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Keftab is a semisynthetic cephalosporin antibiotic intended for oral administration. Chemically, it is designated 7-(D-2-Amino-2-phenylacetamido)-3-methyl-3-cephem-4-carboxylic acid hydrochloride monohydrate, and the chemical formula is C 16 H 17 N 3 O 4 S ·HCl · H 2 O. The molecular weight is 401.87, and it has the following structural formula:
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The nucleus of cephalexin hydrochloride is related to that of other cephalosporin antibiotics. The compound is the hydrochloride salt of cephalexin. The isoelectric point of cephalexin in water is approximately 4.5 to 5.
Cephalexin hydrochloride is in crystalline form and is a monohydrate. It is a white crystalline solid having a bitter taste. Solubility in water is high at room temperature; greater than 10 mg/mL may be dissolved readily.
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 tablet contains cephalexin hydrochloride equivalent to 500 mg (1.439 µmol) cephalexin. The tablets also contain D & C Yellow No. 10, F D & C Blue No. 1, F D & C Red No. 40, magnesium stearate, silicon dioxide, stearic acid, sucrose, titanium dioxide, and other inactive ingredients.
Human Pharmacology --Keftab is acid stable and may be given without regard to meals. It is rapidly absorbed after oral administration. Following doses of 250 mg and 500 mg, average peak serum levels of approximately 9 and 18 µg/mL respectively were obtained at 1 hour and declined to 1.6 and 3.4 µg/mL respectively at 3 hours. Measurable levels were present 6 hours after administration. Cephalexin is excreted in the urine by glomerular filtration and tubular secretion. Studies showed that approximately 70% of the drug was excreted unchanged in the urine within 12 hours. During the first 6 hours, average urine concentrations following the 250-mg and 500-mg doses were approximately 200 µg/mL (range, 54 to 663) and 500 µg/mL (range, 137 to 1,306) respectively. The average serum half-life is 1.1 hours.
Microbiology --In vitro tests demonstrate that the cephalosporins are bactericidal because of their inhibition of cell-wall synthesis. Keftab is active against the following organisms in vitro:
(beta)-hemolytic streptococci
Staphylococcus aureus , including penicillinase-producing strains
Streptococcus pneumoniae
Escherichia coli
Proteus mirabilis
Klebsiella spp.
Haemophilus influenzae
Moraxella (Branhamella) catarrhalis
Note --Most strains of enterococci ( Enterococcus faecalis [formerly Streptococcus faecalis ]) and a few strains of staphylococci are resistant to Keftab. When tested by in vitro methods, staphylococci exhibit cross-resistance between Keftab and methicillin-type antibiotics. Keftab is not active against most strains of Enterobacter spp., Morganella morganii (formerly Proteus morganii ), Serratia spp., and Proteus vulgaris . It has no activity against Pseudomonas or Acinetobacter spp.
Disk Susceptibility Tests --Quantitative methods that require measurement of zone diameters give the most precise estimates of antibiotic susceptibility. One such procedure 1 has been recommended for use with cephalosporin class (cephalothin) disks for testing susceptibility to cephalexin. The currently accepted zone diameter interpretation for the cephalothin disks' is appropriate for determining susceptibility to cephalexin. Interpretations correlate zone diameters of the disk test with MIC values for cephalexin. With this procedure, a report from the laboratory of "resistant" indicates a zone diameter of 14 mm or less and suggests that the infecting organism is not likely to respond to therapy. A report of "susceptibility" indicates a zone diameter of 18 mm or greater. A report of "intermediate susceptibility" indicates zone diameters between 15 and 17 mm and suggests that the organism would be susceptible if the infection is confined to the urine, in which high antibiotic levels can be obtained, or if high dosage is used in other types of infection.
Standardized procedures require use of control organisms. 1 The 30-µg cephalothin disk should give zone diameters between 18 and 23 mm and 25 and 37 mm for the reference strains E. coli ATCC 25922 and S. aureus ATCC 25923 respectively.
Keftab 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 group A (beta)-hemolytic streptococci (Penicillin is the usual drug of choice in the treatment and prevention of streptococcal infections, including the prophylaxis of rheumatic fever. Keftab is generally effective in the eradication of streptococci from the nasopharynx; however, substantial data establishing the efficacy of Keftab in the subsequent prevention of rheumatic fever are not available at present.)
Skin and skin structure infections caused by S. aureus and/or (beta)-hemolytic streptococci.
Bone infections caused by S. aureus and/or P. mirabilis .
Genitourinary tract infections, including acute prostatitis, caused by E. coli, P. mirabilis, and Klebsiella spp.
Note --Culture and susceptibility tests should be initiated prior to and during therapy. Renal function studies should be performed when indicated.
Keftab is contraindicated in patients with known allergy to the cephalosporin group of antibiotics.
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 Keftab.
Pseudomembranous colitis has been reported with virtually all broad-spectrum antibiotics (including macrolides, semisynthetic penicillins, and cephalosporins); therefore, it is important to consider its diagnosis in patients who develop diarrhea in association with the use of antibiotics. Such colitis may range in severity from mild to life threatening.
Treatment with broad-spectrum antibiotics 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.
Mild cases of pseudomembranous colitis usually respond to drug discontinuance alone. In moderate to severe cases, management should include sigmoidoscopy, appropriate bacteriologic studies, and fluid, electrolyte, and protein supplementation. When the colitis does not improve after the drug has been discontinued or when it is severe, treatment with an oral antibacterial drug effective against C. difficile is recommended. Other causes of colitis should be ruled out.
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 Keftab occurs, the drug should be discontinued and the patient treated with the usual agents (eg, epinephrine or other pressor amines, antihistamines, or corticosteroids).
Prolonged use of Keftab 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.
Keftab 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.
As a result of administration of Keftab, a false-positive reaction for glucose in the urine may occur. This has been observed with Benedict' and Fehling' solutions and also with Clinitest® tablets.
Broad-spectrum antibiotics should be prescribed with caution in individuals with a history of gastrointestinal disease, particularly colitis.
Pregnancy -- Pregnancy Category B --Reproduction studies have been performed on rats in doses of 250 or 500 mg/kg/day and have revealed no evidence of impaired fertility or harm to the fetus due to cephalexin. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug 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 µg/mL, then decreased gradually, and had disappeared 8 hours after administration. A decision should be considered to discontinue nursing temporarily during therapy with Keftab.
Pediatric Use --Safety and effectiveness in pediatric patients have not been established.
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. Abdominal pain, gastritis, and dyspepsia 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, slight elevations in aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and elevated creatinine and BUN have been reported.
In addition to the adverse reactions listed above that have been observed in patients treated with Keftab, the following adverse reactions and altered laboratory tests have been reported for cephalosporin class antibiotics:
Adverse Reactions --Allergic reactions, including fever, colitis, renal dysfunction, toxic nephropathy, and hepatic dysfunction, including cholestasis.
Several cephalosporins have been implicated in triggering seizures, particularly in patients with renal impairment when the dosage was not reduced ( see 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 --Increased prothrombin time, increased alkaline phosphatase, and leukopenia.
Signs and Symptoms --Symptoms of oral overdose may include nausea, vomiting, epigastric distress, diarrhea, and hematuria. If other symptoms are present, it is probably secondary to an underlying disease state, an allergic reaction, or toxicity due to ingestion of a second medication.
Treatment --To obtain up-to-date information about the treatment of overdose, a good resource is your certified Regional Poison Control Center. Telephone numbers of certified poison control centers are listed in the Physicians' Desk Reference (PDR) . In managing overdosage, consider the possibility of multiple drug overdoses, interaction among drugs, and unusual drug kinetics in your patient.
Unless 5 to 10 times the normal dose of cephalexin has been ingested, gastrointestinal decontamination should not be necessary.
Protect the patient' airway and support ventilation and perfusion. Meticulously monitor and maintain, within acceptable limits, the patient' vital signs, blood gases, serum electrolytes, etc. Absorption of drugs from the gastrointestinal tract may be decreased by giving activated charcoal, which, in many cases, is more effective than emesis or lavage; consider charcoal instead of or in addition to gastric emptying. Repeated doses of charcoal over time may hasten elimination of some drugs that have been absorbed. Safeguard the patient' airway when employing gastric emptying or charcoal.
Forced diuresis, peritoneal dialysis, hemodialysis, or charcoal hemoperfusion have not been established as beneficial for an overdose of cephalexin; however, it should be extremely unlikely that one of these procedures would be indicated.
The oral median lethal dose of cephalexin in rats is 5,000 mg/kg.
Keftab is administered orally.
The adult dosage ranges from 1 to 4 g daily in divided doses. 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. Cystitis therapy should be continued for 7 to 14 days. For other infections, the usual dosing is every 6 hours. For more severe infections or those caused by less susceptible organisms, larger doses may be needed. If daily doses of Keftab greater than 4 g are required, parenteral cephalosporins, in appropriate doses, should be considered.
Tablets (elliptical-shaped):
500 mg* (dark-green) (UC5395)--(100s) NDC 64455-034-01
Store at controlled room temperature, 59° to 86°F (15° to 30°C).
*Equivalent to cephalexinCAUTION--Federal (USA) law prohibits dispensing without prescription.
Literature revised Oct. 1, 1997
PV 2061 UCP
KEF010B0997
1. 21 CFR 460.1 Federal Register 1987; 838-842.
DJ Pharma, Inc.
Manufactured by
Eli Lilly and Company
Indianapolis, IN, USA 46285
DJ Pharma Inc.
San Diego, CA 92130
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