Generic Name: Cephalexin (multiple manufacturers)
Common Brand Name: Keflex (MiddleBrook Pharmaceuticals – U.S.)
Popularity: Seventeenth most commonly prescribed drug between 2002-2006 (U.S.)
Class: First generation cephalosporin antibiotic
Treatment Uses — For treatment of bacterial infections including group A beta-hemolytic Streptococcus, Staphylococcus, Klebsiella pneumoniae, E. coli, Proteus mirabilis and Shigella. Cephalexin is primarily used in susceptible skin and soft tissue infections, lower respiratory tract infections, bone (osteomyelitis) and joint infections, strep throat (streptococcal pharyngitis), ear infections (otitis media), and urinary tract infections (UTIs). Can be used as prophylaxis against bacterial endocarditis in high risk surgical procedures or dental patients allergic to penicillin, for who pretreatment with antibiotics is indicated. At least one study, however, found cephalexin ineffective for dental prophylaxis. Has been effective in treatment of both acute and chronic sinus infections (sinusitis). Cephalexin has been effective for treatment of infections associated with diverticulitis and for prevention of UTI following prostatectomy (prostate removal). Cephalexin has not been effective for long-term prevention of respiratory tract infections in cystic fibrosis patients. It has also not been effective for treatment of Lyme disease or for prevention or treatment of peritonitis in patients undergoing continuous ambulatory peritoneal dialysis (CAPD).
Antibiotics fall into three major classes according to their mechanism of action: cell walls, protein synthesis, or nucleic acid synthesis. Cell wall agents attack bacterial cell walls. Protein synthesis and nucleic acid agents inhibit the ability of bacteria to synthesize these important components. Cephalexin is a cell wall agent.
Prescribing antibiotics is one of the most challenging aspects of practicing medicine. Tailoring antibiotic use to the precise organism(s) causing infection is the gold standard for treatment, but is a feat easier said than done. Today, preliminary laboratory identification of an organism takes at least 24 hours, and a determination of which antibiotics an organism is sensitive to takes at minimum another 24 hours. While some “on the spot” diagnostic tests are available, their sensitivity and specificity vary considerably. Most antibiotic prescribing is done empirically based on symptoms, current knowledge of the usual community bugs and local antibiotic resistance patterns. For serious infections, initial antibiotic therapy must cover all likely infective organisms that might be present, using broad-spectrum antibiotics. This shotgun approach can lead to development of antibiotic resistance in patients and across communities. MRSA (Methicillin-resistant Staphylococcus aureus) is an example of a resistant organism.
Dosing and Administration — As with other antibiotics featured in “Drug Whys,” cephalexin dosing varies both by the condition and severity of illness being treated. Usual adult oral dosing range is from 1 to 4 grams (1,000 to 4,000 milligrams) daily in four divided doses. For highly susceptible skin infections, 250 milligrams given orally every six hours or 500 milligrams every 12 hours is often sufficient. Larger doses are needed for more severe and less susceptible infections.
Oral dosing for children and infants with strep throat or skin infections is 25 to 100 milligrams per kilogram of patient weight daily, divided into two to four doses, depending on the severity of illness. For mild to moderate infections, use 25 to 50 milligrams per kilogram and for severe infections, 50 to 100 milligrams per kilogram. For otitis media, recommended pediatric dosing is 75 to 100 milligrams per kilogram daily, divided into four doses. Lower doses have a 25 to 50 percent failure rate. Maximum total daily pediatric and adult doses should not exceed 4 grams.
Duration of therapy varies by condition. For strep throat, treatment should continue for at least 10 days. UTIs typically require seven to 10 days of treatment.
Cephalexin can be taken with or without food. Taking it with food can reduce diarrhea, a common side effect. Taking any antibiotic around the clock (i.e., properly spacing doses by the prescribed time intervals) promotes steady serum antibiotic levels and improves effectiveness.
For patients with renal insufficiency or failure, the normal dose of cephalexin should be given every 12 hours. Patients on hemodialysis should receive the normal dose after dialysis. CAPD patients should be given the same dose as patients with renal failure. There are no recommended dosing adjustments for patients with liver dysfunction, or in the geriatric population.
Overdoses of cephalexin usually exhibit significant GI symptoms and hematuria (bloody urine). Care for overdoses should be supportive. Absorption can be reduced by administration of activated charcoal. Gastric decontamination (i.e.: forced emesis or lavage) are rarely necessary unless more than five to 10 times normal doses have been ingested. The average lethal dose of cephalexin in rats exceeds of 5,000 milligrams per kilogram. Cephalexin is removed by hemodialysis.
Pharmacology/Pharmacokinetics/Stability — When taken on an empty stomach, cephalexin achieves peak bloodstream concentrations within one hour. When taken with food or milk, absorption is delayed to about two hours. The average half-life (time needed for half the active drug to be eliminated from the body) of cephalexin in the body is 0.9 hours. In patients with significant renal impairment or renal failure, half-life can be prolonged for up to 16 hours. Nearly all cephalexin is excreted by the kidneys.
During pregnancy, cephalosporin antibiotics are among the safest available. No relationship has been found between cephalexin and birth defects in pregnant women taking the drug in all trimesters. Cephalexin is secreted in breast milk in such low quantities that risk to infants is minimal. Breastfeeding is considered safe for nursing mothers taking cephalexin.
Depending on manufacturer, cephalexin comes in 250, 500 and 750 milligram capsules or tablets as well as an oral powder for mixing a suspension. Colors, shapes and sizes vary by manufacturer. Tablets and capsules should be stored at room temperature between 59 – 86 F. Cephalexin oral suspension is stable for 14 days after mixing if refrigerated.
Cautions and Warnings — Cephalexin should not be used by patients with a history of hypersensitivity or allergy to cephalosporin antibiotics. Caution is advised in patients with significant penicillin allergies, especially penicillin allergies exhibiting full blown anaphylaxis. Cross sensitivity between penicillins and cephalosporins has been noted in approximately 10 percent of allergic patients.
Important Side Effects and Interactions — GI symptoms (nausea, vomiting, and diarrhea) are the most frequent side effects associated with cephalexin, occurring in 1 to 10 percent of patients at usual doses. The most frequent of these is diarrhea. Taking cephalexin with food helps to limit GI side effects. Severe GI side effects may require terminating treatment with cephalexin. Like other antibiotics, cephalexin has occasionally been associated with psuedomembranous colitis, a particularly severe form of painful, often bloody diarrhea accompanied by fever and is caused by a toxin producing superinfection known as Clostridium difficile (or C-diff). Cephalexin has also been associated with Stevens-Johnson syndrome (SJS), a rare, poorly understood hypersensitivity complex that involves sloughing (peeling) of the skin and mucous membranes. SJS can be caused by infections as well as a wide variety of medications and illicit drugs.
A wide range of minor to serious but rarely occurring side effects have been reported with cephalexin. These range from dizziness to seizures. Patient instructions focus on reporting severe GI symptoms, allergic reactions, Stevens-Johnson syndrome, or superinfections (such as vaginal discharge and itching). Diabetic patients are also cautioned that cephalexin can also cause false positive urine glucose tests.
Three drugs are reported to interact with cephalexin. Patients on metformin who take cephalexin may experience increased serum levels of metformin along with increased metformin side effects (GI and headaches). Reduction in metformin dosing may be necessary. Cholestyramine significantly reduces cephalexin absorption (and effectiveness). Cephalexin should be taken one hour before or four to six hours after cholestryramine. Cephalexin also causes a decreased immune response to the oral live typhoid vaccine which should not be given until 24 hours after the last cephalexin dose.
Average Costs — U.S.
250 mg and 500 capsules (generic)
Patient cost: $ 0.48 and 0.33 each*
Large Hospital cost: $0.08 and 0.07 each
*($4.00 at Wal Mart® and Target for 1 month supply)
References:
1. MICROMEDEX® Healthcare Series: Thomson Micromedex, Greenwood Village, Colorado (accessed January, 2008).
2. Albany Medical Center Pharmacy, Albany, New York.
