Approval date: 03/13/2007
Revision date: 09/09/2008
July 31, 2012
August 10, 2015
December 01, 2015
XX/XX/XXXX, XXXX
Loxoprofen Sodium Tablets Instructions
Please read the instructions carefully and use under the guidance of a physician
[Drug Name].
Generic name: Loxoprofen Sodium Tablets
Trade name: Lona
English name: Loxoprofen Sodium Tablets
Hanyu Pinyin：Luosuoluofenna Pian
Ingredients
The active ingredient of this product is loxoprofen sodium. Chemical name: 2-｛4-[(2-oxocyclopentyl)methyl]phenyl} propionic acid sodium salt dihydrate Chemical structure formula.
Molecular Formula: C15H17NaO3-2H2O Molecular Weight: 304.31
Characteristic】This product is a light pink tablet.
Indications
①Anti-inflammatory and analgesic for the following disorders and symptoms
Rheumatoid arthritis, osteoarthritis, lumbago, periarthritis of shoulder joint, neck, shoulder and wrist syndrome, toothache.
②Analgesia and anti-inflammation after surgery, trauma and tooth extraction.
③Antipyretic and analgesic for the following disorders
Acute upper respiratory tract infection (including acute upper respiratory tract infection accompanied by acute bronchitis).
Specification】 60mg (based on C15H17NaO3)
Dosage and Administration
When ① and ② of the indications.
Normally, adults take 60mg (1 tablet) of loxoprofen sodium (as anhydrous substance) by mouth once, 3 times a day. In case of symptoms, 60~120mg (1~2 tablets) can be given orally once.
The dosage should be increased or decreased according to the age and symptoms. In addition, it should not be taken on an empty stomach or as directed by a doctor.
●Indications ③ When.
Usually, when symptoms appear, adults should take 60mg (1 tablet) of loxoprofen sodium (as anhydrous substance) orally once.
It should be increased or decreased according to the age and symptoms, but in principle, the maximum dose is 180mg (3 tablets) twice a day. In addition, the drug should not be taken on an empty stomach, or as prescribed by the doctor.
Adverse reactions]
According to foreign literature (this item includes reports of adverse reactions whose incidence cannot be calculated)
Of the total 13,486 cases, 409 cases (3.03%) reported adverse reactions, mainly digestive symptoms (stomach discomfort, abdominal pain, nausea and vomiting, loss of appetite, etc. 2.25%), swelling and edema (0.59%), skin rash and urticaria, etc. (0.21%), and drowsiness (0.10%) were reported.
1. Major adverse reactions (incidence not known)
(1) Shock and allergic reactions: Shock and allergic reactions (decreased blood pressure, urticaria, pharyngeal edema and dyspnea, etc.) may occur. Therefore, attention should be paid to observation, and if abnormalities occur, the drug should be discontinued immediately and disposed of appropriately.
(2) Granulocyte deficiency, hemolytic anemia, leukopenia, and thrombocytopenia may occur, therefore, blood tests and other observations should be carried out, and if abnormalities occur, the drug should be discontinued immediately and appropriate treatment should be given.
(3) Skin mucous membrane eye syndrome and toxic epidermal necrolysis may occur, therefore, attention should be paid to observation, and if abnormalities occur, the drug should be discontinued quickly and appropriate treatment should be given.
(4) Acute renal impairment, nephrotic syndrome and interstitial nephritis may occur, therefore, attention should be paid to observation, and if abnormalities occur, the drug should be discontinued and appropriate disposition should be given. Special attention should be paid to the use of this drug because hyperkalemia may occur with acute renal insufficiency.
(5) Congestive heart failure may occur. Therefore, attention should be paid to observation, and if abnormalities occur, the drug should be discontinued immediately and appropriate treatment should be given.
(6) Interstitial pneumonia: Interstitial pneumonia with fever, cough, dyspnea, abnormal chest X-ray, eosinophilia, etc. may occur.
(7) Gastrointestinal bleeding: Severe peptic ulcer or gastrointestinal bleeding from the large or small intestine, such as vomiting blood, black stool, and blood in the stool, sometimes accompanied by the occurrence of shock. Patients should be observed and if abnormalities occur, the drug should be discontinued immediately and appropriate disposition made.
(8) Gastrointestinal perforation may occur. If any symptoms occur, including epigastric pain, abdominal pain, etc., the drug should be discontinued immediately and appropriate treatment should be taken.
(9) Stricture and/or obstruction of the small and/or large intestine: Stricture and/or obstruction of the small and/or large intestine ulcers have been reported during the use of this product. Therefore, patients should be closely monitored during use and if any symptoms occur, including nausea and/or vomiting, abdominal pain, abdominal distension, etc., the drug should be stopped immediately and appropriate treatment should be given immediately.
(10) Liver dysfunction and jaundice: Elevated AST (GOT), ALT (GPT) and γ-GTP may occur, accompanied by liver dysfunction with jaundice or sudden onset of hepatitis. Attention should be paid to observation, and if there is any abnormality, the drug should be discontinued immediately and appropriate disposition should be made.
(11) Asthma attack: Acute respiratory disorders such as asthma attack may occur. Attention should be paid to observation, and if there is any abnormality, the drug should be discontinued immediately and appropriate disposition should be made.
(12) Aseptic meningitis: Aseptic meningitis (fever, headache, nausea, vomiting, neck tonicity, confusion, etc.) may occur. Attention should be paid to observation, and if there is any abnormality, the drug should be discontinued immediately and appropriate disposition should be made. (Especially patients with concomitant systemic lupus erythematosus or mixed connective tissue disease are prone to adverse events.)
(13) Rhabdomyolysis: Rhabdomyolysis has been reported during the use of this product. Therefore, patients should be closely monitored during use and any symptoms or abnormal laboratory test indicators, including myalgia, malaise, elevated creatine kinase (creatine phosphokinase), and elevated myoglobin in blood and urine, should be discontinued immediately and appropriate disposition should be made. Special care should be taken when using this product in such patients, as acute renal impairment may occur along with rhabdomyolysis.
2. Significant adverse reactions of other drugs in the same class
Aplastic anemia: It has been reported that aplastic anemia may occur with other non-steroidal anti-inflammatory analgesics.
3. Other adverse reactions
Incidence of adverse reactions 0.1~1.0% not full 0.05~0.1% not full 0.05% not full incidence not known allergic reactions Note) rash pruritus urticaria fever digestive system abdominal pain
Stomach discomfort
Loss of appetite
Nausea and/or vomiting
Diarrhea peptic ulcerNote)
Constipation
Heartburn
Stomatitis indigestion thirst
Abdominal distention
(ulcers of the small and/or large intestineNote) cardiovascular system palpitations increased blood pressure mental nervous system drowsiness
Headache Numbness
Dizziness Blood Anemia
Leukopenia
Eosinophilia
Thrombocytopenia
Liver AST (GOT) rising
Rising ALT (GPT) Rising ALP Urinary system Hematuria
Proteinuria
Difficulty in urination
Decreased urine output Other swelling Facial heat sensation Chest pain
Feeling of tiredness
(Sweating Note) should be discontinued [Contraindication
1. Patients with known hypersensitivity to this product.
2. Patients who have induced asthma, urticaria or allergic reactions after taking aspirin or other non-steroidal anti-inflammatory drugs.
3. Contraindicated in the treatment of perioperative pain during coronary artery bypass graft surgery (CABG).
4. Patients with a history of gastrointestinal bleeding or perforation after application of NSAIDs.
5. Patients with active peptic ulcers/bleeding, or previous recurrent ulcers/bleeding.
6. Patients with severe heart failure (due to inhibition of renal prostaglandin biosynthesis, causing swelling and increased circulating body fluid volume, increasing cardiac workload and potentially worsening symptoms).
7. Patients with severe hematological abnormalities (may cause platelet dysfunction and worsen it).
8. Patients with severe hepatic impairment (adverse reactions of hepatic impairment have been reported and may worsen them) Patients with severe renal impairment (adverse reactions such as acute renal insufficiency and nephrotic syndrome can occur).
【Caution】.
1. Avoid combination with other NSAIDs, including selective COX-2 inhibitors.
2. According to the need of symptom control, use the lowest effective dose in the shortest treatment time, which can minimize the adverse effects.
3. The risk of adverse reactions of gastrointestinal bleeding, ulceration and perforation may occur at any time during treatment with all NSAIDs and may be fatal. These adverse reactions may or may not be accompanied by warning symptoms and regardless of whether the patient has a history of adverse gastrointestinal reactions or a history of serious gastrointestinal events. NSAIDs should be used with caution in patients with a prior history of gastrointestinal disease (ulcerative colitis, Crohn’s disease) to avoid worsening the condition. When a patient experiences gastrointestinal bleeding or ulceration while taking the drug, it should be discontinued. The risk of adverse reactions, especially gastrointestinal bleeding and perforation, increases in frequency with NSAIDs in elderly patients and can be fatal.
4. Clinical trials for multiple COX-2 selective or non-selective NSAIDs drugs lasting up to 3 years have shown that this product may cause an increased risk of serious cardiovascular thrombotic adverse events, myocardial infarction and stroke, the risk of which may be fatal. All NSAIDs, including COX-2 selective or non-selective drugs, may have a similar risk. Patients with cardiovascular disease or risk factors for cardiovascular disease are at greater risk. Physicians and patients should be alert to the occurrence of such events, even in the absence of prior cardiovascular symptoms. Patients should be informed of the signs and/or symptoms of serious cardiovascular safety and the steps to take if they occur.
Patients should be alert for signs and symptoms such as chest pain, shortness of breath, weakness, slurred speech, etc., and should seek medical help as soon as any of these signs or symptoms occur.
5. As with all nonsteroidal anti-inflammatory drugs (NSAIDs), this product can cause new-onset hypertension or worsen existing hypertensive symptoms, either of which can lead to an increased incidence of cardiovascular events. The efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) may be compromised in patients taking thiazides or medullary diuretics when these drugs are administered. Non-steroidal anti-inflammatory drugs (NSAIDs), including this product, should be used with caution in patients with hypertension. Blood pressure should be monitored closely during initiation and throughout the course of treatment with this product.
6. Use with caution in patients with a history of hypertension and/or heart failure (e.g., fluid retention and edema).
7. NSAIDs, including this product, may cause fatal and serious cutaneous adverse reactions such as exfoliative dermatitis, Stevens Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). These serious events can occur without warning. Patients should be informed of the signs and symptoms of serious skin reactions and the product should be discontinued at the first appearance of a skin rash or other signs of an allergic reaction.
8. Use with caution (use with caution in the following patients)
(1) Patients with a past history of peptic ulcer [can cause ulcer recurrence].
(2) Patients with peptic ulcers caused by long-term use of NSAIDs, patients who require long-term use of this product and are treated with misoprostol [Misoprostol is used to treat peptic ulcers caused by NSAIDs, but there are also peptic ulcers that show resistance to misoprostol treatment, so the condition should be closely monitored and administered with caution when using this product continuously].
(3) Patients with hematologic abnormalities or a past history of them [susceptible to adverse reactions such as hemolytic anemia].
(4) Patients with hepatic impairment or previous history of hepatic impairment [may worsen or recur].
(5) Patients with renal impairment or previous history of such impairment [may cause swelling, proteinuria, increased serum creatinine, hyperkalemia and other adverse reactions].
(6) Patients with a past history of allergies.
(7) Patients with bronchial asthma [can worsen the condition].
(8) Patients with ulcerative colitis [potential for worsening of disease].
(9) Patients with Crohn’s disease [potential for worsening].
(10) Elderly persons [refer to [geriatric use]].
9. Important and basic precautions
(1) It should be noted that the treatment of anti-inflammatory and analgesic agents is symptomatic rather than etiological.
(2) When this product is used for chronic diseases (rheumatoid arthritis, osteoarthritis), the following matters should be considered.
a. Clinical tests (urine test, blood test, liver function test, etc.) should be performed regularly when using the drug for a long period of time. If abnormalities occur, the dosage should be reduced or discontinued.
b. Treatment methods other than drug therapy should also be considered.
(3) When this product is used for acute diseases, the following items should be considered.
a. Consider the degree of acute inflammation, pain and fever before administering the drug.
b. In principle, avoid using the same drug for a long time.
c. If etiological therapy is available, it should be used. Aimless use of this product should be avoided.
(4) Closely observe the patient’s condition and pay attention to the occurrence of adverse reactions. In some cases, excessive drop in body temperature, deficiency and cold extremities may occur. Therefore, especially in elderly patients with high fever or patients with combined wasting disorders, close observation of the patient’s condition after administration of the drug should be carried out.
(5) It may mask the symptoms of infection, so when used for inflammation caused by infection, appropriate antibacterial drugs should be combined and observed and administered with caution.
(6) The occurrence of adverse reactions should be paid particular attention to the elderly, and only the minimum necessary dose should be administered with caution.
10. Other precautions
It has been reported that long-term use of NSAIDs may lead to temporary sterility in women.
Pregnant women and nursing mothers
1. This product is contraindicated during pregnancy (including early, middle and late pregnancy) and during delivery.
2. This product should not be used by nursing mothers.
For Children
Due to the lack of safety and efficacy data, this product is contraindicated in children.
Geriatric Use]
The elderly are prone to adverse reactions, so the drug should be administered from a low dose, and the patient’s condition should be observed and administered with caution (refer to [Precautions]).
Drug Interactions
Combined use note
Drug Name Clinical Symptoms and Treatment Mechanism and Risk Factors Coumarin-based anticoagulants (warfarin) can enhance the anticoagulant effect of this class of drugs and should be closely observed and the dosage should be reduced if necessary. The risk of bleeding with factor Xa inhibitors may be increased because this product inhibits the biosynthetic action of prostaglandins, thereby inhibiting platelet aggregation and reducing blood coagulation, which has an additive effect on the anticoagulation of this drug. It is generally believed that the combination of this drug with such drugs may enhance the anticoagulant effect of such drugs. Sulfonylurea hypoglycemic agents (toluenosulfonylurea, etc.) enhance the hypoglycemic effect of this class of drugs and should be closely monitored and the dosage should be reduced if necessary. The protein binding rate of loxoprofen in human is 97.0%, and the trans-hydroxy metabolite is 92.8%. Therefore, when combined with a drug with high protein binding rate, it will increase the active form of the combined drug in blood and enhance the effect of the drug. Neoquinolone antimicrobials (enoxacin, etc.) have the potential to potentiate the spasm-inducing effects of this class of drugs. Neoquinolone antimicrobials inhibit the binding of GABA, an inhibitory neurotransmitter of the central nervous system, to receptors, causing spasm-inducing effects. The combination of this product will enhance the inhibitory effect of neoquinolones. Methotrexate may increase the concentration of methotrexate in the blood and cause enhanced effects, and the dose should be reduced if necessary. Although not yet confirmed, this product inhibits renal prostaglandin biosynthesis, which reduces renal excretion of these drugs and increases blood concentrations. Lithium preparations (lithium carbonate) may cause lithium toxicity by increasing the lithium concentration in the blood, so pay attention to the lithium concentration in the blood and reduce the dosage if necessary. Thiazide diuretics (hydrofluorothiazide and hydrochlorothiazide, etc.) may weaken the diuretic and hypotensive effects of these drugs. This product inhibits renal prostaglandin biosynthesis and reduces water and sodium excretion. Antihypertensive drugs (e.g., angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists) may reduce the antihypertensive effect. Inhibition of prostaglandin biosynthesis may reduce the antihypertensive effect of these drugs. Renal function may deteriorate. It is generally believed that the inhibition of prostaglandin biosynthesis by this product leads to a decrease in renal blood flow. Drug overdose]
Emergency treatment should be given in case of overdose, including emetic or gastric lavage, oral activated charcoal, antacids or (and) diuretics, and monitoring and other supportive treatment.
Pharmacology and Toxicology
Pharmacological effects
Loxoprofen sodium is a non-steroidal anti-inflammatory drug of phenylpropanoic acid class, which has good analgesic and anti-inflammatory effects, especially strong analgesic effects, and its mechanism of action is to inhibit prostaglandin synthesis, and its point of action is cyclooxygenase. Loxoprofen sodium is a precursor drug, which is absorbed through the digestive tract and transformed into the active metabolite trans-OH body to act.
Toxicological studies
Genotoxicity: Loxoprofen sodium has not been shown to be mutagenic when administered orally.
Reproductive toxicity: Loxoprofen sodium was administered to rats at 2, 4 and 8 mg/kg/day before or during early gestation, and the 8 mg/kg administration group showed a decrease in the number of corpus luteum, the number of implantations and the number of viable fetuses. In the organogenesis test (2, 4 and 8 mg/kg/day in rats and 2, 10 and 50 mg/kg/day in rabbits), there was no effect on the ability to continue gestation, delivery and nursing, and no lethal or teratogenic effects on embryos and fetuses, and no damage to newborn fetuses were observed in the 8 mg/kg administration group of rats. It did not affect the continued pregnancy of rabbits, and no lethal, teratogenic or developmental inhibitory effects on embryos were found. In the perinatal and lactation administration tests (0.25, 0.5, 1, 2, 4 and 8 mg/kg/day in rats), prolonged gestation, maternal death during delivery and increased number of stillbirths were observed in the group administered above 1 mg/kg, and a slight increase in neonatal fetal mortality was observed in the group administered at 0.5 mg/kg.
Carcinogenicity: Loxoprofen sodium was not found to be carcinogenic by oral administration.
Pharmacokinetics]
According to the literature, the product is rapidly absorbed after oral administration, and there are trans-OH bodies (active metabolites) in the blood in addition to loxoprofen (prototype). The time to reach the highest blood concentration is about 30 minutes for loxoprofen and about 50 minutes for trans-OH bodies, both with a half-life of about 1 hour and 15 minutes. Absorption is followed by rapid excretion in the urine, mostly as glucuronide conjugates of loxoprofen or trans-OH bodies, with 50% of the dose excreted within 8 hours of administration. In healthy volunteers, oral dosing (80 mg once; 3 times a day) for 5 days was not significantly different from single dosing and no accumulation was observed.
Storage】Seal and store.
Package】 Aluminum-plastic blister package, plus pharmaceutical composite film bag. 12 tablets/plate, 1 plate, 2 plates, 3 plates, 4 plates per package, 1 package per box.
Expiration date】 24 months.
【Execution standard
Approval number】 State Drug Administration H20050437
Manufacturer
Company Name: Disha Pharmaceutical Group Co.
Production Address: Weihai Economic and Technological Development Zone, mesa town, Dong’an Road, No. 399
Postal Code: 264205
Telephone: (0631) 5920760
Fax: (0631) 5923070 5923072
Web address: http://www.disha.com.cn