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Indications/Uses
For the treatment of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, and other rheumatic disorders.
For the treatment of pain and other discomforts associated with minor surgery, oral surgery, tonsillectomy, anorectal surgery, childbirth, sports injuries, and accidental trauma.
For the treatment of pain and other discomforts associated with minor surgery, oral surgery, tonsillectomy, anorectal surgery, childbirth, sports injuries, and accidental trauma.
Dosage/Direction for Use
Like other non-steroidal anti-inflammatory drugs (NSAIDs), the lowest effective dose of diclofenac should be used for the shortest possible time. Therefore, after observing the response to initial therapy with this product, the dose and frequency should be adjusted to suit individual patient needs.
Usual Adult Dose: Orally, 1 tablet every 8 to 12 hours.
Or, as prescribed by a physician.
Usual Adult Dose: Orally, 1 tablet every 8 to 12 hours.
Or, as prescribed by a physician.
Overdosage
Symptoms following acute overdoses are usually limited to lethargy, drowsiness, nausea, vomiting, and epigastric pain, which are generally reversible with supportive care. GI bleeding can occur. Hypertension, acute renal failure, respiratory depression, and coma may occur, but are rare. Anaphylactoid reactions have been reported with therapeutic ingestions of NSAIDs, and may occur following an overdose.
There is no specific antidote. Emesis and/or activated charcoal (60 to 100 g in adults, 1 to 2 g/kg in children) and/or osmotic cathartic may be indicated in patients seen within 4 hours of ingestion with symptoms or following a large overdose (5 to 10 times the usual dose). Forced diuresis, alkalinization of urine, hemodialysis or hemoperfusion may not be useful due to high protein binding.
There is no specific antidote. Emesis and/or activated charcoal (60 to 100 g in adults, 1 to 2 g/kg in children) and/or osmotic cathartic may be indicated in patients seen within 4 hours of ingestion with symptoms or following a large overdose (5 to 10 times the usual dose). Forced diuresis, alkalinization of urine, hemodialysis or hemoperfusion may not be useful due to high protein binding.
Administration
Should be taken with food: Take immediately after meals.
Contraindications
Known hypersensitivity to diclofenac or other ingredients in the product.
Patients with complete or partial syndrome of nasal polyps, or in whom asthma, anaphylaxis, urticaria, rhinitis, or other allergic-type reactions are precipitated by aspirin or other NSAIDs. Severe, rarely fatal, anaphylactoid reactions to NSAIDs have been reported in such patients.
Patients with a history of GI bleeding or perforation related to previous NSAID therapy.
Patients with active gastric, duodenal or peptic ulcer, active GI bleeding or perforation, regional ulcer, gastritis or ulcerative colitis.
Patients with severe heart, liver or kidney failure.
Patients with established congestive heart failure (New York Heart Association II-IV), ischemic heart disease, or peripheral artery disease.
Cerebrovascular bleeding or other bleeding disorders.
Inflammatory bowel disease.
Known hyperkalemia.
Dengue fever, since NSAIDs may increase the risk of bleeding.
Third trimester of pregnancy, because of the risk of premature closure of the fetal ductus arteriosus and delay labor and birth.
Breastfeeding women, because of the potential for serious adverse reactions in breastfed infants.
Children and adolescents younger than 16 years old.
Treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery.
Patients with complete or partial syndrome of nasal polyps, or in whom asthma, anaphylaxis, urticaria, rhinitis, or other allergic-type reactions are precipitated by aspirin or other NSAIDs. Severe, rarely fatal, anaphylactoid reactions to NSAIDs have been reported in such patients.
Patients with a history of GI bleeding or perforation related to previous NSAID therapy.
Patients with active gastric, duodenal or peptic ulcer, active GI bleeding or perforation, regional ulcer, gastritis or ulcerative colitis.
Patients with severe heart, liver or kidney failure.
Patients with established congestive heart failure (New York Heart Association II-IV), ischemic heart disease, or peripheral artery disease.
Cerebrovascular bleeding or other bleeding disorders.
Inflammatory bowel disease.
Known hyperkalemia.
Dengue fever, since NSAIDs may increase the risk of bleeding.
Third trimester of pregnancy, because of the risk of premature closure of the fetal ductus arteriosus and delay labor and birth.
Breastfeeding women, because of the potential for serious adverse reactions in breastfed infants.
Children and adolescents younger than 16 years old.
Treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery.
Warnings
Cardiovascular Risk: Diclofenac, particularly at higher doses, is associated with an increased risk of cardiovascular adverse events (such as myocardial infarction, stroke or thrombotic events, which can be fatal) that is comparable to COX-2 inhibitors. The risk may increase with the dose and duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk.
For patients with a high risk of developing an adverse cardiovascular event, other management strategies that do NOT include NSAIDs, particularly COX-2 inhibitors and diclofenac, should be considered first.
Treatment with diclofenac is not recommended in patients with pre-existing cardiovascular disease (congestive heart failure, ischemic heart disease, peripheral arterial disease), cerebrovascular disease, uncontrolled hypertension or patients with risk factors for cardiovascular disease (e.g. hypertension, hyperlipidemia, diabetes mellitus and smoking). These patients should be treated with diclofenac only after careful consideration.
Use of NSAIDs, such as diclofenac, can promote sodium retention in a dose-dependent manner, through a renal mechanism, which can result in increased blood pressure and/or exacerbation of congestive heart failure.
Gastrointestinal Risk: NSAIDs, including diclofenac, cause an increased risk of serious GI adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients are at greater risk for serious GI events.
For patients with a high risk of developing an adverse cardiovascular event, other management strategies that do NOT include NSAIDs, particularly COX-2 inhibitors and diclofenac, should be considered first.
Treatment with diclofenac is not recommended in patients with pre-existing cardiovascular disease (congestive heart failure, ischemic heart disease, peripheral arterial disease), cerebrovascular disease, uncontrolled hypertension or patients with risk factors for cardiovascular disease (e.g. hypertension, hyperlipidemia, diabetes mellitus and smoking). These patients should be treated with diclofenac only after careful consideration.
Use of NSAIDs, such as diclofenac, can promote sodium retention in a dose-dependent manner, through a renal mechanism, which can result in increased blood pressure and/or exacerbation of congestive heart failure.
Gastrointestinal Risk: NSAIDs, including diclofenac, cause an increased risk of serious GI adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients are at greater risk for serious GI events.
Special Precautions
General: Frail or debilitated patients may tolerate side effects less well and therefore special care should be taken in treating this population. As with other NSAIDs, caution should be used in the treatment of elderly patients who are more likely to be suffering from impaired renal, hepatic or cardiac function. For high risk patients, alternate therapies that do not involve NSAIDs should be considered.
Diclofenac is NOT recommended for use with other NSAIDs, with the exception of low-dose aspirin for cardiovascular prophylaxis, because of the absence of any evidence demonstrating synergistic benefits and the potential for additive adverse reactions (see Interactions).
Multiple diclofenac-containing preparations (including diclofenac potassium) should not be used concomitantly.
Cardiovascular Effects (see Warnings): Cardiovascular Thrombotic Events: Patients should remain alert for the signs and symptoms of serious arteriothrombotic events (e.g. chest pain, shortness of breath, weakness, slurring of speech), which can occur without warnings. Patients should be instructed to see a physician immediately in case of such an event.
There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious cardiovascular thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID does increase the risk of serious GI events.
Hypertension: NSAIDs can lead to the onset of new hypertension or worsening of pre-existing hypertension, either of which may contribute to the increased incidence of cardiovascular events. Patients taking thiazides or loop diuretics may have impaired response to these therapies when taking NSAIDs. NSAIDs, including diclofenac, should be used with caution in patients with hypertension. Blood pressure should be monitored closely during the initiation of NSAID treatment and throughout the course of therapy.
Congestive Heart Failure and Edema: Fluid retention and edema have been observed in some patients taking NSAIDs. Diclofenac should be used with caution in patients with fluid retention or heart failure.
Endocrine/Metabolic Effects: Diclofenac is NOT a substitute for corticosteroids. They do NOT treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to exacerbation of corticosteroid-responsive illness. Patients on prolonged corticosteroid therapy should have their therapy tapered slowly if a decision is made to discontinue corticosteroids (see Interactions).
Gastrointestinal (GI) Effects (see Warnings): NSAIDs, including diclofenac, can increase the risk of serious GI adverse events including inflammation, bleeding, ulceration, and perforation of the stomach, small or large intestines, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs.
NSAIDs should be prescribed with extreme caution in those with a history of ulcer disease or GI bleeding since these patients have a greater than 10-fold increased risk for developing a GI bleed compared with patients with neither of these risk factors. Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include concomitant use of oral corticosteroids or anticoagulants, longer duration of NSAID therapy, smoking, use of alcohol, older age, and poor general health status.
Physicians and patients should remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy and promptly initiate additional evaluation and treatment if a serious GI adverse event is suspected. This should include discontinuation of the NSAID until a serious GI adverse event is ruled out. Alternate therapies that do not involve NSAIDs should be considered especially for high-risk patients.
Close medical surveillance and caution should be exercised in patients with ulcerative colitis or with Crohn's disease as these conditions may be exacerbated.
Genitourinary Effects: Some NSAIDs are associated with persistent urinary symptoms (bladder pain, dysuria, urinary frequency), hematuria or cystitis. The onset of these symptoms may occur at any time after the initiation of therapy with an NSAID. Should urinary symptoms occur, in the absence of an alternate explanation, treatment with diclofenac should be stopped to ascertain if symptoms disappear. This should be done before urological investigations or treatments are carried out.
Caution should be exercised when initiating treatment with diclofenac in patients with considerable dehydration.
Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of an NSAID may cause a dose-dependent reduction in prostaglandin formation and secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and angiotensin-converting enzyme (ACE) inhibitors, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state.
Advanced Renal Disease: There are no controlled studies on the use of diclofenac in patients with advanced renal disease. Therefore, treatment with diclofenac is not recommended in these patients. If diclofenac therapy must be initiated, close monitoring of the patient's renal function is advised.
Anaphylactoid Reactions (see Contraindications): Anaphylactoid reactions may occur in patients without known prior exposure to NSAIDs. Diclofenac should not be given to patients with the aspirin triad. This symptom complex typically occurs in asthmatic patients who experience rhinitis with or without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs. Diclofenac should be administered with caution in patients with pre-existing asthma and emergency help should be sought in cases where an anaphylactoid reaction occurs.
Skin Reactions: As with other NSAIDs, diclofenac, can cause serious skin adverse events such as exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN or Lyell's syndrome), which can be fatal. These serious events may occur without warning. Patients should be informed about the signs and symptoms of serious skin manifestations and use of the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity.
Use of diclofenac may cause photosensitivity upon exposure to sunlight or ultraviolet light causing symptoms such as sunburn, skin rash, skin blisters, pruritus, erythema and discolouration.
Hepatic Effects: Borderline elevations of one or more liver tests may occur in up to 15% of patients taking NSAIDs including diclofenac. These laboratory abnormalities may progress, may remain unchanged, or may be transient with continuing therapy. In patients with chronic treatment with diclofenac, periodic monitoring of transaminases is recommended. Notable elevations of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) (approximately three or more times the upper limit of normal) have been reported in approximately 2 to 4% of patients, including marked elevations (eight or more times the upper limit of normal) in about 1% of patients. Rare cases of severe hepatic reactions, including jaundice and fatal fulminant hepatitis, liver necrosis and hepatic failure, some with fatal outcomes have been reported.
Patients with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal liver test has occurred, should be evaluated for evidence of the development of a more severe hepatic reaction while on therapy with NSAIDs including diclofenac. Discontinue diclofenac if clinical signs and symptoms consistent with liver disease develop or if systemic manifestations occur (e.g., eosinophilia, rash).
Caution is called for when using diclofenac in patients with hepatic porphyria, since it may trigger an attack.
Hematologic Effects: Anemia is sometimes seen in patients receiving NSAIDs including diclofenac. This may be due to fluid retention, occult or gross GI blood loss, or an incompletely described effect upon erythropoiesis. Patients on long-term treatment with NSAIDs, including diclofenac, should have their hemoglobin or hematocrit checked if they exhibit any signs or symptoms of anemia.
In some patients, NSAIDs inhibit platelet aggregation and have been shown to prolong bleeding time. Unlike aspirin, their effect on platelet function is quantitatively less, of short duration, and reversible. Patients receiving diclofenac who may be adversely affected by alterations in platelet function, such as those with coagulation disorders or patients receiving anticoagulants, should be carefully monitored.
Aseptic Meningitis: Rarely, with some NSAIDs, the symptoms of aseptic meningitis (stiff neck, severe headaches, nausea and vomiting, fever or clouding of consciousness) have been observed. Patients with autoimmune disorders (systemic lupus erythematosus, mixed connective tissue diseases, etc.) seem to be pre-disposed. Therefore, in such patients, the doctor must be vigilant to the development of this complication.
Effects on the Ability to Drive and Use Machine: Some patients may experience drowsiness, dizziness, blurred vision, vertigo, insomnia, depression, tinnitus or hearing loss with the use of NSAIDs, such as diclofenac. If patients experience such adverse reaction(s) they should refrain from driving, operating machinery, or carrying out activities that require alertness.
Use in Children (<16 years old): Safety and effectiveness in pediatric patients have not been established (see Contraindications).
Use in Elderly (≥65 years old): Elderly and frail or debilitated patients are more susceptible to a variety of adverse reactions from NSAIDs; the incidence of these adverse reactions increases with dose and duration of treatment. In addition, these patients are less tolerant to ulceration and bleeding. Most reports of fatal GI events are in this population. Older patients are also at risk of lower esophageal injury including ulceration and bleeding.
For such patients, consideration should be given to a starting dose lower than the one usually recommended, with individual adjustment when necessary and under close supervision.
Diclofenac is NOT recommended for use with other NSAIDs, with the exception of low-dose aspirin for cardiovascular prophylaxis, because of the absence of any evidence demonstrating synergistic benefits and the potential for additive adverse reactions (see Interactions).
Multiple diclofenac-containing preparations (including diclofenac potassium) should not be used concomitantly.
Cardiovascular Effects (see Warnings): Cardiovascular Thrombotic Events: Patients should remain alert for the signs and symptoms of serious arteriothrombotic events (e.g. chest pain, shortness of breath, weakness, slurring of speech), which can occur without warnings. Patients should be instructed to see a physician immediately in case of such an event.
There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious cardiovascular thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID does increase the risk of serious GI events.
Hypertension: NSAIDs can lead to the onset of new hypertension or worsening of pre-existing hypertension, either of which may contribute to the increased incidence of cardiovascular events. Patients taking thiazides or loop diuretics may have impaired response to these therapies when taking NSAIDs. NSAIDs, including diclofenac, should be used with caution in patients with hypertension. Blood pressure should be monitored closely during the initiation of NSAID treatment and throughout the course of therapy.
Congestive Heart Failure and Edema: Fluid retention and edema have been observed in some patients taking NSAIDs. Diclofenac should be used with caution in patients with fluid retention or heart failure.
Endocrine/Metabolic Effects: Diclofenac is NOT a substitute for corticosteroids. They do NOT treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to exacerbation of corticosteroid-responsive illness. Patients on prolonged corticosteroid therapy should have their therapy tapered slowly if a decision is made to discontinue corticosteroids (see Interactions).
Gastrointestinal (GI) Effects (see Warnings): NSAIDs, including diclofenac, can increase the risk of serious GI adverse events including inflammation, bleeding, ulceration, and perforation of the stomach, small or large intestines, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs.
NSAIDs should be prescribed with extreme caution in those with a history of ulcer disease or GI bleeding since these patients have a greater than 10-fold increased risk for developing a GI bleed compared with patients with neither of these risk factors. Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include concomitant use of oral corticosteroids or anticoagulants, longer duration of NSAID therapy, smoking, use of alcohol, older age, and poor general health status.
Physicians and patients should remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy and promptly initiate additional evaluation and treatment if a serious GI adverse event is suspected. This should include discontinuation of the NSAID until a serious GI adverse event is ruled out. Alternate therapies that do not involve NSAIDs should be considered especially for high-risk patients.
Close medical surveillance and caution should be exercised in patients with ulcerative colitis or with Crohn's disease as these conditions may be exacerbated.
Genitourinary Effects: Some NSAIDs are associated with persistent urinary symptoms (bladder pain, dysuria, urinary frequency), hematuria or cystitis. The onset of these symptoms may occur at any time after the initiation of therapy with an NSAID. Should urinary symptoms occur, in the absence of an alternate explanation, treatment with diclofenac should be stopped to ascertain if symptoms disappear. This should be done before urological investigations or treatments are carried out.
Caution should be exercised when initiating treatment with diclofenac in patients with considerable dehydration.
Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of an NSAID may cause a dose-dependent reduction in prostaglandin formation and secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and angiotensin-converting enzyme (ACE) inhibitors, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state.
Advanced Renal Disease: There are no controlled studies on the use of diclofenac in patients with advanced renal disease. Therefore, treatment with diclofenac is not recommended in these patients. If diclofenac therapy must be initiated, close monitoring of the patient's renal function is advised.
Anaphylactoid Reactions (see Contraindications): Anaphylactoid reactions may occur in patients without known prior exposure to NSAIDs. Diclofenac should not be given to patients with the aspirin triad. This symptom complex typically occurs in asthmatic patients who experience rhinitis with or without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs. Diclofenac should be administered with caution in patients with pre-existing asthma and emergency help should be sought in cases where an anaphylactoid reaction occurs.
Skin Reactions: As with other NSAIDs, diclofenac, can cause serious skin adverse events such as exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN or Lyell's syndrome), which can be fatal. These serious events may occur without warning. Patients should be informed about the signs and symptoms of serious skin manifestations and use of the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity.
Use of diclofenac may cause photosensitivity upon exposure to sunlight or ultraviolet light causing symptoms such as sunburn, skin rash, skin blisters, pruritus, erythema and discolouration.
Hepatic Effects: Borderline elevations of one or more liver tests may occur in up to 15% of patients taking NSAIDs including diclofenac. These laboratory abnormalities may progress, may remain unchanged, or may be transient with continuing therapy. In patients with chronic treatment with diclofenac, periodic monitoring of transaminases is recommended. Notable elevations of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) (approximately three or more times the upper limit of normal) have been reported in approximately 2 to 4% of patients, including marked elevations (eight or more times the upper limit of normal) in about 1% of patients. Rare cases of severe hepatic reactions, including jaundice and fatal fulminant hepatitis, liver necrosis and hepatic failure, some with fatal outcomes have been reported.
Patients with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal liver test has occurred, should be evaluated for evidence of the development of a more severe hepatic reaction while on therapy with NSAIDs including diclofenac. Discontinue diclofenac if clinical signs and symptoms consistent with liver disease develop or if systemic manifestations occur (e.g., eosinophilia, rash).
Caution is called for when using diclofenac in patients with hepatic porphyria, since it may trigger an attack.
Hematologic Effects: Anemia is sometimes seen in patients receiving NSAIDs including diclofenac. This may be due to fluid retention, occult or gross GI blood loss, or an incompletely described effect upon erythropoiesis. Patients on long-term treatment with NSAIDs, including diclofenac, should have their hemoglobin or hematocrit checked if they exhibit any signs or symptoms of anemia.
In some patients, NSAIDs inhibit platelet aggregation and have been shown to prolong bleeding time. Unlike aspirin, their effect on platelet function is quantitatively less, of short duration, and reversible. Patients receiving diclofenac who may be adversely affected by alterations in platelet function, such as those with coagulation disorders or patients receiving anticoagulants, should be carefully monitored.
Aseptic Meningitis: Rarely, with some NSAIDs, the symptoms of aseptic meningitis (stiff neck, severe headaches, nausea and vomiting, fever or clouding of consciousness) have been observed. Patients with autoimmune disorders (systemic lupus erythematosus, mixed connective tissue diseases, etc.) seem to be pre-disposed. Therefore, in such patients, the doctor must be vigilant to the development of this complication.
Effects on the Ability to Drive and Use Machine: Some patients may experience drowsiness, dizziness, blurred vision, vertigo, insomnia, depression, tinnitus or hearing loss with the use of NSAIDs, such as diclofenac. If patients experience such adverse reaction(s) they should refrain from driving, operating machinery, or carrying out activities that require alertness.
Use in Children (<16 years old): Safety and effectiveness in pediatric patients have not been established (see Contraindications).
Use in Elderly (≥65 years old): Elderly and frail or debilitated patients are more susceptible to a variety of adverse reactions from NSAIDs; the incidence of these adverse reactions increases with dose and duration of treatment. In addition, these patients are less tolerant to ulceration and bleeding. Most reports of fatal GI events are in this population. Older patients are also at risk of lower esophageal injury including ulceration and bleeding.
For such patients, consideration should be given to a starting dose lower than the one usually recommended, with individual adjustment when necessary and under close supervision.
Use In Pregnancy & Lactation
Pregnancy: Pregnancy Category C. Diclofenac is CONTRAINDICATED for use during the third trimester of pregnancy because of risk of premature closure of the ductus arteriosus and the potential to prolong labor and birth. Caution should be exercised in prescribing diclofenac during the first and second trimesters of pregnancy (see Contraindications).
Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or the embryo-fetal development. Data from epidemiological studies suggest an increased risk of miscarriage and of cardiac malformation after use of a prostaglandin synthesis inhibitor in early pregnancy.
The use of diclofenac, as with any drug known to inhibit cyclooxygenase/prostaglandin synthesis, may impair fertility and is not recommended in women attempting to conceive. Therefore, in women who have difficulties conceiving, or who are undergoing investigation of infertility, withdrawal of diclofenac should be considered.
Lactation: Like other NSAIDs, diclofenac passes into breast milk in small amounts. Therefore diclofenac should not be administered during breast feeding in order to avoid undesirable effects in the infant.
Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or the embryo-fetal development. Data from epidemiological studies suggest an increased risk of miscarriage and of cardiac malformation after use of a prostaglandin synthesis inhibitor in early pregnancy.
The use of diclofenac, as with any drug known to inhibit cyclooxygenase/prostaglandin synthesis, may impair fertility and is not recommended in women attempting to conceive. Therefore, in women who have difficulties conceiving, or who are undergoing investigation of infertility, withdrawal of diclofenac should be considered.
Lactation: Like other NSAIDs, diclofenac passes into breast milk in small amounts. Therefore diclofenac should not be administered during breast feeding in order to avoid undesirable effects in the infant.
Adverse Reactions
The most frequently reported adverse effects (1 to 10%) are abdominal pain, abnormal renal function, anemia, constipation, decreased appetite, diarrhea, dizziness, dyspepsia, edema, elevated liver enzymes, flatulence, GI ulcers (gastric/duodenal), gross bleeding/perforation, headache, heartburn, increased bleeding time, nausea, pruritus, rashes, tinnitus, vertigo, and vomiting.
Less common adverse effects (<1% of patients) include: Blood and Lymphatic System: Agranulocytosis, aplastic anemia, bruising in the extremities and abdomen, eosinophilia, hematoma formation, hemolytic anemia, inhibit platelet aggregation, leukopenia, lymphadenopathy, pancytopenia, prolong bleeding time, purpura, rectal bleeding, spontaneous bleeding, stomatitis, thrombocytopenia.
Immune System: Anaphylaxis and anaphylactoid reactions (including hypotension and shock), angioedema (including facial edema), asthma, bronchospasm, chest tightness, dyspnea, eosinophilic pneumonitis, hypersensitivity, laryngeal edema, potentially severe hypotension, swelling of the eyelids, tongue, lips, pharynx or larynx, urticaria, wheezing.
Metabolism and Nutrition: Anorexia, appetite changes, hyperglycemia, hyponatremia, weight changes.
Psychiatric: Anxiety, confusion, depression, disorientation, drowsiness, hallucinations, insomnia, irritability, nervousness, nightmare, psychotic disorder.
Nervous System: Aseptic meningitis, cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage), coma, convulsions, dream abnormalities, dysgeusia impaired concentration, memory impairment, meningitis, migraine, myoclonus, paresthesia, tingling sensation, tremors.
Eye: Conjunctivitis, optic neuritis, visual impairment (blurred vision, diplopia).
Cardiovascular: Angina, arrhythmia, chest pain, circulatory shock or distress, congestive heart failure, hypertension, hypotension, myocardial infarction, palpitations, syncope, tachycardia, thrombophlebitis, vasculitis.
Respiratory, Thoracic and Mediastinal: Asthma, bronchitis, dyspnea, pharyngitis, pneumonia, pneumonitis, respiratory depression.
Gastrointestinal (GI): Coated tongue, colitis, diaphragm-like intestinal strictures, dry mouth, eructation, esophageal lesions, esophagitis, exacerbation of colitis and Crohn's disease, gastric or peptic ulcers, gastritis, GI hemorrhage, glossitis, hematemesis, hemorrhagic diarrhea, melena, pancreatitis, perforation or GI bleeding, stomatitis.
Hepatic: Abnormal liver function, cholestasis, hepatitis (including asymptomatic, acute, chronic, and fulminant), hepatocellular necrosis, jaundice, liver failure.
Skin and Subcutaneous Tissue: Alopecia, angioedema, bullous eruptions, ecchymosis, eczema, erythema multiforme, erythema, exfoliative dermatitis, Henoch-Schonlein purpura, increased sweating, photosensitivity, purpura, SJS, TEN or Lyell's syndrome, urticaria.
Renal and Urinary: Cystitis, dysuria, hematuria, increased blood urea nitrogen and serum creatinine concentrations, nephrotic syndrome, oliguria/polyuria, papillary necrosis, proteinuria, renal calculi, renal failure, tubulointerstitial nephritis, urinary tract infection.
General Disorders and Administration Site Conditions: Asthenia, malaise, tiredness.
Others: Back, leg or joint pain, death, fever, hearing impairment, impotence, infection, sepsis.
Less common adverse effects (<1% of patients) include: Blood and Lymphatic System: Agranulocytosis, aplastic anemia, bruising in the extremities and abdomen, eosinophilia, hematoma formation, hemolytic anemia, inhibit platelet aggregation, leukopenia, lymphadenopathy, pancytopenia, prolong bleeding time, purpura, rectal bleeding, spontaneous bleeding, stomatitis, thrombocytopenia.
Immune System: Anaphylaxis and anaphylactoid reactions (including hypotension and shock), angioedema (including facial edema), asthma, bronchospasm, chest tightness, dyspnea, eosinophilic pneumonitis, hypersensitivity, laryngeal edema, potentially severe hypotension, swelling of the eyelids, tongue, lips, pharynx or larynx, urticaria, wheezing.
Metabolism and Nutrition: Anorexia, appetite changes, hyperglycemia, hyponatremia, weight changes.
Psychiatric: Anxiety, confusion, depression, disorientation, drowsiness, hallucinations, insomnia, irritability, nervousness, nightmare, psychotic disorder.
Nervous System: Aseptic meningitis, cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage), coma, convulsions, dream abnormalities, dysgeusia impaired concentration, memory impairment, meningitis, migraine, myoclonus, paresthesia, tingling sensation, tremors.
Eye: Conjunctivitis, optic neuritis, visual impairment (blurred vision, diplopia).
Cardiovascular: Angina, arrhythmia, chest pain, circulatory shock or distress, congestive heart failure, hypertension, hypotension, myocardial infarction, palpitations, syncope, tachycardia, thrombophlebitis, vasculitis.
Respiratory, Thoracic and Mediastinal: Asthma, bronchitis, dyspnea, pharyngitis, pneumonia, pneumonitis, respiratory depression.
Gastrointestinal (GI): Coated tongue, colitis, diaphragm-like intestinal strictures, dry mouth, eructation, esophageal lesions, esophagitis, exacerbation of colitis and Crohn's disease, gastric or peptic ulcers, gastritis, GI hemorrhage, glossitis, hematemesis, hemorrhagic diarrhea, melena, pancreatitis, perforation or GI bleeding, stomatitis.
Hepatic: Abnormal liver function, cholestasis, hepatitis (including asymptomatic, acute, chronic, and fulminant), hepatocellular necrosis, jaundice, liver failure.
Skin and Subcutaneous Tissue: Alopecia, angioedema, bullous eruptions, ecchymosis, eczema, erythema multiforme, erythema, exfoliative dermatitis, Henoch-Schonlein purpura, increased sweating, photosensitivity, purpura, SJS, TEN or Lyell's syndrome, urticaria.
Renal and Urinary: Cystitis, dysuria, hematuria, increased blood urea nitrogen and serum creatinine concentrations, nephrotic syndrome, oliguria/polyuria, papillary necrosis, proteinuria, renal calculi, renal failure, tubulointerstitial nephritis, urinary tract infection.
General Disorders and Administration Site Conditions: Asthenia, malaise, tiredness.
Others: Back, leg or joint pain, death, fever, hearing impairment, impotence, infection, sepsis.
Drug Interactions
NSAIDs such as diclofenac have the following interactions: See table.
Laboratory Parameters: Diclofenac increases platelet aggregation time but does not affect bleeding time, plasma thrombin clotting time, plasma fibrinogen, or factors V and VII to XII. Statistically significant changes in prothrombin and partial thromboplastin times have been reported in normal volunteers. The mean changes were observed to be less than 1 second in both instances, and are unlikely to be clinically important.
Persistently abnormal or worsening renal, hepatic or hematological test values should be followed up carefully since they may be related to therapy.
Tell the doctor if the patient is taking other medicines, including vitamins, supplements, and herbal medicines.
Persistently abnormal or worsening renal, hepatic or hematological test values should be followed up carefully since they may be related to therapy.
Tell the doctor if the patient is taking other medicines, including vitamins, supplements, and herbal medicines.
Storage
Store at temperatures not exceeding 30°C.
Action
Pharmacology: Pharmacodynamics: Diclofenac sodium exhibits anti-inflammatory, analgesic and antipyretic activities by inhibiting cyclooxygenase (COX)-1 and COX-2 isoenzymes. These enzymes are found throughout the body and produce prostaglandins, which are important mediators of pain, fever, and adaptive and protective reactions in many organs and (inflamed) tissues.
When used concomitantly with opioids for the management of post-operative pain, diclofenac significantly reduces the need for opioids.
Pharmacokinetics: Diclofenac sodium is almost completely absorbed from the gastrointestinal (GI) tract after oral administration. However, the drug undergoes extensive first pass metabolism in the liver with only about 50 to 60% of a diclofenac dose reaching the systemic circulation as unchanged drug. Peak plasma concentrations occur within 2 to 3 hours (range: 1 to 4 hours) after oral intake. The area under the plasma concentration-time curve (AUC) increases linearly with single diclofenac sodium doses of 25 to 150 mg.
Food decreases the onset and rate of absorption of enteric-coated diclofenac sodium resulting in a delayed and decreased peak plasma concentration but the extent of absorption is not affected substantially. When single doses of diclofenac sodium enteric-coated tablets are taken with food, the onset of absorption is usually delayed by 1 to 4.5 hours but may be delayed for up to 12 hours in some patients.
After administration of 75 mg diclofenac by IM injection, absorption sets in immediately, and mean peak plasma concentrations of about 2.558 ± 0.96 mcg/ml (8 mcmol/L) are reached after about 20 minutes. When 75 mg diclofenac is administered as an IV infusion over 2 hours, mean peak plasma concentrations are about 1.875 ± 0.436 mcg/ml (5.9 mcmol/L). Shorter infusions result in higher peak plasma concentrations, while longer infusions give plateau concentrations proportional to the infusion rate after 3 to 4 hours. This is in contrast to the rapid decline in plasma concentrations seen after peak levels have been achieved with oral, rectal or IM administration.
The AUC after IM or IV administration is about twice as large as it is following oral or rectal administration as this route avoids "first-pass" metabolism. Pharmacokinetic behavior does not change after repeated administration. No accumulation occurs provided the recommended dosage intervals are observed.
Diclofenac is distributed into synovial fluid, achieving peak synovial fluid concentrations about 60 to 70% of those attained in plasma after oral administration; however, synovial fluid concentrations of diclofenac and its metabolites substantially exceed those in plasma after 3 to 6 hours. Diclofenac appears to be eliminated from synovial fluid less rapidly than from plasma. The apparent total volume of distribution of diclofenac is 1.3 to 1.4 L/kg.
Diclofenac was detected in a low concentration (100 ng/mL) in breast milk. The estimated amount ingested by the infant consuming breast milk is equivalent to a 0.03 mg/kg/day dose.
Diclofenac is extensively but reversibly bound to plasma proteins, mainly albumin. In vitro studies showed that the drug is 99 to 99.8% protein-bound. In patients with rheumatoid arthritis, protein binding of diclofenac in synovial fluid appears to be lower than in plasma.
Following IV administration of diclofenac sodium in healthy adults, the half-life of diclofenac is approximately 3 minutes in the initial distribution phase, 16 minutes in the intermediate phase, and 1 to 2 hours in the terminal phase.
Oral diclofenac is rapidly and extensively metabolized in the liver. Its elimination half-life was approximately 1.2 to 2 hours. In humans the major metabolite is the 4'-hydroxy compound. About 20 to 30% of an oral dose is excreted in the urine while 10 to 20% is excreted in the bile. In mice and rats, diclofenac and its metabolites were shown to cross the placenta.
Special Population: Hepatic Insufficiency: Patients with hepatic disease may require reduced doses of diclofenac compared to patients with normal hepatic function since hepatic metabolism accounts for almost 100% of diclofenac elimination.
Renal Insufficiency: The elimination half-life in patients with moderate renal impairment appears to be similar to that in patients with normal renal function.
When used concomitantly with opioids for the management of post-operative pain, diclofenac significantly reduces the need for opioids.
Pharmacokinetics: Diclofenac sodium is almost completely absorbed from the gastrointestinal (GI) tract after oral administration. However, the drug undergoes extensive first pass metabolism in the liver with only about 50 to 60% of a diclofenac dose reaching the systemic circulation as unchanged drug. Peak plasma concentrations occur within 2 to 3 hours (range: 1 to 4 hours) after oral intake. The area under the plasma concentration-time curve (AUC) increases linearly with single diclofenac sodium doses of 25 to 150 mg.
Food decreases the onset and rate of absorption of enteric-coated diclofenac sodium resulting in a delayed and decreased peak plasma concentration but the extent of absorption is not affected substantially. When single doses of diclofenac sodium enteric-coated tablets are taken with food, the onset of absorption is usually delayed by 1 to 4.5 hours but may be delayed for up to 12 hours in some patients.
After administration of 75 mg diclofenac by IM injection, absorption sets in immediately, and mean peak plasma concentrations of about 2.558 ± 0.96 mcg/ml (8 mcmol/L) are reached after about 20 minutes. When 75 mg diclofenac is administered as an IV infusion over 2 hours, mean peak plasma concentrations are about 1.875 ± 0.436 mcg/ml (5.9 mcmol/L). Shorter infusions result in higher peak plasma concentrations, while longer infusions give plateau concentrations proportional to the infusion rate after 3 to 4 hours. This is in contrast to the rapid decline in plasma concentrations seen after peak levels have been achieved with oral, rectal or IM administration.
The AUC after IM or IV administration is about twice as large as it is following oral or rectal administration as this route avoids "first-pass" metabolism. Pharmacokinetic behavior does not change after repeated administration. No accumulation occurs provided the recommended dosage intervals are observed.
Diclofenac is distributed into synovial fluid, achieving peak synovial fluid concentrations about 60 to 70% of those attained in plasma after oral administration; however, synovial fluid concentrations of diclofenac and its metabolites substantially exceed those in plasma after 3 to 6 hours. Diclofenac appears to be eliminated from synovial fluid less rapidly than from plasma. The apparent total volume of distribution of diclofenac is 1.3 to 1.4 L/kg.
Diclofenac was detected in a low concentration (100 ng/mL) in breast milk. The estimated amount ingested by the infant consuming breast milk is equivalent to a 0.03 mg/kg/day dose.
Diclofenac is extensively but reversibly bound to plasma proteins, mainly albumin. In vitro studies showed that the drug is 99 to 99.8% protein-bound. In patients with rheumatoid arthritis, protein binding of diclofenac in synovial fluid appears to be lower than in plasma.
Following IV administration of diclofenac sodium in healthy adults, the half-life of diclofenac is approximately 3 minutes in the initial distribution phase, 16 minutes in the intermediate phase, and 1 to 2 hours in the terminal phase.
Oral diclofenac is rapidly and extensively metabolized in the liver. Its elimination half-life was approximately 1.2 to 2 hours. In humans the major metabolite is the 4'-hydroxy compound. About 20 to 30% of an oral dose is excreted in the urine while 10 to 20% is excreted in the bile. In mice and rats, diclofenac and its metabolites were shown to cross the placenta.
Special Population: Hepatic Insufficiency: Patients with hepatic disease may require reduced doses of diclofenac compared to patients with normal hepatic function since hepatic metabolism accounts for almost 100% of diclofenac elimination.
Renal Insufficiency: The elimination half-life in patients with moderate renal impairment appears to be similar to that in patients with normal renal function.
MedsGo Class
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)
Features
Dosage
50 mg
Ingredients
- Diclofenac
Packaging
Enteric-Coated Tablet 100's
Generic Name
Diclofenac Sodium
Registration Number
DRP-2612
Classification
Prescription Drug (RX)
Product Questions
Questions
