▶ Specification : 10 capsules
▶ Category : Antipyretic, analgesic, anti-inflammatory
Dexibuprofen 300mg
○ Adults : Orally administer 300mg as dexibuprofen 2 to 4 times daily. Do not exceed 1,200mg dexibuprofen per day.
+ Indications
1. Chronic multiple arthritis, rheumatoid arthritis
2. Arthrosis
3. Ankylosing spondylitis
4. Painful edema or inflammation after trauma or surgery
5. Adjuvant to treatment of infection accompanied by inflammation, pain and fever
1. Warnings
1) Persons who regularly consume at least 3 alcoholic drinks daily must consult a physician or pharmacist before taking this drug or other fever and pain medications. Taking this drug may cause liver damage in such patients.
2) Cardiovascular risks : Nonsteroidal anti-inflammatory drugs including this drug can increase the risk of severe or fatal cardiovascular thrombosis, myocardial infarction and stroke. These risks may increase with the duration of administration. Patients with cardiovascular disease or cardiovascular disease risk factors may be subject to higher risk. The physician and patient must carefully monitor presentation of such cardiovascular symptoms. The same applies for patients without a history of cardiovascular disease. The patient must be informed beforehand of severe cardiovascular toxicity indicators and/or symptoms, and actions to be taken in the case that these symptoms present.
Patients with uncontrolled hypertension, congestive heart failure (NYHA II-III), established ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with ibuprofen after careful consideration and high doses (1,200mg/day) should be avoided. Careful consideration should also be exercised before initiating long-term treatment of patients with risk factors for cardiovascular events (e.g. hypertension, hyperlipidemia, diabetes mellitus, and smoking), particularly if high doses of ibuprofen (≥ 1,400mg/day) are required.
Clinical trials have shown that use of high dose (2400mg/day) ibuprofen may slightly increase the risk of arterial thrombus symptoms (myocardial infarction or stroke). Results of general epidemiologic studies have shown no proof of association between low dose ibuprofen (e.g. up to 1,200mg/day) and increased risk of arterial thrombus symptoms. Limited data is available on arterial thrombus risks of dexibuprofen, but it is appropriate to assume the risk of high dose dexibuprofen (1200mg/day) is similar to that of high does ibuprofen (2400mg/day).
3) Gastroenteric risk : Nonsteroidal anti-inflammatory drugs including this drug can increase the risk of severe or fatal gastroenteric adverse reactions including bleeding, ulcers and perforation of the stomach or intestines. These adverse reactions may occur during the duration of administration without warning symptoms. Elderly patients may have a higher risk of severe gastroenteric adverse reactions. The likelihood of severe gastroenteric adverse reactions may increase with the duration of administration, but short-term administration does not completely rule out such risks. Careful monitoring of symptoms or signs of gastroenteric ulcers or bleeding is required while administering this drug. If severe gastroenteric adverse reaction is suspected, additional evaluation and treatment must immediately be carried out. Discontinuing administration of NSAIDs until severe gastroenteric adverse reaction is ruled out may be a method of treatment. For high-risk patients, other alternative treatments not associated with NSAIDs should be considered.
2. The following patients should not take this drug.
1) Patients with gastroenteric ulcers, signs thereof, or history of recurrence thereof
2) Patients with bleeding in the stomach or intestines, cerebral blood vessels, or other
3) Patients with severe blood disorders
4) Patients with severe liver impairment
5) Patients with severe renal impairment
6) Patients with severe heart failure
7) Patients with severe hypertension
8) Patients with hypersensitivity to this drug and ingredients of this drug
9) Patients with bronchial asthma or a history thereof
10) Patients with a history of asthma, hives or allergic reaction to aspirin or other NSAIDs (including COX-2 inhibitors) (Rare severe and fatal anaphylactic reaction after administration of NSAIDs reported in such patients.)
11) Treatment of pain before and after coronary artery bypass graft (CABG)
12) Pregnant mothers more than 6 months into pregnancy (Administration of this drug in the terminal stages of pregnancy, like NSAIDs, can lead to early closure of the ductus arteriosus of the fetus.)
13) Patients with inflammatory bowel disease such as Crohn’s Disease or ulcerative colitis
14) Patients with a history of gastroenteric bleeding or perforation due to previous treatment with NSAIDs
3. Avoid the following drugs while taking this drug.
1) Aspirin
(1) No consistent evidence of increased severe cardiovascular thrombus reaction associated with NSAID use due to concomitant administration with aspirin. As concomitant administration of this drug with aspirin may increase the risk of severe gastroenteric adverse reaction, as with other NSAIDs, concomitant use of the two drugs is generally not recommended.
(2) Concomitant administration with aspirin may inhibit the action of this drug and other NSAIDs.
2) Do not concomitantly administer with other NSAIDs; may increase risk of adverse reaction such as gastroenteric adverse reaction and gastroenteric bleeding.
3) Methotrexate at high doses (15mg/week or higher) : Concomitant administration with NSAIDs may delay excretion of methotrexate from renal tubes, increasing fatal methotrexate blood toxicity; do not administer concomitantly with high-dose methotrexate used in anti-cancer therapy.
4. Do not do the following while taking this drug.
1) Transfer to breast milk has been reported, with possibility of severe adverse reactions in infants. In light of the importance of administering this drug, either breastfeeding or administration of this drug should be discontinued.
2) Taking this drug may lead to dizziness or fatigue as an adverse reaction, limiting the patient’s reaction ability. Patients operating vehicles or machinery should take this drug with caution. No particular caution is necessary for single or short-term administration.
3) Long-term high-dose administration may cause headache.
5. The following should consult a physician, dentist, or pharmacist before taking this drug.
1) Patients with blood disorders or a history of the same
2) Patients with a bleeding tendency (platelet function disorder may occur.)
3) Patients with liver impairment or a history of the same
4) Patients with renal impairment or a history of the same
5) Patients with fluid retention or heart failure
6) Patients with hypertension
7) Patients with a history of hypersensitivity
8) Patients with systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD)
9) Elderly patients (Elderly patients are prone to adverse reaction; begin administration at small doses and administer the lowest minimum dose and administer carefully, observing the state of the patient for presentation of adverse reactions.)
10) Children 6 years or older (Safety and efficacy not established in children less than 6 years old. Carefully administer the minimum required dose in children 6 years or older, and watch carefully for appearance of adverse reactions.)
11) Patients with stomach cancer
12) Patients with alcoholism
13) Pregnant women in early and mid-term pregnancy [metabolic toxicity observed in animal tests (reduced implantation and survival count observed at high doses), with reports of persistent fetal circulation (PFC)], women planning pregnancy (like other prostaglandin synthase inhibitors, this drug reduces fecundity. Women with difficulty getting pregnant or receiving infertility testing should consider discontinuing administration of this drug.), potentially pregnant women
14) Patients with ischemic heart disease, peripheral arterial disease, cerebrovascular disease
15) Patients with cardiovascular disease risk factors (e.g. hypertension, hyperlipidemia, diabetes, smoking)
16) Patients with hepatic porphyria (use of this drug may lead to seizures.)
17) Patients who have received serious surgical intervention causing shortage of blood
18) Patients taking diuretics or ACE inhibitors
19) Patients with blood clotting disorder or taking anticoagulants
20) Patients with previous history of intestinal tract ulcers due to prolonged administration of NSAIDs who require long-term administration of this drug and are undergoing concurrent treatment of digestive ulcers with misoprostol, etc. (As some digestive ulcers exhibit resistance to treatment with misoprostol, observe progression sufficiently when administering this drug.)
21) Patients taking the following drugs
(1) Corticosteroids, alcohol : Risk of gastroenteric adverse reaction and gastroenteric bleeding
(2) Digoxgin, phenytoin : May increase plasma concentration.
(3) Probenecid, sulfinpyrazone : Inhibits action of probenecid and sulfinpyrazone, slowing excretion of dexibuprofen.
(4) Sulfonylurea : May increase hypoglycemic effects of sulfonylurea
(5) ACE inhibitors or angiotensin II receptor blocker : There are reports that NSAIDs may reduce the anti-hypertensive effect of ACE inhibitors or angiotensin II receptor blockers; keep interactions in mind when administering this drug and ACE inhibitors or angiotensin II receptor blockers concomitantly.
(6) Diuretics : Clinical trials and post-marketing surveillance have shown that suppression of prostaglandin synthesis in the kidneys by this drug may reduce the sodium excretion effect of furosemide and thiazide diuretics in some patients. During concomitant administration of these drugs and NSAIDs, observe closely for renal impairment symptoms and signs of renal failure.
(7) Lithium : NSAIDs may increase serum lithium concentration by suppressing prostaglandin synthesis in the kidneys, and reduce the renal clearance rate of lithium. Accordingly, observe carefully for signs of lithium toxicity when administering concomitantly with NSAIDs.
(8) Coumarin anticoagulants (warfarin, etc.) : Warfarin and NSAIDs may exhibit synergistic effects with respect to gastroenteric bleeding; patients concomitantly administered the two drugs may have higher risk of severe gastroenteric bleeding compared to cases of single administration; administer carefully and observe closely, reducing dose if necessary.
(9) Baclofen : Baclofen toxicity is increased.
(10) Immunosuppressants (cyclosporine, ticlopidine, sirolimus) : Concomitant administration with NSAIDs may increase the renal toxicity of cyclosporine, ticlopidine and sirolimus.
(11) Thrombolytics, ticlopidine, antithrombotics : Dexibruprofen suppresses COX in platelets and suppresses clumping of platelets; concomitant administration of dexibuprofen with thrombolytics, ticlopidine and antithrombotics carries the risk of increased antiplatelet effects
(12) Drugs that increase blood potassium concentrations (e.g. potassium-sparing diuretics, ACE inhibitors, angiotensin-II receptor blockers, immunosuppressants such as cyclosporine or tacrolimus, trimethoprim, heparin, etc.) : Concomitant administration may result in hyperkalemia; regular observation of potassium levels is necessary.
(13) CYP2C8 or CYP2C9 inducers (e.g. rifampicin, phenobarbitals) : May increase metabolism of this drug and reduce the drug effect.
(14) Methotrexate at low doses (15mg/week or less) : Concomitant administration with NSAIDs may delay excretion of methotrexate from renal tubes, increasing fatal methotrexate blood toxicity; proceed carefully when administering concomitantly.
(15) Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs) : Concomitant administration with this drug may increase the risk of gastroenteric bleeding.
(16) Persons taking low dose aspirin with the purpose of preventing myocardial infarction or stroke (this drug reduces the effect of aspirin, and may increase the risk of severe gastroenteric adverse reactions.) Laboratory data has shown that concomitant administration of ibuprofen and aspirin (acetyl salicylic acid) may suppress the anti-platelet clumping effect of low dose aspirin. Extrapolation with this data has shown that although there are some uncertainties, general or long-term use of ibuprofen may reduce the heart protecting effect of low dose aspirin. There is no data on dexibuprofen, but it is fair to assume that there is a similar interaction between dexibuprofen and low dose aspirin.
6. In the following cases, immediately discontinue administration of this drug and consult a physician, dentist or pharmacist. If possible, the patient should take this document with him/her when consulting.
1) Shock : Shock symptoms may appear rarely; observe sufficiently. Discontinue administration immediately if symptoms such as chest discomfort, chills, difficulty breathing, and drops in blood pressure.
2) Blood diseases : Aplastic anemia, hemolytic anemia, granulocytopenia, leukopenia, non-granulocytosis, platelet aggregation, thrombocytopenia, platelet dysfunction (prolonged bleeding time) and eosinophil may rarely appear. Observe sufficiently with blood tests, etc., and immediately discontinue administration if there are anomalies.
3) Digestive system : Discontinue administration in case of indigestion, abdominal distention, heartburn, upper abdominal pain, diarrhea or constipation; sometimes loss of appetite, nausea, vomiting, abdominal pains, stomach discomfort; rarely, esophagitis, esophageal stenosis, diverticulosis, non-specific bleeding colitis, ulcerative colitis or Crohn’s disease, digestive ulcers, gastric bleeding, gastric perforation, bloody stool, gastritis, pancreatitis; very rarely, thirst or stomatitis.
4) Skin : Erythema multiforme, systemic lupus erythematosus, hair loss, sometimes angioedema, rarely mucocutaneous ocular syndrome (Stevens-Johnson syndrome) and toxic epidermal necrolysis (Lyells syndrome) may appear; discontinue administration in these cases.
5) Hypersensitivity : Sometimes rashes, hives, itchiness, purpura, rarely asthma attacks, eczema, anaphylactic reaction, and photosensitivity reaction may occur; discontinue administration in these cases.
6) Liver : Rarely, jaundice, elevated Alt, elevated AST, elevated ALP, hepatic function anomalies, hepatitis, etc.
7) Respiratory system : Sometimes rhinitis, bronchospasm, risk of acute pneumonia in rare cases in cardiac failure patients
8) Sensory system : Discontinue administration in the rare event of visual impairment. Rarely, difficulty hearing, ringing in ears, and taste disorders may appear.
9) Psychoneural : Fatigue, sleepiness, headache, dizziness, sometimes anxiety, derangement, depression, rarely aseptic meningitis are reported. Immediately discontinue administration in the event of symptoms such as severe headache, nausea, vomiting, insomnia, neck stiffness, fever or loss of consciousness, and consult a physician. Patients with autoimmune diseases (systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD)) should take carefully. Rarely, psychosis, anxiety, excitation, orientation disturbance, and reversible toxic amblyopia may occur.
10) Circulative system : Rarely, drops in blood pressure, rise in blood pressure, and palpitations, etc.
11) Kidneys : May rarely cause acute renal failure. In case of symptoms such as oliguria or hematuria, or test results showing elevated protein levels in urine, BUN, elevated blood creatinine, or hyperkalemia, discontinues administration and take appropriate action. Reduced urine amount, systemic edema accompanied by languor and shortness of breath, as well as rare renal papillary necrosis, nephrotic syndrome, and interstitial nephritis may occur.
12) Cardiovascular : Peripheral edema may appear, and risk of acute pulmonary edema may increase in patients with heart failure. Fluid retention may appear in patients with hypertension or renal failure. Hypertension or renal failure may occur in elderly patients.
13) Endocrine : Reduced female fecundity
14) Misc. : Sometimes periorbital edema, very rarely malaise, fever, nosebleeds, exacerbation of inflammation, etc.
7. Misc. precautions when administering this drug
1) Before administering this drug, consider the potential risks and benefits of this drug and other treatments. This drug should be administered at the lowest effective dose for the shortest period possible, according to the treatment objectives of each patient.
2) Mind that treatment using analgesics and anti-inflammatory agents is symptomatic, not causal treatment.
3) Consider the following when using for chronic illnesses
(1) For patients administering this drug for prolonged periods, carry out clinical tests (urine tests, complete blood count (CBC) tests, physicochemical and other blood tests, liver function tests, etc.) at regular intervals, and take appropriate action such as reducing dose or a drug holiday. If necessary, carry out regular blood coagulation testing (if anticoagulants are being administered), blood potassium concentration tests (if potassium-sparing drugs are being administered) or blood lithium concentration tests. In the case of clinical symptoms associated with liver or kidney disease, or systemic signs (e.g. eosinophilia, rashes) or abnormal liver function or kidney function test results continue or are exacerbated, discontinue administration of this drug.
(2) Consider treatment other than drug therapy.
4) Consider the following when using for acute illness.
(1) Administer with consideration for the degree of acute inflammation, pain and fever.
(2) By principle, avoid long-term administration of the same drug.
(3) If a causal therapy exists, carry out said therapy.
(4) By principle, long-term administration should be within 5 days.
5) Sufficiently observe the state of the patient, and watch out for presentation of adverse reactions. In particular, carefully monitor the patient after administration to infants, children, elderly patients or patients with wasting disease as symptoms such as excessive drops in body temperature, collapse and coldness of limbs may appear.
6) Due to the pharmacological characteristics of this drug, this drug may keep other symptoms and signs of inflammation from appearing, and delaying diagnosis of infective complications under painful and non-infective conditions. When using this drug against inflammations due to infection, administer concomitantly with suitable antibacterial agents and administer carefully with sufficient observation.
7) Gastroenteric adverse reactions : Extreme care is necessary when prescribing this drug or other NSAIDs to patients with a history of ulcerative disease or gastroenteric bleeding. In the case of patients with histories of digestive ulcer disease and/or gastroenteric bleeding, risk of gastroenteric bleeding was increased by 10 times or more when administered NSAIDs compared to patients without such risks. Other risk factors increasing risk of gastroenteric bleeding include concomitant therapy with oral corticosteroids or anticoagulants, prolonged use of NSAIDs, alcohol consumption, old age, and weak state of health. As most voluntary reports of fatal gastroenteric adverse reactions are from elderly and weak persons; special care is necessary when administering this drug to such patients.
8) Hypertension : NSAIDs including this drug may cause hypertension, exacerbate existing hypertension, and thereby increase the rate of occurrence of cardiovascular adverse cases. Taking of NSAIDs by a patient taking thiazide diuretics or loop diuretics may reduce reaction to these therapies. NSAIDs including this drug should be administered carefully to patients with hypertension. Blood pressure must be closely monitored at the time of first administration of this drug and during the duration of administration.
9) Ischemic heart failure and edema : Fluid retention and edema was observed in some patients taking NSAIDs including this drug. This drug must be administered carefully to patients with fluid retention or heart failure.
10) Prolonged administration of NSAIDs may lead to renal papillary necrosis or other kidney damage. Special attention is necessary in elderly patients or patients with heart failure, renal failure, liver failure, and patients taking diuretics or ACE inhibitors, as prostaglandin plays an important role in maintaining kidney blood flow. In most cases, pre-therapeutic state is recovered when administration is discontinued.
11) Developed renal disease : No controlled clinical trials of this drug in patients with developed renal disease. Accordingly, administration of this drug to patients with developed renal disease is not recommended. If administration of this drug must be started, the patient’s renal function must be observed closely.
12) Administration of NSAIDs including this drug may result in elevated liver function figures. These abnormal test values may be exacerbated as treatment continues, may remain unchanged, or may be temporary. Also, there are rare reports of severe liver-related adverse reactions such as jaundice, fatal fulminant hepatitis, liver necrosis, liver failure (sometimes fatal) due to administration of NSAIDs including this drug. In the case of patients with symptoms and/or signs of impaired liver function or patients with abnormal liver function test results, observe carefully for worsening of liver function during the duration of administration. In the case of clinical symptoms or systemic signs associated with liver disease (e.g. acidophilia, rashes), discontinue administration of this drug.
13) Administration of NSAIDs including this drug may result in anemia. In cases of symptoms or signs of anemia due to long-term administration of this drug, hemoglobin or hematocrit levels should be tested. NSAIDs suppress clumping of platelets, with extending bleeding times in some patients. Unlike aspirin, the effects of this drug on platelet function are relatively small, reversible, and sustained for a short period of time. Patients with coagulation-related disease or taking anti-coagulants, and other cases where modulation of platelet function may have negative effects should be closely monitored when this drug is administered.
14) Anaphylactic reaction : As with other NSAIDs, anaphylactic reaction may occur in patients with no previous exposure to the drug. These complex symptoms typically occur in asthma cases with potentially fatal severe bronchial with or without nasal polyps after administration of aspirin or other NSAIDs. Emergency treatment is necessary in the case of such anaphylactic reactions.
15) Skin reactions : This drug may cause serious skin adverse reactions such as exfoliative dermatitis, mucocutaneous ocular syndrome (Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell’s Syndrome), which may be fatal. These severe adverse reactions may appear without warning symptoms. In most cases, these adverse reactions occur within the first month or administration. The patient should know of these serious skin symptoms and signs, and administration of the drug must be discontinued upon first appearance of symptoms and signs such as skin rashes or other hypersensitivity symptoms.
16) Some asthma patients may react sensitively to aspirin. Use of aspirin in aspirin-sensitive asthma patients may be associated with fatal severe bronchospasm. In such aspirin-sensitive patients, cross reactions between aspirin and other NSAIDs, including bronchospasm, have been reported. Accordingly, do not administer this drug to such aspirin-sensitive patients.
17) This drug may not be used as a substitute for corticoid agents or as a drug for treatment of corticoid deficiency. Sudden discontinuation of administration of corticosteroids may lead to exacerbation of corticosteroid-reactive diseases. To administer this drug to patients having taken corticosteroids for a prolonged time, slowly reduce doses.
18) Temporary infertility was reported in patients taking NSAIDs for prolonged periods.
19) Note that treatment using anti-inflammatory drugs and analgesics is symptomatic, not causal therapy.
20) Impact on clinical test scores : Rarely, elevated urea nitrogen, transaminase, and alkaline phosphatase, reduced hemoglobin and hematocrit scores, reduced platelet clumping, and extended bleeding time may occur.
21) Results of domestic post-marketing surveillance (syrup)
- The results of domestic post-marketing surveillance over 4 years with 654 and 469 patients, respectively for drug review are as follow.
(1) PMS with 654 patients showed an adverse event rate of 0.61% regardless of causal relationship (4 out of 654 patients, 4 cases). Rate was 0.15% for irritability, facial edema, indigestion, and itchiness (1 out or 654 patients, 1 case).
Rate of drug adverse reactions whose causal relationship with this drug could not be ruled out was 0.46% (3 out or 654 patients, 3 cases); Rate was 0.15% each for irritability, facial edema and itchiness (1 out of 654 patients, 1 case). Unexpected drug adverse reaction was 0.15% (1 out or 654 patients, 1 case) for irritability.
Voluntarily reported adverse events during the domestic PMS period were 1 case of anaphylactic shock and 1 case of rashes. As the reports were from a population of uncertain size, the frequency of such cases and their causal relationship with this drug are difficult to estimate.
(2) In the PMS with 469 patients, the adverse event rate regardless of causal relationship was 1.07% (5 out of 469 patients, 5 cases). These were 0.85% for diarrhea (4 out of 469 patients, 4 cases) and 0.21% for vomiting (1 out of 469 patients, 1 case). No drug adverse reactions were reported. No severe or unexpected adverse events were reported.
8. Action for administration of excessive doses
When excessive doses of this drug are administered, prompt medical attention is required even without clear symptoms or signs (gastric irrigation or dilution by drinking water. Vomiting may be attempted without 60 minutes of taking).
9. Storage precautions
1) Keep out of reach of children.
2) Avoid direct sunlight, and store with lid tightly closed in a cool place with low humidity.
3) Placing a drug in a different container may cause accidents and is undesirable from a quality perspective.
Dexibuprofen 300mg
○ Adults : Orally administer 300mg as dexibuprofen 2 to 4 times daily. Do not exceed 1,200mg dexibuprofen per day.
+ Indications
1. Chronic multiple arthritis, rheumatoid arthritis
2. Arthrosis
3. Ankylosing spondylitis
4. Painful edema or inflammation after trauma or surgery
5. Adjuvant to treatment of infection accompanied by inflammation, pain and fever
1. Warnings
1) Persons who regularly consume at least 3 alcoholic drinks daily must consult a physician or pharmacist before taking this drug or other fever and pain medications. Taking this drug may cause liver damage in such patients.
2) Cardiovascular risks : Nonsteroidal anti-inflammatory drugs including this drug can increase the risk of severe or fatal cardiovascular thrombosis, myocardial infarction and stroke. These risks may increase with the duration of administration. Patients with cardiovascular disease or cardiovascular disease risk factors may be subject to higher risk. The physician and patient must carefully monitor presentation of such cardiovascular symptoms. The same applies for patients without a history of cardiovascular disease. The patient must be informed beforehand of severe cardiovascular toxicity indicators and/or symptoms, and actions to be taken in the case that these symptoms present.
Patients with uncontrolled hypertension, congestive heart failure (NYHA II-III), established ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with ibuprofen after careful consideration and high doses (1,200mg/day) should be avoided. Careful consideration should also be exercised before initiating long-term treatment of patients with risk factors for cardiovascular events (e.g. hypertension, hyperlipidemia, diabetes mellitus, and smoking), particularly if high doses of ibuprofen (≥ 1,400mg/day) are required.
Clinical trials have shown that use of high dose (2400mg/day) ibuprofen may slightly increase the risk of arterial thrombus symptoms (myocardial infarction or stroke). Results of general epidemiologic studies have shown no proof of association between low dose ibuprofen (e.g. up to 1,200mg/day) and increased risk of arterial thrombus symptoms. Limited data is available on arterial thrombus risks of dexibuprofen, but it is appropriate to assume the risk of high dose dexibuprofen (1200mg/day) is similar to that of high does ibuprofen (2400mg/day).
3) Gastroenteric risk : Nonsteroidal anti-inflammatory drugs including this drug can increase the risk of severe or fatal gastroenteric adverse reactions including bleeding, ulcers and perforation of the stomach or intestines. These adverse reactions may occur during the duration of administration without warning symptoms. Elderly patients may have a higher risk of severe gastroenteric adverse reactions. The likelihood of severe gastroenteric adverse reactions may increase with the duration of administration, but short-term administration does not completely rule out such risks. Careful monitoring of symptoms or signs of gastroenteric ulcers or bleeding is required while administering this drug. If severe gastroenteric adverse reaction is suspected, additional evaluation and treatment must immediately be carried out. Discontinuing administration of NSAIDs until severe gastroenteric adverse reaction is ruled out may be a method of treatment. For high-risk patients, other alternative treatments not associated with NSAIDs should be considered.
2. The following patients should not take this drug.
1) Patients with gastroenteric ulcers, signs thereof, or history of recurrence thereof
2) Patients with bleeding in the stomach or intestines, cerebral blood vessels, or other
3) Patients with severe blood disorders
4) Patients with severe liver impairment
5) Patients with severe renal impairment
6) Patients with severe heart failure
7) Patients with severe hypertension
8) Patients with hypersensitivity to this drug and ingredients of this drug
9) Patients with bronchial asthma or a history thereof
10) Patients with a history of asthma, hives or allergic reaction to aspirin or other NSAIDs (including COX-2 inhibitors) (Rare severe and fatal anaphylactic reaction after administration of NSAIDs reported in such patients.)
11) Treatment of pain before and after coronary artery bypass graft (CABG)
12) Pregnant mothers more than 6 months into pregnancy (Administration of this drug in the terminal stages of pregnancy, like NSAIDs, can lead to early closure of the ductus arteriosus of the fetus.)
13) Patients with inflammatory bowel disease such as Crohn’s Disease or ulcerative colitis
14) Patients with a history of gastroenteric bleeding or perforation due to previous treatment with NSAIDs
3. Avoid the following drugs while taking this drug.
1) Aspirin
(1) No consistent evidence of increased severe cardiovascular thrombus reaction associated with NSAID use due to concomitant administration with aspirin. As concomitant administration of this drug with aspirin may increase the risk of severe gastroenteric adverse reaction, as with other NSAIDs, concomitant use of the two drugs is generally not recommended.
(2) Concomitant administration with aspirin may inhibit the action of this drug and other NSAIDs.
2) Do not concomitantly administer with other NSAIDs; may increase risk of adverse reaction such as gastroenteric adverse reaction and gastroenteric bleeding.
3) Methotrexate at high doses (15mg/week or higher) : Concomitant administration with NSAIDs may delay excretion of methotrexate from renal tubes, increasing fatal methotrexate blood toxicity; do not administer concomitantly with high-dose methotrexate used in anti-cancer therapy.
4. Do not do the following while taking this drug.
1) Transfer to breast milk has been reported, with possibility of severe adverse reactions in infants. In light of the importance of administering this drug, either breastfeeding or administration of this drug should be discontinued.
2) Taking this drug may lead to dizziness or fatigue as an adverse reaction, limiting the patient’s reaction ability. Patients operating vehicles or machinery should take this drug with caution. No particular caution is necessary for single or short-term administration.
3) Long-term high-dose administration may cause headache.
5. The following should consult a physician, dentist, or pharmacist before taking this drug.
1) Patients with blood disorders or a history of the same
2) Patients with a bleeding tendency (platelet function disorder may occur.)
3) Patients with liver impairment or a history of the same
4) Patients with renal impairment or a history of the same
5) Patients with fluid retention or heart failure
6) Patients with hypertension
7) Patients with a history of hypersensitivity
8) Patients with systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD)
9) Elderly patients (Elderly patients are prone to adverse reaction; begin administration at small doses and administer the lowest minimum dose and administer carefully, observing the state of the patient for presentation of adverse reactions.)
10) Children 6 years or older (Safety and efficacy not established in children less than 6 years old. Carefully administer the minimum required dose in children 6 years or older, and watch carefully for appearance of adverse reactions.)
11) Patients with stomach cancer
12) Patients with alcoholism
13) Pregnant women in early and mid-term pregnancy [metabolic toxicity observed in animal tests (reduced implantation and survival count observed at high doses), with reports of persistent fetal circulation (PFC)], women planning pregnancy (like other prostaglandin synthase inhibitors, this drug reduces fecundity. Women with difficulty getting pregnant or receiving infertility testing should consider discontinuing administration of this drug.), potentially pregnant women
14) Patients with ischemic heart disease, peripheral arterial disease, cerebrovascular disease
15) Patients with cardiovascular disease risk factors (e.g. hypertension, hyperlipidemia, diabetes, smoking)
16) Patients with hepatic porphyria (use of this drug may lead to seizures.)
17) Patients who have received serious surgical intervention causing shortage of blood
18) Patients taking diuretics or ACE inhibitors
19) Patients with blood clotting disorder or taking anticoagulants
20) Patients with previous history of intestinal tract ulcers due to prolonged administration of NSAIDs who require long-term administration of this drug and are undergoing concurrent treatment of digestive ulcers with misoprostol, etc. (As some digestive ulcers exhibit resistance to treatment with misoprostol, observe progression sufficiently when administering this drug.)
21) Patients taking the following drugs
(1) Corticosteroids, alcohol : Risk of gastroenteric adverse reaction and gastroenteric bleeding
(2) Digoxgin, phenytoin : May increase plasma concentration.
(3) Probenecid, sulfinpyrazone : Inhibits action of probenecid and sulfinpyrazone, slowing excretion of dexibuprofen.
(4) Sulfonylurea : May increase hypoglycemic effects of sulfonylurea
(5) ACE inhibitors or angiotensin II receptor blocker : There are reports that NSAIDs may reduce the anti-hypertensive effect of ACE inhibitors or angiotensin II receptor blockers; keep interactions in mind when administering this drug and ACE inhibitors or angiotensin II receptor blockers concomitantly.
(6) Diuretics : Clinical trials and post-marketing surveillance have shown that suppression of prostaglandin synthesis in the kidneys by this drug may reduce the sodium excretion effect of furosemide and thiazide diuretics in some patients. During concomitant administration of these drugs and NSAIDs, observe closely for renal impairment symptoms and signs of renal failure.
(7) Lithium : NSAIDs may increase serum lithium concentration by suppressing prostaglandin synthesis in the kidneys, and reduce the renal clearance rate of lithium. Accordingly, observe carefully for signs of lithium toxicity when administering concomitantly with NSAIDs.
(8) Coumarin anticoagulants (warfarin, etc.) : Warfarin and NSAIDs may exhibit synergistic effects with respect to gastroenteric bleeding; patients concomitantly administered the two drugs may have higher risk of severe gastroenteric bleeding compared to cases of single administration; administer carefully and observe closely, reducing dose if necessary.
(9) Baclofen : Baclofen toxicity is increased.
(10) Immunosuppressants (cyclosporine, ticlopidine, sirolimus) : Concomitant administration with NSAIDs may increase the renal toxicity of cyclosporine, ticlopidine and sirolimus.
(11) Thrombolytics, ticlopidine, antithrombotics : Dexibruprofen suppresses COX in platelets and suppresses clumping of platelets; concomitant administration of dexibuprofen with thrombolytics, ticlopidine and antithrombotics carries the risk of increased antiplatelet effects
(12) Drugs that increase blood potassium concentrations (e.g. potassium-sparing diuretics, ACE inhibitors, angiotensin-II receptor blockers, immunosuppressants such as cyclosporine or tacrolimus, trimethoprim, heparin, etc.) : Concomitant administration may result in hyperkalemia; regular observation of potassium levels is necessary.
(13) CYP2C8 or CYP2C9 inducers (e.g. rifampicin, phenobarbitals) : May increase metabolism of this drug and reduce the drug effect.
(14) Methotrexate at low doses (15mg/week or less) : Concomitant administration with NSAIDs may delay excretion of methotrexate from renal tubes, increasing fatal methotrexate blood toxicity; proceed carefully when administering concomitantly.
(15) Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs) : Concomitant administration with this drug may increase the risk of gastroenteric bleeding.
(16) Persons taking low dose aspirin with the purpose of preventing myocardial infarction or stroke (this drug reduces the effect of aspirin, and may increase the risk of severe gastroenteric adverse reactions.) Laboratory data has shown that concomitant administration of ibuprofen and aspirin (acetyl salicylic acid) may suppress the anti-platelet clumping effect of low dose aspirin. Extrapolation with this data has shown that although there are some uncertainties, general or long-term use of ibuprofen may reduce the heart protecting effect of low dose aspirin. There is no data on dexibuprofen, but it is fair to assume that there is a similar interaction between dexibuprofen and low dose aspirin.
6. In the following cases, immediately discontinue administration of this drug and consult a physician, dentist or pharmacist. If possible, the patient should take this document with him/her when consulting.
1) Shock : Shock symptoms may appear rarely; observe sufficiently. Discontinue administration immediately if symptoms such as chest discomfort, chills, difficulty breathing, and drops in blood pressure.
2) Blood diseases : Aplastic anemia, hemolytic anemia, granulocytopenia, leukopenia, non-granulocytosis, platelet aggregation, thrombocytopenia, platelet dysfunction (prolonged bleeding time) and eosinophil may rarely appear. Observe sufficiently with blood tests, etc., and immediately discontinue administration if there are anomalies.
3) Digestive system : Discontinue administration in case of indigestion, abdominal distention, heartburn, upper abdominal pain, diarrhea or constipation; sometimes loss of appetite, nausea, vomiting, abdominal pains, stomach discomfort; rarely, esophagitis, esophageal stenosis, diverticulosis, non-specific bleeding colitis, ulcerative colitis or Crohn’s disease, digestive ulcers, gastric bleeding, gastric perforation, bloody stool, gastritis, pancreatitis; very rarely, thirst or stomatitis.
4) Skin : Erythema multiforme, systemic lupus erythematosus, hair loss, sometimes angioedema, rarely mucocutaneous ocular syndrome (Stevens-Johnson syndrome) and toxic epidermal necrolysis (Lyells syndrome) may appear; discontinue administration in these cases.
5) Hypersensitivity : Sometimes rashes, hives, itchiness, purpura, rarely asthma attacks, eczema, anaphylactic reaction, and photosensitivity reaction may occur; discontinue administration in these cases.
6) Liver : Rarely, jaundice, elevated Alt, elevated AST, elevated ALP, hepatic function anomalies, hepatitis, etc.
7) Respiratory system : Sometimes rhinitis, bronchospasm, risk of acute pneumonia in rare cases in cardiac failure patients
8) Sensory system : Discontinue administration in the rare event of visual impairment. Rarely, difficulty hearing, ringing in ears, and taste disorders may appear.
9) Psychoneural : Fatigue, sleepiness, headache, dizziness, sometimes anxiety, derangement, depression, rarely aseptic meningitis are reported. Immediately discontinue administration in the event of symptoms such as severe headache, nausea, vomiting, insomnia, neck stiffness, fever or loss of consciousness, and consult a physician. Patients with autoimmune diseases (systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD)) should take carefully. Rarely, psychosis, anxiety, excitation, orientation disturbance, and reversible toxic amblyopia may occur.
10) Circulative system : Rarely, drops in blood pressure, rise in blood pressure, and palpitations, etc.
11) Kidneys : May rarely cause acute renal failure. In case of symptoms such as oliguria or hematuria, or test results showing elevated protein levels in urine, BUN, elevated blood creatinine, or hyperkalemia, discontinues administration and take appropriate action. Reduced urine amount, systemic edema accompanied by languor and shortness of breath, as well as rare renal papillary necrosis, nephrotic syndrome, and interstitial nephritis may occur.
12) Cardiovascular : Peripheral edema may appear, and risk of acute pulmonary edema may increase in patients with heart failure. Fluid retention may appear in patients with hypertension or renal failure. Hypertension or renal failure may occur in elderly patients.
13) Endocrine : Reduced female fecundity
14) Misc. : Sometimes periorbital edema, very rarely malaise, fever, nosebleeds, exacerbation of inflammation, etc.
7. Misc. precautions when administering this drug
1) Before administering this drug, consider the potential risks and benefits of this drug and other treatments. This drug should be administered at the lowest effective dose for the shortest period possible, according to the treatment objectives of each patient.
2) Mind that treatment using analgesics and anti-inflammatory agents is symptomatic, not causal treatment.
3) Consider the following when using for chronic illnesses
(1) For patients administering this drug for prolonged periods, carry out clinical tests (urine tests, complete blood count (CBC) tests, physicochemical and other blood tests, liver function tests, etc.) at regular intervals, and take appropriate action such as reducing dose or a drug holiday. If necessary, carry out regular blood coagulation testing (if anticoagulants are being administered), blood potassium concentration tests (if potassium-sparing drugs are being administered) or blood lithium concentration tests. In the case of clinical symptoms associated with liver or kidney disease, or systemic signs (e.g. eosinophilia, rashes) or abnormal liver function or kidney function test results continue or are exacerbated, discontinue administration of this drug.
(2) Consider treatment other than drug therapy.
4) Consider the following when using for acute illness.
(1) Administer with consideration for the degree of acute inflammation, pain and fever.
(2) By principle, avoid long-term administration of the same drug.
(3) If a causal therapy exists, carry out said therapy.
(4) By principle, long-term administration should be within 5 days.
5) Sufficiently observe the state of the patient, and watch out for presentation of adverse reactions. In particular, carefully monitor the patient after administration to infants, children, elderly patients or patients with wasting disease as symptoms such as excessive drops in body temperature, collapse and coldness of limbs may appear.
6) Due to the pharmacological characteristics of this drug, this drug may keep other symptoms and signs of inflammation from appearing, and delaying diagnosis of infective complications under painful and non-infective conditions. When using this drug against inflammations due to infection, administer concomitantly with suitable antibacterial agents and administer carefully with sufficient observation.
7) Gastroenteric adverse reactions : Extreme care is necessary when prescribing this drug or other NSAIDs to patients with a history of ulcerative disease or gastroenteric bleeding. In the case of patients with histories of digestive ulcer disease and/or gastroenteric bleeding, risk of gastroenteric bleeding was increased by 10 times or more when administered NSAIDs compared to patients without such risks. Other risk factors increasing risk of gastroenteric bleeding include concomitant therapy with oral corticosteroids or anticoagulants, prolonged use of NSAIDs, alcohol consumption, old age, and weak state of health. As most voluntary reports of fatal gastroenteric adverse reactions are from elderly and weak persons; special care is necessary when administering this drug to such patients.
8) Hypertension : NSAIDs including this drug may cause hypertension, exacerbate existing hypertension, and thereby increase the rate of occurrence of cardiovascular adverse cases. Taking of NSAIDs by a patient taking thiazide diuretics or loop diuretics may reduce reaction to these therapies. NSAIDs including this drug should be administered carefully to patients with hypertension. Blood pressure must be closely monitored at the time of first administration of this drug and during the duration of administration.
9) Ischemic heart failure and edema : Fluid retention and edema was observed in some patients taking NSAIDs including this drug. This drug must be administered carefully to patients with fluid retention or heart failure.
10) Prolonged administration of NSAIDs may lead to renal papillary necrosis or other kidney damage. Special attention is necessary in elderly patients or patients with heart failure, renal failure, liver failure, and patients taking diuretics or ACE inhibitors, as prostaglandin plays an important role in maintaining kidney blood flow. In most cases, pre-therapeutic state is recovered when administration is discontinued.
11) Developed renal disease : No controlled clinical trials of this drug in patients with developed renal disease. Accordingly, administration of this drug to patients with developed renal disease is not recommended. If administration of this drug must be started, the patient’s renal function must be observed closely.
12) Administration of NSAIDs including this drug may result in elevated liver function figures. These abnormal test values may be exacerbated as treatment continues, may remain unchanged, or may be temporary. Also, there are rare reports of severe liver-related adverse reactions such as jaundice, fatal fulminant hepatitis, liver necrosis, liver failure (sometimes fatal) due to administration of NSAIDs including this drug. In the case of patients with symptoms and/or signs of impaired liver function or patients with abnormal liver function test results, observe carefully for worsening of liver function during the duration of administration. In the case of clinical symptoms or systemic signs associated with liver disease (e.g. acidophilia, rashes), discontinue administration of this drug.
13) Administration of NSAIDs including this drug may result in anemia. In cases of symptoms or signs of anemia due to long-term administration of this drug, hemoglobin or hematocrit levels should be tested. NSAIDs suppress clumping of platelets, with extending bleeding times in some patients. Unlike aspirin, the effects of this drug on platelet function are relatively small, reversible, and sustained for a short period of time. Patients with coagulation-related disease or taking anti-coagulants, and other cases where modulation of platelet function may have negative effects should be closely monitored when this drug is administered.
14) Anaphylactic reaction : As with other NSAIDs, anaphylactic reaction may occur in patients with no previous exposure to the drug. These complex symptoms typically occur in asthma cases with potentially fatal severe bronchial with or without nasal polyps after administration of aspirin or other NSAIDs. Emergency treatment is necessary in the case of such anaphylactic reactions.
15) Skin reactions : This drug may cause serious skin adverse reactions such as exfoliative dermatitis, mucocutaneous ocular syndrome (Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell’s Syndrome), which may be fatal. These severe adverse reactions may appear without warning symptoms. In most cases, these adverse reactions occur within the first month or administration. The patient should know of these serious skin symptoms and signs, and administration of the drug must be discontinued upon first appearance of symptoms and signs such as skin rashes or other hypersensitivity symptoms.
16) Some asthma patients may react sensitively to aspirin. Use of aspirin in aspirin-sensitive asthma patients may be associated with fatal severe bronchospasm. In such aspirin-sensitive patients, cross reactions between aspirin and other NSAIDs, including bronchospasm, have been reported. Accordingly, do not administer this drug to such aspirin-sensitive patients.
17) This drug may not be used as a substitute for corticoid agents or as a drug for treatment of corticoid deficiency. Sudden discontinuation of administration of corticosteroids may lead to exacerbation of corticosteroid-reactive diseases. To administer this drug to patients having taken corticosteroids for a prolonged time, slowly reduce doses.
18) Temporary infertility was reported in patients taking NSAIDs for prolonged periods.
19) Note that treatment using anti-inflammatory drugs and analgesics is symptomatic, not causal therapy.
20) Impact on clinical test scores : Rarely, elevated urea nitrogen, transaminase, and alkaline phosphatase, reduced hemoglobin and hematocrit scores, reduced platelet clumping, and extended bleeding time may occur.
21) Results of domestic post-marketing surveillance (syrup)
- The results of domestic post-marketing surveillance over 4 years with 654 and 469 patients, respectively for drug review are as follow.
(1) PMS with 654 patients showed an adverse event rate of 0.61% regardless of causal relationship (4 out of 654 patients, 4 cases). Rate was 0.15% for irritability, facial edema, indigestion, and itchiness (1 out or 654 patients, 1 case).
Rate of drug adverse reactions whose causal relationship with this drug could not be ruled out was 0.46% (3 out or 654 patients, 3 cases); Rate was 0.15% each for irritability, facial edema and itchiness (1 out of 654 patients, 1 case). Unexpected drug adverse reaction was 0.15% (1 out or 654 patients, 1 case) for irritability.
Voluntarily reported adverse events during the domestic PMS period were 1 case of anaphylactic shock and 1 case of rashes. As the reports were from a population of uncertain size, the frequency of such cases and their causal relationship with this drug are difficult to estimate.
(2) In the PMS with 469 patients, the adverse event rate regardless of causal relationship was 1.07% (5 out of 469 patients, 5 cases). These were 0.85% for diarrhea (4 out of 469 patients, 4 cases) and 0.21% for vomiting (1 out of 469 patients, 1 case). No drug adverse reactions were reported. No severe or unexpected adverse events were reported.
8. Action for administration of excessive doses
When excessive doses of this drug are administered, prompt medical attention is required even without clear symptoms or signs (gastric irrigation or dilution by drinking water. Vomiting may be attempted without 60 minutes of taking).
9. Storage precautions
1) Keep out of reach of children.
2) Avoid direct sunlight, and store with lid tightly closed in a cool place with low humidity.
3) Placing a drug in a different container may cause accidents and is undesirable from a quality perspective.
