State Food and Drug Administration: revision of amoxicillin (sodium) and clavulanate potassium preparation manual

In order to further ensure the safety of drug use by the public, the State Drug Administration decided to revise the instructions of amoxicillin (sodium) and clavulanate potassium preparations (including injection, tablet, suspension, granule and capsule) in terms of adverse reactions, contraindications and precautions The relevant matters are hereby announced as follows: 1、 All manufacturers of amoxicillin (sodium) and clavulanate potassium preparations shall, in accordance with the measures for the administration of drug registration and other relevant provisions, put forward supplementary applications for the revision of the instructions in accordance with the revision requirements of amoxicillin and clavulanate potassium oral preparation instructions (see Annex 1) or amoxicillin sodium and clavulanate potassium injection instructions (see Annex 2), on April 26, 2019 Report to the provincial drug regulatory authorities for the record If the revised contents involve drug labels, they shall be revised together; the instructions and other contents of the labels shall be consistent with the original approved contents Replace all drug instructions and labels that have been delivered within 6 months after the supplementary application is filed Each amoxicillin (sodium) and clavulanate potassium preparation manufacturer shall carry out in-depth research on the mechanism of new adverse reactions, take effective measures to do a good job in the publicity and training of the use and safety issues, and immediately notify the drug operators and users of the changes in the content related to the safety of drug use in an appropriate way to guide doctors and pharmacists in the rational use of drugs 2、 Clinicians and pharmacists should carefully read the revised contents of amoxicillin (sodium) and clavulanate potassium preparation instructions, and make full benefit / risk analysis according to the newly revised instructions when selecting drugs 3、 Patients should strictly follow the doctor's instructions and read the instructions carefully before using the medicine 4、 Each provincial drug regulatory department shall urge the above-mentioned drug manufacturing enterprises in the administrative region to do a good job in the revision of the corresponding instructions and the replacement of labels and instructions according to the requirements; organize strict investigation and punishment of the illegal behaviors according to law It is hereby announced Appendix 1 revision requirements of amoxicillin and clavulanate potassium oral preparation specification I General requirements of Specification Revision The revision of the manual of amoxicillin and clavulanate potassium oral preparation is mainly aimed at the three parts of [adverse reactions], [contraindications] and [precautions], and the following principles should be followed: if the revised content is more strict and comprehensive than the relevant content approved by the State Drug Administration, the manual should be modified according to the revision opinions In principle, the relevant contents approved by the SDA shall not be deleted If the original approved contents are more comprehensive or stricter than the current revision, the original approved contents shall be retained 2、 [adverse reactions] should include skin and accessory lesions such as rash, pruritus, urticaria, flushing, erythema multiforme, Stevens Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis (erythroderma) and acute generalized exanthematous pustulosis Gastrointestinal damage: nausea, vomiting, dyspepsia, abdominal distention, diarrhea, gastritis, stomatitis, glossitis, black hair tongue, pseudomembranous enteritis, hemorrhagic colitis Immune dysfunction and infection: vascular edema, candidiasis of skin and mucosa, double infection, serum sickness like syndrome (urticaria with arthritis, arthralgia, myalgia and fever), asthma, severe anaphylaxis like reaction, anaphylactic shock Nervous system damage: dizziness, headache, dizziness, insomnia, agitation, anxiety, fidgety, behavior change, confusion of consciousness, convulsion Blood system damage: leukopenia (including neutropenia) and thrombocytopenia, thrombocytopenic purpura, eosinophilia, thrombocytopenia, prolonged prothrombin time, agranulocytosis and hemolytic anemia Urinary system damage: hematuria, crystalline urine, interstitial nephritis, acute renal damage (including acute renal failure, creatinine rise) Hepatobiliary damage: transaminase rise, hepatitis and cholestatic jaundice Other damages: palpitation, cyanosis, dyspnea, chest tightness, shivering 3、 [contraindications] should include the following contents: 1 Penicillin skin test positive reaction, allergy to this product and other penicillin drugs and infectious mononucleosis patients are forbidden 2 Patients with amoxicillin and clavulanate potassium related cholestasis or liver function impairment were forbidden 4、 [notes] it should include the following contents: 1 It should be used with caution for those who are allergic to cephalosporins and those who have history of allergic diseases such as asthma, allergic rhinitis and urticaria 2 The product has cross sensitivity with other penicillins and cephalosporins In case of allergic reaction, stop using the product immediately and take corresponding measures 3 This product has cross resistance with other penicillins and cephalosporins such as ampicillin 4 When the estimated glomerular filtration rate is less than 30ml / min, it should be used with caution For patients with renal dysfunction, the dosage or administration interval should be adjusted according to the glomerular filtration rate; hemodialysis can affect the blood concentration of amoxicillin in this product, so this product should be taken one time after hemodialysis 5 When using high-dose amoxicillin, it is suggested that patients should take enough liquid and ensure enough urine output to reduce the possibility of amoxicillin crystal urine 6 Use with caution in patients with liver dysfunction 7 If the product is used for a long time or a large dose, the function of liver, kidney and hematopoietic system should be checked regularly, and the serum potassium or sodium should be tested 8 When warfarin is used in combination, the dosage of oral anticoagulant may need to be adjusted to maintain the required anticoagulant level 9 The drug is a time-dependent antibiotic, which should be used in strict accordance with the instructions, and the interval between multiple applications should not be less than 6 hours 10 In order to reduce gastrointestinal reactions, oral preparations should be taken with meals 11 This product contains aspartame, which can be metabolized to phenylalanine Patients with phenylketonuria should use it carefully and consult a specialist if necessary (only applicable to the product manual containing aspartame in the excipients; aspartame, alias: aspartame, sweetener, proteoglycan, Tianle, aspartame) 12 The long-term use of this product will occasionally cause the over growth of non sensitive bacteria Pseudomembranous colitis has been reported with antibiotics If the patient has persistent or severe diarrhea or abdominal colic, the treatment should be stopped immediately and the patient should be further examined 13 In order to ensure the effectiveness of the treatment and avoid bacterial drug resistance, the medicine should be used according to the doctor's order to avoid omission or early discontinuation 14 For gonorrhea patients suspected of syphilis damage, dark field examination should be carried out before using this product, and serum test should be carried out once a month for at least 4 months 15 Interference to laboratory test indexes: (1) the urine sugar test by copper sulfate method can be false positive, but the glucose enzyme test method is not affected When taking this product, it is recommended to use the urine sugar test based on the glucose oxidase reaction; (2) it can affect the determination value of serum alanine aminotransferase or aspartate aminotransferase (Note: if other contents of the manual are inconsistent with the above revision requirements, they shall be revised together.) Appendix 2 Revision requirements for amoxicillin sodium and clavulanate potassium injection instructions I General requirements for revision of instructions This revision of amoxicillin sodium and clavulanate potassium injection instructions is mainly aimed at the three parts of [adverse reactions], [contraindications] and [precautions], and the following principles should be followed: if the content of this revision is more strict and comprehensive than the relevant content approved by the State Drug Administration, the instructions should be modified according to the revision opinions In principle, the relevant contents approved by the SDA shall not be deleted If the original approved contents are more comprehensive or stricter than the current revision, the original approved contents shall be retained 2、 [adverse reactions] should include skin and accessory lesions such as rash, pruritus, urticaria, flushing, erythema multiforme, Stevens Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis (erythroderma) and acute generalized exanthematous pustulosis Gastrointestinal damage: nausea, vomiting, dyspepsia, abdominal distention, diarrhea, gastritis, stomatitis, glossitis, black hair tongue, pseudomembranous enteritis, hemorrhagic colitis Immune dysfunction and infection: drug fever, allergic vasculitis, angioedema, candidiasis of skin and mucous membrane, double infection, serum sickness like syndrome (urticaria with arthritis, arthralgia, myalgia and fever), asthma, severe anaphylaxis like reaction, anaphylactic shock Nervous system damage: dizziness, headache, dizziness, insomnia, agitation, anxiety, fidgety, behavior change, confusion of consciousness, convulsion Damage to the injection site: pain, phlebitis or thrombophlebitis at the injection site Blood system damage: leukopenia (including neutropenia) and thrombocytopenia, thrombocytopenic purpura, eosinophilia, thrombocytopenia, prolonged prothrombin time, agranulocytosis and hemolytic anemia Urinary system damage: hematuria, crystalline urine, interstitial nephritis, acute renal damage (including acute renal failure, creatinine rise) Hepatobiliary damage: transaminase rise, hepatitis and cholestatic jaundice Other damages: palpitation, cyanosis, dyspnea, chest tightness, shivering 3、 [contraindications] should include the following contents: 1 Penicillin skin test positive reaction, allergy to this product and other penicillin drugs and infectious mononucleosis patients are forbidden 2 Patients who had amoxicillin sodium and clavulanate potassium related cholestasis or liver function injury were forbidden 4、 [notes] it should include the following contents: 1 It should be used with caution for those who are allergic to cephalosporins and those who have history of allergic diseases such as asthma, allergic rhinitis and urticaria 2 The product has cross sensitivity with other penicillins and cephalosporins In case of allergic reaction, stop using the product immediately and take corresponding measures 3 This product has cross resistance with other penicillins and cephalosporins such as ampicillin 4 This product should be administered immediately after dissolution, and the remaining solution should be discarded and can not be reused The prepared solution cannot be frozen 5 This product will reduce the stability in the solution containing glucose, dextran or acid carbonate, so this product cannot be mixed with the solution containing the above substances 6 This product solution shall not be mixed with blood products, protein containing liquids (such as hydrolyzed protein, etc.) in vitro, or with intravenous lipid emulsion 7 This product cannot be mixed with aminoglycoside antibiotics in vitro, because this product can make the latter lose activity 8 When the estimated glomerular filtration rate is less than 30ml / min, it should be used with caution For patients with renal dysfunction, the dosage or administration interval should be adjusted according to the glomerular filtration rate; hemodialysis can affect the blood concentration of amoxicillin in this product, so this product should be added once after hemodialysis 9 When using high-dose amoxicillin, it is recommended that the patient take enough liquid and ensure enough urine output to reduce the possibility of amoxicillin crystal urine 10 Use with caution in patients with liver dysfunction 11 If the product is used for a long time or a large dose, the function of liver, kidney and hematopoietic system should be checked regularly, and the serum potassium or sodium should be tested 12 When warfarin is used in combination, the dosage of oral anticoagulant may need to be adjusted to maintain the required anticoagulant level 13 The drug is a time-dependent antibiotic, which should be used in strict accordance with the instructions, and the interval between multiple applications should not be less than 6 hours 14 This product should be given by intravenous injection or intravenous drip, not applicable