Approval Date: 2007Year03Month 23day
Modification Date:2008Year07month07dayday
2015Year span>08month31Day
2018YearOctoberMarch09Day
Diclofenac Sodium Extended Release Tablets Instructions
Please read the instructions carefully and use under the guidance of a physicianPlease read the instructions carefully and use under the guidance of a physician “font-family:Times New Roman”>
[Drug Name].
Generic Name: Diclofenac Sodium Extended Release Tablets
Trade Name: Diagen
English Name: Diclofenac Sodium Sustained Release Tablets
Hanyu Pinyin: Shuanglüfensuanna Huanshi Pian
[Ingredients
The main ingredient of this product is: diclofenac sodium.
Chemical name: Sodium 2-[(2,6-dichlorophenyl)amino]-phenylacetate.
Chemical structure formula.
Molecular Formula: C14H10Cl2NNaO2
Molecular weight: 318.13
[Properties
This product is a pink film-coated tablet. [Indications]
1. Relief of rheumatoid arthritis, osteoarthritis. spondyloarthropathy, gouty arthritis, rheumatoid arthritis and other chronic arthritis of various kinds with acute onset or persistent symptoms of joint swelling and pain.
2. Various soft tissue rheumatic pains, such as shoulder pain, tenosynovitis, bursitis, myalgia and post-exercise injurious pain.
3. Acute mild to moderate pain such as: pain after surgery, trauma, strain, etc., primary dysmenorrhea, toothache, headache, etc.
[Specifications
0.1g
[dosage
Dosage
As a general recommendation, the dosage should be adjusted accordingly for different individuals and should be given at the shortest possible As a general recommendation, the dose should be adjusted accordingly for each individual and should be given in the shortest possible interval. As a general recommendation, the dose should be adjusted accordingly for each individual and should be given at the shortest possible interval.
Adults
The recommended dose of this product is once a day, per dose100mg (1tablet). span>, or as directed by a physician.
For mild and long-term treatment patients, take daily100mg.
For patients with more severe symptoms at night and early morning, it should be taken in the evening100mg.
Special Populations
Children and adolescents under 18 years of age.
Due to the high dose of this product, it is not recommended for children and adolescents.
Elderly (patients 65 years of age or older):
Older patients generally No adjustment of the starting dose is required; however, caution should be exercised with respect to the underlying condition, especially in frail and low weight elderly patients, who should be given the lowest effective dose.
Renal impairment:
This product should not be used in patients with renal failure (eGFR<15 mL/min/1.73 m2) (see contraindications).
No specific studies have been performed in patients with renal impairment, therefore no specific dose adjustment is recommended. Caution is advised when giving this product to patients with renal impairment (see PRECAUTIONS).
Hepatic Impairment:
Not to be used in patients with hepatic failure This product should not be used in patients with hepatic failure (see Contraindications).
No specific studies have been performed in patients with hepatic impairment, therefore no Special dose adjustments are recommended. Caution is advised when giving this product to patients with mild to moderate hepatic impairment (see PRECAUTIONS).
Dosing Method
Pills must be swallowed whole and delivered with liquid, not divided or chewed. It should be taken with food.
[Adverse Reactions]
According to foreign literature A summary of the list of adverse drug reactions
MedDRASystematic organ classification lists the clinical trials from which /systematic organs are derived and family:Arial”>or spontaneous or literature-reported adverse drug reactions (Table 1). In the classification of each system organ, adverse reactions were ranked by frequency of occurrence, with the most common ranked first. Among each common group, adverse drug reactions were listed in descending order of severity. In addition, the corresponding common category for each adverse drug reaction was based on the following provisions (CIOMS III); very common ( >1/10); common (≥1/100 ~ <1/10); occasional (≥1/1,000 ~ <1/100); rare (≥1/10,000 ~ <1/1,000); very rare (<1/10,000). The following table shows the adverse effects of this and / or other dosage forms of diclofenac during short-term or long-term use.
Table =”font-family:Times New Roman”>1
Diseases of the blood and lymphatic system Very rare:Thrombocytopenia, leukopenia, anemia (including hemolytic and aplastic anemia), and granulocyte deficiency. Immune System Disorders Rare:Hypersensitivity, allergic, and anaphylactic-like reactions (including hypotension and shock). Very rare:Angioedema (including facial edema). Psychiatric Very rare:Disorientation, depression, insomnia, nightmares, irritability, psychotic disorders. All types of neurological disorders Common: Headache and dizziness. Rare:Drowsiness. Very rare:Sensory abnormalities, memory impairment, convulsions, anxiety, tremors, aseptic meningitis Taste disorders, cerebrovascular accidents. Ocular organ disease Very rare:Visual impairment, blurred vision, diplopia. Ear and Labyrinthine Disorders Common:Glare. Very rare:Tinnitus, hearing impairment. Heart disorders occasional*:
Frequency unknownmyocardial infarction, heart failure, palpitations, chest pain .
KounisKounis span style=”font-family:Arial”>SyndromeVascular and Lymphatic Vascular Disorders Very rare:Hypertension, vasculitis. Respiratory, thoracic and mediastinal disorders Rare: Asthma (including dyspnea). Very rare:Pneumonia. Gastrointestinal Disorders Common:Nausea, vomiting, diarrhea, indigestion, abdominal pain, gas and bloating, loss of appetite. Rare:Gastritis, gastrointestinal bleeding, vomiting blood, blood in stool, black stool, gastrointestinal ulcer (with or without bleeding, gastrointestinal stricture, or gastrointestinal perforation that may lead to peritonitis). Very rare:Colitis (including hemorrhagic colitis, ischemic colitis, exacerbated ulcerative colitis and Crohn’s disease), Constipation, stomatitis, tongue inflammation, esophageal disease, intestinal diaphragm disease, pancreatitis. Diseases of the hepatobiliary system Common:Elevated transaminases. Rare:Hepatitis, jaundice, liver disease. Very rare:Fulminant hepatitis with hepatic necrosis and liver failure. Dermal and subcutaneous tissue disorders Common: Rash. Rare:Hives. Very rare:Dermatitis herpetiformis, eczema, erythema erythema multiforme,Stevens-Johnson Syndrome, toxic epidermal necrolysis () span style=”font-family:Times New Roman”>Lyell’s syndrome), exfoliative dermatitis, alopecia areata, photosensitivity reactions, purpura, allergic purpura, pruritus. Kidney and urinary tract disorders Very rare:Acute kidney injury (acute renal failure), hematuria, proteinuria, nephrotic syndrome, interstitial nephritis, and renal papillary necrosis. Systemic diseases and various reactions at the site of administration Rare:Oedema. *Frequency response from data on high-dose long-term treatment( 150 mg/day) .
Arterial embolic events
The meta-analysis and pharmacoepidemiological data point to a small increase in the risk of atheroembolic events with diclofenac events (eg, myocardial infarction), especially when administered at high doses (150 mg/day) and during long-term treatment course (see Precautions).
Visual impairment (e.g., visual impairment, blurred vision, or diplopia) appears to be a class effect of NSAIDs that is usually reversible after discontinuation of the drug. The likely mechanism by which visual impairment occurs is inhibition of synthesis of prostaglandins and other related compounds that affect retinal blood flow regulation, leading to possible visual changes. If these symptoms occur during treatment with diclofenac, consider receiving an eye exam to rule out other causes.
[Contraindications]- Patients with known hypersensitivity to this product.
– As with other NSAIDs, this product is contraindicated in patients with asthma, angioedema, urticaria, or anaphylactic reactions following administration of aspirin or other NSAIDs. (See Precautions and Adverse Reactions)
– Contraindicated for the treatment of perioperative pain in coronary artery bypass graft surgery (CABG).
– Patients with a history of gastrointestinal bleeding or perforation after administration of NSAIDs. (See Precautions and Adverse Reactions)
– Patients with active peptic ulceration/bleeding or previous recurrent ulceration/bleeding.
– Patients with severe heart failure. (see precautions)
– Patients with hepatic failure.
– Patients with renal failure. (eGFR <15 mL/min/1.73m2)
– Last trimester of pregnancy (see Dosing in Pregnant and Lactating Women).
[Precautions].
Avoid coadministration with other NSAIDs, including selective COX-2 (Cyclooxygenase-2) inhibitors (see Drug Interactions).
Adverse effects can be minimized by using the lowest effective dose for the shortest duration of therapy, as needed to control symptoms.
Gastrointestinal effects
The risk of adverse effects of gastrointestinal bleeding, ulceration, and perforation may occur at any time during treatment with all NSAIDs and may be fatal. These adverse reactions may or may not be accompanied by warning symptoms and regardless of whether the patient has a history of adverse gastrointestinal reactions or a history of serious gastrointestinal events. NSAIDs should be used with caution in patients with a prior history of gastrointestinal disease (ulcerative colitis, Crohn’s disease) to avoid worsening the condition. When a patient experiences gastrointestinal bleeding or ulceration while taking the drug, it should be discontinued. The frequency of adverse reactions with NSAIDs increases in elderly patients. When a patient experiences gastrointestinal bleeding or ulceration while taking the drug, the risk may be fatal and treatment should be discontinued.
For all NSAIDs, including diclofenac, close medical monitoring and attention, if necessary, should be given to patients with a history of gastrointestinal warning disorder or gastrointestinal (GI) ulceration, bleeding, or perforation after taking this product, (see Adverse Reactions). In patients with a history of ulceration, especially in patients with bleeding or perforation, and in elderly patients, increasing the dose of NSAIDs raises the risk of GI bleeding.
To reduce gastrointestinal risk in patients with a history of ulceration, especially with bleeding or perforation, and in older patients, treatment should be initiated and maintained at the lowest effective dose.
Combination therapy with protective medications (eg, proton pump inhibitors or misoprostol) may be considered for the above patients and for patients requiring concomitant use of medications containing low-dose acetylsalicylic acid/aspirin or other medications that may increase gastrointestinal risk.
As with other NSAIDs, patients with a history of gastrointestinal toxicity, especially in older patients, must have all abnormal abdominal symptoms (especially gastrointestinal bleeding) documented. Caution is recommended for patients on concomitant use of the following medications that increase the risk of ulceration or bleeding: e.g., corticosteroids, anticoagulants, antiplatelet agents, or selective 5HT reuptake inhibitors (see Drug Interactions).
Patients with ulcerative colitis or Crohn’s disease should also be closely monitored medically because of the potential for worsening conditions in these patients (see Adverse Reactions).
Cardiovascular effects
Clinical trials of multiple COX-2-selective or non-selective NSAIDs drugs lasting up to 3 years have shown that this product may cause an increased risk of serious cardiovascular thrombotic adverse events, myocardial infarction, and stroke, and that the risk may be fatal. All NSAIDs, including COX-2 selective or non-selective drugs, may have a similar risk. Patients with cardiovascular disease or risk factors for cardiovascular disease are at greater risk. Physicians and patients should be alert to the occurrence of such events, even in the absence of prior cardiovascular symptoms. Patients should be informed of the signs and/or symptoms of serious cardiovascular safety and the steps to take if they occur.
Patients should be alert for signs and symptoms such as chest pain, shortness of breath, weakness, and slurred speech, and should seek medical help as soon as any of these signs or symptoms occur.
Treatment with this product is generally not recommended in patients with established cardiovascular disease (congestive heart failure, established ischemic heart disease, peripheral arterial disease) or uncontrolled hypertension. If needed, patients with diagnosed cardiovascular disease, uncontrolled hypertension, or significant cardiovascular disease risk factors (eg, hypertension, hyperlipidemia, diabetes mellitus, and smoking) should be treated with this product only after careful consideration and only at a dose of ≤100 mg daily for treatment durations longer than 4 weeks.
Because the risk of cardiovascular disease from diclofenac increases with increasing dose and duration of exposure, the lowest effective dose should be given for the shortest possible period of time. The patient’s need for symptom relief and response to therapy should be reassessed periodically, especially if the duration of therapy exceeds 4 weeks.
Hypertension
Like all nonsteroidal anti-inflammatory drugs (NSAIDs), this product can cause new-onset hypertension or worsen the symptoms of existing hypertension, either of which can lead to an increased incidence of cardiovascular events. The efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) may be compromised in patients taking thiazides or medullary diuretics when these drugs are administered. Non-steroidal anti-inflammatory drugs (NSAIDs), including this product, should be used with caution in patients with hypertension. Blood pressure should be monitored closely during initiation and throughout the course of therapy with this product.
Caution should be used in patients with a history of hypertension and/or heart failure (e.g., fluid retention and edema).
Skin Reactions
NSAIDs, including this product, may cause fatal, serious skin adverse reactions such as exfoliative dermatitis, Stevens Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). These serious events can occur without warning. Patients should be informed of the signs and symptoms of a serious skin reaction and the product should be discontinued at the first appearance of a skin rash or other signs of an allergic reaction.
Hematologic effects
As with other NSAIDs, a blood count is recommended if this product is taken for a long time.
As with other NSAIDs, this product may transiently inhibit platelet coagulation. Patients with coagulation disorders should be closely monitored.
Respiratory effects (previous asthma)
In patients with asthma, seasonal allergic rhinitis, nasal mucosal edema (eg, nasal polyps), chronic obstructive pulmonary disease, or chronic infections of the respiratory tract (especially if associated with allergic rhinitis-like symptoms), nonsteroidal drug-like reactions such as asthma exacerbations (so-called analgesics/analgesics-intolerant asthma), Quincke’s edema, or urticaria will be more common than in other patients. Therefore, particular caution should be exercised in these patients (be prepared for emergencies). Patients with allergies to other substances, such as skin reactions, pruritus, or urticaria, should also be noted.
Hepatic effects
Patients with severe hepatic impairment should be placed under close medical supervision during the administration of diclofenac sodium because their condition may be exacerbated.
As with other NSAIDs, including diclofenac, one or more liver enzymes can be elevated. Therefore liver function should be monitored as a precautionary measure when taking this product long-term. The product should be discontinued if abnormal liver function findings persist or worsen, if clinical signs or symptoms are consistent with the development of liver disease or if other manifestations develop (e.g., eosinophilia, rash). Hepatitis may occur in the absence of any prodromal symptoms during the use of diclofenac.
Patients with hepatic porphyria should be cautioned because the administration of this product may precipitate an attack.
Renal effects
Because of reports showing an association between fluid retention and edema and NSAID therapy (including diclofenac), patients with cardiac or renal insufficiency, patients with a history of hypertension, elderly patients, patients treated with diuretics or medications that can significantly affect renal function, and patients with substantial extracellular fluid deficiency from any cause, such as major surgery Patients before and after major surgery should be administered with special caution (see contraindications). As a precautionary measure, renal function should be monitored when diclofenac sodium is administered to the above patients. Return to pretreatment status is usually possible after discontinuation of the drug.
Interactions with NSAIDs
Concomitant use with systemic NSAIDs, including cyclooxygenase-2 selective inhibitors, should be avoided because of the potential for increased adverse effects (see Drug Interactions).
Masking of signs of infection
As with other NSAIDs, diclofenac may mask the manifestations and symptoms of infection due to its pharmacologic effects.
Special Populations
Diagnosed with cardiovascular disease or significant cardiovascular risk factors
Treatment with this product is generally not recommended in patients with diagnosed cardiovascular disease or uncontrolled hypertension. If needed, patients with diagnosed cardiovascular disease, uncontrolled hypertension, or significant cardiovascular risk factors should be treated with this product only after careful consideration and only at a dose of ≤100 mg daily for treatment durations longer than 4 weeks.
Renal impairment
This product should not be used in patients with renal failure (eGFR <15 mL/min/1.73 m2) (see Contraindications).
No specific studies have been performed in patients with renal impairment, so no specific dose adjustments have been recommended. Caution is advised when giving this product to patients with renal impairment.
Hepatic impairment
This product should not be used in patients with hepatic failure (see Contraindications).
No specific studies have been performed in patients with hepatic impairment, so no specific dose adjustments have been recommended. Caution is advised when giving this product to patients with mild to moderate hepatic impairment.
This product should be used with caution in patients with restricted sodium intake because of its sodium content.
Interference with diagnosis: This product may cause a decrease in serum uric acid levels and an increase in urinary uric acid levels.
Patients with visual disturbances, dizziness, vertigo, drowsiness, or other central nervous system disorders should not drive or operate machinery after taking this product.
Because this product contains sucrose, it is not recommended for patients with the following rare genetic problems: fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase deficiency.
[For pregnant and lactating women].
Women of childbearing age
This study was not conducted and no reliable references are available.
Pregnant women
There are insufficient data on the use of diclofenac in pregnant women. Some epidemiologic studies suggest an increased risk of miscarriage following the use of prostaglandin synthesis inhibitors (e.g., NSAIDs) in early pregnancy, but the overall data are inconclusive. This product is contraindicated in women in the first six months of pregnancy unless the potential benefit to the mother outweighs the risk to the fetus. As with other NSAIDs, diclofenac is contraindicated in the second trimester because of the potential for contractile weakness in the last trimester and the potential for premature atresia of the ductus arteriosus and fetal renal impairment with secondary amniotic fluid hypohydramnios in the fetus (see Contraindications) (see Preclinical Safety Data).
Lactating women
Like other NSAIDs, diclofenac passes into breast milk in small amounts and should be avoided during lactation to avoid adverse effects on the fetus.
Fertility
As with other NSAIDs, the use of diclofenac sodium has the potential to impair female fertility; therefore, it is not recommended for use in women who are preparing to become pregnant, and discontinuation of diclofenac sodium should be considered for women who are having difficulty conceiving and undergoing infertility testing.
[Pediatric use]
Because of the high dose of this product, it should not be taken by children and adolescents.
[For elderly use]
Older patients generally do not require starting dose adjustment; however, medication should be administered with caution based on underlying medical conditions, especially in frail and low weight elderly patients, who should be given the lowest effective dose.
As with all NSAIDs, for gastrointestinal disease or gastrointestinal Patients with a history of ulcer disease, bleeding, or perforation should be closely monitored medically (see Adverse Reactions). Because the risk of gastrointestinal bleeding increases significantly with dosing in patients with a history of ulcer disease, especially in patients with combined bleeding or perforation and in elderly patients, this drug is not recommended for use in patients with a history of ulcer disease.
Patients with a history of gastrointestinal toxicity, especially in older patients, must document All abnormal abdominal symptoms (especially gastrointestinal bleeding). In patients with a history of ulceration, especially in those with bleeding or perforation and in elderly patients, both the initial and maintenance dose should be maintained at the lowest effective dose level in order to reduce gastrointestinal toxicity.
As with other NSAIDs, since reports have shown that fluid retention and edema are associated with NSAID therapy, special caution should be exercised when administering the drug to patients with cardiac or renal insufficiency, patients with a history of hypertension, elderly patients, patients taking diuretics or medications that can significantly affect renal function, and patients with any cause of extracellular fluid loss (e.g., patients before or after major surgery) (see Contraindications). Monitoring of renal function is recommended as a preventive measure when such patients are taking this product. If renal adverse reactions occur, patients are usually able to return to their pre-treatment status after discontinuation of this product.
[Drug Interactions]
The following interactions exist between this product and/or other dosage forms of diclofenac.
Observed interactions
CYP2C9 Inhibitors: Caution should be taken with the co-prescription of diclofenac and CYP2C9 inhibitors (e.g., voriconazole). It may cause significant increases in peak diclofenac plasma concentrations and exposure.
Lithium preparations: Diclofenac can increase plasma lithium concentrations when used concomitantly with lithium. Plasma lithium levels should be measured.
Digoxin: Diclofenac can increase plasma digoxin concentrations when used concomitantly with digoxin. Plasma digoxin levels should be measured.
Diuretics and antihypertensives: As with other NSAIDs, the antihypertensive effect of diclofenac may be reduced when used in combination with diuretics and antihypertensives (eg, beta-blockers, angiotensin-converting enzyme inhibitors). Therefore, when used in combination, the drug should be administered with caution and the patient’s blood pressure should be checked regularly, especially in elderly patients. Patients should be adequately hydrated, and consideration should be given to monitoring renal function after the initiation of initial combination therapy and to checking it periodically thereafter, especially in patients using a combination of diuretics and angiotensin-converting enzyme inhibitors, which can increase the risk of nephrotoxicity (see Precautions). When used with furosemide, the latter has diminished sodium excretion and antihypertensive effects.
Cyclosporine and Tacrolimus: Diclofenac, like other NSAIDs, may increase the nephrotoxicity of cyclosporine and tacrolimus because of the effect on renal prostaglandins. Therefore lower doses should be used in patients treated with cyclosporine or tacrolimus than in nonusers.
Drugs known to cause hyperkalemia: Elevated serum potassium levels may occur in combination with potassium-preserving diuretics, cyclosporine, tacrolimus, or methotrexate, and therefore serum potassium levels should be monitored frequently (see PRECAUTIONS).
Quinolone antibiotics: There have been isolated reports of possible convulsions from the combination of quinolone antibiotics with NSAIDs.
Anticipated interactions
Other NSAIDs and Corticosteroids: Diclofenac may increase the frequency of gastrointestinal adverse reactions when used in combination with other NSAIDs or corticosteroids. (See PRECAUTIONS).
Anticoagulants and antiplatelet agents: may increase the risk of bleeding when used in combination, and therefore should be used with caution (see PRECAUTIONS). Although clinical studies have not found an effect of diclofenac on the action of anticoagulants, an increased risk of bleeding has been reported when diclofenac is combined with anticoagulants. Therefore, this group of patients should be closely monitored.
Selective 5hydroxytryptamine reuptake inhibitors (SSRIs): Combination with NSAIDs, including diclofenac, may increase the risk of gastrointestinal bleeding (see PRECAUTIONS).
Antidiabetic agents: Clinical studies have shown that diclofenac can be combined with oral hypoglycemic agents without affecting their clinical efficacy. However, there are case reports of dose adjustment of oral hypoglycemic agents due to hypoglycemic and hyperglycemic reactions during the use of diclofenac. Therefore, monitoring of blood glucose levels is necessary as a precautionary measure for the combination.
There have been isolated reports of metabolic acidosis when diclofenac is used concomitantly with metformin, especially in patients with pre-existing renal impairment.
Phenytoin: When this product is combined with phenytoin, monitoring of phenytoin plasma concentrations is recommended because of the potential for elevated phenytoin exposure.
Methotrexate: NSAIDs (including diclofenac) should be used with caution for 24 hours before and after treatment with methotrexate because methotrexate blood levels may be elevated and its toxicity may be increased.
CYP2C9 inducers: Care should be taken with the co-prescription of diclofenac and CYP2C9 inducers (eg, rifampin). It may cause a significant reduction in diclofenac plasma concentrations and exposure.
Drinking alcohol or coadministration with certain NSAIDs may increase the incidence of side effects and carry a risk of ulcerogenicity. Prolonged use with acetaminophen may increase the toxic effects on the kidneys.
The blood level of this product is increased when used with verapamil and nifedipine.
Probenecid decreases the excretion of this product and increases the blood concentration, thus increasing toxicity, so it is advisable to reduce the dose of this product when used together.
[Drug overdose
Symptoms
There is no typical clinical There is no information on the typical clinical symptoms of diclofenac overdose. Overdose may cause the following symptoms: vomiting, gastrointestinal bleeding, diarrhea, dizziness, tinnitus, or convulsions. In severe cases, this may lead to acute renal failure or liver damage.
Therapeutic measures
For acute toxicity of NSAIDs (including diclofenac ) in acute poisoning, the main focus is on necessary supportive therapy and symptomatic treatment. For complications, such as hypotension, renal failure, convulsions, gastrointestinal dysfunction, and respiratory depression, supportive therapy and symptomatic treatment should be administered.
Some special measures such as diuresis, dialysis or hemodialysis are likely to be effective in promoting The NSAIDs (including diclofenac) are not overly helpful because of their high protein binding and high metabolism.
Activated charcoal should be used in cases of ingestion of potentially toxic doses, gastric emptying (e.g. vomiting, gastric lavage) should be used in cases of ingestion of potentially lethal doses.
[Pharmacology and Toxicology]
Pharmacological effects
Diclofenac sodium is a non-steroidal compound that produces by inhibiting the synthesis of prostaglandins It has analgesic, anti-inflammatory and antipyretic effects by inhibiting the synthesis of prostaglandins.
Toxicological studies
Preclinical safety data for diclofenac were obtained from acute and repeated dosing toxicity studies, genotoxicity, and carcinogenicity studies, which suggested no specific hazard in humans at therapeutic doses.
No significant effects of diclofenac on fertility were seen in rats. No teratogenic effects were seen in mice, rats, or rabbits. Embryotoxicity, obstructed labor, prolonged labor, low live birth rate, and intrauterine growth retardation were seen with diclofenac at maternal toxicity doses, with no significant effects on perinatal development of the offspring. The minor effects of diclofenac on reproductive parameters and birth are related to the pharmacological effects of this type of prostaglandin synthesis inhibitor (see Contraindications and Use in Pregnant and Lactating Women).
[Pharmacokinetics]
According to foreign literature:
Uptake
Recovery of the prototype diclofenac from urine and its hydroxylated metabolites can be judged that diclofenac is released and absorbed in the same amounts as enteric tablets. However, the systemic bioavailability of diclofenac was only 82% of that of the enteric-coated tablets at the same dose (possibly due to a release rate dependent”first over””first over span>effect). Because of the slow release of the active substance in this product, its peak blood levels are lower than those of patients using enteric-coated tablets.
Average intake4hours after100mgslow-release tablets reached a mean peak0.5 µg/mL(1.6 µmol/L).
Food has no clinical effect on the absorption and systemic bioavailability of this product.
On the other hand, when taking this product100mg for 24hours, the mean plasma concentration was 13ng/m Roman”> 13ng/mL. Absorption was linearly correlated with the dose used.
About half of diclofenac is metabolized during the first passage through the liver (“first pass”effect). Thus the area under the oral blood concentration curve (AUC) is only half the area under the blood concentration curve for the same dose of non-intestinal administration.
No change in pharmacokinetic parameters after repeated dosing. No accumulation occurred after dosing at the recommended dose and dosing interval.
Use of this product during treatment100mgonce/day minimum concentration of about22 ng/mL(70 nmol/L).
Distribution
The plasma protein binding rate of diclofenac was99.7% , mainly bound to albumin (99.4%). The apparent volume of distribution 0.12~0.17 L/kg.
Diclofenac can enter the synovial fluid and when plasma concentrations reach a peak of about2 to 4hours after the peak plasma concentration, the highest drug concentration in the synovial fluid was measured. The apparent elimination half-life of the drug in synovial fluid is 3 to 6hours. When the plasma concentration reaches a peak of 2hours, the concentration of the active substance in the synovial fluid reaches both higher than its concentration in the plasma and is maintained12hours.
Diclofenac was detected in the milk of one nursing mother at a very low concentration (100 ng/mL). The total expected intake of breastfed infants is comparable to a dose of 0.03 mg/kg/day.
Metabolism
Part of the prototype molecule undergoes glucuronidation for biotransformation, but the main transformation pathways are mono-, poly- and methylation reactions, yielding several phenolic acid metabolites (3′-hydroxy 4′-hydroxyl, hydroxyl, 4′-hydroxyl Roman”>5′-hydroxyl, 4′,5′-hydroxyl, hydroxyl, and 3′-hydroxyl-4′-methoxy-diclofenac), most of which is glucuronidated. Two of the metabolites are biologically active, but their activity is much less than that of diclofenac.
Elimination
In plasma, the total clearance of diclofenac was 263 ± 56 mL/min (mean ± standard deviation). Its plasma elimination half-life was 1 to 2 hours. The four metabolites (including the two active metabolites) also have a short plasma half-life of 1 to 3hours. 3′-hydroxy-4′-methoxy-Diclofenac has a relatively long plasma half-life. However, this metabolite is practically inactive.
About60% of the administered dose is excreted via urine as glucuronidation conjugates of the prototype molecule and as metabolites, most of the latter also being converted to glucuronidation conjugates. Less than1% is excreted as prototypes. The remainder is excreted in the feces as metabolites via the bile.
Linear/Nonlinear
The absorption is linearly proportional to the dose.
Special Populations
Elderly patients:
No drug absorption, metabolism, or excretion in relation to age.
Renal damage
In patients with known renal insufficiency, treat at the usual When treated at a single dose, the prototype drug does not accumulate as evidenced by the metabolic kinetics of the single dose. When creatinine clearance is less than 10 mL/min, the calculated steady-state plasma levels of the resulting hydroxyl metabolite are approximatelyhigher than normal. span>4fold. However, these metabolites are eventually cleared via bile.
Liver damage
In patients with chronic hepatitis or non-degenerative cirrhosis patients, the metabolic kinetics and metabolism of diclofenac are the same as in patients without liver disease.
[Storage
Storage in airtight container.
[Packaging
Aluminum-plastic packaging, each small box (1) 6 tablets (2) 10 tablets (3) 12 tablets (4) 20 tablets (5) 24 tablets
[Expiration date
18 months.
[Execution Standard
[approval number]
State Pharmacopoeia H10970209
[manufacturer]
Company Name: Sinopharm Zhigun (Shenzhen) Pingshan Pharmaceutical Co.
Manufacturing Address: No.18 Qinglan San Road, Pingshan New District, Shenzhen, China
Postal Code: 518118
Phone Number; 400-880-2335
Fax number: (0755) 82411002 (0755) 82429265
Service Email: [email protected]
Website: www.szzhijun.com