Instructions for Melox tablets 15 mg No. 10
Composition
active ingredient: meloxicam;
1 tablet contains meloxicam 15 mg;
Excipients: sodium citrate*; lactose monohydrate; microcrystalline cellulose; povidone; crospovidone; colloidal anhydrous silica; magnesium stearate.
* Dihydrate.
Dosage form
Pills.
Main physicochemical properties: tablets are light yellow, round, flat, with a break line on one side. Diameter approximately 10.5 mm. Thickness: 2.85-3.35 mm.
Pharmacotherapeutic group
Nonsteroidal anti-inflammatory drugs (NSAIDs) and antirheumatic drugs. ATC code M01A C06.
Pharmacological properties
Pharmacodynamics
Melox 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. 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 well absorbed from the gastrointestinal tract after oral administration, with an absolute bioavailability of 90% (capsules). Tablets, oral suspension and capsules have shown bioequivalence. After a single dose of meloxicam, peak plasma concentrations are achieved within 5-6 hours for solid oral dosage forms (capsules and tablets).
With multiple dosing, steady-state concentrations are reached within 3-5 days. Once-daily dosing results in mean plasma concentrations with relatively small peak fluctuations: in the range of 0.4-1.0 μg/ml for 7.5 mg and 0.8-2.0 μg/ml for 15 mg, respectively (Cmin and Cmax at steady state, respectively). Mean steady-state plasma concentrations of meloxicam are reached within 5-6 hours for tablets, capsules and oral suspension, respectively.
Simultaneous food intake or the use of inorganic antacids does not affect the absorption of the drug.
Distribution. Meloxicam is highly bound to plasma proteins, mainly albumin (99%). Meloxicam penetrates into the synovial fluid, where the concentration is half that in blood plasma. The volume of distribution is low, averaging 11 l after intramuscular or intravenous administration, and shows individual variations 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 contribute to the metabolism to a lesser extent. 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 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 after oral, intramuscular and intravenous administration. 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. 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, AUC values were higher and 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.
Indication
Short-term symptomatic treatment of exacerbations of osteoarthritis. Long-term symptomatic treatment of rheumatoid arthritis and ankylosing spondylitis.
Contraindication
Hypersensitivity to meloxicam or to other components of the drug, or to active substances with a similar effect, such as NSAIDs, aspirin. Meloxicam should not be prescribed to patients who have experienced symptoms of asthma, nasal polyps, angioedema or urticaria after taking aspirin or other NSAIDs; III trimester of pregnancy (see section "Use during pregnancy and lactation"); children under 16 years of age; 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; history of gastrointestinal bleeding, cerebrovascular bleeding or other blood clotting disorders; severe heart failure; treatment of perioperative pain in coronary artery bypass grafting (CABG).
Interaction with other medicinal products and other types of interactions
Interaction studies have only been conducted with adults.
Risks associated with hyperkalemia
Some medicinal products or therapeutic groups may contribute to hyperkalaemia: potassium salts, potassium-sparing diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, non-steroidal anti-inflammatory drugs, (low molecular weight or unfractionated) heparins, ciclosporin, 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: Combination with other NSAIDs is not recommended (see section 4.4), including acetylsalicylic acid at doses ≥ 500 mg per dose or ≥ 3 g total daily dose).
Corticosteroids (e.g. glucocorticoids): Concomitant use with corticosteroids requires caution due to increased risk of gastrointestinal bleeding or ulceration.
Anticoagulants or heparin used in geriatric practice or at therapeutic doses. 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 in geriatric practice or at therapeutic doses is not recommended (see section "Special instructions").
In other cases, heparin should be used with caution due to the increased risk of bleeding. Careful monitoring of the INR (international normalized ratio) is necessary if the combination is proven to be unavoidable.
Thrombolytic and antiplatelet agents: 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). As with the following drugs, the antihypertensive effect of beta-blockers may be reduced (due to inhibition of vasodilating prostaglandins).
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.
Intrauterine contraceptives:
NSAIDs may reduce the effectiveness of intrauterine contraceptives.
There have been previous reports of decreased efficacy of NSAID intrauterine devices, which requires further confirmation.
Lithium. There is evidence that NSAIDs increase the level of lithium in the blood plasma (due to a decrease in the renal excretion of lithium), which can reach toxic levels. The simultaneous use of lithium and NSAIDs is not recommended (see section "Special instructions"). If combination therapy is necessary, careful monitoring of the content of lithium in the blood plasma is necessary at the beginning of treatment, during dose adjustment and when discontinuing treatment with meloxicam.
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 using low doses of methotrexate, in particular in patients with impaired renal function. If combined treatment is necessary, blood counts and renal function should be monitored. Caution should be exercised if 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 haematological toxicity of methotrexate may be increased by treatment with NSAIDs (see information above) (see section "Adverse reactions").
Pemetrexed. When meloxicam is co-administered with pemetrexed in patients with mild to moderate renal impairment (creatinine clearance 45 to 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, particularly 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: 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 was found when co-administered with antacids, cimetidine, and digoxin.
Application features
Adverse reactions can be minimised by using the lowest effective dose for the shortest period of time necessary to control symptoms (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 relieve 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 in order to ensure that they are completely cured before starting therapy with meloxicam. Patients treated with meloxicam and patients with a history of such cases should be regularly monitored for possible recurrence.
Gastrointestinal disorders.
As with other NSAIDs, 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 higher with increasing NSAID doses in patients with a history of ulcer, particularly complicated by bleeding or perforation (see section 4.3), and in elderly patients. In such patients, treatment should be initiated at the lowest effective dose. Combination therapy with protective agents (such as misoprostol or proton pump inhibitors) should be considered for such patients, as well as for patients who require concomitant use of low-dose aspirin or other agents that increase gastrointestinal risks (see information below and section 4.5).
The use of meloxicam is not recommended in patients receiving concomitant medications that may increase the risk of ulceration or bleeding, including heparin, as a radical therapy or in geriatric practice, anticoagulants such as warfarin, or other non-steroidal anti-inflammatory drugs, including 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.
In patients taking NSAIDs (including Meloxicam), elevations of one or more liver function tests may occur. These laboratory abnormalities may progress, may remain unchanged, or may be transient with continued treatment. 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.
Patients with symptoms or suspected liver dysfunction, or who have had abnormal liver function tests, should be evaluated for the development of symptoms of more severe liver failure during Melox therapy. If clinical signs and symptoms are consistent with the development of liver disease or if systemic manifestations of the disease (e.g. eosinophilia, rash, etc.) are observed, Melox 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.
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 (e.g. 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 consideration. Such consideration is necessary before initiating long-term treatment in patients with risk factors for cardiovascular disease (such as hypertension, hyperlipidemia, diabetes mellitus, smoking).
NSAIDs may increase the risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which may be 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.
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 blisters or mucosal lesions), meloxicam treatment 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 has developed Stevens-Johnson syndrome or toxic epidermal necrolysis while using meloxicam, the drug should not be restarted at any time in the future.
Anaphylactic reactions.
As with other NSAIDs, anaphylactic reactions may occur in patients with no known reaction to Melox. Melox should not be used in patients with the aspirin triad. This symptom complex occurs in patients with asthma who have reported 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 anaphylactoid reaction occurs.
As with most NSAIDs, isolated cases of increased serum transaminases, increased serum bilirubin or other liver function parameters, as well as increased serum creatinine and blood urea nitrogen, and other laboratory abnormalities have been reported. 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, by inhibiting the vasodilatory effects of renal prostaglandins, may induce functional renal failure due to a decrease in 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:
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, the dose may not be reduced (creatinine clearance greater than 25 ml/min).
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 "Interaction with other medicinal products and other forms of interaction"). As a result, edema, heart failure or hypertension may be precipitated or aggravated in susceptible patients. Therefore, clinical monitoring is recommended in patients at risk (see sections "Dosage and administration" and "Contraindications").
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. 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.
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).
Melox 15 mg tablets contain lactose, therefore this drug is not recommended for patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.
Masking inflammation and fever.
The pharmacological action of Melox to reduce fever and inflammation may complicate the diagnosis of suspected non-infectious pain conditions.
Corticosteroid treatment.
Melox cannot be a likely substitute for corticosteroids in the treatment of corticosteroid insufficiency.
Hematological effects.
Anemia may occur in patients receiving NSAIDs, including Meloxicam. This may be due to fluid retention, gastrointestinal bleeding of unknown origin, or macroscopic or incompletely described effects on erythropoiesis. Patients on long-term treatment with NSAIDs, including Meloxicam, should have their hemoglobin or hematocrit monitored if they develop symptoms of anemia.
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 taking Melox who may have adverse effects related to changes in platelet function, including coagulation disorders, or patients receiving anticoagulants should be carefully monitored.
Patients with asthma may have aspirin-sensitive asthma. The use of aspirin in patients with aspirin-sensitive asthma has been associated with severe bronchospasm, which may be fatal. Because of cross-reactivity, including bronchospasm, between aspirin and other NSAIDs, Meloxicam should not be used in patients sensitive to aspirin and should be prescribed with caution in patients with pre-existing 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. However, based on the pharmacodynamic profile and the observed adverse reactions, it can be assumed that meloxicam is likely to have no or negligible influence on these activities. 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
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.
Pregnancy. Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryo-foetal development. Epidemiological data suggest an increased risk of miscarriage and of cardiac malformations and gastroschisis after use of 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 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. If meloxicam is used by a woman attempting to conceive or during the first and second trimesters of pregnancy, the dosage and duration of treatment should be kept to the minimum.
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 woman and the fetus:
possibility of 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 Melox, NSAIDs are known to pass into breast milk. Therefore, use is not recommended in women who are breastfeeding.
Method of administration and doses
Administer orally.
The total daily amount of the drug should be taken once, washed down with water or other liquid, during meals.
Adverse reactions can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.4). The patient's need for symptomatic relief and response to treatment should be reassessed periodically.
Exacerbation of osteoarthritis:
7.5 mg/day (half a 15 mg tablet). If necessary, the dose can be increased to 15 mg/day (1 15 mg tablet).
Rheumatoid arthritis, ankylosing spondylitis:
15 mg/day (1 tablet of 15 mg).
See also the section “Special patient categories” below.
According to the therapeutic effect, the dose can be reduced to 7.5 mg/day (half a 15 mg tablet).
DO NOT EXCEED THE DOSE OF 15 mg/day.
Special categories of patients.
Elderly patients and patients at increased risk of developing adverse reactions.
The recommended dose for long-term treatment of rheumatoid arthritis and ankylosing spondylitis in elderly patients is 7.5 mg/day. Patients at increased risk of adverse reactions should start treatment with 7.5 mg/day (see section 4.4).
Kidney failure.
For patients with severe renal insufficiency who are on dialysis, the dose should not exceed 7.5 mg per day.
No dose reduction is required in patients with mild to moderate renal impairment (i.e., patients with creatinine clearance above 25 mL/min) (for patients with severe renal impairment not requiring dialysis, see section 4.3).
Liver failure.
No dose reduction is required in patients with mild to moderate hepatic impairment (for patients with severe hepatic impairment, see section "Contraindications").
Children
Melox, 15 mg tablets, is contraindicated in children under 16 years of age (see section "Contraindications").
Overdose
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.
In case of NSAID overdose, symptomatic and supportive measures are recommended. Studies have shown that the elimination of meloxicam is accelerated by taking 4 oral doses of cholestyramine 3 times a day.
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 (e.g. 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, may occur, especially in elderly patients (see section "Special instructions"). Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease (see section "Special instructions"). Gastritis has been observed less frequently after administration.
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 < 1/10); uncommon (≥ 1/1000 < 1/100); rare (≥ 1/10000 < 1/1000); very rare (<1/10000); unknown (cannot be determined from available data).
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.
Cases of agranulocytosis have been reported very rarely (see Selected serious and/or common adverse reactions).
On the part of the immune system:
infrequently - allergic reactions, except anaphylactic or anaphylactoid;
not known - anaphylactic reaction, anaphylactoid reaction, including shock.
Mental disorders:
rarely - mood swings, nightmares;
unknown - confusion, disorientation, insomnia.
From the nervous system:
often - headache
infrequently - dizziness, drowsiness.
On the part of the organs of vision:
Rare: 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 - feeling of palpitations.
Heart failure has been reported in association with NSAID treatment.
Vascular disorders:
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 aspirin and other NSAIDs;
unknown - upper respiratory tract infections, cough.
From the digestive tract:
very often - digestive system disorders: dyspepsia, nausea, vomiting, abdominal pain, constipation, flatulence, diarrhea;
infrequently - occult or macroscopic gastrointestinal bleeding, stomatitis, gastritis, belching;
rarely – colitis, gastroduodenal ulcer, esophagitis;
very rarely - gastrointestinal perforation.
Gastrointestinal bleeding, ulceration or perforation may be severe and potentially fatal, especially in the elderly (see section 4.4).
unknown – pancreatitis.
From the hepatobiliary system:
infrequently - abnormal liver function tests (e.g. increased transaminases or bilirubin);
very rarely – hepatitis;
unknown - jaundice, liver failure.
