CEPHALEXIN

Cephalexin, USP 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 has the molecular formula C 16 H 17 N 3 O 4 S • H 2 O and the molecular weight is 365.41. Cephalexin 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 is a monohydrate. It is a white crystalline solid having a bitter taste. Solubility in water is low at room temperature; 1 or 2 mg/mL may be dissolved readily, but higher concentrations are obtained with increasing difficulty. 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 capsule contains cephalexin USP equivalent to 250 mg or 500 mg of anhydrous cephalexin. The capsules also contain the following inactive ingredients D&C Yellow 10, FD&C Blue 1, FD&C Green 3, FD&C Yellow 6, ferric oxide black, gelatin, magnesium stearate, microcrystalline cellulose, potassium hydroxide, propylene glycol, shellac and titanium dioxide. Molecular Structure

Cephalexin Capsules USP are indicated for the treatment of the following infections when caused by susceptible strains of the designated microorganisms: Respiratory tract infections caused by Streptococcus pneumoniae and Streptococcus pyogenes . (Penicillin is the usual drug of choice in the treatment and prevention of streptococcal infections, including the prophylaxis of rheumatic fever. Cephalexin is generally effective in the eradication of streptococci from the nasopharynx; however, substantial data establishing the efficacy of cephalexin in the subsequent prevention of rheumatic fever are not available at present.) Otitis media due to Streptococcus pneumoniae , Haemophilus influenzae , Staphylococcus aureus , Streptococcus pyogenes , and Moraxella catarrhalis . Skin and skin structure infections caused by Staphylococcus aureus and/or Streptococcus pyogenes . Bone infections caused by Staphylococcus aureus and/or Proteus mirabilis . Genitourinary tract infections, including acute prostatitis, caused by Escherichia coli , Proteus mirabilis , and Klebsiella pneumoniae. Note – Culture and susceptibility tests should be initiated prior to and during therapy. Renal function studies should be performed when indicated. 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 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 is administered orally. Adults: The adult dosage ranges from 1 to 4 g daily in divided doses. The usual adult dose is 250 mg every 6 hours. For the following infections, a dosage of 500 mg may be administered every 12 hours: streptococcal pharyngitis, skin and skin structure infections, and uncomplicated cystitis in patients over 15 years of age. Cystitis therapy should be continued for 7 to 14 days. For more severe infections or those caused by less susceptible organisms, larger doses may be needed. If daily doses of Cephalexin greater than 4 g are required, parenteral cephalosporins, in appropriate doses, should be considered. Pediatric Patients: The usual recommended daily dosage for pediatric patients is 25 to 50 mg/kg in divided doses. For streptococcal pharyngitis in patients over 1 year of age and for skin and skin structure infections, the total daily dose may be divided and administered every 12 hours. In severe infections, the dosage may be doubled. In the therapy of otitis media, clinical studies have shown that a dosage of 75 to 100 mg/kg/day in 4 divided doses is required. In the treatment of ß-hemolytic streptococcal infections, a therapeutic dosage of cephalexin should be administered for at least 10 days.

Cephalexin is contraindicated in patients with known allergy to the cephalosporin group of antibiotics.

Gastrointestinal: Onset of pseudomembranous colitis may occur during or after antibacterial treatment. (See WARNINGS ) Nausea and vomiting have been reported rarely. The most frequent side effect has been diarrhea. It was very rarely severe enough to warrant cessation of therapy. Dyspepsia, gastritis, and abdominal pain have also occurred. As with some penicillins and some other cephalosporins, transient hepatitis and cholestatic jaundice have been reported rarely. Hypersensitivity: Allergic reactions in the form of rash, urticaria, angioedema, and, rarely, erythema multiforme, Stevens-Johnson syndrome, or toxic epidermal necrolysis have been observed. These reactions usually subsided upon discontinuation of the drug. In some of these reactions, supportive therapy may be necessary. Anaphylaxis has also been reported. Other reactions have included genital and anal pruritus, genital moniliasis, vaginitis and vaginal discharge, dizziness, fatigue, headache, agitation, confusion, hallucinations, arthralgia, arthritis, and joint disorder. Reversible interstitial nephritis has been reported rarely. Eosinophilia, neutropenia, thrombocytopenia, hemolytic anemia and slight elevations in AST and 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 altered laboratory tests have been reported for cephalosporin class antibiotics: Adverse Reactions: Fever, colitis, aplastic anemia, hemorrhage, renal dysfunction, and toxic nephropathy. Several cephalosporins have been implicated in triggering seizures, particularly in patients with renal impairment when the dosage was not reduced (see INDICATIONS AND USAGE and PRECAUTIONS, General ). If seizures associated with drug therapy should occur, the drug should be discontinued. Anticonvulsant therapy can be given if clinically indicated. Altered Laboratory Tests: Prolonged prothrombin time, increased BUN, increased creatinine, elevated alkaline phosphatase, elevated bilirubin, elevated LDH, pancytopenia, leukopenia, and agranulocytosis.

Metformin: In healthy subjects given single 500 mg doses of cephalexin and metformin, plasma metformin mean C max and AUC increased by an average of 34 % and 24 %, respectively, and metformin mean renal clearance decreased by 14 %. No information is available about the interaction of cephalexin and metformin following multiple doses of either drug. Although not observed in this study, adverse effects could potentially arise from co-administration of cephalexin and metformin by inhibition of tubular secretion via organic cationic transporter systems. Accordingly, careful patient monitoring and dose adjustment of metformin is recommended in patients concomitantly taking cephalexin and metformin. Probenicid: As with other ß-lactams, the renal excretion of cephalexin is inhibited by probenecid.