Date of approval.
Date of revision.
Cefaclor extended release tablets instructions
Please read the instructions carefully and use under the guidance of a physician
This product is contraindicated in patients with known hypersensitivity to cefaclor and other cephalosporin antibiotics.
Drug Name
Generic name: Cefaclor Sustained-Release Tablets
English name: Cefaclor Sustained Release Tablets
Hanyu Pinyin: Toubaokeluo Huanshipian
Ingredients
The main ingredient of this product is cefaclor.
Chemical name: (6R,7R)-7-[(R)-2-amino-2-phenylacetamido]-3-chloro-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid monohydrate
Chemical structure formula.
Molecular formula: C15H14ClN3O4S-H2O
Molecular weight: 385.82
Properties
This product is a blue film-coated tablet, after removing the film coating, it appears off-white to light yellow.
Indications
Cefaclor extended-release tablets are indicated for the following infections caused by sensitive pathogenic bacteria.
Acute bronchitis and acute exacerbation of chronic bronchitis: caused by Streptococcus pneumoniae, Haemophilus influenzae (including β-lactamase-producing strains), Haemophilus parainfluenzae (including β-lactamase-producing strains), Cattamora (including β-lactamase-producing strains) and Staphylococcus aureus.
Pharyngitis and tonsillitis: caused by Streptococcus pyogenes (group A streptococci). (Penicillin is generally the drug of choice for the treatment and prevention of streptococcal infections, including prophylaxis of rheumatic fever. Although cefaclor extended-release tablets are usually effective in clearing streptococci from the oropharynx; there is not enough information to confirm that cefaclor extended-release tablets prevent rheumatic fever attacks).
Pneumonia: caused by Streptococcus pneumoniae, Haemophilus influenzae (including beta-lactamase-producing strains), and Cattamora (including beta-lactamase-producing strains).
Sinusitis: caused by Streptococcus pneumoniae (penicillin-sensitive strains only), Haemophilus influenzae (including β-lactamase-producing strains), and Cattamora (including β-lactamase-producing strains).
Simple lower urinary tract infections: including cystitis and asymptomatic bacteriuria caused by Escherichia coli, Klebsiella pneumoniae, Aspergillus chimaera, and Staphylococcus saprophyticus.
Skin soft tissue infections: caused by Streptococcus pyogenes (group A streptococci), Staphylococcus aureus (including β-lactamase-producing strains), and Staphylococcus epidermidis (including β-lactamase-producing strains).
Bacteriological studies are required to clarify the pathogenic diagnosis and to determine the susceptibility of the pathogenic bacteria to cefaclor. Treatment is initiated after the appropriate specimens are obtained. Adjust antibacterial drugs according to culture and drug sensitivity results.
Specification
0.375g (based on C15H14ClN3O4S)
Dosage
Cefaclor extended-release tablets can be administered orally without regard to meals. However, taking with food can increase the absorption of cefaclor extended-release tablets. Tablets should not be broken, crushed or chewed when taken.
The recommended dose for pharyngitis, tonsillitis and soft tissue skin infections is 375 mg (one tablet) twice daily. The recommended dose for lower urinary tract infections is 375 mg (one tablet) twice daily. The recommended dose for bronchitis is 375 mg (one tablet) twice daily. The recommended dose for pneumonia and sinusitis is 750mg (two tablets) twice daily.
For the treatment of infections caused by Streptococcus pyogenes (group A streptococcus), a course of cefaclor extended-release tablets is required for at least 10 days.
[Adverse Reactions].
Most of the adverse reactions observed in clinical trials with Cefaclor Extended Release Tablets were mild and transient. Discontinuation of treatment due to drug-related adverse reactions accounted for 1.7%. The following adverse reactions were reported in clinical trials of oral cefaclor extended-release tablets. Unless otherwise mentioned, the incidence was less than 1%.
Gastrointestinal reactions: diarrhea (3.4%), nausea (2.5%), vomiting and dyspepsia.
Allergic reactions: rash, urticaria, or pruritus occurred in about 1.7% of patients. In a controlled clinical trial with cefaclor extended-release tablets, one serum sickness-like reaction occurred in 3272 patients (0.03%).
Serum sickness-like reactions have been reported in patients applying cefaclor. These reactions are characterized by polymorphic erythema, rash and other cutaneous manifestations with arthritis/arthralgia, fever or no fever, and differ from typical serum sickness in that lymphadenopathy and proteinuria are rare, no immune complexes enter the circulation, and no sequelae of the reaction occur. Occasionally, a single symptom may occur, but it does not represent a serum sickness-like reaction. Further studies have shown that seropathy-like reactions appear to be associated with metabolic reactions, often occurring during or after the second course of cefaclor. These reactions have been reported to occur more frequently in children than in adults, with rates ranging from 0.5% (1/200) in one trial to 0.024% (2/8346) in all clinical trials (0.055% in children in clinical trials) to 0.003% (1/38,000) in spontaneous event reports. Signs and symptoms usually occurred several days after initiation of treatment and resolved within a few days after discontinuation of treatment; occasionally, short-term hospitalization was required for such reactions (mean length of stay 2-3 days based on post-marketing surveillance data). For those patients requiring hospitalization, symptoms at admission range from mild to severe, with severe reactions occurring more frequently in children. Antihistamines and glucocorticoids may accelerate the disappearance of signs and symptoms. No serious sequelae have been reported.
Hematologic and lymphatic system: erythrocytosis.
Genitourinary system: vaginal candidiasis (2.5%) and vaginitis (1.7%)
Central nervous system: headache, dizziness and drowsiness
Liver: transient elevated serum glutamic aminotransferase (ALT), serum glutamic aminotransferase (AST) and alkaline phosphatase (ALP)
Kidney: transient elevation of serum urea nitrogen (BUN) or creatinine.
Laboratory tests: transient thrombocytopenia, leukopenia, lymphocytosis, neutropenia, and abnormal urinalysis.
In addition to the adverse reactions observed above in patients taking cefaclor extended-release tablets, the following adverse reactions and laboratory abnormalities are seen in patients treated with cefaclor.
Erythema multiforme, fever, allergic reactions (which may occur more frequently in patients with a history of penicillin allergy), Stevens-Johnson syndrome, direct positive Coomb’s test, and genital pruritus. Pseudomembranous enteritis can occur during or after discontinuation of antibiotic therapy. Pseudomembranous enteritis has been reported following the administration of large amounts of broad-spectrum antibiotics. Allergic reactions can present with isolated symptoms, including angioneurotic edema, weakness, edema (both facial and extremity), dyspnea, sensory abnormalities, syncope, and vasodilation.
It is rare for allergic symptoms to persist for several months.
The following adverse reactions are rare in patients treated with cefaclor.
Toxic epidermolysis bullosa, reversible interstitial nephritis, abnormal liver function including cholestasis. Prolonged prothrombin time, reversible hyperactivity, hypersensitivity, insomnia, increased muscle tone, aplastic anemia, granulocyte deficiency, and hemolytic anemia when cefaclor is combined with warfarin.
In addition to the above adverse reactions, the following adverse reactions have been reported in patients treated with beta-lactams: enterocolitis, abnormal renal function, toxic nephropathy, biliary depression jaundice, eosinophilia, abnormal liver function tests, abnormal renal function tests, and candidiasis.
Certain beta-lactam antibiotics can cause seizures, especially if the dose administered is not reduced in patients with renal insufficiency. If seizures related to drug therapy occur, treatment should be discontinued and the decision to give anticonvulsant drugs should be based on the clinical situation.
[Contraindications
Cefaclor is contraindicated in patients with known hypersensitivity to cefaclor and other cephalosporin antibiotics.
Precautions]
General precautions: Drug-resistant bacteria may be selected and multiply during treatment, especially during long course therapy. Careful observation of the patient’s condition is important and appropriate measures should be taken in case of secondary infection.
Warnings
Before applying Cefaclor extended-release tablets, take a careful history to determine if the patient is allergic to cephalosporins, penicillins, or other drugs. Use this product with caution in patients with penicillin allergy. Antimicrobial drugs should be used with caution in patients with any form of hypersensitivity, especially to drugs. Discontinue treatment if the patient is allergic to Cefaclor extended-release tablets. Administer epinephrine and other emergency management measures in patients with severe acute allergic reactions.
Antimicrobial drugs, including cefaclor extended-release tablets, should be used with caution in patients with any form of allergic reaction, especially in those with drug allergy.
Virtually all broad-spectrum antibacterial drugs (including macrolides, semisynthetic penicillins, and cephalosporins) have been reported to cause pseudomembranous enterocolitis; therefore, the possibility of this disease should be considered in any patient applying broad-spectrum antibacterial drugs who develops diarrhea. The severity of pseudomembranous enterocolitis can range from mild to life-threatening. Mild cases of enterocolitis can be treated by discontinuing antibacterial drugs, while moderate to severe cases require appropriate management measures.
Use in Pregnant and Lactating Women
Use in pregnant women: Reproduction studies were conducted in rats, mice and ferrets, administering doses up to 12 times the maximum human dose in the former and up to 3 times the maximum human dose in the latter. These studies showed that cefaclor did not impair fertility and did not show any evidence of fetal harm. However, adequate, well-controlled studies have not been performed in pregnant women. Because animal reproduction studies are not always predictive of human response, cefaclor extended-release tablets should be used in pregnant women only when truly indicated.
Labor and Delivery: The effect of Cefaclor Delayed-Release Tablets on labor and delivery has not been studied and should be given only when indicated.
Lactation: No studies have been conducted with Cefaclor Extended-Release Tablets. Small amounts of cefaclor have been detected in breast milk after administration of cefaclor 500 mg during lactation. The mean concentrations were 0.18, 0.20, 0.21 and 0.16 μg/ml at 2, 3, 4 and 5 hours after dosing, respectively. only trace amounts were detected 1 hour after dosing. The effect on the breastfed child is unknown. Cefaclor extended-release tablets should be used with caution in nursing women.
Pediatric use]
The efficacy and safety in children have not been established.
For Elderly]
Not available. Refer to [Dosage].
Drug Interactions
Drug Interaction: Within 1 hour of administration of Cefaclor extended-release tablets, the application of antacids containing magnesium and aluminum hydroxide reduces the total absorption; H2-blockers do not affect the absorption rate and total absorption of Cefaclor extended-release tablets. As with other β-lactams, propofol inhibited the renal tubular secretion and excretion of cefaclor, and presumably so did cefaclor extended-release tablets. No other drug interactions were observed in the course of clinical trials.
Laboratory Test Interactions: Application of Cefaclor Extended-Release Tablets may result in a false-positive urine glucose test. Patients taking cephalosporin antibiotics may have a false positive urine glucose test with Benedict’s and Fehling’s reagents and Clinitest test strips, but not with Tes-Tape (urine glucose test strip, Eli Lilly and Company, USP).
Drug overdose
Signs and symptoms: Symptoms of toxicity following an overdose of cefaclor extended-release tablets include nausea, vomiting, upper abdominal discomfort, and diarrhea. The severity of epigastric discomfort and diarrhea is related to the dose administered. If other symptoms are present, they may be secondary to an underlying disorder, allergic reaction, or other toxic effects.
Treatment: When managing an overdose, consider the potential for multiple drug overdose, drug-drug interactions, and abnormal pharmacokinetics of the patient. Keep the patient’s airway open and maintain ventilation and blood perfusion. Carefully monitor and maintain the patient’s vital signs, blood gases, and serum electrolytes whenever possible. Administration of activated charcoal reduces the absorption of gastrointestinal drugs and in many cases is more effective than gastric lavage and enema; therefore, the use of activated charcoal as an alternative to gastric lavage or a combination of both may be considered. Repeated administration of activated charcoal can accelerate the excretion of absorbed drugs. When gastric lavage or activated charcoal is administered, the patient’s airway should be protected.
The benefit of mandatory diuresis, peritoneal dialysis, hemodialysis or activated charcoal hemoperfusion for cefaclor overdose has not been established.
Pharmacology and Toxicology
Pharmacological effects
Cefaclor is a second-generation cephalosporin, an oral semi-synthetic antimicrobial agent with broad-spectrum anti-Gram-positive and Gram-negative bacterial effects, and its mechanism of action is the same as other cephalosporins, mainly through the inhibition of cell wall synthesis to achieve bactericidal effects. Cefaclor is stable to β-lactamase of some bacteria, so some β-lactamase producing microorganisms may be sensitive to cefaclor.
In vitro and clinical studies have confirmed the antibacterial activity of cefaclor against most of the following microorganisms.
Gram-positive bacteria: Staphylococcus aureus (including β-lactamase-producing strains), Staphylococcus epidermidis (including β-lactamase-producing strains), Staphylococcus saprophyticus, Streptococcus pyogenes (group A streptococci), Streptococcus pneumoniae; cefaclor is not effective against methicillin sodium-resistant staphylococci.
Gram-negative bacteria: Haemophilus parainfluenzae, Haemophilus influenzae (including β-lactamase-producing strains), Catamorax (including β-lactamase-producing strains), Escherichia coli, Klebsiella pneumoniae, Aspergillus chimaerae.
Note: Pseudomonas spp.; Calcium Acetate immobilis; most Enterococcus spp.; Enterobacter spp.; Morganella spp.; Proteus mirabilis; β-lactamase-negative, ampicillin-resistant Haemophilus influenzae; indole-positive Aspergillus spp. and Serratia spp. are resistant to cefaclor.
Toxicological studies
No information is available on the genotoxicity, carcinogenicity and effects on fertility of cefaclor. Results of reproductive toxicity tests in mice, rats and ferrets showed no significant toxic reactions at doses up to 3-5 times the maximum recommended human dose (based on body surface area). Since the above information was obtained from animal tests, it does not fully predict the outcome of clinical use.
Pharmacokinetics]
Cefaclor extended-release tablets are well absorbed after oral administration. Although Cefaclor extended-release tablets can be taken on an empty stomach or after a meal, food can increase its total absorption. Using Cefaclor as a reference, the bioavailability of Cefaclor extended-release tablets is greater than 90% when administered 1 hour after a meal. When administered on an empty stomach, the bioavailability of cefaclor extended-release tablets was 77% of that of cefaclor. The mean peak blood concentration (postprandial and fasting) of cefaclor extended-release tablets is 40-90 minutes behind and lower than that of cefaclor (fasting state). Concurrent use of H2-blockers did not affect the absorption rate or total absorption. The application of antacids containing magnesium and aluminum hydroxide within 1 hour of administration of cefaclor extended-release tablets did not affect its absorption rate, but its total absorption was reduced by 17%.
The mean peak blood concentrations were 4, 8, and 11 μg/ml for 2.5-3 hours after administration of 375 mg, 500 mg, and 750 mg of cefaclor extended-release tablets, respectively, and no accumulation was observed when the drug was administered twice daily.
The plasma half-life in healthy subjects was dose-independent and averaged about 1 hour (0.6-0.9 hours). In elderly subjects (>65 years of age) with normal serum creatinine values, the higher peak plasma concentrations and the larger area under the curve during drug administration were the result of mild renal decompensation, but were not clinically significant. Therefore, no dose adjustment is required in elderly subjects with normal renal function. Cefaclor is not metabolized in human body.
Storage】Store in a cool, dark and dry place under shade and seal.
Package】 Polyester/aluminum composite rigid PVC solid pharmaceutical rigid tablets with pharmaceutical aluminum foil blister package, 8 tablets/plate×1 plate/box; 6 tablets/plate×1 plate/box; 6 tablets/plate×2 plate/box; 4 tablets/plate×1 plate/box.
Expiration date】 18 months
【Execution standard
【Approval number】 State Drug Certificate H20020456
[Drug Marketing Licensee
Name: Zhejiang Anglicon Pharmaceutical Co.
Registered Address: No. 1000, Shengzhou Avenue North, Shengzhou City, Zhejiang Province
Postal Code: 312400
Contact：0575-83108588
Fax: 0575-83101736
Website: http://www.alkpharm.com
【Manufacturing enterprise】.
Company name: Zhejiang Anglicon Pharmaceutical Co.
Address: No.1000 North Shengzhou Avenue, Shengzhou City, Shaoxing
Postcode：312400
Contact：0575-83108588
Fax: 0575-83101736
Website: http://www.alkpharm.com