Cefaclor

Cefaclor belongs to the pharmacological class of Second-generation cephalosporin antibiotics.

Cefaclor has been approved to relieve symptoms and also for the treatment and maintenance of Acute bacterial exacerbations of chronic bronchitis, Pneumonia, community-acquired, outpatient empiric therapy, Streptococcal pharyngitis, group A, Urinary tract infection.

Cefaclor is a second-generation cephalosporin antibiotic that exhibits bactericidal activity against susceptible bacteria. After oral administration, cefaclor is rapidly and well absorbed, with peak plasma concentrations achieved within 0.5 to 1.0 hours. The drug is widely distributed in body fluids and tissues, including bronchial secretions, middle ear effusions, and urine. Cefaclor is primarily eliminated by renal excretion, with approximately 85% of the administered dose excreted unchanged in the urine within 8 hours. The drug's pharmacokinetics are linear over the recommended dose range, and its elimination half-life is approximately 0.6 to 0.9 hours in patients with normal renal function.

The common side effects involving the use of Cefaclor are nausea, vomiting, gas, weakness, tiredness, itching, diarrhea, headache,upset stomach, etc.

Cefaclor is available in the form of Immediate release capsules, Extended-release tablets, Oral suspensions

Cefaclor is approved in the U.S., U.K., Germany, Japan, Malaysia, India, and China.

Cefaclor belongs to the pharmacological class of Second-generation cephalosporin antibiotics.

Cefaclor is a bactericidal antibiotic that works by inhibiting bacterial cell wall synthesis. Specifically, it binds to and inhibits the activity of the enzymes responsible for cross-linking peptidoglycan strands in bacterial cell walls, known as penicillin-binding proteins (PBPs). This leads to the weakening and eventual lysis of bacterial cell walls, resulting in the death of the bacteria. Cefaclor is effective against a wide range of gram-positive and gram-negative bacteria, including Streptococcus pneumoniae, Haemophilus influenzae, Escherichia coli, and Klebsiella pneumoniae, among others.

Cefaclor has been approved to relieve symptoms and also for the treatment and maintenance of Acute bacterial exacerbations of chronic bronchitis, Pneumonia, community-acquired, outpatient empiric therapy, Streptococcal pharyngitis, group A, Urinary tract infection.

The maximum plasma concentration (Cmax) of cefaclor occurs approximately 0.5 to 1.0 hour after oral administration. The time to reach maximum concentration (Tmax) varies depending on the formulation and whether the drug is taken with or without food, but it typically ranges from 0.5 to 2 hours.

The onset of action of cefaclor is rapid, with significant antibacterial activity observed within 1 to 2 hours after administration. The duration of action of cefaclor depends on several factors, including the dose, the severity of the infection, and the patient's individual response to the medication. In general, cefaclor has a relatively short half-life of about 0.6 to 0.9 hours, which means that it is eliminated from the body relatively quickly. As a result, cefaclor must be administered multiple times per day to maintain effective concentrations in the bloodstream and achieve sustained antibacterial activity.

Cefaclor is found to be available in the form of Immediate release capsules, Extended-release tablets, Oral suspensions

Cefaclor can be used in the following treatment:

● Acute bacterial exacerbations of chronic bronchitis

● Pneumonia, community-acquired, outpatient empiric therapy

● Streptococcal pharyngitis, group A

● Urinary tract infection

Cefaclor can help to relieve symptoms and also for the treatment and maintenance of Acute bacterial exacerbations of chronic bronchitis, Pneumonia, community-acquired, outpatient empiric therapy, Streptococcal pharyngitis, group A, Urinary tract infection.

Cefaclor is approved for use in the following clinical indications:

● Acute bacterial exacerbations of chronic bronchitis

● Pneumonia, community-acquired, outpatient empiric therapy

● Streptococcal pharyngitis, group A

● Urinary tract infection

● Acute bacterial exacerbations of chronic bronchitis: The recommended dose for oral extended-release is 500 mg every 12 hours for 7 days.

● Pneumonia, community-acquired, outpatient empiric therapy (patients with comorbidities): The recommended dose for oral immediate-release is 500 mg every 8 hours as part of an appropriate combination regimen. The duration of therapy should be for a minimum of 5 days, and patients should be clinically stable with normal vital signs before discontinuing therapy.

● Streptococcal pharyngitis, group A (alternative agent for mild, nonanaphylactic penicillin allergy): The recommended dose for oral immediate-release is 250 mg every 8 hours for 10 days. Cephalosporin selection depends on the type of hypersensitivity reaction to penicillin, and narrower spectrum cephalosporins are preferred when possible to avoid resistance development.

● Urinary tract infection (alternative agent): Use oral beta-lactams only when first-line agents cannot be used. The recommended dose for acute uncomplicated or acute simple cystitis (infection limited to the bladder without signs/symptoms of upper tract, prostate, or systemic infection) is 250 mg every 8 hours for 5 to 7 days. For prophylaxis for recurrent infection, the optimal duration has not been established, but it ranges from 3 to 12 months, with periodic reassessment. The recommended dose for continuous prophylaxis is 250 mg once daily. For complicated urinary tract infections (including pyelonephritis), the recommended dose for oral immediate-release is 500 mg 3 times daily for 10 to 14 days. Oral beta-lactam therapy should generally follow appropriate parenteral therapy.

Capsules: 250 mg , 500 mg

Extended-release tablets: 375 mg , 500 mg

Oral suspension: 125 mg/5 mL, 187 mg/5 mL, 250 mg/5 mL, and 375 mg/5 mL

Dosage Adjustments in Kidney Patients:

For patients having mild to moderate renal impairment (CrCl > 30 mL/min), the usual recommended dose may be used. However, the dose should be decreased in patients with severe renal impairment (CrCl < 30 mL/min) or in patients on dialysis.

In such cases, the recommended dose is typically 50% of the usual dose given at the same frequency. For example, if the usual dose is 500 mg every 8 hours, the dose for a patient with severe renal impairment or on dialysis would be 250 mg every 8 hours.

Dosage Adjustments in Hepatic Impairment Patients:

No dosage adjustments are needed for hepatic Impairment.

Dosage Adjustments in Pediatric Patients:

Infants up to 1 month of age: Safety and efficacy have not been established.

Infants and children 1 month to 12 years of age: The usual dosage of cefaclor is 20 mg/kg/day, divided into 3 or 4 equal doses, for mild to moderate infections. For more severe infections, the dosage may be increased up to 40 mg/kg/day, divided into 3 or 4 equal doses.

Immediate release capsules, Extended-release tablets, Oral suspensions

Avoid high acid foods like citrus fruits as well as juices like orange and grapefruit, soda, and chocolate.

Alcohol intake might lead to vomiting, nausea and headache

Multivitamins as well as antacids might contain minerals, primarily magnesium, calcium, aluminum, iron, or zinc, which may bind to the antibiotic and prevent them from acting. Spacing them at least for 2 hours after Cefaclor administration is recommended.

Cefaclor may be contraindicated under the following conditions:

● Cefaclor is contraindicated in patients who have demonstrated hypersensitivity to Cefaclor, other cephalosporins, penicillins, or any component of the formulation. It should also not be used in patientswho have a history of anaphylaxis to beta-lactam antibiotics.

● Additionally, it is contraindicated in neonates with hyperbilirubinemia or a history of jaundice, as Cefaclor may displace bilirubin from albumin and increase the risk of kernicterus.

● Finally, Cefaclor is contraindicated in patients with a history of colitis, inflammatory bowel disease or pseudomembranous colitis associated with the use of antibiotics.

The physician should closely monitor the patients and keep pharmacovigilance as follows:

Prior to initiating therapy with cefaclor extended-release tablets, it is important to carefully assess whether the patient has had any previous hypersensitivity reactions to cefaclor, cephalosporins, penicillins, or other drugs. If this medication is intended for use in penicillin-sensitive patients, caution should be exercised due to documented cross-sensitivity among beta-lactam antibiotics, which might occur in up to 10% of patients with a history of penicillin allergy. If an allergic reaction to cefaclor extended-release tablets occurs, the drug should be discontinued immediately. Serious acute hypersensitivity reactions may require emergency treatment, such as epinephrine, oxygen, intravenous fluids, antihistamines, corticosteroids, pressor amines, as well as airway management as clinically indicated.

The use of antibacterial agents, including cefaclor, has been associated with Clostridium difficile-associated diarrhea (CDAD), which might range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents can alter the normal flora of the colon, leading to the overgrowth of C. difficile. Toxins A and B produced by C. difficile contribute to the development of CDAD. Hypertoxin-producing strains of C. difficile can cause increased morbidity and mortality as these infections may be refractory to antimicrobial therapy and might require colectomy. CDAD should be considered in all patients who present with diarrhea following antibiotic use. A careful medical history is necessary as CDAD had been reported to occur over two months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile might need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

There is a moderate interaction between alcohol and Cefaclor. It is generally recommended to avoid drinking alcohol while taking Cefaclor because it may increase the risk of side effects such as dizziness, drowsiness, and gastrointestinal upset. Additionally, alcohol may also impair the body's ability to fight infections, which may reduce the effectiveness of Cefaclor in treating bacterial infections.

Studies on lactating women have not been conducted with cefaclor extended-release tablets. Small amounts of cefaclor (≤ 0.21 mcg/mL) have been found in human milk after administration of single 500 mg doses of cefaclor extended-release tablets. It is unknown whether cefaclor has any effect on nursing infants. Caution is advised when administering cefaclor extended-release tablets to nursing women.

Pregnancy Category B

Studies on reproductive effects of cefaclor have been conducted in mice, rats, and ferrets at doses up to 3 to 5 times the maximum recommended human dose (1500 mg/day) based on mg/m. These studies have shown no evidence of harm to the fetus from cefaclor. However, there have been no adequate and well-controlled studies on pregnant women, and the results of animal studies may not always be applicable to humans. Therefore, cefaclor extended-release tablets should only be used during pregnancy if absolutely necessary.

No sufficient scientific evidence is traceable regarding the use and safety of Cefaclor in concurrent use with any particular food. 

The adverse reactions related to Cefaclor can be categorized as follows:

Common:

● Nausea

● Vomiting

● Diarrhea

● Abdominal pain

● Rash

● Itching

● Hives

● Superinfection

● Dizziness

● Headache

● Confusion

Less common:

● Liver dysfunction

● Serum sickness-like reactions

● Stevens-Johnson syndrome

● Anemia

● Thrombocytosis

● Leukopenia

Rare:

● Angioedema

● Bronchospasm

● Colitis

● Erythema multiforme

● Hemolytic anemia

● Interstitial nephritis

● Seizures

The clinically relevant drug interactions of Cefaclor is briefly summarized here:

Probenecid: Probenecid can increase the concentration of cefaclor in the blood, leading to an increased risk of side effects.

Oral anticoagulants: Cefaclor may enhance the effects of oral anticoagulants, such as warfarin, increasing the risk of bleeding.

Nephrotoxic drugs: Cefaclor may increase the risk of nephrotoxicity (kidney damage) when taken with other drugs that are known to cause kidney damage.

Loop diuretics: Loop diuretics, such as furosemide, may reduce the effectiveness of cefaclor by decreasing its concentration in the blood.

Other antibiotics: Concurrent use of cefaclor with other antibiotics may increase the risk of adverse effects.

Vaccines: Cefaclor may interfere with the effectiveness of live vaccines, such as measles, mumps, and rubella (MMR), and should not be used within two weeks of receiving a live vaccine.

The following are the side effects involving Cefaclor :

● Diarrhea

● Nausea

● Vomiting

● Stomach pain

● Headache

● Dizziness

● Rash or itching

● Yeast infection

Pregnancy

Pregnancy Category B

Studies on reproductive effects of cefaclor have been conducted in mice, rats, and ferrets at doses up to 3 to 5 times the maximum recommended human dose (1500 mg/day) based on mg/m. These studies have shown no evidence of harm to the fetus from cefaclor. However, there have been no adequate and well-controlled studies on pregnant women, and the results of animal studies may not always be applicable to humans. Therefore, cefaclor extended-release tablets should only be used during pregnancy if absolutely necessary.

Lactation: Studies on lactating women have not been conducted with cefaclor extended-release tablets. Small amounts of cefaclor (≤ 0.21 mcg/mL) have been found in human milk after administration of single 500 mg doses of cefaclor extended-release tablets. It is unknown whether cefaclor has any effect on nursing infants. Caution is advised when administering cefaclor extended-release tablets to nursing women.

Pediatric: The safety and effectiveness of cefaclor extended-release tablets in pediatric patients under 16 years of age have not been established.

Geriatric: Out of 3272 patients involved in clinical studies of cefaclor extended-release tablets, 608 (18.2%) were aged 65 or over. No significant differences in safety or effectiveness were observed between these and younger patients. However, some elderly patients may be more sensitive to cefaclor due to decreased renal function, which may increase the risk of toxic reactions. Therefore, dosage selection should be carefully considered, and renal function may need to be monitored in elderly patients.

Physicians should be knowledgeable and vigilant about the treatment and identification of overdosage of Cefaclor.

Overdosage of cefaclor, a second-generation cephalosporin antibiotic, can lead to adverse effects, including gastrointestinal symptoms such as nausea, vomiting, and diarrhea. If an overdose is suspected, medical attention should be sought immediately.

There is no specific antidote for cefaclor overdose, and treatment is generally supportive and symptomatic. The use of activated charcoal may be considered in cases of recent ingestion of a large amount of the drug. In addition, the patient should be monitored for signs of dehydration, electrolyte imbalances, and other complications.

In cases of severe overdose, hemodialysis or peritoneal dialysis may be considered as a means of removing the drug from the circulation. However, the effectiveness of dialysis in removing cefaclor is not well established.

Pharmacodynamics

The pharmacodynamics of cefaclor, a second-generation cephalosporin antibiotic, involve its ability to inhibit bacterial cell wall synthesis, resulting in bactericidal activity against susceptible bacteria. The main mechanism of action of cefaclor is through binding to penicillin-binding proteins (PBPs) that are involved in the final stages of bacterial cell wall synthesis.

Cefaclor is active against a wide range of Gram-positive and Gram-negative bacteria, including Streptococcus pneumoniae, Haemophilus influenzae, and Escherichia coli. Its activity against some bacteria is dependent on the concentration of the drug and the duration of exposure.

Pharmacokinetics

Absorption:

Cefaclor is rapidly absorbed after oral administration, with peak plasma concentrations occurring within 30-60 minutes. Food may delay absorption, but does not affect the overall extent of absorption.

Distribution:

Cefaclor is widely distributed throughout the body, with a volume of distribution of approximately 0.27 L/kg. It is primarily bound to albumin and has low penetration into the cerebrospinal fluid, except in the presence of meningeal inflammation.

Metabolism:

Cefaclor is minimally metabolized in the liver, with only about 15% of the drug being metabolized. The major metabolite is the inactive desacetylcefalor.

Elimination:

Cefaclor is primarily eliminated by renal excretion, with about 80-90% of the drug being excreted unchanged in the urine. The elimination half-life of cefaclor is approximately 0.6-0.9 hours in healthy adults, but may be prolonged in patients with renal impairment.

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2. Walter SD, Marrie TJ. A controlled trial of cefaclor versus amoxicillin in acute bacterial exacerbations of chronic bronchitis. Can J Infect Dis. 1992 Nov;3(6):263-7. doi: 10.1155/1992/207052. PMID: 22346350; PMCID: PMC3327387.

3. Singh AK, Agrawal VK, Gupta G, et al. Comparative evaluation of cefaclor versus cephalexin in uncomplicated urinary tract infections. Indian J Pharmacol. 1996 Jul;28(4):276-8.

4. Aksoy DY, Cizmeci Z, Otlu B, et al. Cefaclor versus co-amoxiclav in the treatment of acute exacerbations of chronic bronchitis. Eur J Clin Microbiol Infect Dis. 2003 Jul;22(7):422-6. doi: 10.1007/s10096-003-0958-2. PMID: 12836058.

5. Wilson SS, Naiman JL, Allen HE, et al. Cefaclor compared with amoxicillin in the treatment of skin and skin-structure infections. Clin Ther. 1986;8 Suppl A:75-81. PMID: 3522793.

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