CEPHALEXIN

Cephalexin tablets, USP contain the active ingredient cephalexin, which is a semisynthetic cephalosporin antibiotic intended for oral administration. It is 7-(D-α-amino-α-phenylacetamido)-3-methyl-3-cephem-4-carboxylic acid, monohydrate. Cephalexin monohydrate, USP has the molecular formula C 16 H 17 N 3 O 4 S•H 2 O and the molecular weight is 365.40. Cephalexin monohydrate, USP has the following structural formula: The nucleus of cephalexin is related to that of other cephalosporin antibiotics. The compound is a zwitterion; i.e., the molecule contains both a basic and an acidic group. The isoelectric point of cephalexin in water is approximately 4.5 to 5. The crystalline form of cephalexin which is available as a monohydrate. It is a white to almost white powder with granules. Slightly soluble in water, practically insoluble in alcohol, chloroform and in ether. It dissolves in dilute solutions of acids and alkali hydroxides. The cephalosporins differ from penicillins in the structure of the bicyclic ring system. Cephalexin has a D-phenylglycyl group as substituent at the 7-amino position and an unsubstituted methyl group at the 3-position. Each film-coated tablet contains cephalexin monohydrate USP equivalent to 250 mg or 500 mg of cephalexin. The tablet also contains colloidal silicon dioxide, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polysorbate 80, sodium starch glycolate, and titanium dioxide. FDA approved dissolution test specifications differ from USP. str

Cephalexin tablets are indicated for the treatment of the following infections when caused by susceptible strains of the designated microorganisms: Respiratory tract infections caused by susceptible isolates of Streptococcus pneumoniae and Streptococcus pyogenes Otitis media due to susceptible isolates of Streptococcu pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Streptococcus pyogenes , and Moraxella Catarrhalis. Skin and skin structure infections caused by susceptible isolates of the following Gram-positive bacteria: Staphylococcus aureus , and Streptococcus pyogenes . Bone infections caused by susceptible isolates of Staphylococcus aureus and Proteus Mirabilis. Genitourinary tract infections, including acute prostatitis, caused by susceptible isolates of Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniare. To reduce the development of drug-resistant bacteria and maintain the effectiveness of cephalexin tablets and other antibacterial drugs, cephalexin tablets should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they 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.

Cephalexin tablets are administered orally. Adults and Pediatric 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. Treatment is administered for 7 to 14 days. For more severe infections larger doses of oral cephalexin may be needed, up to 4 grams in two to four equally divided doses. Pediatric Patients (over 1 year of age) The recommended total daily dose of oral cephalexin for pediatric patients is 25 to 50 mg/kg 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. In the treatment of otitis media, the recommended daily dose is 75 to 100 mg/kg/day in equally divided doses. Dosage adjustments in Adults and Pediatric Patients at Least 15 years of Age with Renal Impairment Administer the following dosing regimens for cephalexin tablets to patients with renal impairment (see PRECAUTIONS ). Table 1. Recommended Dose Regimen for Patients with Renal Impairment 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.

Cephalexin tablets are contraindicated in patients with known allergy to cephalexin or other members of the cephalosporin class of antibacterial drugs.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The most frequent adverse reaction was diarrhea. Nausea and vomiting, dyspepsia, gastritis, and abdominal pain have also occurred. As with penicillins and other cephalosporins, transient hepatitis and cholestatic jaundice have been reported. Other reactions have included hypersensitivity reactions, genital and anal pruritus, genital candidiasis, vaginitis and vaginal discharge, dizziness, fatigue, headache, agitation, confusion, hallucinations, arthralgia, arthritis, and joint disorder. Reversible interstitial nephritis has been reported. Eosinophilia, neutropenia, thrombocytopenia, hemolytic anemia, and slight elevations in aspartate transaminase (AST) and alanine transaminase (ALT) have been reported. In addition to the adverse reactions listed above that have been observed in patients treated with cephalexin, the following adverse reactions and other altered laboratory tests have been reported for cephalosporin class antibacterial drugs: Other Adverse Reactions : Fever, colitis, aplastic anemia, hemorrhage, renal dysfunction, and toxic nephropathy. Altered Laboratory Tests : Prolonged prothrombin time, increased blood urea nitrogen (BUN), increased creatinine, elevated alkaline phosphatase, elevated bilirubin, elevated lactate dehydrogenase (LDH), pancytopenia, leukopenia, and agranulocytosis.

Metformin: Administration of cephalexin 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 and metformin (see CLINICAL PHARMACOLOGY ). Probenecid: The renal excretion of cephalexin is inhibited by probenecid. Coadministration of probenecid with cephalexin is not recommended. Drug/laboratory Test Interactions: A false-positive reaction may occur when testing for the presence of glucose in the urine using Benedict's solution or Fehling's solutions.