Date of approval: February 20, 2007
Date of revision: Year Month Day
Amoxicillin Clavulanic Acid Potassium Dry Mix Suspension Instructions
Please read the instructions carefully and use under the guidance of a physician
Drug Name
Generic name: Amoxicillin potassium clavulanate dry suspension
Trade name: Auxin®
English Name: Amoxicillin and Clavulanate Potassium for Oral Suspension
Hanyu Pinyin: Amoxilin Kelaweisuanjia Ganhunxuanji
Ingredients
This product is a compound preparation, its composition is: Amoxicillin (according to C16H19N3O5S) and Clavulanate ratio of 7:1.
Characteristic】It is white or off-white powder.
Indications
This product is used for the treatment of the following infections.
1. Upper respiratory tract infections (including ear, nose and throat): such as recurrent tonsillitis, sinusitis, otitis media.
2. lower respiratory tract infections: such as acute and chronic bronchitis (especially for severe infections), lobar pneumonia, bronchopneumonia.
3. Urinary tract infections: such as cystitis (especially for recurrent infections or complicated infections, excluding prostatitis)
4. Skin and soft tissue infections: such as cellulitis, animal bites combined with wound infections.
5. Oral infections: e.g. severe gingival abscesses combined with maxillofacial cellulitis.
Local official antibiotic prescribing guidelines and local sensitivity data should be followed for proper use of antibiotics.
Specification】0.2285g (Cl6H19N3O5S 0.2g with C8H9NO5 0.0285g).
【Dosage】.
Usage: Prepare a 228mg/5ml suspension with warm water and take orally.
Dosage is as follows.
Adults and children over 6 years old
Mild and moderate infections (upper respiratory tract infections, e.g. recurrent tonsillitis; lower respiratory tract infections; skin and soft tissue infections): 28.6mg per kg body weight per day (amoxicillin 25mg, clavulanic acid 3.6mg).
More serious infections (upper respiratory tract infections, e.g. otitis media and sinusitis; lower respiratory tract infections, e.g. bronchopneumonia; urinary tract infections): 51.4 mg per kg body weight per day (amoxicillin 45 mg, clavulanic acid 6.4 mg).
The following table shows the recommended dosage for children aged 2-6 years
(dosage of prepared 228mg/5ml suspension of this product) 28.6mg per kg body weight per day
(Mild to moderate infections) 2-6 years old (13-21 kg) 5.0ml once, twice a day 51.4mg per kg of body weight per day
(more serious infection) 2-6 years old (weight 13-21 kg) 10.0ml twice a day
Children 2 months-2 years old: (Children under 2 years old should calculate the dosage according to their body weight) (The dosage of the prepared product 228mg/5ml suspension: 2 times a day, each dosage is shown in the following table:) Body weight
(kg) 28.6mg per kg body weight per day
(Mild to moderate infection) 51.4mg per kg of body weight per day
(more serious infection)2 0.6 ml once 1.1 ml3 0.9 ml once 1.7 ml4 1.3 ml once 2.3 ml5 1.6 ml once 2.8 ml6 1.9 ml once 3.4 ml7 2.2 ml once 3.9 ml8 2.5 ml once 4.5 ml9 2.8 ml once 5.0 ml10 3.1 ml once at 5.6 ml11 3.4 ml once at 6.1 ml12 3.8 ml once at 6.8 ml13 4.1 ml once at 7.4 ml14 4.4 ml once at 7.9 ml15 4.7 ml once at 8.4 ml Infants less than 2 months of age are not recommended for the use of this product 228 mg/5 ml dry suspension due to inexperience.
Infants with renal insufficiency: 228 mg/5 ml of this product in dry suspension is not recommended.
Renal impairment.
No dose adjustment is necessary if the glomerular filtration rate >30 ml/min in children; if the glomerular filtration rate <30 ml/min, the use of this product 228 mg/5 ml dry suspension is not recommended.
Hepatic insufficiency.
Pay attention to the dose used and monitor liver function regularly; there is not enough information on the recommended dose based on liver function.
Dosage.
Take this product at the beginning of a meal to minimize gastrointestinal reactions and for optimal absorption. The duration of treatment should be based on disease needs, but generally should not exceed 14 days. The dose can be optionally administered as an intravenous drip and then switched to oral maintenance.
Adverse reactions
1. skin and its adnexal damage: rash, pruritus, urticaria, flushing, erythema multiforme, Stevens-Johnson syndrome, toxic necrolytic epidermolysis bullosa, exfoliative dermatitis (erythrodermatitis) and acute generalized eruptive impetigo and drug reactions to systemic symptoms (DRESS).
2. gastrointestinal damage: nausea, vomiting, dyspepsia, bloating, diarrhea, gastritis, stomatitis, tongue inflammation, black hairy tongue, pseudomembranous enteritis, colitis, hemorrhagic colitis.
3. immune disorders and infections: angioedema, candidiasis of the skin and mucous membranes, secondary infections, serum sickness-like syndrome (urticaria with arthritis, arthralgia, myalgia and fever), asthma, severe allergic-like reactions, cough, anaphylaxis, anaphylactic vasculitis.
4. neurological damage: dizziness, headache, vertigo, insomnia, agitation, anxiety, irritability, behavioral changes, confusion, convulsions and reversible hyperfunction, convulsions, aseptic meningitis.
5. Hematologic damage: leukopenia (including neutropenia) and thrombocytopenia, thrombocytopenic purpura, eosinophilia, thrombocytosis, prolonged prothrombin time, granulocyte deficiency, and hemolytic anemia.
6. Urological damage: hematuria, crystalluria, interstitial nephritis, acute kidney injury (including acute renal failure and elevated creatinine), vaginal pruritus, ulcers and abnormal secretions.
7. Hepatobiliary damage: elevated transaminases, hepatitis and cholestatic jaundice, elevated blood bilirubin and or alkaline phosphatase.
8. Other damage: dyspnea, palpitations, cyanosis, chest tightness, chills.
9. Other dosing-related events: Very rare tooth surface staining after dosing in children, mostly in patients taking the suspension. Tooth brushing can prevent and remove tooth surface staining.
Contraindications
1. Contraindicated in patients with positive penicillin skin test reaction, hypersensitivity to this product and other penicillins, and patients with infectious mononucleosis.
2. Contraindicated in patients who have experienced cholestasis or hepatic impairment associated with amoxicillin clavulanate potassium.
Precautions]
1. Before taking this product, patients should be carefully asked about their allergy history and whether they are allergic to penicillin, cephalosporins or other allergens. Serious and occasionally fatal allergic (anaphylactic) reactions have been reported in patients treated with penicillin. This reaction is more likely to occur in patients with a history of penicillin allergy (see [Contraindications]).
2. Use with caution in patients with hypersensitivity to cephalosporins and a history of allergic diseases such as asthma, allergic rhinitis, eczema, kwashiorkor fever, and urticaria.
3. There is cross-sensitivity between this product and other penicillins and cephalosporins. If an allergic reaction develops, discontinue the product immediately and take appropriate measures. Severe and occasionally fatal allergic reactions (anaphylaxis) have been reported in patients treated with penicillin, and this reaction is more likely to occur in patients with a history of penicillin allergy. If an allergic reaction occurs, amoxicillin-clavulanic acid should be discontinued and appropriate replacement therapy administered. Severe allergic reactions require immediate emergency treatment with epinephrine. Oxygen administration, intravenous steroid infusion and airway management, including intubation, may also be required.
4. There is cross-resistance between this product and other penicillins and cephalosporins such as ampicillin.
5. Please refer to [Dosage] for the administration of this product in patients with impaired renal function.
6. When high doses of amoxicillin are administered, patients are advised to consume sufficient fluids and ensure adequate urinary output to reduce the likelihood of amoxicillin crystalluria.
7. Use with caution in patients with hepatic insufficiency. Hepatic function changes have been observed in individual patients taking this product. Because the clinical significance of such changes has not been determined, caution must be exercised in the use of this product in patients with hepatic insufficiency. Severe reversible cholestatic jaundice has been reported, and this sign and symptom may also occur six weeks after discontinuation of the drug.
8. For long-term or high-dose use, periodic checks of hepatic, renal, and hematopoietic system function and testing of serum potassium or sodium should be performed.
9. When combined with warfarin, appropriate monitoring must be performed and the dose of oral anticoagulant may need to be adjusted to maintain the required anticoagulation level.
10. The drug is a time-dependent antibiotic and should be used strictly as directed, with no less than 6 hours between doses.
11. To minimize gastrointestinal reactions, the oral formulation should be taken with a meal.
12. Prolonged use of this product may occasionally cause overgrowth of non-susceptible bacteria. Pseudomembranous colitis has been reported with antibiotics. If a patient develops persistent or severe diarrhea, or develops abdominal cramps, treatment should be discontinued immediately and the patient should be further examined.
To ensure the effectiveness of treatment and to avoid the development of bacterial resistance, medication should be administered regularly as prescribed, avoiding omission or early discontinuation.
14. Patients with suspected gonorrhea with syphilis should undergo dark-field examination prior to the use of this product and receive serological tests once a month for at least 4 months.
15. Interference with laboratory test indicators.
(1) The copper sulfate method of urine glucose test may be false positive, but the glucose enzyme test method is not affected. When taking this product, it is recommended to apply the urine glucose test based on the glucose oxidase reaction.
(2) May affect the value of serum alanine aminotransferase or portal aminotransferase assay.
(2) May affect serum alanine aminotransferase or portal aminotransferase assay values. 16. Combinations of amoxicillin and potassium clavulanate in different ratios are not interchangeable.
17. Please open the middle bag only before use and finish the middle bag within 30 days after opening.
Pregnant women and nursing mothers
Pregnancy
Reproductive toxicity tests in animals (rats and mice) have shown no teratogenic effects when given orally or parenterally. In a separate study of premature rupture of membranes (pPROM), an increased risk of neonatal necrotizing small bowel colitis has been reported with prophylactic treatment with this product. The use of this product in pregnant women is limited and, as with all drugs, it should be avoided in pregnant women, especially during the third trimester, unless deemed necessary by the physician.
Lactation
Both amoxicillin and potassium clavulanate are excreted into breast milk (the effect of clavulanic acid on breastfed infants is not known). Therefore, diarrhea and mucosal fungal infections may occur in breastfed infants and breastfeeding may have to be terminated. The possibility of sensitization should be considered. Amoxicillin/clavulanic acid should be used during breastfeeding only after a benefit/risk assessment by a competent physician.
For pediatric use, see [Dosage].
For geriatric use, see [Dosage].
Drug Interactions
Probenecid
This product is not recommended for use in combination with probenecid. Probenecid may decrease renal tubular secretion of amoxicillin. The combination may result in increased blood levels and prolonged half-life of amoxicillin, but does not affect the blood levels of clavulanic acid.
Oral anticoagulants
Rare cases of increased international normalized ratio (INR) in patients on maintenance acenocoumarol or warfarin combined with a course of amoxicillin have been reported in the literature. If a combination is necessary, prothrombin time (PT) and international normalized ratio (INR) should be carefully monitored as amoxicillin is added and discontinued. In addition, the dose of oral anticoagulant may need to be adjusted (see [Precautions] and [Adverse Reactions]).
Motilmicronate
A decrease in the active metabolite mycophenolic acid (MPA) of approximately 50% from pre-dose concentrations has been reported in patients receiving morte-mescaline after initiation of oral amoxicillin plus clavulanic acid. Changes in levels before and after administration may not accurately reflect changes in total MPA exposure. Therefore, in the absence of clinical evidence of graft deactivation, a change in the dose of mycophenolate mofetil is not usually necessary. However, close clinical monitoring should be performed during combination therapy and shortly after antibiotic therapy.
Other drugs
Although there is no information on the combination of this product with allopurinol, the combination of amoxicillin and allopurinol may increase the likelihood of allergic skin reactions.
As with other antibiotics, this product may affect intestinal flora, leading to decreased estrogen reabsorption and reduced efficacy of combined oral contraceptive use.
Overdose]
Signs and symptoms of overdose
Gastrointestinal symptoms and disturbances in water and electrolyte balance may be evident. Amoxicillin crystalluria has been observed to lead to renal failure in some cases. (See [Precautions])
Convulsions may occur in patients with impaired renal function or those receiving high doses.
Amoxicillin has been reported to precipitate in the bladder catheter, especially after high dose intravenous administration. Patency should be checked periodically.
Treatment of poisoning
Gastrointestinal symptoms may be treated symptomatically with attention to water/electrolyte balance.
Amoxicillin/clavulanic acid can be cleared from the circulation by hemodialysis.
Pharmacological Toxicology]
Bacterial resistance is mainly due to the fact that bacteria can produce β-lactamase, which destroys antibiotics before they can act on pathogenic bacteria. Clavulanic acid in this product can prevent the emergence of bacterial resistance by blocking the action of β-lactamase, so that bacteria are more sensitive to amoxicillin and can be killed quickly. Although clavulanic acid by itself has almost no antibacterial effect, the combination with amoxicillin makes this product a broad-spectrum antibiotic with wide clinical value.
The following is a list of classifications based on the in vitro susceptibility of bacteria to this product.
In vitro susceptibility of bacteria to amoxicillin clavulanate potassium
If clinical trials have demonstrated clinical efficacy of this product, an asterisk (*) is used to indicate that
Bacteria that do not produce β-lactamase are indicated using (†). An isolate is considered sensitive to this product if it is sensitive to amoxicillin. Commonly susceptible bacterial species Gram-positive aerobic bacteria.
Bacillus anthracis
Enterococcus faecalis
Listeria monocytogenes
Nocardia stellaris
Streptococcus pyogenes*†
Streptococcus lactis *†
Streptococcus spp. (β-hemolytic streptococci) *†
Staphylococcus aureus (methicillin-susceptible)*
Staphylococcus saprophyticus (methicillin-susceptible)
Coagulase-negative staphylococci (methicillin-sensitive)
Gram-negative aerobic bacteria.
Bordetella pertussis
Haemophilus influenzae*
Haemophilus parainfluenzae
Helicobacter pylori
Moraxella mucosae*
Gonococcus
Pasteurella multocida
Vibrio cholerae
Others.
Burkholderia sp.
Leptospira
Gram-positive anaerobic bacteria of pale dense spirochetes.
Clostridium spp.
Peptococcus niger
Streptococcus macropepticus
Streptococcus microdigestive
Streptococcus digestiveis spp. Gram-negative anaerobic bacteria.
Bacteroides fragilis
Bacteroidetes spp.
Carbon Dioxide Fibrobacter spp.
Aikenia erosionis
Clostridium nucleatum
Clostridium spp.
Violetomonas spp.
Prevotella spp. Bacterial Gram-negative aerobic bacteria that may appear to acquire drug resistance.
Escherichia coli*
Klebsiella oxytoca
Klebsiella pneumoniae*
Klebsiella spp.
Aspergillus chimaericus
Aspergillus oryzae
Aspergillus spp.
Salmonella spp.
Shigella spp. Gram-positive aerobic bacteria.
Corynebacterium spp.
Enterococcus faecalis
Streptococcus pneumoniae*†
Streptococcus straw green intrinsically resistant bacteria Gram-negative aerobic bacteria.
Bacillus immobilis spp.
Fusobacterium citricum spp.
Enterobacter spp.
Hymenolepis hafniae
Legionella pneumophila
Morganella morganii
Propionibacterium spp.
Pseudobacterium
Serratia spp.
Stenotrophomonas maltophilia
Yersinia spp. Other.
Chlamydia pneumoniae
Chlamydia psittaci
Chlamydia spp.
Coxiella spp.
Mycoplasma spp. This product contains amoxicillin and clavulanic acid, so infections caused by amoxicillin-susceptible bacteria are treated effectively with this product; mixed infections caused by amoxicillin-susceptible bacteria and b-lactamase-producing bacteria are also treated effectively with this product.
Pharmacokinetics]
Absorption
Amoxicillin and clavulanic acid in 228mg/5ml dry suspension are completely dissolved in water at physiological pH, and are rapidly absorbed orally, with the best absorption at the beginning of meals.
Pharmacokinetic studies in children administered orally 3 times/day and 2 times/day found that the clearance kinetics in children with well-developed renal function were the same as those in adults.
Amoxicillin/clavulanic acid produced serum concentrations of amoxicillin and clavulanic acid similar to those produced by oral administration of the same dose of amoxicillin or clavulanic acid alone.
Distribution
The pharmacokinetic parameters of the two components of this product: amoxicillin and clavulanic acid are very similar. The serum protein binding of amoxicillin and clavulanic acid is very low, with approximately 70% present in the free form in the serum.
A doubling of the dose of this product is associated with a corresponding doubling of its blood concentration.
When given intravenously, effective therapeutic concentrations of amoxicillin and clavulanic acid were detected in tissues and interstitial fluid. Effective therapeutic concentrations of amoxicillin and clavulanic acid were detected in gallbladder, peritoneal tissue, skin, fat, and muscle tissue; and in body fluids, including synovial fluid, peritoneal fluid, bile, and pus.
Protein binding of amoxicillin and clavulanic acid is low, and studies have shown that approximately 25% of the total plasma drug content of clavulanic acid and 18% of amoxicillin are present in protein-bound form. Animal tests showed no accumulation of the components in any organ.
As with most penicillins, amoxicillin can be secreted into breast milk. Trace amounts of clavulanic acid can also be detected in milk.
Animal reproduction studies have shown that both amoxicillin and clavulanic acid can cross the placenta. However, there is no evidence of infertility or damage to the fetus.
Metabolism
Some of the amoxicillin is excreted in the urine as inactive penicillic acid (in amounts equivalent to 10% to 25% of the initial dose). Clavulanic acid is extensively metabolized in the body to 2,5-dihydro-4-(2-hydroxyethyl)-5-oxo-1hydro-pyrrole-3-carboxylic acid and 1-amino-4-hydroxy-2-butanone, which are eliminated via urine and feces and exhaled carbon dioxide.
Excretion
As with other penicillins, amoxicillin is eliminated primarily by the kidneys; clavulanic acid may or may not be eliminated by the kidneys. Approximately 60-70% of amoxicillin and approximately 40-65% of clavulanic acid are excreted in the urine as prototypes 6 hours after a single oral dose of 250/125 mg or 500/125 mg tablets.
Combined use of probenecid delays the excretion of amoxicillin, but not the renal excretion of clavulanic acid (see [Drug Interactions]).
Storage】Seal and store in a dry place below 25℃.
Package】Packaged in aluminum-plastic film, 6 packs/box, 12 packs/box, 24 packs/box, 120 packs/box or 480 packs/box.
【Validity】24 months.
【Executive Standard】JX20190261
【Pharmaceutical Product Registration Certificate Number
(1) 6 packs/box, 12 packs/box: HC20160005; (2) 24 packs/box, 480 packs/box: HC20160006; (3) 120 packs/box: HC20160007.
[Drug marketing license holder
Name: Ao Mei Pharmaceutical Factory
Registered office: Ao Mei Pharmaceutical Center, 1&8 Wang Fu Street, Yuen Long Industrial Estate, New Territories, Hong Kong
【Manufacturing enterprise】.
Company Name: Ao Mei Pharmaceutical Factory
Production Address: Ao Mei Pharmaceutical Centre, 8 Wang Fu Street, Yuen Long Industrial Estate, New Territories, Hong Kong
Tel: (852) 26750230 Fax: (852) 26759328
Website: http://www.brightfuture.com.hk
Email: [email protected]