Cephalexin 250 MG Oral Capsule
Generic Name: CEPHALEXIN
Brand Name: Cephalexin
- Substance Name(s):
7 • Metformin: increased metformin concentrations.
Monitor for hypoglycemia.
(7.1) • Probenecid- The renal excretion of cephalexin capsules is inhibited by probenecid.
Co-administration of probenecid with cephalexin capsules is not recommended.
(7.2) • Administration of cephalexin capsules may result in a false-positive reaction for glucose in the urine (7.3).
7.1 Metformin Administration of cephalexin capsules with metformin results in increased plasma metformin concentrations and decreased renal clearance of metformin.
Careful patient monitoring and dose adjustment of metformin is recommended in patients concomitantly taking cephalexin capsules and metformin [ see Clinical Pharmacology (12.3) ] .
7.2 Probenecid The renal excretion of cephalexin capsules is inhibited by probenecid.
Co-administration of probenecid with cephalexin capsules is not recommended.
7.3 Interaction with Laboratory or Diagnostic Testing A false-positive reaction may occur when testing for the presence of glucose in the urine using Benedict’s solution or Fehling’s solution.
10 Symptoms of oral overdose may include nausea, vomiting, epigastric distress, diarrhea, and hematuria.
In the event of an overdose, institute general supportive measures.
Forced diuresis, peritoneal dialysis, hemodialysis, or charcoal hemoperfusion have not been established as beneficial for an overdose of cephalexin.
11 Cephalexin Capsules, USP are a semisynthetic cephalosporin antibacterial drug intended for oral administration.
It is 7-(D-α-Amino-α-phenylacetamido)-3-methyl-3-cephem-4-carboxylic acid monohydrate.
Cephalexin has the molecular formula C16H17N3O4S∙H2O and the molecular weight is 365.41.
Cephalexin has the following structural formula: Each capsule contains cephalexin monohydrate equivalent to 250 mg or 500 mg of cephalexin.
The capsules also contain colloidal silicon dioxide, D&C Yellow No.
10, FD&C Blue No.
2, gelatin, magnesium stearate, sodium starch glycolate, and titanium dioxide.
16 /STORAGE AND HANDLING Cephalexin Capsules, USP are supplied as follows: • 250 mg Capsules, bottles of 100 with child-resistant closure NDC 0143-9898-01 • 250 mg Capsules, bottles of 500 NDC 0143-9898-05 • 500 mg Capsules, bottles of 100 with child-resistant closure NDC 0143-9897-01 • 500 mg Capsules, bottles of 500 NDC 0143-9897-05 Cephalexin Capsules, USP should be stored at 20º to 25ºC (68º to 77ºF) [see USP Controlled Room Temperature].
Dispense in a tight, light-resistant container using a child resistant closure.
8.5 Geriatric Use Of the 701 subjects in 3 published clinical studies of cephalexin, 433 (62%) were 65 and over.
No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients.
This drug is substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function.
Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection [ see Warnings and Precautions (5.4) ].
DOSAGE FORMS AND STRENGTHS
3 Cephalexin Capsules USP, 250mg: a white to off-white powder filled into size 2 capsules (white opaque and dark green opaque) that are imprinted with identity code “J1” on the dark green opaque cap, and “J1” on the white opaque body in edible black ink.
Cephalexin Capsules USP, 500mg: a white to off-white powder filled into size 0 capsules (light green opaque and dark green opaque) that are imprinted with identity code “J2” on the dark green opaque cap, and “J2” on the light green opaque body in edible black ink.
Capsules: 250 mg, 500 mg (3)
MECHANISM OF ACTION
12.1 Mechanism of Action Cephalexin is a cephalosporin antibacterial drug [see Microbiology (12.4)] .
INDICATIONS AND USAGE
1 Cephalexin capsules are a cephalosporin antibacterial drug indicated for the treatment of the following infections caused by susceptible isolates of designated bacteria: • 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 capsules and other antibacterial drugs, cephalexin capsules 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 capsules are indicated for the treatment of respiratory tract infections caused by susceptible isolates of Streptococcus pneumoniae and Streptococcus pyogenes.
1.2 Otitis Media Cephalexin capsules are indicated for the treatment of otitis media caused by susceptible isolates of Streptococcus pneumoniae , Haemophilus influenzae , Staphylococcus aureus , Streptococcus pyogenes , and Moraxella catarrhalis.
1.3 Skin and Skin Structure Infections Cephalexin capsules are 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 .
1.4 Bone Infections Cephalexin capsules are indicated for the treatment of bone infections caused by susceptible isolates of Staphylococcus aureus and Proteus mirabilis.
1.5 Genitourinary Tract Infections Cephalexin capsules are indicated for the treatment of genitourinary tract infections, including acute prostatitis, caused by susceptible isolates of Escherichia coli , Proteus mirabilis , and Klebsiella pneumoniae .
1.6 Usage To reduce the development of drug-resistant bacteria and maintain the effectiveness of cephalexin capsules and other antibacterial drugs, cephalexin capsules 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.
8.4 Pediatric Use The safety and effectiveness of cephalexin capsules in pediatric patients was established in clinical trials for the dosages described in the dosage and administration section [ see Dosage and Administration (2.2) ] .
8.1 Pregnancy Risk Summary Available data from published epidemiologic studies and pharmacovigilance case reports over several decades with cephalosporin use, including cephalexin capsules use in pregnant women have not established drug-associated risks of major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Data).
Animal reproduction studies with mice and rats using oral doses of cephalexin that are 0.6- and 1.2-times the maximum recommended human dose (MRHD) based on body surface area during organogenesis revealed no evidence of harm to the fetus (see Data).
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
In the U.S.
general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Data Human Data While available studies cannot definitively establish the absence of risk, published data from epidemiologic studies and postmarketing case reports over several decades have not identified a consistent association with cephalosporin use, including cephalexin capsules, during pregnancy, and major birth defects, miscarriage, or other adverse maternal or fetal outcomes.
Available studies have methodologic limitations, including small sample size, retrospective data collection, and inconsistent comparator groups.
Animal Data In animal reproduction studies, pregnant mice and rats administered oral cephalexin doses of 250 or 500 mg/kg/day (approximately 0.6 and 1.2 times the MRHD) based on body surface area, respectively during the period of organogenesis showed no adverse effects on embryofetal development.
In a pre-and post-natal developmental toxicity study, pregnant rats that received oral doses of 250 or 500 mg/kg/day of cephalexin from Day 15 of pregnancy to litter Day 21 showed no adverse effects on parturition, litter size, or growth of offspring.
WARNING AND CAUTIONS
5 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) • Clostridium 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 capsules.
Before therapy with cephalexin capsules 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 capsules occurs, discontinue the drug and institute appropriate treatment.
5.2 Clostridium difficile -Associated Diarrhea Clostridium difficile – associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including cephalexin capsules, 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 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 capsules.
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 capsules 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 capsules 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.
DOSAGE AND ADMINISTRATION
2 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 to14 days depending on the infection type and severity.
(2) • Dosage adjustment is required in patients with severe and end stage renal disease (ESRD) defined as creatinine clearance below 30 mL/min.
(2.3) 2.1 Adults and Pediatric Patients at Least 15 Years of Age The usual dose of oral cephalexin capsules 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 capsules may be needed, up to 4 grams daily in two to four equally divided doses.
2.2 Pediatric Patients (over 1 year of age) The recommended total daily dose of oral cephalexin capsules 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.
2.3 Dosage Adjustments in Adult and Pediatric Patients at Least 15 Years of Age with Renal Impairment Administer the following dosing regimens for cephalexin capsules to patients with renal impairment [see Warnings and Precautions (5.4) and Use in Specific Populations (8.6) ].
Recommended Dose Regimen for Patients with Renal Impairmen t Renal function Dose regimen recommendation Creatinine clearance ≥ 60 mL/min No dose adjustment Creatinine clearance 30 to 59 mL/min No dose adjustment; maximum daily dose should not exceed 1 g Creatinine clearance 15 to 29 mL/min 250 mg, every 8 hours or every 12 hours Creatinine clearance 5 to 14 mL/min not yet on dialysis* 250 mg, every 24 hours Creatinine clearance 1 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.