2 English reference Naproxen [Xiangya Medical Dictionary]
RS 3540[ Xiangya Medical Dictionary]
Naproxen See Naproxen [Xiangya Medical Dictionary]
Summary Naproxen is a non-steroidal anti-inflammatory drug with antipyretic and analgesic effects, which is white or white-like crystalline powder. Tasteless or almost tasteless. It is a prostaglandin synthase inhibitor with anti-inflammatory, antipyretic and analgesic effects. Can be used for treating rheumatic arthritis, rheumatoid arthritis, osteoarthritis, ankylosing spondylitis and myalgia. Oral absorption is rapid and complete, and the absorption rate decreases when taken together with food and foods containing magnesium and aluminum. The absorption of sodium bicarbonate is accelerated. It mainly damages gastrointestinal tract, nervous system and blood system, causing allergic reaction.
4 Naproxen Pharmacopoeia Standard 4. 1 Name 4. 1. 1 Chinese name Naproxen
4. 1.2 Chinese Pinyin Naipusheng
4. 1.3 English name Naproxen
4.2 structural formula 4.3 molecular formula and molecular weight c14h14o2o3 230.26
4.4 Source (name) and content (potency) This product is (+)(S)α methyl 6 methoxy 2 naphthylacetic acid. The content of C 14H 14O3 should be no less than 98.5% in terms of dry products.
4.5 Properties This product is white or white-like crystalline powder; Tasteless or almost tasteless.
This product is soluble in methanol, ethanol or chloroform, slightly soluble in ether and almost insoluble in water.
4.5. 1 melting point The melting point of this product (Appendix C of Pharmacopoeia II, 20 10) is 153 ~ 158℃.
4.5.2 Take this product by specific rotation, weigh it accurately, add chloroform to dissolve it and dilute it quantitatively to make a solution containing about 10mg per 1ml, and measure it according to law (Appendix VI E of Pharmacopoeia Part II, 20 10), with specific rotation of +63.0 to +68.5.
4.6 Identification (1) Take this product, add methanol to make a solution containing 30μg per 1ml, and determine it by ultraviolet-visible spectrophotometry (Appendix Ⅳ a of Pharmacopoeia II, 20 10 edition). At 262 nm, 27 1 nm, 3 17 nm and 337 nm.
(2) The infrared absorption spectrum of this product should be consistent with that of the reference substance (Figure 432: Collection of infrared spectrum of drugs).
4.7 Check 4.7. 1 chloride Take 0.50g of this product, add 50ml of water, shake 10 minute, filter (filter paper is wetted with dilute nitric acid first), take 25ml of continuous filtrate, check it according to law (Appendix VIII A of Pharmacopoeia Part II, 20 10 edition), and make a control solution with 7.5ml of sodium chloride standard solution.
4.7.2 Operation of related substances in the dark. Take an appropriate amount of this product, add an appropriate amount of mobile phase, shake it thoroughly to dissolve it, and dilute it quantitatively to make a solution containing 0.5mg per 1ml as the test solution; Take a proper amount of 6 methoxy 2 naphthoketone (impurity I) as reference substance, add mobile phase to dissolve, and dilute quantitatively to make a solution containing 50μg per kloc-0/ml as reference substance solution; Accurately measure 1 ml test solution and 2 ml control solution respectively, put them in the same 200 ml volumetric flask, dilute them to scale with mobile phase, and shake them evenly as control solution. According to high performance liquid chromatography (20 10 version of Pharmacopoeia, Part II, Appendix ⅴ D). Octadecylsilane bonded silica gel is used as filler; Using methanol -0.0 1 mol/L potassium dihydrogen phosphate solution (75∶25) and phosphoric acid as mobile phase, the pH value was adjusted to 3.0; The detection wavelength is 240 nm. The theoretical plate number is not less than 5000 calculated by naproxen peak, and the separation degree between naproxen peak and adjacent impurity peak should meet the requirements. Take 20μl of control solution, inject it into the liquid chromatograph, and adjust the detection sensitivity so that the peak height of naproxen chromatographic peak is about 20% of the full range; Accurately measure 20μl of the test solution and the reference solution, inject them into the liquid chromatograph respectively, and record the chromatogram until the retention time of the principal component peak is 2.5 times. If there is a chromatographic peak with the same retention time as the impurity peak in the chromatogram of the test sample, its peak area shall not be larger than that of the impurity I peak in the reference solution (0.1%); The peak area of other single impurities shall not exceed 2 times (0.2%) of the peak area of impurity I in the control solution; The sum of impurity peak areas shall not be greater than that of naproxen in the control solution (0.5%).
4.7.3 Take this product from loss on drying and dry it at 105℃ for 3 hours, and the weight loss shall not exceed 0.5% (Appendix VIII L of Pharmacopoeia II, 20 10).
4.7.4 Take this product 1.0g as residue on ignition, and check it according to law (Appendix VIII N of Pharmacopoeia II, 20 10), and the residue shall not exceed 0. 1%.
4.7.5 Take the residue left under the heavy metal residue on ignition, and check it according to law (the second method in Appendix VIII H of Pharmacopoeia 20 10), and the content of heavy metals shall not exceed 20 parts per million.
4.8 Content determination Take about 0.5g of this product, weigh it accurately, add 45ml of methanol to dissolve it, then add 15ml of water and 3 drops of phenolphthalein indicator, titrate with sodium hydroxide titrant (0. 1mol/L), and correct the titration result with blank test. Every 1ml sodium hydroxide titration solution (0. 1mol/L) is equivalent to 23.03mg c 14h 14o 3.
Class 4.9 Non-steroidal anti-inflammatory drugs for antipyretic and analgesic purposes.
4. 10 storage and shading, sealed preservation.
4. 1 1 preparation (1) naproxen tablets? (2) Naproxen suppository? (3) Naproxen capsules (4) Naproxen granules
4. 12 Edition People's Republic of China (PRC) Pharmacopoeia 20 10 Edition
5 instructions for naproxen 5. 1 drug name naproxen
5.2 English names naproxen, anaaprox, mnpa, naprosyn, naxen, naproxine,
5.3 Naproxen alias Xiaotongling; Methoxynapropionic acid; Napson; Methoxy propionic acid; Sindak; Old four ding; Naproxen; Nakson
5.4 classification of endocrine system drugs >: gout and hyperuricemia drugs
5.5 dosage form 1.0. 1g, 0. 125g, 0.25g；;
2. Sustained release tablets: 500mg；;
3. Capsules: 0. 125g, 0.2g and 0.25g per capsule.
4. Sustained-release capsules: 250mg；;
5. Suppository: 0.25g; ;
6. Naproxen sodium tablets: 275mg；;
7. Sodium injection: 275 mg (2 ml).
5.6 The pharmacological action of naproxen is a long-acting antipyretic, analgesic and anti-inflammatory drug. Animal experiments show that its anti-inflammatory effect is about 1l times that of butazone, and its analgesic effect is about 7 times that of aspirin, and its effect on inflammatory pain is better than that of traumatic pain. The antipyretic effect is about 22 times that of aspirin. Its remarkable feature is low toxicity, and its adverse reactions to gastrointestinal tract and nervous system are obviously less than those of aspirin and indomethacin. The mechanism of action is similar to salicylic acid, which mainly inhibits prostaglandin synthase, thus blocking inflammatory mediators. At the same time, it can also inhibit platelet adhesion and aggregation, but this effect may induce bleeding symptoms. Naproxen sodium salt is absorbed faster and the peak time is faster. The sustained-release preparation has slow release and good bioavailability, and the drug is gradually released when it enters the intestinal alkaline environment. Therefore, the sustained-release tablets or capsules are only taken orally/kloc-0 times a day, and the blood concentration is relatively stable, which can continuously relieve pain within 24 hours.
5.7 Pharmacokinetics of Naproxen Naproxen Oral absorption is rapid and complete. Sodium bicarbonate can accelerate its absorption and aluminum hydroxide can delay its absorption. It can be widely distributed in human tissues, especially in joint cavity, bone and muscle tissues. It can pass through the blood cerebrospinal fluid barrier, placental barrier, and can also enter milk. It is partially metabolized in the body and slowly excreted from the urine in the form of prototypes and metabolites. The elimination half-life is about 13 ~ 14h. Naproxen can also be absorbed by rectal administration, but the peak time is slow. Healthy adults take naproxen 500mg, tmax5.08h, Cmax40.8μg/ml, T 1/2 15.3 h, and the excretion rate of naproxen is consistent with the disappearance rate in plasma. The binding rate with plasma protein is above 99%. About 95% is excreted in urine, of which 10% is the original drug and the rest is the metabolite. Less than 5% is excreted through the intestine. Food can reduce the absorption rate of naproxen, but it does not affect the absorption degree.
5.8 Indications of Naproxen Clinical treatment of rheumatoid arthritis, proliferative osteoarthropathy, ankylosing spondylitis, acute gout, chronic degenerative diseases of motor system (such as joints, muscles and tendons), mild and moderate pain (such as dysmenorrhea and postoperative pain) has definite curative effect.
5.9 The contraindication of naproxen is 1. People who are allergic to aspirin and naproxen are prohibited.
2. Severe active peptic ulcer with bleeding is prohibited.
3. Those who are receiving anticoagulant therapy and have bleeding tendency are prohibited.
5. 10 Precautions 1. Use with caution in patients with chronic digestive tract ulcer and history of digestive tract ulcer, pregnant women and lactating women, and children under 14.
2. Coagulation mechanism or platelet dysfunction, asthma, cardiac insufficiency, hypertension, renal insufficiency patients with caution.
3. Long-term use should regularly check the liver and kidney function and hemogram.
5. 1 1 naproxen 1 ADR. Nausea, vomiting, indigestion, constipation, heartburn, stomachache or discomfort, dizziness, headache, lethargy, tinnitus, shortness of breath, dyspnea, asthma, itchy skin and edema of lower limbs, the incidence rate is generally 3% ~ 9%;
2. Blurred vision or visual impairment, hearing loss, diarrhea, oral pain, palpitation, hyperhidrosis, etc. The incidence rate is1%~ 3%;
3. Gastrointestinal bleeding, renal damage, urticaria, allergic skin rash's disease, depression, myasthenia, abnormal hemogram and liver function damage are rare, and the incidence rate is 1% ~ 3%.
4. Occasionally can cause granulocytopenia, thrombocytopenia, interstitial nephritis, nephrotic syndrome.
5. Usage and dosage of 1 2 naproxen1 (1) Anti-rheumatism: 250mg each time, twice a day (morning and evening 1 time), or 250mg each morning and evening, 500mg each time at night; (2) Analgesia: 500mg for the first time, 250mg for each time thereafter, and every 6-8 hours 1 time if necessary; (3) Anti-gout: 750mg for the first time, 250mg each time thereafter, every 8 hours 1 time, until the acute attack stops; (4) Dysmenorrhea: 500mg for the first time, 250mg each time if necessary, every 6-8 hours 1 time.
2. intramuscular injection: every time 100 ~ 200mg, every day 1 time.
3. Rectal administration: 250mg each time, twice a day.
5. 13 drug interaction 1. When naproxen is combined with heparin, dicoumarin and other anticoagulants, the anticoagulation effect is enhanced, which may lead to bleeding tendency and gastrointestinal ulcer.
2. Naproxen combined with salicylic acid did not enhance the curative effect, but enhanced the gastrointestinal adverse reactions;
3. Naproxen can reduce the sodium excretion and blood pressure of furosemide;
4. When naproxen is combined with probenecid, the plasma concentration of naproxen increases and t 1/2 is prolonged, which can increase the curative effect, but the adverse reactions also increase accordingly;
5. Naproxen can inhibit lithium excretion with urine and increase the plasma concentration of lithium;
6. When drinking alcohol or combining with other anti-inflammatory drugs (non-steroidal anti-inflammatory drugs or glucocorticoids), gastrointestinal adverse reactions increase and there is a risk of ulcer attack.
7. When combined with oral hypoglycemic drugs, it can increase its curative effect and has the risk of hypoglycemia;
8. When combined with central depressants, it can increase the analgesic effect.
5. 14 expert comments Naproxen is a phenylpropionic acid nonsteroidal anti-inflammatory and analgesic drug, and its curative effect is basically the same as ibuprofen. It has strong anti-inflammatory, anti-rheumatic, antipyretic and analgesic effects. Animal experiments have confirmed that the anti-inflammatory effect of naproxen is about 1 1 times that of phenylbutazone, the analgesic effect is 7 times that of aspirin, and the antipyretic effect is 22 times that of aspirin. Naproxen has the characteristics of high efficiency and low toxicity. A large number of clinical data show that naproxen is effective in treating rheumatoid arthritis. The total effective rate reported abroad is more than 86%, and the domestic observation result is 90%, which can make the indexes such as rheumatoid factor, erythrocyte sedimentation rate and anti-chain "O" return to normal or turn negative. The moderate pain can be relieved within 1 hour after taking naproxen for analgesia, and the analgesia lasts for more than 7 hours. Used in 20 cases of acute gout, the first dose is 600 ~ 750 mg, and then maintained at 250 ~ 300 mg, once every 8 hours. The total dose was 2.4 ~ 4.5 g, of which 75% (15 cases) could relieve swelling and pain within 24 ~ 48 hours, 3 cases were normal and 2 cases were ineffective. In the therapeutic dose range, the adverse reactions of naproxen are lighter than those of aspirin, tolmetin and ibuprofen, and the incidence is also low.
6 Naproxen poisoning Naproxen (methoxynapropionic acid, Xiaotongling) is a prostaglandin synthase inhibitor with anti-inflammatory, antipyretic and analgesic effects. Can be used for treating rheumatic arthritis, rheumatoid arthritis, osteoarthritis, ankylosing spondylitis and myalgia. Oral absorption is rapid and complete, and the absorption rate decreases when taken together with food and foods containing magnesium and aluminum. The absorption of sodium bicarbonate is accelerated. The plasma concentration of the drug reached its peak 2 ~ 4 hours after oral administration, and more than 99% of it combined with plasma protein in blood. The half-life of plasma is 12 ~ 15 hours, and it is metabolized in the liver, and about 95% is excreted in urine in the form of prototype and metabolite. The usual dosage is 0.2 ~ 0.3g/ time, 2 ~ 3 times /d, which mainly damages gastrointestinal tract, nervous system and blood system and causes allergic reaction. [ 1]
6. 1 The clinical manifestations of adverse reactions are as follows [2]:
1. Digestive system? Occasionally nausea, vomiting, anorexia, constipation, gastrointestinal bleeding, etc.
2. Nervous system headache, dizziness, insomnia or lethargy.
3. Cardiovascular palpitation or bradycardia, heart failure, etc.
4. Hematologic thrombocytopenia, leukopenia, aplastic anemia, immune hemolytic anemia and prolonged bleeding time.
5. Eyes and ears? Visual impairment, tinnitus and hearing loss.
6. skin? Rash, ecchymosis, itching, angioneurotic edema, hyperhidrosis and exfoliative dermatitis.
7. Others? Menstrual disorders, liver and kidney damage, etc.
6.2 The treatment points of naproxen poisoning are [3]: