of patients during clinical trials with NSAIDs. In addition, rare cases of severe 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 signs of hepatic dysfunction or abnormal liver function tests should be evaluated for the development of more severe hepatic impairment during therapy with ALSOKAM. If clinical signs and symptoms suggest the possibility of liver disease or if systemic manifestations of the disease (e.g. eosinophilia, rash, etc.) are observed, ALSOKAM should be discontinued.
Cardiovascular disorders.
Close monitoring 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) is associated with a small increased risk of vascular thrombotic events (such as myocardial infarction or stroke). There is insufficient evidence to exclude such a risk with use.
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 evaluation. Such evaluation is necessary before initiating long-term treatment in patients with risk factors for cardiovascular disease (e.g. hypertension, hyperlipidemia, diabetes mellitus, smoking).
NSAIDs increase the risk of serious cardiovascular thrombotic events, myocardial infarction and stroke, which can be fatal. The increased risk is related to the duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease are at increased risk of thrombotic events.
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 highest 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. progressive skin rash, often with blisters or mucosal lesions), meloxicam should be discontinued. It is important to promptly diagnose and discontinue any drugs that may cause severe skin reactions: Stevens-Johnson syndrome or toxic epidermal necrolysis. 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, treatment with the drug should not be resumed at any time in the future.
Anaphylactic reactions.
As with other NSAIDs, anaphylactic reactions may occur in patients who have not previously reacted to meloxicam. ALSOKAM should not be used in patients with the aspirin triad. This symptom complex occurs in patients with asthma who have experienced rhinitis, with or without nasal polyps, or who have experienced severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs. Emergency care should be sought if an anaphylactic reaction occurs.
Liver parameters and kidney function.
In the treatment of NSAIDs, isolated cases of increased serum transaminases, serum bilirubin or other liver function parameters, increased serum creatinine and blood urea nitrogen, as well as other laboratory abnormalities have been observed. In most cases, these abnormalities were minor and transient. If significant or persistent confirmation of such abnormalities occurs, meloxicam should be discontinued and control tests should be 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 renal function, including urine output, is recommended in patients with the following risk factors:
- old age;
- concomitant 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 (serum albumin 25 g/l or ≥ 10 according to the Child-Pugh classification).
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 may interfere with the natriuretic effects of diuretics. In addition, the antihypertensive effect of antihypertensive drugs may be reduced (see section 4.5). As a result, edema, heart failure or hypertension may be precipitated or exacerbated in susceptible patients. Therefore, clinical monitoring is recommended in patients at risk of sodium, potassium and water retention (see sections 4.2 and 4.3).
Hyperkalemia.
Hyperkalemia may be caused by diabetes mellitus or concomitant use of medicinal products that increase potassium levels (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 suspended for at least 5 days prior to, on the day of, and for at least 2 days following 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. Caution should be exercised when treating elderly patients with NSAIDs, as they 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).
With intramuscular use of NSAIDs, abscess or necrosis may occur at the injection site.
Meloxicam may impair 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 (see section 4.6).
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 ALSOKAM, aimed at reducing fever and inflammation, may reduce the usefulness of diagnostic data in determining complications of a suspected non-infectious painful condition.
Corticosteroid treatment.
The drug ALSOKAM cannot be a substitute for corticosteroids in the treatment of corticosteroid insufficiency.
Hematological effects.
Anemia may occur in patients receiving NSAIDs, including ALSOCAM. This may be due to fluid retention, gastrointestinal bleeding of unknown origin or macroscopic bleeding, or effects on erythropoiesis. During long-term treatment with NSAIDs, including ALSOCAM, the patient's hemoglobin or hematocrit should be monitored if symptoms and signs of anemia are present.
NSAIDs inhibit platelet aggregation and may prolong bleeding time in some patients. Unlike aspirin, their effect on platelet function is quantitatively smaller, short-lived, and reversible. Patients prescribed ALSOCAM who may have adverse effects on platelet function, such as coagulation disorders, and patients receiving anticoagulants should be carefully monitored.
Use in patients with asthma.
Patients with asthma may have aspirin-induced asthma. The use of aspirin in patients with aspirin-induced asthma has been associated with severe bronchospasm, which may be fatal. Because of cross-reactivity, including bronchospasm, between aspirin and other NSAIDs, ALSOKAM should not be used in patients sensitive to aspirin and should be used with caution in patients with asthma.
Ability to influence reaction speed when driving vehicles or other mechanisms
There are no specific studies on the effects of the drug on the ability to drive or use machines. Given the pharmacodynamic profile and adverse reactions of meloxicam, no significant effect on these activities is expected. However, patients who have experienced visual disturbances, including blurred vision, dizziness, drowsiness, vertigo or other central nervous system disorders, are advised to refrain from driving or using machines.
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 of cardiac malformations and gastroschisis following the use of prostaglandin synthesis inhibitors in early pregnancy. The absolute risk of cardiac malformations increases from less than 1% to approximately 1.5%. This risk is thought 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. For women attempting to conceive and for pregnant women during the first and second trimesters, the dosage and duration of treatment with meloxicam should be kept as low as possible.
During 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:
prolongation of bleeding time, anti-aggregation effect, even at very low doses; suppression of uterine contractions, leading to delayed or prolonged labor.
Therefore, meloxicam is contraindicated during the third trimester of pregnancy.
Breastfeeding. Although there are no specific data for ALSOKAM, NSAIDs are known to pass into breast milk. Therefore, use is not recommended in women who are breastfeeding.
Fertility: Meloxicam, 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 planning pregnancy or undergoing investigation of infertility, discontinuation of meloxicam should be considered.
Method of administration and doses
Dosage.
One injection of 15 mg once daily.
DO NOT EXCEED THE DOSE OF 15 mg/day.
The patient's need for symptomatic relief and response to treatment should be assessed periodically.
Special categories of patients.
Elderly patients (see Pharmacokinetics section)
The recommended dose for elderly patients is 7.5 mg per day (half a 1.5 ml ampoule) (see also the subsection “Patients at increased risk of developing adverse reactions” and the section “Special instructions for use”).
Patients at increased risk of adverse reactions (see section "Special warnings and precautions for use")
For patients at increased risk of adverse reactions, such as those with a history of gastrointestinal disease or risk factors for cardiovascular disease, treatment should be initiated at a dose of 7.5 mg per day (half a 1.5 ml ampoule).
Kidney failure.
This medicinal product is contraindicated in patients with severe renal impairment not undergoing haemodialysis (see section “Contraindications”).
For patients with end-stage renal failure on hemodialysis, 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 (i.e., patients with creatinine clearance above 25 mL/min).
Liver failure.
No dose reduction is required in patients with mild to moderate hepatic impairment. The drug is contraindicated in patients with severe hepatic impairment (see section "Contraindications").
Method of application.
For intramuscular use.
The 10 mg/ml solution for injection is administered by deep intramuscular injection into the upper outer quadrant of the buttock using strict aseptic technique. 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 blood vessel.
The injection should be stopped immediately if severe pain occurs during the injection.
If the patient has a hip prosthesis, the injection should be given in the other buttock.
To continue treatment, oral forms of the drug (tablets) should be used.
Children
ALSOKAM, solution for injection 10 mg/ml, is contraindicated in children (under 18 years of age) (see section “Contraindications”).
Overdose
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 administration of 4 oral doses of cholestyramine 3 times daily results in accelerated elimination of meloxicam.
Adverse reactions
Research and epidemiological data suggest that the use of some NSAIDs (especially at high doses and with long-term treatment) slightly increases the 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 observed side effects are of gastrointestinal origin. Peptic ulcer, perforation or gastrointestinal bleeding, sometimes fatal, especially in elderly patients, may occur (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 the use of NSAIDs (see section "Special warnings and precautions for use"). Gastritis has been observed less frequently.
Severe skin reactions 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:
uncommon - anemia;
rare - deviations of blood parameters 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” below).
On the part of the immune system:
uncommon - allergic reactions, except anaphylactic or anaphylactoid;
frequency unknown - anaphylactic shock, anaphylactic reaction, anaphylactoid reaction, including shock.
Mental disorders:
isolated - mood swings, nightmares;
frequency unknown - confusion, disorientation, insomnia.
From the nervous system:
frequent - headache;
Infrequent: dizziness, drowsiness.
On the part of the organs of vision:
rare - visual function disorders, including blurred vision; conjunctivitis.
From the side of the organs of hearing and vestibular apparatus:
infrequent - dizziness;
