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Cephalexin
Keflex is a semisynthetic cephalosporin antibiotic intended for oral administration. It is 7-(D-a-Amino-a-phenylacetamido)- 3-methyl-3-cephem-4-carboxylic acid monohydrate. Cephalexin has the molecular formula C16H17N3O4S·H2O and the molecular weight is 365.41. 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 Pulvule contains cephalexin monohydrate equivalent to 250 mg (720 mcmol) or 500 mg (1,439 mcmol) of cephalexin. The Pulvules also contain cellulose, Dy & C Yellow No. 10, F Dy & C Blue No. 1, F Dy & C Yellow No. 6, gelatin, magnesium stearate, silicone, titanium dioxide, and other inactive ingredients. Each capsule manufactured by Mylan contains cephalexin monohydrate equivalent to 250 mg (720 mcmol) or 500 mg (1,439 mcmol) of cephalexin. The capsules also contain cellulose, F Dy & C Blue No. 1, gelatin, magnesium stearate, silicone, titanium dioxide, and other inactive ingredients. After mixing, each 5 ml of Keflex, for oral suspension, will contain cephalexin monohydrate equivalent to 125 mg (360 mcmol) or 250 mg (720 mcmol) of cephalexin. The suspensions also contain flavors, methylcellulose, silicone, sodium lauryl sulfate, and sucrose. The 125-mg suspension contains F Dy & C Red No. 40, and the 250-mg suspension contains F Dy & C Yellow No. 6. Each capsule manufactured by Biocraft contains cephalexin monohydrate equivalent to 250 mg (720 mcmol) or 500 mg (1,439 mcmol) of cephalexin. Inactive ingredients: magnesium stearate, silicone dioxide and may contain talc. Capsul shell and print constituents: black iron oxide, Dy & C Yellow #10 aluminium lake, FD & C blue #1 aluminium lake, FD & C Blue #2 aluminium lake, FD & C Red #40 aluminium lake, gelatin, pharmaceutical glaze modified in SD-45, silcon dioxide or carbomethylcellulose sodium, sodium lauryl sulfate, titanium dioxide and may contian propylene glyceryl. In addition, the 250 mg capsule shell contains yellow iron oxide. Each tablet manufactured by Biocraft contains cephalexin monohydrate equivalent to 250 mg (720 mcmol) or 500 mg (1,439 mcmol) of cephalexin. Inactive ingredients: hydroxypropyl methylcellulose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polysorbate 90, sodium starch glycolate and titanium dioxide.
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 mcg/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 1 g doses were approximately 1000, 2200, and 5000 mcg/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 INDICATIONS AND USAGE.
Aerobes, Gram-positive:
Aerobes, Gram-negative: 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. Susceptibility Testing Diffusion Techniques: Quantitative methods that require measurement of zone diameters provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standard procedure1 that has been recommended for use with disks to test the susceptibility of microorganisms to cephalexin, uses the 30-mcg cephalothin disk. Interpretation involves correlation of the diameter obtained in the disk test with the minimal inhibitory concentration (MIC) for cephalexin. Reports from the laboratory providing results of the standard single-disk susceptibility test with a 30-mcg cephalothin disk should be interpreted according to the criteria found in TABLE 1.
Measurement of MIC or MBC and achieved antimicrobial compound concentrations may be appropriate to guide therapy in some infections. Standardized susceptibility test procedures require the use of laboratory control microorganisms. The 30-mcg cephalothin disk should provide the zone diameters in these laboratory test quality control strains (see TABLE 2).
As with standard diffusion techniques, dilution methods require the use of laboratory control microorganisms. Standard cephalothin powder should provide the MIC values seen in TABLE 4.
Cephalexin is indicated for the treatment of the following infections when caused by susceptible strains of the designated microorganisms: Respiratory tract infections caused by S. pneumoniae and S. 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 S. pneumoniae, H. influenzae, staphylococci, streptococci, and M. catarrhalis Skin and skin structure infections caused by staphylococci and/or streptococci Bone infections caused by staphylococci and/or P. mirabilis Genitourinary tract infections, including acute prostatitis, caused byE. coli, P. mirabilis, and K. pneumoniae Note: Culture and susceptibility tests should be initiated prior to and during therapy. Renal function studies should be performed when indicated.
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 (see TABLE 5).
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 b-hemolytic streptococcal infections, a therapeutic dosage of cephalexin should be administered for at least 10 days. HOW SUPPLIED Oral Suspension: After mixing, store in refreigerator. May be kept for 14 days without significant loss of potency. Shake well before using. Keep tightly closed. Pulvules: The 250 mg Pulvules are a white powder filled into size 2 Para0-Posilok Caps (opaque white and opaque light green) that are imprinted with "Dista" and identity code "H69" on the green cap, and Keflex 250 on the white body in edible black ink. The 500 mg Pulvules are a white powder filled into an elongated, size 0 Para-Posilok Caps (opaque light green and opaque dark green) that are imprinted with "Dista" and identity code "H71" on the light green cap, and Keflex 500 on the dark green body in edible black ink. Storage: Store at controlled room temperature, 15° to 30°C (59° to 86°F).
1. National Committee for Clinical Laboratory Standards: Performance standards for antimicrobial disk susceptibility tests¾5th ed. Approved Standard NCCLS Document M2-A5, Vol 13, No 24, NCCLS, Villanova, PA, 1993. 2. National Committee for Clinical Laboratory Standards: Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically¾3rd ed. Approved Standard NCCLS Document M7-A3, Vol 13, No 25, NCCLS, Villanova, PA, 1993.
Gastrointestinal: Symptoms of pseudomembranous colitis may appear either during or after antibiotic treatment. 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, and slight elevations in AST and ALT have been reported.
No information provided.
BEFORE CEPHALEXIN THERAPY IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE CONCERNING PREVIOUS HYPERSENSITIVITY REACTIONS TO CEPHALOSPORINS AND PENICILLIN. CEPHALOSPORIN C DERIVATIVES SHOULD BE GIVEN CAUTIOUSLY TO PENICILLIN-SENSITIVE PATIENTS. SERIOUS ACUTE HYPERSENSITIVITY REACTIONS MAY REQUIRE EPINEPHRINE AND OTHER EMERGENCY MEASURES. There is some clinical and laboratory evidence of partial cross-allergenicity of the penicillins and the cephalosporins. Patients have been reported to have had severe reactions (including anaphylaxis) to both drugs. Any patient who has demonstrated some form of allergy, particularly to drugs, should receive antibiotics cautiously. No exception should be made with regard to cephalexin. Pseudomembranous colitis has been reported with nearly all antibacterial agents, including cephalexin, and may range from mild to life threatening. Therefore, it is important to consider this diagnosis in patients with diarrhea subsequent to the administration of antibacterial agents. Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin produced by Clostridium difficile is a primary cause of antibiotic-associated colitis. After the diagnosis of pseudomembranous colitis has been established, appropriate therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation, and treatment with an antibacterial drug clinically effective against Clostridium difficile colitis.
General Patients should be followed carefully so that any side effects or unusual manifestations of drug idiosyncrasy may be detected. If an allergic reaction to cephalexin occurs, the drug should be discontinued and the patient treated with the usual agents (e.g., epinephrine or other pressor amines, antihistamines, or corticosteroids). Prolonged use of cephalexin 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. Positive direct Coombs' tests have been reported during treatment with the cephalosporin antibiotics. In hematologic studies or in transfusion cross-matching procedures when antiglobulin tests are performed on the minor side or in Coombs' testing of newborns whose mothers have received cephalosporin antibiotics before parturition, it should be recognized that a positive Coombs' test may be due to the drug. Cephalexin should be administered with caution in the presence of markedly impaired renal function. Under such conditions, careful clinical observation and laboratory studies should be made because safe dosage may be lower than that usually recommended. Indicated surgical procedures should be performed in conjunction with antibiotic therapy. As a result of administration of cephalexin, a false-positive reaction for glucose in the urine may occur. This has been observed with Benedict's and Fehling's solutions and also with Clinitest tablets. As with other b-lactams, the renal excretion of cephalexin is inhibited by probenecid. Broad-spectrum antibiotics should be prescribed with caution in individuals with a history of gastrointestinal disease, particularly colitis. Pregnancy Category B The daily oral administration of cephalexin to rats in doses of 250 or 500 mg/kg prior to and during pregnancy, or to rats and mice during the period of organogenesis only, had no adverse effect on fertility, fetal viability, fetal weight, or litter size. Note that the safety of cephalexin during pregnancy in humans has not been established. Cephalexin showed no enhanced toxicity in weanling and newborn rats as compared with adult animals. Nevertheless, because the studies in humans cannot rule out the possibility of harm, cephalexin should be used during pregnancy only if clearly needed. Nursing Mothers The excretion of cephalexin in the milk increased up to 4 hours after a 500-mg dose; the drug reached a maximum level of 4 mcg/ml, then decreased gradually, and had disappeared 8 hours after administration. Caution should be exercised when cephalexin is administered to a nursing woman.
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