Date of approval.
Date of revision.
Amoxicillin Tablets Instruction
[Drug Name].
Generic name: Amoxicillin Tablets
English name: Amoxicillin Tablets
Hanyu Pinyin: Amoxilin Pian
Ingredients
The main ingredient of this product is amoxicillin.
Chemical name: (2S,5R,6R)-3,3-dimethyl-6-[(R)-(-)-2-amino-2-(4-hydroxyphenyl)acetylamino]-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid trihydrate
Chemical structure formula.
Molecular formula: C16H19N3O5S-3H2O
Molecular weight: 419.46
Properties]: This product is a light orange tablet.
【Indications】.
Amoxicillin is indicated for the following infections in adults and children caused by sensitive bacteria (non-β-lactamase-producing strains).
1. Streptococcus haemolyticus, Streptococcus pneumoniae, Staphylococcus or Haemophilus influenzae caused by otitis media, sinusitis, pharyngitis, tonsillitis and other upper respiratory tract infections.
2. Genitourinary tract infections caused by Escherichia coli, Streptococcus oxysporum or Enterococcus faecalis.
3. Skin and soft tissue infections caused by Streptococcus haemolyticus, Staphylococcus or Escherichia coli.
4. Lower respiratory tract infections such as acute bronchitis and pneumonia caused by Streptococcus haemolyticus, Streptococcus pneumoniae, Staphylococcus or Haemophilus influenzae.
5. Combined with other drugs to eradicate H. pylori.
The use should refer to the official guidelines for clinical application of antibacterial drugs.
Specification】0.25g according to C16H19N3O5S
Dosage
Take orally, with water.
Adults and children
Treatment should be continued for at least 48 to 72 hours after the patient is asymptomatic or has obtained evidence of bacterial eradication. Treatment for at least 10 days is recommended for any infection caused by Streptococcus pyogenes to prevent the development of acute rheumatic fever. In some infections, treatment may take several weeks. Continued clinical and/or bacteriologic follow-up may be necessary for several months after discontinuation of treatment.
Children are advised to take the appropriate dosage form.
Site of infection Severity of infection1
Degree Adults and children weighing ≥40kg Usual dosage Children weighing <40kg (>3 months) Usual dosage Ear, nose, throat infections
Skin soft tissue infections
Genitourinary tract infection
Mild to moderate infections
Severe infections 500 mg once every 12 hours or 250 mg once every 8 hours
500 mg once every 8 hours
25 mg/kg/day in 2 divided doses (1 dose every 12 hours) or 20 mg/kg/day in 3 divided doses (1 dose every 8 hours)
45 mg/kg/day in 2 divided doses (1 dose every 12 hours) or 40 mg/kg/day in 3 divided doses (1 dose every 8 hours) Lower respiratory tract infection mild to moderate or severe infection
500 mg once every 8 hours
45 mg/kg/day in 2 divided doses (1 dose every 12 hours) or 40 mg/kg/day in 3 divided doses (1 dose every 8 hours) Infections caused by bacteria with moderate susceptibility to amoxicillin should be referred to the recommended dosing for serious infections.
Therapeutic dose for H. pylori infection
The recommended oral dose for adults is 1 g of amoxicillin given twice daily (every 12 hours) in combination with other medications.
Please refer to the instructions for other drugs used in combination and related guidelines.
Patients with renal impairment
Patients with impaired renal function generally do not require dose reduction unless the impairment is severe.
Patients with a glomerular filtration rate of 10 to 30 mL/min should receive 500 mg or 250 mg every 12 hours depending on the severity of the infection.
Patients with a glomerular filtration rate of less than 10 mL/min should receive 500 mg or 250 mg every 24 hours, depending on the severity of the infection.
Hemodialysis patients should receive 500 mg or 250 mg every 24 hours depending on the severity of the infection. Additional doses should be received during and at the end of dialysis.
There are currently no dosing recommendations for pediatric patients with renal impairment.
Hepatic Impairment
Caution is required in administration and periodic monitoring of liver function (see [Precautions] and [Adverse Reactions]).
Elderly
Dose adjustment may not be considered. However, caution should be exercised in dose selection because of the greater potential for reduced renal function in the elderly (see [Geriatric Use]).
Adverse reactions]
The most common adverse drug reactions reported abroad are diarrhea, nausea and rash.
The following table lists the adverse drug reactions in foreign clinical studies and post-marketing surveillance of amoxicillin according to the MedDRA Systematic Organ Classification.
The following terms are used to classify the incidence of adverse reactions.
Very common (≥1/10)
Common (≥1/100 to <1/10)
Rare (≥1/1,000 to <1/100)
Rare (≥1/10,000 to <1/1,000)
Very rare (<1/10,000)
Unknown (cannot be estimated from available data)
Infectious and invasive diseases Very rare Cutaneous mucocutaneous candidiasis Blood and lymphatic system diseases Very rare Reversible leukopenia (including severe neutropenia or granulocyte deficiency), reversible thrombocytopenia, and hemolytic anemia
Prolonged bleeding time and prothrombin time (see [Precautions]). Immune system disorders very rare severe allergic reactions, including angioneurotic edema, anaphylactic reactions, serum sickness, and allergic vasculitis (see [Precautions]). Unknown Hirschsprung’s reaction (see [Precautions]). Neurological disorders very rare spasms, vertigo, convulsions (see [Precautions]). Gastrointestinal system disordersForeign clinical trial data*Common diarrhea and nausea*Rare vomitingForeign post-marketing dataVery rareAntibiotic-associated colitis (including pseudomembranous enteritis, hemorrhagic colitis, see [Precautions]).
Black tongue diseaseHepatobiliary system disordersVery rareHepatitis and cholestatic jaundice.Moderately elevated AST and/or ALTDermal and subcutaneous tissue disordersForeign clinical trial data*Common rash*Rarely urticaria and pruritusForeign postmarketing dataVery rareDermal reactions such as erythema multiforme, Stevens Johnson syndrome, toxic epidermolysis bullosa, exfoliative dermatitis maculosa, acute generalized eruptive pustulosis (AGEP), and drug reactions with eosinophilia and systemic symptoms (DRESS) (see [Precautions]). Very rare renal and urological disorders: interstitial nephritis
Crystalluria (see [Precautions] and [Overdose]) *The incidence of these adverse events is derived from clinical studies of approximately 6,000 adult and pediatric patients taking amoxicillin abroad.
[Contraindications
Contraindicated in patients with penicillin hypersensitivity and positive penicillin skin test.
Contraindicated in patients with severe tachyphylaxis (e.g., anaphylactic reactions) to other beta-lactam agents (e.g., cephalosporins, carbapenems, monocyclic beta-lactams).
Precautions]
Allergic reactions
Before starting treatment with amoxicillin, carefully inquire about previous history of allergy to penicillins, cephalosporins and other β-lactams. Sodium penicillin skin test must be done before use and is contraindicated in positive reactions. Serious and occasionally fatal hypersensitivity reactions (including allergic reactions and severe cutaneous adverse reactions) have been reported in patients treated with penicillin. These reactions are more likely to occur in patients with a history of penicillin allergy as well as in allergic individuals. If an allergic reaction occurs, amoxicillin should be discontinued and appropriate replacement therapy administered.
Non-sensitive microorganisms
Amoxicillin is not suitable for the treatment of certain types of infections unless the pathogen has been documented and is known to be highly sensitive to amoxicillin or the pathogen is likely to be suitable for treatment with amoxicillin. This is especially true when treating urinary tract infections and those with severe infections of the ear, nose, and throat.
Convulsions
Convulsions may occur in patients with impaired renal function, in patients receiving high doses, or in patients with precipitating factors (e.g., history of seizures, epilepsy under treatment, or meningeal disease).
Renal impairment
Patients with renal impairment require dose adjustment based on the degree of impairment (see [DOSAGE AND ADMINISTRATION]).
Skin reactions
The presence of generalized erythema with pustules at the start of treatment may be a symptom of acute generalized eruptive pustulosis (AGEP) (see [Adverse Reactions]). This reaction requires discontinuation of amoxicillin and prohibition of any subsequent treatment.
Amoxicillin should be avoided if infectious mononucleosis is suspected, as the development of a measles-like rash following amoxicillin use may be associated with this condition.
Hirschsprung’s reaction
Hirschsprung’s reaction (see [Adverse Reactions]) has been seen abroad with the use of amoxicillin for Lyme disease. It directly affects the bactericidal activity of amoxicillin against Lyme disease Burkholderia sp. This is a common self-limiting result of antimicrobial therapy for Lyme disease.
Overgrowth of non-susceptible microorganisms
Long-term use of amoxicillin may lead to overgrowth of non-susceptible organisms.
Almost all antimicrobial drugs have been reported to cause antibiotic-associated colitis, which may range in severity from mild to life-threatening (see [Adverse Reactions]). Therefore, the most important thing is to diagnose whether the patient has pre-existing diarrhea or diarrhea resulting from antibiotic use. If antibiotic-associated colitis occurs, amoxicillin should be discontinued immediately, a physician should be consulted, and appropriate therapy should be initiated. Anti-peristaltic agents are contraindicated in this situation.
Long-term treatment
Organ system function, including renal, hepatic and hematopoietic function, should be evaluated periodically during long-term treatment. Elevated liver enzymes and changes in blood cell counts have been reported (see [Adverse Reactions]).
Anticoagulants
Prolongation of prothrombin time has rarely been reported in patients treated with amoxicillin. Appropriate monitoring should be performed when administered concomitantly with anticoagulants. Dose adjustment of oral anticoagulants may be required to achieve the desired level of anticoagulation (see [Drug Interactions] and [Adverse Reactions]).
Crystalluria
Primarily in amoxicillin injection therapy, patients have experienced decreased urine output and small amounts of urine crystals have been observed. When high doses of amoxicillin are given, it is best to maintain adequate fluid intake and urine volume in order to reduce the likelihood of amoxicillin crystalluria. Patients with bladder cannulation should have their catheters checked periodically (see [Adverse Reactions] and [Drug Overdose]).
Interference with diagnostic testing
Amoxicillin in serum and urine may interfere with certain laboratory tests. Due to the high concentration of amoxicillin in the urine, false positives are often seen using chemical methods.
It is recommended that the glucose oxidase method be used when testing urine glucose during amoxicillin therapy.
The presence of amoxicillin may affect the results of estriol measurements in pregnant women.
Development of drug-resistant bacteria
Prescribing amoxicillin to patients with an undiagnosed or not highly suspected bacterial infection may not benefit the patient and increase the formation of drug-resistant bacteria.
Effect on ability to drive and use machines
Studies on the effects on the ability to drive and use machines have not been conducted. However, adverse reactions (e.g., allergic reactions, dizziness, convulsions) may occur, which may affect the ability to drive and use machines (see [ADVERSE REACTIONS]).
Pregnant women and nursing mothers
Pregnancy
Animal studies have not shown direct or indirect reproductive toxicity. Limited data suggest that human use of amoxicillin during pregnancy does not increase the risk of congenital malformations. Amoxicillin may be used during pregnancy when the potential therapeutic benefit outweighs the potential risk associated with treatment.
Lactation
Amoxicillin can be secreted into breast milk in small amounts and may be a risk of sensitization. As a result, breastfed infants may develop diarrhea and mucosal fungal infections, and breastfeeding may have to be terminated. Amoxicillin should only be used during lactation after a physician’s assessment of benefit/risk.
Fertility
There are no data on the effect of amoxicillin on human fertility. Reproduction studies in animals have shown no effect on fertility.
For pediatric use] see [Dosage].
Dosage adjustment is not necessary for geriatric use (see [Dosage]). However, because of the greater potential for reduced renal function in the elderly, caution should be exercised in dose selection, with optional monitoring of renal function.
Drug Interactions
Probenecid
Combined use with probenecid is not recommended. Probenecid reduces renal tubular secretion of amoxicillin. Concomitant use of probenecid may result in increased blood levels and prolonged retention time of amoxicillin.
Allopurinol
Combination with amoxicillin during allopurinol treatment may increase the likelihood of allergic skin reactions.
Tetracyclines
Tetracyclines and other antibacterial drugs may interfere with the bactericidal effect of amoxicillin.
Oral anticoagulants
Oral anticoagulants and penicillin antibiotics are widely used in practice, and no interactions have been reported. However, according to the literature, patients using vinblastine or warfarin in combination with a course of amoxicillin have had an increase in the international normalized ratio. If a combination is necessary, prothrombin time and international normalized ratio should be carefully monitored as amoxicillin is added and withdrawn. In addition, the dose of oral anticoagulant may need to be adjusted (see [Precautions] and [Adverse Reactions]).
Methotrexate
Penicillins may reduce the excretion of methotrexate, leading to an increase in potential toxicity.
[Drug overdose].
Signs and symptoms of overdose.
Gastrointestinal symptoms (e.g., nausea, vomiting, and diarrhea), and disturbances in water-electrolyte balance may be evident. Amoxicillin crystalluria has been observed to lead to renal failure in some cases. Convulsions may occur in patients with impaired renal function or those receiving high doses (see [Precautions] and [Adverse Reactions]).
Treatment of Toxicity.
Gastrointestinal symptoms may be treated symptomatically, with attention to water and electrolyte balance. Amoxicillin can be cleared from the circulation by hemodialysis.
[Pharmacokinetics].
Absorption
Amoxicillin is completely dissolved in physiological pH aqueous solution. It is rapidly absorbed after oral administration. After oral administration, the bioavailability of amoxicillin is about 70%. The time to peak blood concentration (Tmax) is about 1h.
The results of pharmacokinetic studies of 250 mg of amoxicillin administered three times daily in healthy volunteers under fasting conditions are as follows.
CmaxTmax *AUC (0-24h)T ½(μg/ml)(h)(μg.h/ml)(h)3.3 ± 1.121.5 (1.0-2.0)26.7 ± 4.561.36 ± 0.56*Median value (range)In the dose range of 250-3000 mg, the bioavailability was linear with the dose (measured Cmax and AUC values). Absorption is not affected by feeding.
Hemodialysis clears amoxicillin.
Distribution
Amoxicillin has a protein binding rate of approximately 18% and an apparent volume of distribution of approximately 0.3 to 0.4 L/kg.
After intravenous administration, amoxicillin is distributed in the gallbladder, abdominal tissue, skin, fat, muscle tissue, synovial and peritoneal fluid, bile, and pus. Amoxicillin is not adequately distributed into the cerebrospinal fluid.
In animal studies, there was no evidence of significant tissue retention of drug derivatives. As with most penicillins, amoxicillin can be detected in breast milk (see [Dosage for Pregnant and Lactating Women]).
Amoxicillin has been shown to cross the placental barrier (see [Dosage for Pregnant and Lactating Women]).
Biotransformation
A portion of amoxicillin is excreted in the urine as inactive penicillin-thiazolic acid, equivalent to 10% to 25% of the initial dose.
Clearance
Amoxicillin is primarily cleared by the kidneys.
In healthy subjects, the mean clearance half-life of amoxicillin is approximately 1 h and the mean total clearance is approximately 25 L/h. A single administration of 250 mg or 500 mg of amoxicillin results in the excretion of approximately 60-70% of amoxicillin in the urine as a prototype drug within 6 h. Several studies have shown that 50-85% of amoxicillin is excreted in the urine during a 24-h cycle.
The combination of probenecid delays the excretion of amoxicillin (see [Drug Interactions]).
Age
The elimination half-life of amoxicillin is similar for children 3 months to 2 years of age, older children, and adults. In very young children (including premature neonates), dosing intervals should not exceed twice daily during the first week of life due to immature renal elimination pathways. Care should be taken in dose selection and possibly monitoring of renal function in older patients due to the greater likelihood of decreased renal function.
Gender
There was no significant effect of gender on the pharmacokinetics of amoxicillin after oral administration to healthy male and female subjects.
Renal Function Impairment
The total serum clearance of amoxicillin decreases proportionally with decreased renal function (see [DOSAGE AND ADMINISTRATION] and [PRECAUTIONS]).
Hepatic impairment
Patients with hepatic impairment should take with caution and monitor liver function regularly.
Storage】 Keep tightly closed at room temperature.
Package】 Double aluminum package, 8 tablets/plate.
Expiration date】 24 months
Marketing Authorization Holder
Name of Marketing Authorization Holder: Kunming Yuanrui Pharmaceutical Co.
Address of the licensee: Huashi Road, Yanglin Industrial Development Zone, Yunnan
Postal Code: 651701
Contact: 0871-67974906
Fax number: 0871-67974900
Manufacturer
Company name: Kunming Yuanrui Pharmaceutical Co.
Production Address: Yunnan Yanglin Industrial Development Zone, Huashi Road
Postal Code: 651701
Telephone number: 0871-67974906
Fax number: 0871-67974900
Web address: http://www.yuanruizhiyao.com