cephalexin 500 MG Oral Tablet

INDICATIONS AND USAGE Cephalexin USP is a cephalosporin antibacterial drug indicated for the treatment of the following infections caused by susceptible isolates of designated bacteria in adults and pediatric patients aged one year and older: Respiratory tract infection ( 1.1 ) Otitis media ( 1.2 ) Skin and skin structure infections ( 1.3 ) Bone infections ( 1.4 ) Genitourinary tract infections ( 1.5 ) To reduce the development of drug-resistant bacteria and maintain the effectiveness of cephalexin and other antibacterial drugs, cephalexin for oral suspension should be used only to treat infections that are proven or strongly suspected to be caused by bacteria. ( 1.6 ) 1.1 Respiratory Tract Infections Cephalexin for oral suspension is indicated for the treatment of respiratory tract infections caused by susceptible isolates of Streptococcus pneumoniae and Streptococcus pyogenes in adults and pediatric patients aged one year and older. 1.2 Otitis Media Cephalexin for oral suspension is indicated for the treatment of otitis media caused by susceptible isolates of Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Streptococcus pyogenes , and Moraxella catarrhalis in adults and pediatric patients aged one year and older. 1.3 Skin and Skin Structure Infections Cephalexin for oral suspension is indicated for the treatment of skin and skin structure infections caused by susceptible isolates of the following Gram-positive bacteria: Staphylococcus aureus and Streptococcus pyogenes in adults and pediatric patients aged one year and older. 1.4 Bone Infections Cephalexin for oral suspension is indicated for the treatment of bone infections caused by susceptible isolates of Staphylococcus aureus and Proteus mirabilis in adults and pediatric patients aged one year and older . 1.5 Genitourinary Tract Infections Cephalexin for oral suspension is indicated for the treatment of genitourinary tract infections, including acute prostatitis, caused by susceptible isolates of Escherichia coli , Proteus mirabilis , and Klebsiella pneumoniae in adults and pediatric patients aged one year and older . 1.6 Usage To reduce the development of drug-resistant bacteria and maintain the effectiveness of cephalexin for oral suspension and other antibacterial drugs, cephalexin for oral suspension should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information is available, this information should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

DOSAGE AND ADMINISTRATION Adults and patients at least 15 years of age The usual dose is 250 mg every 6 hours, but a dose of 500 mg every 12 hours may be administered ( 2.1 ). Pediatric patients (over 1 year of age) • Otitis media: 75 to 100 mg/kg in equally divided doses every 6 hours ( 2.2 ) • All other indications: 25 to 50 mg/kg given in equally divided doses ( 2.2 ) • In severe infections: 50 to 100 mg/kg may be administered in equally divided doses ( 2.2 ) Duration of therapy ranges from 7 to 14 days depending on the infection type and severity. ( 2 ) See full prescribing information directions for mixing cephalexin for oral suspension ( 2.3 ) Dosage adjustment is required in patients with severe and end stage renal disease (ESRD) defined as creatinine clearance below 30 mL/min. ( 2.4 ) 2.1 Recommended Dosage for Adults and Pediatric Patients at Least 15 Years of Age The recommended dosage of oral cephalexin is 250 mg every 6 hours, but a dose of 500 mg every 12 hours may be administered. Treatment is administered for 7 to 14 days. For more severe infections larger doses of oral cephalexin may be needed, up to 4 grams daily in two to four equally divided doses. 2.2 Recommended Dosage for Pediatric Patients (over 1 year of age) The recommended total daily dose of oral cephalexin for pediatric patients is 25 to 50 mg/kg given in equally divided doses for 7 to 14 days. In the treatment of β-hemolytic streptococcal infections, duration of at least 10 days is recommended. In severe infections, a total daily dose of 50 to 100 mg/kg may be administered in equally divided doses. For the treatment of otitis media, the recommended daily dose is 75 to 100 mg/kg given in equally divided doses. See Table 1 for the dosage of Cephalexin for oral suspension by weight for pediatric patients. Table 1: Dosage by Weight of Cephalexin for Oral Suspension for Pediatric Patients *teaspoon =tsp Weight of Pediatric Patient Cephalexin for Oral Suspension (125 mg/5mL) Cephalexin for Oral Suspension (250 mg/5mL) OPTION 1 Dosage Dosage 10 kg ½ to 1 tsp * four times a day ¼ to ½ tsp four times a day 20 kg 1 to 2 tsp four times a day ½ to 1 tsp four times a day 40 kg 2 to 4 tsp four times a day 1 to 2 tsp four times a day OPTION 2 10 kg 1 to 2 tsp two times a day ½ to 1 tsp two times a day 20 kg 2 to 4 tsp two times a day 1 to 2 tsp two times a day 40 kg 2 to 4 tsp two times a day 2 to 4 tsp two times a day 2.3 Direction for Mixing cephalexin for oral susapension 125 mg/5 mL (100 mL when mixed): Prepare suspension time at dispensing. Add to the bottle a total of 69 mL of water. For ease in preparation, tap bottle to loosen powder, add the water in 2 portions, shaking well after each addition. The resulting suspension will contain cephalexin monohydrate equivalent to 125 mg cephalexin in each 5 mL (teaspoonful). 125 mg/5 mL (200 mL when mixed): Prepare suspension time at dispensing. Add to the bottle a total of 138 mL of water. For ease in preparation, tap bottle to loosen powder, add the water in 2 portions, shaking well after each addition. The resulting suspension will contain cephalexin monohydrate equivalent to 125 mg cephalexin in each 5 mL (teaspoonful). 250 mg/5 mL (100 mL when mixed): Prepare suspension time at dispensing. Add to the bottle a total of 69 mL of water. For ease in preparation, tap bottle to loosen powder, add the water in 2 portions, shaking well after each addition. The resulting suspension will contain cephalexin monohydrate equivalent to 250 mg cephalexin in each 5 mL (teaspoonful). 250 mg/5 mL (200 mL when mixed): Prepare suspension time at dispensing. Add to the bottle a total of 138 mL of water. For ease in preparation, tap bottle to loosen powder, add the water in 2 portions, shaking well after each addition. The resulting suspension will contain cephalexin monohydrate equivalent to 250 mg cephalexin in each 5 mL (teaspoonful). After mixing, the different concentrations and volumes of the suspension as described above, store in refrigerator. The suspension may be kept for 14 days without significant loss of potency. 2.4 Dosage in Adult and Pediatric Patients at Least 15 Years of Age with Renal Impairment Administer the following dosing regimens for cephalexin for oral suspension to patients with renal impairment [ see Warnings and Precautions (5.4) and Use in Specific Populations (8.6) ]. See Table 2 for the dosage in adults and pediatric patients at least 15 years of age with renal impairment. Table 2. Recommended Cephalexin Dosage for Adult Patients and Pediatric Patients (at Least 15 Years of Age) with Renal Impairment Renal function (Creatinine clearance) Dosage recommendation Greater than or equal to 60 mL/min No dosage adjustment 30 mL/min to 59 mL/min No dosage adjustment; maximum daily dose should not exceed 1 g 15 mL/min to 29 mL/min 250 mg, every 8 hours or every 12 hours 5 mL/min to 14 mL/min not yet on dialysis * 250 mg, every 24 hours 1 mL/min to 4 mL/min not yet on dialysis * 250 mg, every 48 hours or every 60 hours * There is insufficient information to make dose adjustment recommendations in patients on hemodialysis.

WARNINGS AND PRECAUTIONS Serious hypersensitivity (anaphylactic) reactions: Prior to use, inquire regarding history of hypersensitivity to beta-lactam antibacterial drugs. Discontinue the drug if signs or symptoms of an allergic reaction occur and institute supportive measures. ( 5.1 ) Clostridioides difficile -associated diarrhea (CDAD): Evaluate if diarrhea occurs. ( 5.2 ) Direct Coomb's Test Seroconversion: If anemia develops during or after cephalexin therapy, evaluate for drug-induced hemolytic anemia. ( 5.3 ) Seizure Potential : Use lower dose in patients with renal impairment. ( 5.4 ) 5.1 Hypersensitivity Reactions Allergic reactions in the form of rash, urticaria, angioedema, anaphylaxis, erythema multiforme, Stevens-Johnson syndrome, or toxic epidermal necrolysis have been reported with the use of cephalexin. Before therapy with cephalexin for oral suspension is instituted, inquire whether the patient has a history of hypersensitivity reactions to cephalexin, cephalosporins, penicillins, or other drugs. Cross-hypersensitivity among beta-lactam antibacterial drugs may occur in up to 10% of patients with a history of penicillin allergy. If an allergic reaction to cephalexin for oral suspension occurs, discontinue the drug and institute appropriate treatment. 5.2 Clostridioides difficile -Associated Diarrhea Clostridioides difficile -associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including cephalexin, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile . C. difficile produces toxins A and B, which contribute to the development of CDAD. Hypertoxin-producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has 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 may 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. 5.3 Direct Coombs’ Test Seroconversion Positive direct Coombs' tests have been reported during treatment with the cephalosporin antibacterial drugs including cephalexin. Acute intravascular hemolysis induced by cephalexin therapy has been reported. If anemia develops during or after cephalexin therapy, perform a diagnostic work-up for drug-induced hemolytic anemia, discontinue cephalexin and institute appropriate therapy. 5.4 Seizure Potential Several cephalosporins have been implicated in triggering seizures, particularly in patients with renal impairment when the dosage was not reduced. If seizures occur, discontinue cephalexin for oral suspension. Anticonvulsant therapy can be given if clinically indicated. 5.5 Prolonged Prothrombin Time Cephalosporins may be associated with prolonged prothrombin time. Those at risk include patients with renal or hepatic impairment, or poor nutritional state, as well as patients receiving a protracted course of antibacterial therapy, and patients receiving anticoagulant therapy. Monitor prothrombin time in patients at risk and manage as indicated. 5.6 Development of Drug-Resistant Bacteria Prescribing cephalexin for oral suspension in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. Prolonged use of cephalexin for oral suspension may result in the overgrowth of nonsusceptible organisms. Careful observation of the patient is essential. If superinfection occurs during therapy, appropriate measures should be taken.

CONTRAINDICATIONS Cephalexin capsules are contraindicated in patients with known hypersensitivity to cephalexin or other members of the cephalosporin class of antibacterial drugs. Patients with known hypersensitivity to cephalexin or other members of the cephalosporin class of antibacterial drugs. ( 4 )

CLINICAL PHARMACOLOGY Human Pharmacology Cephalexin is acid stable and may be given without regard to meals. It is rapidly absorbed after oral administration. Following doses of 250 mg, 500 mg, and 1 g, average peak serum levels of approximately 9, 18, and 32 µg/mL respectively were obtained at 1 hour. Measurable levels were present 6 hours after administration. Cephalexin is excreted in the urine by glomerular filtration and tubular secretion. Studies showed that over 90% of the drug was excreted unchanged in the urine within 8 hours. During this period, peak urine concentrations following the 250 mg, 500 mg, and 1g doses were approximately 1000, 2200, and 5000 µg/mL respectively. Microbiology In vitro tests demonstrate that the cephalosporins are bactericidal because of their inhibition of cell-wall synthesis. Cephalexin has been shown to be active against most strains of the following microorganisms both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section. Aerobes, Gram-positive: Staphylococcus aureus (including penicillinase-producing strains) Streptococcus pneumoniae (penicillin-susceptible strains) Streptococcus pyogenes Aerobes, Gram-negative: Escherichia coli Haemophilus influenzae Klebsiella pneumoniae Moraxella (Branhamella) catarrhalis Proteus mirabilis Note: Methicillin-resistant staphylococci and most strains of enterococci (Enterococcus faecalis [formerly Streptococcus faecalis]) are resistant to cephalosporins, including cephalexin. It is not active against most strains of Enterobacter spp., Morganella morganii, and Proteus vulgaris. It has no activity against Pseudomonas spp. or Acinetobacter calcoaceticus. Penicillin-resistant Streptococcus pneumoniae is usually cross-resistant to beta-lactam antibiotics. Susceptibility Tests Dilution techniques Quantitative methods are used to determine antimicrobial minimal inhibitory concentrations (MIC's). These MIC's provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MIC's should be determined using a standardized procedure. Standardized procedures are based on a dilution method1-3 (broth or agar) or equivalent with standardized inoculum concentrations and standardized concentrations of cephalothin powder. The MIC values should be interpreted according to the following criteria: MIC (µg/mL) Interpretation ≤8 Susceptible (S) 16 Intermediate (I) ≥32 Resistant (R) A report of "Susceptible" indicates that the pathogen is likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable. A report of "Intermediate" indicates that the result should be considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of drug can be used. This category also provides a buffer zone which prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of "Resistant" indicates that the pathogen is not likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable; other therapy should be selected. Standardized susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures. Standard cephalothin powder should provide the following MIC values: Microorganism MIC (µg/mL) E. coli ATCC 25922 4 to 16 S. aureus ATCC 29213 0.12 to 0.5 Diffusion techniques Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure2,3 requires the use of standardized inoculum concentrations. This procedure uses paper disks impregnated with 30 µg cephalothin to test the susceptibility of microorganisms to cephalexin. Reports from the laboratory providing results of the standard single-disk susceptibility test with a 30 µg cephalothin disk should be interpreted according to the following criteria: Zone Diameter (mm) Interpretation ≥18 Susceptible (S) 15 to 17 Intermediate (I) ≤14 Resistant (R) Interpretation should be as stated above for results using dilution techniques. Interpretation involves correlation of the diameter obtained in the disk test with the MIC for cephalexin. As with standard dilution techniques, diffusion methods require the use of laboratory control microorganisms that are used to control the technical aspects of the laboratory procedures. For the diffusion technique, the 30 µg cephalothin disk should provide the following zone diameters in these laboratory test quality control strains: Microorganism Zone Diameter (mm) E. coli ATCC 25922 15 to 21 S. aureus ATCC 25923 29 to 37 Close