Meloxicam Tablets Instructions

[Date of Approval
[Date of revision
 Meloxicam Tablets Instructions
Please read the instructions carefully and use under the guidance of a physician
 Drug Name]
Generic Name: Meloxicam Tablets
Trade name: Hongqiang
English name: Meloxicam Tablets
Chinese Pinyin: Meiluoxikang Pian
Ingredients
The main ingredient of this product is meloxicam.
Chemical name: 2-methyl-4-hydroxy-N-(5-methyl-2-thiazolyl) -2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide
Chemical structure formula.
Molecular formula: C14H13N3O4S2
Molecular weight: 351.40
Excipients: lactose, microcrystalline cellulose, cross-linked povidone, povidone, sodium citrate, silicon dioxide, magnesium stearate
Properties
This product is light yellow or yellow tablets.
Indications
-Short-term symptom treatment in case of exacerbation of osteoarthritis symptoms.
-Long-term symptom treatment for rheumatoid arthritis and ankylosing spondylitis.
Specification
7.5mg
Dosage and Administration
Take orally.
-When symptoms of osteoarthritis worsen: 1 tablet once, once a day. If symptoms do not improve, the dose may be increased to 2 tablets once, once a day if needed; 7.5mg per tablet.
-Rheumatoid arthritis, ankylosing spondylitis: 2 tablets once a day, or depending on the response after treatment, the dose may be reduced to 1 tablet once a day; 7.5 mg per tablet (see “Special Populations”).
Daily dose should not exceed 15mg/day.
The total daily dose should be taken as a single dose with water or other fluids with food. Using the lowest effective dose for the shortest period of time to control symptoms may minimize adverse effects (see [Precautions]). Patients should be re-evaluated periodically for symptom relief and treatment response, especially in patients with osteoarthritis.
Special Populations.
Elderly patients and patients at increased risk of adverse reactions.
In elderly patients, the recommended dose for long-term treatment of rheumatoid arthritis and ankylosing spondylitis is 7.5 mg/day. The starting dose for patients at increased risk of adverse reactions is 7.5 mg/day.
Patients with renal insufficiency.
In patients with severe renal failure requiring dialysis, the dose should not exceed 7.5 mg/day.
Patients with mild to moderate renal insufficiency (i.e., patients with creatinine clearance greater than 25 ml/min) do not require a dose reduction.
Patients with severe renal failure not requiring dialysis, see [Contraindications].
Patients with hepatic insufficiency.
No dose reduction is required in patients with mild to moderate hepatic insufficiency.
Patients with severe hepatic insufficiency, see [Contraindications].
Children and Adolescents.
This product should not be used in children and adolescents under 16 years of age.
[Adverse Reactions].
According to foreign literature: the adverse reactions listed below may be related to the administration of this product.
The following conventions are used to indicate the incidence of adverse reactions.
Very common (≥10%), common (1% to 10% with 1%), occasional (0.1% to 1% with 0.1%), rare (0.01% to 0.1% with 0.01%), very rare (<0.01%)
Blood and lymphatic system disorders.
Occasional: anemia
Rare: abnormal blood counts (including changes in white blood cell counts), leukopenia, thrombocytopenia
Concomitant administration of potentially myelotoxic drugs, particularly methotrexate, is a predisposing factor for the development of hematocrit.
Very rare granulocyte deficiencies have been reported.
Immune system disorders.
Occasionally: other tachyphylactic hypersensitivity reactions
Frequency unknown: allergic reactions, anaphylactoid reactions, anaphylaxis (injections only)
Psychiatric disorders.
Rare: mood changes, nightmares
Frequency unknown: confused states of consciousness, disorientation
Neurological disorders.
Common: headache
Occasional: dizziness, drowsiness
Eye disorders.
Rare: conjunctivitis, visual disturbances, including blurred vision
Ear and vagus disorders.
Occasional: vertigo
Rare: Tinnitus
Cardiac disorders.
Rare: palpitations
Events of heart failure associated with the use of NSAIDs have been reported.
Vascular disease.
Occasionally: elevated blood pressure, flushing
Respiratory, thoracic and mediastinal disorders.
Rare: Asthma attacks can occur in some patients with allergy to aspirin or other NSAIDs.
Gastrointestinal disorders.
Common: abdominal pain, indigestion, diarrhea, nausea, vomiting
Occasionally: occult or significant gastrointestinal bleeding, gastritis, stomatitis, constipation, flatulence, belching
Rare: gastroduodenal ulcer, colitis, esophagitis
Very rare: gastrointestinal perforation
Gastrointestinal bleeding, ulcers or perforations can be fatal.
Hepatobiliary disease.
Occasionally: abnormal liver function tests (e.g., elevated transaminases or bilirubin)
Very rare: hepatitis
Skin and subcutaneous tissue disorders.
Occasionally: angioedema, rash, pruritus
Rare: toxic epidermolysis bullosa, Stevens-Johnson syndrome, urticaria
Very rare: dermatitis herpetiformis, erythema multiforme
Frequency unknown: photosensitivity reaction
Renal and urinary disorders.
Occasionally: water and sodium retention, hyperkalemia, abnormal renal function tests (elevated serum creatinine and/or serum urea)
Very rare: acute renal failure
Reproductive and breast disorders.
Occasionally: delayed ovulation
Frequency unknown: female infertility
Systemic and administration site disorders.
Occasionally: edema
Contraindications
This product is contraindicated in the following conditions.
-Persons with known hypersensitivity to meloxicam or any of the excipients of this product, and those with lactose intolerance.
-Due to the potential for cross-sensitivity, this product is contraindicated in patients who develop asthma, nasal polyps, angioedema or urticaria after taking aspirin or other non-steroidal anti-inflammatory drugs.
-Treatment of perioperative pain associated with coronary artery bypass grafting (CABG).
-Active or new-onset gastrointestinal ulcers/perforations
-Active inflammatory bowel disease (Crohn’s disease or ulcerative colitis).
-severe hepatic insufficiency.
-severe renal insufficiency without dialysis
-significant gastrointestinal bleeding, new cerebral hemorrhage or other bleeding disorders
-Uncontrolled severe heart failure.
-During pregnancy or lactation.
-Contraindicated in patients who have had a rejection reaction to the excipients used in the product due to a very rare genetic disorder (see [Precautions]).
-Contraindicated in children and adolescents under 16 years of age.
Precautions]
As with other NSAIDs, fatal gastrointestinal bleeding, ulceration or perforation may occur at any time of treatment, with or without concomitant aura or history of severe gastrointestinal disease, and the consequences of these events are usually more severe in the elderly.
As with other NSAIDs, caution should be exercised when treating patients with a history of gastrointestinal disease. Patients with gastrointestinal symptoms should be monitored. If peptic ulcer or gastrointestinal bleeding occurs, the product should be discontinued.
As with other NSAIDs, caution should be exercised when using this product in patients taking anticoagulant medications.
Serious cutaneous adverse reactions (some fatal, such as exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis) have rarely been reported in connection with NSAID use. Patients are at highest risk for these reactions early in treatment, with the vast majority of events occurring within the first month of treatment initiation. Patients should discontinue the product as soon as they begin to develop a rash, mucosal damage, or any other signs of hypersensitivity.
NSAIDs may increase the risk of serious cardiovascular embolic events, myocardial infarction and fatal events such as stroke. This risk may increase with increasing duration of use. Patients with cardiovascular disease or with corresponding risk factors may be at greater risk.
NSAIDs have an inhibitory effect on the synthesis of renal prostaglandins that play a supportive role in maintaining renal perfusion. In patients with reduced renal blood flow and blood volume, administration of NSAIDs may promote the development of renal failure. However, renal function usually returns to pre-treatment levels after discontinuation of NSAIDs.
The following patients are at highest risk for these reactions: elderly patients, dehydrated patients, patients with congestive heart failure, patients with cirrhosis, patients with nephrotic syndrome with significant renal disease, patients on concomitant diuretics, ACE inhibitors or angiotensin II receptor antagonists, and patients with reduced blood volume due to major surgery performed. The urine output and renal function of these patients should be closely monitored at the start of treatment.
In rare cases, NSAIDs can cause interstitial nephritis, glomerulonephritis, renal medullary necrosis, or nephrotic syndrome.
The dose should not exceed 7.5 mg in patients with end-stage renal failure treated with hemodialysis. no dose reduction is required in patients with mild to moderate renal insufficiency (i.e., patients with creatinine clearance above 25 ml/min).
As with other NSAIDs, occasional increases in serum aminotransferases or other liver function parameters have been reported. Most cases are only mild and transient above the normal range. If the abnormality is significant or persistent, the product should be discontinued and follow-up testing should be performed.
No dose reduction is required in patients with clinically stable cirrhosis.
Weak or tired patients tolerate adverse reactions poorly and should therefore be closely monitored. As with other NSAIDs, caution should be exercised when treating elderly patients who are more likely to have renal, hepatic and cardiac impairment.
The use of NSAIDs may cause sodium, potassium and water retention and interfere with the sodium-removal effects of diuretics. As a result, susceptible patients may develop or worsen heart failure or hypertension.
As with other NSAIDs, meloxicam may mask the symptoms of infectious disease.
Concomitant use of meloxicam and any drug that inhibits cyclooxygenase/prostaglandin synthesis can impair fertility and is therefore not recommended for women who are preparing to become pregnant. Therefore, women who are unable to conceive or are investigating infertility should consider discontinuing meloxicam.
For related drug interactions that require special attention, see [Drug Interactions].
This product contains lactose: It should not be taken by people with rare genetic disorders lactose intolerance such as galactosemia.
Effects on the ability to drive and operate machinery
The effect of this product on the ability to drive a vehicle and operate machinery has not been specifically studied. However, patients should be informed in advance of the possibility of adverse reactions similar to visual impairment, including blurred vision, dizziness, drowsiness, vertigo and other central nervous system disturbances.
Therefore, this product should be used with caution when driving or operating machinery.
If patients experience any of these reactions, they should avoid these potentially hazardous tasks such as driving or operating machinery.
For Pregnant and Lactating Women]
Fertility
As with any other drug known to inhibit cyclooxygenase/prostaglandin synthesis, meloxicam may impair female fertility and is therefore not recommended for women who are preparing to become pregnant. Women who have difficulty conceiving or are being tested for infertility should consider discontinuing the drug.
Pregnancy
Inhibition of prostaglandin synthesis may have adverse effects on pregnancy and/or embryo/fetal development. Epidemiological studies suggest an increased risk of miscarriage, cardiac malformations and abdominal clefts following the use of prostaglandin synthesis inhibitors in early pregnancy. The absolute risk of cardiovascular malformations increases from less than 1% to approximately 1.5%. The risk increases with dose and duration of therapy. In animal models, administration of prostaglandin synthesis inhibitors can increase preimplantation and postimplantation failure and lead to embryo-fetal death. In addition, administration of prostaglandin synthesis inhibitors during the organogenesis phase has been reported to increase the incidence of multiple malformations, including cardiovascular malformations, in preclinical studies.
Meloxicam should not be used in the early and middle stages of pregnancy unless it is truly necessary. If meloxicam is used in women who are preparing to conceive or in the early and middle stages of pregnancy, the dose should be kept low and the course of treatment should be as short as possible.
In late pregnancy, all prostaglandin synthesis inhibitors may have the following effects
*Effects on the fetus.
Cardiopulmonary toxicity (premature closure of the arterial ducts and pulmonary hypertension)
Renal insufficiency, which may progress to renal failure with hypoamniotic fluid.
At the end of pregnancy, effects on the mother and the newborn.
Bleeding time may be prolonged and anti-aggregation effects may still occur at very low doses.
Inhibition of uterine contractions, resulting in prolonged labor.
Therefore, meloxicam should be contraindicated in late pregnancy.
Lactation
Although there is no specific experience with the use of meloxicam during lactation, NSAIDs are known to pass into breast milk. Therefore, it is not recommended for use in nursing women.
[Pediatric Use].
This product should not be used in children and adolescents under 16 years of age.
Geriatric use]
Compared to young adults, the steady-state mean plasma clearance is slightly lower in the elderly.
In elderly patients, the recommended dose for long-term treatment of rheumatoid arthritis and ankylosing spondylitis is 7.5 mg/day.
Side effects are usually less well tolerated in elderly patients and should be carefully monitored.
[Drug Interactions].
Interaction studies have only been conducted in adult patients.
Risks associated with hyperkalemia.
Certain drugs or treatments may promote hyperkalemia: potassium salts, potassium conserving diuretics, angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, nonsteroidal anti-inflammatory drugs, (low molecular weight or generic) heparin, cyclosporine, tacrolimus, and methotrexate.
The development of hyperkalemia may depend on the presence of associated factors.
This risk is increased when the above drugs are combined with meloxicam.
Pharmacodynamic interactions.
Other NSAIDs and acetylsalicylic acid.
Combination of meloxicam with other NSAIDs and acetylsalicylic acid (single dose ≥ 500 mg or total daily dose ≥ 3 g) is not recommended.
Corticosteroids (e.g., glucocorticoids).
Caution should be exercised when combining meloxicam with corticosteroids due to the increased risk of bleeding or gastrointestinal ulceration.
Anticoagulants or heparin.
Greatly increase the risk of bleeding by inhibiting platelet function and damaging the gastroduodenal mucosa. NSAIDs may potentiate the effects of anticoagulants, such as warfarin (see [Precautions]). Concomitant use of NSAIDs and anticoagulants or heparin in geriatrics or in curative doses is not recommended (see [Precautions]).
For the remaining conditions in which heparin is used (e.g., prophylactic doses), caution is required due to the increased risk of bleeding.
If combination cannot be avoided, careful monitoring of INR is required.
Thrombolytics and antiplatelet agents.
Increases the risk of bleeding by inhibiting platelet function and damaging the gastroduodenal mucosa.
Selective 5-hydroxytryptamine reuptake inhibitors (SSRIs).
Increases the risk of gastrointestinal bleeding.
Diuretics, ACE inhibitors and angiotensin II receptor antagonists.
NSAIDs may reduce the effects of diuretics and other antihypertensive drugs. In some patients with impaired renal function (e.g., dehydrated patients with impaired renal function or elderly patients), the combination of ACE inhibitors or angiotensin II receptor antagonists and agents that inhibit cyclooxygenase may lead to further deterioration of renal function, including possible acute renal failure, which is usually reversible. Therefore, special caution should be exercised when combining, especially in elderly patients. After initiation of combination therapy, patients should be adequately hydrated and renal function should be monitored regularly (see [Precautions]).
Other antihypertensive agents (e.g., beta-blockers).
As for the latter, the antihypertensive effect of beta-blockers is reduced (due to inhibition of prostaglandin-vasodilatory effects).
Calcium-regulated phosphatase inhibitors (e.g., cyclosporine, tacrolimus).
Through renal prostaglandin-mediated effects, NSAIDs may increase the nephrotoxicity of calcium-regulated phosphatase inhibitors. Renal function should be measured during co-administration. Careful monitoring of renal function is recommended, especially in elderly patients.
Deferasirox.
The combination of meloxicam and Deferasirox may increase the risk of gastrointestinal adverse reactions. Caution should be exercised when these drugs are used in combination.
Pharmacokinetic interactions: Effect of meloxicam on the pharmacokinetics of other drugs
Lithium.
NSAIDs have been reported to increase lithium concentrations in the blood (by reducing renal excretion of lithium), possibly to concentrations that produce toxicity. Combining lithium with NSAIDs is not recommended (see [Precautions]). If combination is required, plasma lithium concentrations should be carefully monitored at the initiation, adjustment, and discontinuation of meloxicam therapy.
Methotrexate.
NSAIDs can decrease methotrexate secretion from the renal tubules, thereby increasing methotrexate plasma concentrations. Therefore, concomitant use of NSAIDs is not recommended for patients receiving higher doses of methotrexate (>15 mg/week) (see [Precautions]).
For patients receiving lower doses of methotrexate, the risk of interaction between NSAIDs and methotrexate should also be considered, particularly in patients with renal insufficiency. If a combination is required, blood counts and renal function should be monitored. Special care should be taken within 3 days of the combination of NSAIDs and methotrexate, as methotrexate plasma concentrations may be elevated and cause increased toxicity.
Although the pharmacokinetics of methotrexate (15 mg/week) are not correspondingly affected by meloxicam co-administration, consideration should be given to the fact that combination therapy with NSAIDs amplifies the hematologic toxicity of methotrexate (see above).
Pemetrexed.
In patients with mild to moderate renal insufficiency (creatinine clearance of 45 to 79 ml/min), if meloxicam is administered concomitantly with pemetrexed, meloxicam should be discontinued 5 days prior to, on the day of, and 2 days after pemetrexed administration. If meloxicam is required in combination with pemetrexed, patients should be monitored closely, especially for bone marrow suppression and gastrointestinal adverse effects. Combination of meloxicam with pemetrexed is not recommended in patients with severe renal insufficiency (creatinine clearance less than 45 ml/min).
In patients with normal renal function (creatinine clearance ≥ 80 ml/min), a 15 mg dose of meloxicam may decrease the elimination of pemetrexed, thereby increasing the incidence of adverse events with pemetrexed. Therefore, caution should be exercised when 15 mg meloxicam is combined with pemetrexed in the treatment of patients with normal renal function (creatinine clearance ≥ 80 ml/min).
Pharmacokinetic interactions: Effect of other drugs on the pharmacokinetics of meloxicam
Abciximide.
By affecting the hepatic-intestinal circulation, elimination of meloxicam is accelerated by elimination of biliary amines, resulting in a 50% increase in the clearance of meloxicam and a decrease in the half-life to 13 ± 3 hours. This interaction was clinically significant.
No clinically relevant pharmacokinetic drug interactions were observed with concomitant use of antacids, cimetidine, and digoxin.
[Drug overdose].
Acute overdose symptoms with NSAIDs are usually limited to lethargy, drowsiness, nausea, vomiting, and epigastric pain and are usually recovered with supportive therapy. Gastrointestinal bleeding may occur. Severe toxicity may result in hypertension, acute renal failure, hepatic dysfunction, respiratory depression, coma, convulsions, cardiovascular collapse, and cardiac arrest. Allergic-like reactions have been reported with NSAIDs, which may occur after overdose.
Symptomatic and supportive therapy should be administered to patients after NSAID overdose. Clinical trials have shown that 4 g of abciximide administered orally three times a day accelerates the elimination of meloxicam.
If you forget to take the medication
Do not take a double dose to make up for a missed pill. Simply take the next dose at the normal dosing time.
Pharmacology and Toxicology
Pharmacodynamic properties
Meloxicam is a non-steroidal anti-inflammatory agent in the xicam family with anti-inflammatory, analgesic and antipyretic properties.
Meloxicam has anti-inflammatory activity in all standard models of inflammation. As with other non-steroidal anti-inflammatory drugs, its exact mechanism of action is not known. However, all non-steroidal anti-inflammatory drugs share at least one mechanism of action (including meloxicam): inhibition of the biosynthesis of prostaglandins, a known mediator of inflammation.
Preclinical Safety (Toxicology) Information
Preclinical studies have shown that the toxicological profile of meloxicam is the same as with the application of other non-steroidal anti-inflammatory drugs: gastrointestinal ulceration and erosion, and renal papillary necrosis at high doses in two animal species in long-term toxicity studies.
Adverse effects were observed at doses 5 to 10 times higher than the clinical dose (7.5-15 mg) when administered at mg/kg (75 kg human body weight). As with all prostaglandin synthesis inhibitors, embryotoxicity has been reported to occur at the end of gestation. Neither in vivo nor in vitro tests have shown any mutagenicity. No carcinogenicity was found in rats and mice at higher than clinical doses.
Pharmacokinetics]
Absorption
Meloxicam is well absorbed through the gastrointestinal tract, with an absolute bioavailability of 90% after oral administration (capsules).
Tablets, oral suspensions and capsules are bioequivalent.
After a single administration of meloxicam, the median maximum plasma concentration was reached within 2 hours for oral suspension and within 5-6 hours for oral solid formulations (capsules and tablets). After multiple doses, steady state is reached within 3 to 5 days. Once-daily administration resulted in relatively small fluctuations in peak and trough mean blood concentrations, ranging from 0.4 to 1.0 μg/ml and 0.8 to 2.0 μg/ml for the 7.5 mg dose and the 15 mg dose, respectively (Cmin and Cmax at steady state, respectively). For tablets, capsules and oral suspensions, meloxicam reached maximum mean steady-state plasma concentrations within 5 to 6 hours after administration, respectively. Concomitant feeding or use of inorganic antacids did not alter the extent of meloxicam absorption after oral administration.
Distribution
Meloxicam binds very strongly (99%) to plasma proteins, i.e. albumin. Meloxicam is able to penetrate into the synovial fluid at a concentration of about half the plasma concentration.
The volume of distribution after intramuscular or intravenous administration is small, about 11 L, and varies between individuals up to 7% to 20%. The volume of distribution of multiple oral doses of meloxicam (7.5-15 mg) is approximately 16 L, with a coefficient of variation ranging from 11% to 32%.
Biotransformation
Meloxicam undergoes substantial hepatic biotransformation.
Four different metabolites of meloxicam without pharmacological activity were present in the urine.
The major metabolite is 5′-carboxymeloxicam (60% of the dose), which is produced by oxidation of the intermediate metabolite 5′-hydroxycarboxymethylmeloxicam, which is also excreted in small amounts (9% of the dose). In vitro studies suggest that CYP 2C9 plays an important role in this metabolic pathway and that CYP 3A4 isoenzymes also play a role. The patient’s peroxidase facilitates the formation of the other two metabolites, which account for 16% and 4% of the given dose, respectively.
Elimination
Meloxicam is eliminated primarily as a metabolite, in equal amounts in urine and feces. Less than 5% of the daily dose is excreted in its original form via the feces, and only very small amounts of the original compound are excreted via the urine.
The mean elimination half-life after oral, intramuscular and intravenous administration is between 13 and 25 hours. Total plasma clearance after a single oral, intravenous or rectal administration is approximately 7 to 12 ml/min.
Linear/non-linear
The pharmacokinetics of meloxicam are linear over the therapeutic dose range of 7.5 to 15 mg after oral or intramuscular administration.
Special Populations
Patients with hepatic/renal insufficiency.
Both hepatic insufficiency and mild to moderate renal insufficiency have no significant effect on the pharmacokinetics of meloxicam. Total drug clearance was significantly higher in subjects with moderate renal insufficiency. Protein binding was decreased in patients with end-stage renal failure. In patients with end-stage renal failure, increased volume of distribution may result in higher free meloxicam concentrations and therefore the dose should not exceed 7.5 mg daily (see [DOSAGE AND ADMINISTRATION]).
Elderly Patients.
The mean pharmacokinetic parameters in elderly male subjects were similar to those in younger male subjects. Older female subjects exhibited higher AUCs and longer elimination half-lives compared to all male and female younger subjects. The mean steady-state plasma clearance at steady state was slightly lower in older subjects than in younger subjects.
Storage]
Store under shade and seal.
Packaging
Aluminum-plastic plate packing, 10 tablets per plate, 1 plate per bag, 1 bag per box. Storage]
Expiration date】
12 months
【Execution standard
 Approval number
State Drug Certificate H20010207
Manufacturer
Company Name: Yangtze River Pharmaceutical Group Co.
Address: No. 1, Yangzijiang South Road, Taizhou City, Jiangsu Province
Postal Code: 225321
Telephone number: 400-988-1999
Fax number: (0523) 86976161
Website: www.yangzijiang.com