Cephalexin is an oral, first-generation cephalosporin antibiotic with excellent activity against most gram-positive bacteria. Cephalexin is used primarily in the treatment of otitis media and infections of the respiratory tract (e.g., pharyngitis, tonsillitis, lobar pneumonia) caused by susceptible staphylococci, Streptococcus pneumoniae, and group A beta-hemolytic streptococci. Cephalexin (Keflex(R)) was approved by the FDA in 1971. Cephalexin hydrochloride (Keftab(R)) was later approved on October 29, 1987.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
-Cephalexin is administered orally. All dosage forms may be administered without regard to meals.
-Cephalexin and cephalexin hydrochloride are commercially available as monohydrates; the dosage is expressed as cephalexin base.
Oral Solid Formulations
-Capsules: Swallow whole with a drink of water.
Oral Liquid Formulations
-Oral suspension: Shake well prior to each use. To ensure accurate dosage, measure dose with a calibrated oral syringe, spoon, or measuring cup.
Reconstitution of oral suspension:
-Follow the manufacturer's directions for mixing; the water volume is usually added in 2 aliquots, shaking well after each addition.
-After mixing, store oral suspension in a refrigerator. May be kept for 14 days without significant loss of potency. Shake well before using. Keep tightly closed.
Gastrointestinal adverse reactions (nausea, vomiting, diarrhea) generally occur in less than 5% of patients receiving cephalexin. Other gastrointestinal effects include abdominal pain, gastritis, and dyspepsia. As with other cephalosporins and penicillins, transient hepatitis and cholestatic jaundice have been reported rarely. Colitis has also been reported with the cephalosporin class.
Allergic reactions (i.e., rash, angioedema, and urticaria) have been observed with cephalexin. Erythema multiforme, Stevens-Johnson syndrome or toxic epidermal necrolysis have been reported rarely. Approximately 1% to 3% of treatment courses in the general population result in some kind of dermatologic allergic reaction. These reactions usually resolve upon discontinuation of the drug. Anaphylaxis or anaphylactoid reactions have also been reported and are likely to occur in 0.0001% to 0.1% of patients.
Cephalexin has been associated with acute generalized exanthematous pustulosis (AGEP). The nonfollicular, pustular, erythematous rash starts suddenly, is associated with fever above 38 degrees C, and is distinct from pustular psoriasis, although biopsy results in each reveal spongiform subcorneal pustules. Drugs are the main cause of AGEP. A period of 2-3 weeks after an inciting drug exposure appears necessary for a first episode of AGEP. Unintentional reexposure may cause a second episode within 2 days. Clinical presentation is diverse with cutaneous lesions beyond erythema and pustules present in half of the cases. For example, bullous lesions, edema, purpura, pruritus, and mucosal erosions are possible. The mean duration of the pustules is 9.7 days followed by an annular desquamation, as long as the causative drug or factor is discontinued. The physiopathological mechanisms of AGEP have not been determined but the pathological criteria of edema, leukocytoclastic vasculitis, eosinophil exocytosis, and keratinocyte focal necrosis are distinctive. Pustule confluence or very small pustules may lead a clinician to make an incorrect diagnosis of TEN, of drug-induced erythroderma, or of staphylococcal scalded skin syndrome.
Nephrotoxicity occurs very rarely during therapy with cephalexin, but patients with renal dysfunction, patients receiving other nephrotoxic drugs, and patients over 50 years of age may be more susceptible. Interstitial nephritis (less than 1%), a hypersensitivity reaction, has been reported with many of the cephalosporins, including rarely with cephalexin. Renal dysfunction, increased BUN and creatinine (azotemia), and toxic nephropathy have been reported with the cephalosporin class.
Seizures (< 1%) are rare, but a serious complication of cephalosporin therapy. More commonly associated with penicillins, the epileptogenic properties of both penicillins and cephalosporins are thought to be related to their beta-lactam ring. High doses and administration to patients with renal impairment (when the dosage was not reduced) are associated with an increased risk of seizures. Discontinue the drug if seizures occur; if clinically indicated, anticonvulsant therapy can be used.
Reported adverse reactions with cephalexin include dizziness, fatigue, headache, agitation, confusion, hallucinations, arthralgia, arthritis, and joint disorder. There are rare reports of neutropenia, thrombocytopenia, and hemolytic anemia, which have all been reported in less than 1% of patients on cephalosporin therapy. Elevated hepatic enzymes (slight increases in AST and ALT) has been reported in 1 to 7% of patients during cephalosporin use. Eosinophilia has been reported with cefazolin and occurs in 2.7 to 8.2% of patients receiving cephalosporins. Laboratory abnormalities and adverse reactions reported with cephalosporin-class antibiotics include fever, aplastic anemia, hemorrhage (bleeding), prolonged prothrombin time (hypoprothrombinemia) (less than 1%), increased BUN, increased creatinine, elevated alkaline phosphatase, elevated bilirubin, elevated LDH, pancytopenia, leukopenia, and agranulocytosis.
Microbial overgrowth and superinfection can occur with antibiotic use. C. difficile-associated diarrhea (CDAD) or pseudomembranous colitis has been reported with cephalexin. If pseudomembranous colitis is suspected or confirmed, ongoing antibacterial therapy not directed against C. difficile may need to be discontinued. Institute appropriate fluid and electrolyte management, protein supplementation, C. difficile-directed antibacterial therapy, and surgical evaluation as clinically appropriate. Other adverse reactions reported with cephalexin include genital and anal pruritus (pruritus ani) as well as local candidiasis such as thrush, genital moniliasis, as well as symptoms of vaginitis and vaginal discharge.
Cephalexin does not treat viral infection (e.g., common cold). Prescribing in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria (antimicrobial resistance). Patients should be told to complete the full course of treatment, even if they feel better earlier.
Cephalexin is contraindicated for use in patients with cephalosporin hypersensitivity. Cephalosporins cause hypersensitivity reactions in <= 5% of patients receiving them. A variety of hypersensitivity reactions ranging from mild rash to fatal anaphylaxis may occur. Serum sickness reactions are a form of hypersensitivity to cephalosporins and may occur after a second course of cephalosporin therapy. Certain individuals may be more susceptible to allergic reactions to cephalosporins. The structural similarity between cephalexin and penicillin means that cross-reactivity can occur. The incidence of cross-reactivity to cephalosporins is approximately up to 10% in patients with a documented history of allergy to penicillin. Cephalexin should be administered with caution to individuals with a history of hypersensitivity to penicillin. Patients who have experienced severe, immediate-type penicillin hypersensitivity (e.g., acute bronchospasm, anaphylaxis, severe dermatologic reactions) should not receive cephalexin. The health care professional should have immediate availability of agents used in the treatment of severe anaphylaxis in the event of a serious allergic reaction to cephalexin.
Cephalexin should be used with caution in patients with renal impairment or renal failure since the drug is eliminated via renal mechanisms. The degree of renal impairment and the severity of the infection will determine if renal dose adjustments or dosage interval adjustments are required. Dosages may need to be reduced in these patients. Cephalexin may rarely worsen renal function; pre-existing renal impairment may increase the risk of drug-induced renal toxicity.
Consider pseudomembranous colitis in patients presenting with diarrhea after antibacterial use. Careful medical history is necessary as pseudomembranous colitis has been reported to occur over 2 months after the administration of antibacterial agents. Almost all antibacterial agents, including cephalexin, have been associated with pseudomembranous colitis or C. difficile-associated diarrhea (CDAD) which may range in severity from mild to life-threatening. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.
Data from published epidemiologic studies and pharmacovigilance case reports over several decades with cephalosporin use, including cephalexin, in human pregnancy have not established drug-associated risks or major birth defects, miscarriage, or adverse maternal or fetal outcomes. Animal reproduction studies using oral cephalexin doses that are 0.6- and 1.2-times the maximum recommended human dose (MRHD) based on body surface revealed no evidence of harm to the fetus.
Cephalexin is present in human breast milk. The Relative Infant Dose (RID) is considered to be less than 1% of the maternal weight-adjusted dose. There are no data on the effects of cephalexin on the breast-fed child or on milk production. Consider the benefits of breast-feeding along with the mother's clinical need for cephalexin and any potential adverse effects on breast-fed child from cephalexin or from the underlying maternal condition. In a mother being treated for a breast infection with cephalexin (500 mg PO every 6 hours) and probenecid, breast milk concentrations of cephalexin and probenecid were 0.745 and 0.964 mcg/mL, respectively. These concentrations correspond to infant doses of 112 mcg/kg/day for cephalexin and 145 mcg/kg/day probenecid assuming a milk consumption of 150 mL/kg/day. This dose of cephalexin is significantly lower (i.e. less than 1%) than doses prescribed for infants and children. In this case report, the nursing infant had severe diarrhea and discomfort and was crying; it is unclear whether these same effects would have been seen with cephalexin monotherapy. As with other oral antibiotics, alterations in the infant gut flora resulting in diarrhea may be expected; however, significant systemic effects do not appear to be common. Previous American Academy of Pediatrics (AAP) recommendations did not evaluate the use of cephalexin during breast-feeding; however, several other cephalosporins, such as cefazolin, cefprozil, and cefadroxil, were considered to be usually compatible with breast-feeding.
All cephalosporins, including cephalexin, may rarely cause hypothrombinemia and have the potential to cause bleeding. The mechanism is usually via the inhibition of normal gut flora and decreases in normal vitamin K synthesis, leading to coagulopathy. Cephalosporins which contain the NMTT side chain (i.e., cefoperazone, cefamandole, cefotetan) have been associated with an increased risk of hypoprothrombinemia. Cephalosporins should be used cautiously when there is a need for prolonged antibiotic therapy or other risk factors (e.g., malnutrition). Patients with a preexisting coagulopathy (e.g., vitamin K deficiency) may be at higher risk for developing bleeding complications.
Cephalosporins have also been reported to cause false-positive results in urine glucose tests that contain cupric sulfate solution (e.g., Benedict's reagent, Clinitest); patients with diabetes mellitus who use urinary testing methods may receive caution regarding this interference. In addition, positive direct Coombs' tests have been reported in patients receiving cephalosporins, including cephalexin. If hematological testing is done in patients receiving cephalosporins, a false-positive Coombs' test may be caused by the antibiotic.
Cephalexin is renally eliminated. In clinical studies of cephalexin, no overall differences in safety or effectiveness were observed between geriatric and younger adults. However, because geriatric patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities. According to OBRA, use of antibiotics should be limited to confirmed or suspected bacterial infections. Antibiotics are non-selective and may result in the eradication of beneficial microorganisms while promoting the emergence of undesired ones, causing secondary infections such as oral thrush, colitis, or vaginitis. Any antibiotic may cause diarrhea, nausea, vomiting, anorexia, and hypersensitivity reactions.
Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: Escherichia coli, Haemophilus influenzae (beta-lactamase negative), Klebsiella pneumoniae, Moraxella catarrhalis, Proteus mirabilis, Staphylococcus aureus (MSSA), Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes (group A beta-hemolytic streptococci)
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.
This drug may also have activity against the following microorganisms: Streptococcus agalactiae (group B streptococci)
NOTE: Some organisms may not have been adequately studied during clinical trials; therefore, exclusion from this list does not necessarily negate the drug's activity against the organism.
For the treatment of upper respiratory tract infections, including group A beta-hemolytic streptococcal (GAS) pharyngitis (primary rheumatic fever prophylaxis) and tonsillitis:
-for the treatment of nonspecific upper respiratory tract infections:
Oral dosage:
Adults: 250 mg PO every 6 hours or 500 mg PO every 12 hours for 7 to 14 days. Up to 4 g/day may be used.
Infants*, Children, and Adolescents: 25 to 50 mg/kg/day PO in 2 to 4 divided doses for 7 to 14 days. Up to 100 mg/kg/day (Max: 4 g/day) may be used.
-for the treatment of group A beta-hemolytic streptococcal (GAS) pharyngitis (primary rheumatic fever prophylaxis) and tonsillitis:
Oral dosage:
Adults: 500 mg PO every 12 hours for 10 days as an alternative in patients allergic to penicillin.
Infants*, Children, and Adolescents: 20 mg/kg/dose (Max: 500 mg/dose) PO every 12 hours for 10 days as an alternative in patients allergic to penicillin.
For the treatment of lower respiratory tract infections (LRTIs), including community-acquired pneumonia (CAP):
-for the treatment of nonspecific lower respiratory tract infections (LRTIs):
Oral dosage:
Adults: 250 mg PO every 6 hours or 500 mg PO every 12 hours for 7 to 14 days. Doses up to 4 g/day PO divided in 2 to 4 doses may be needed for severe infections.
Infants*, Children, and Adolescents: 25 to 50 mg/kg/day PO divided in 2 to 4 doses (Max: 2 g/day) for mild to moderate infections or 50 to 100 mg/kg/day PO divided in 3 to 4 doses (Max: 4 g/day) for severe infections.
-for the treatment of community-acquired pneumonia (CAP):
Oral dosage:
Infants 4 to 11 months*, Children, and Adolescents: 75 to 100 mg/kg/day PO divided in 3 or 4 doses (Max: 4 g/day) for 10 days. Guidelines recommend cephalexin as initial therapy for mild infections or oral step-down therapy for infections due to methicillin-sensitive S. aureus (MSSA).
For the treatment of skin and skin structure infections, including impetigo, cellulitis, erysipelas, skin abscesses, furunculosis, carbuncle, diabetic foot ulcer*, and surgical incision site infections:
-for the treatment of unspecified skin and skin structure infections:
Oral dosage:
Adults: 250 mg PO every 6 hours or 500 mg PO every 12 hours for 7 to 14 days. Up to 4 g/day may be used.
Infants*, Children, and Adolescents: 25 to 50 mg/kg/day PO in 2 to 4 divided doses for 7 to 14 days. Up to 100 mg/kg/day (Max: 4 g/day) may be used.
-for the treatment of impetigo:
Oral dosage:
Adults: 250 mg PO every 6 hours or 500 mg PO every 12 hours for 5 to 7 days.
Infants*, Children, and Adolescents: 25 to 50 mg/kg/day PO in 2 to 4 divided doses (Max: 1 g/day) for 5 to 7 days.
-for the treatment of nonpurulent skin infections, such as cellulitis and erysipelas:
Oral dosage:
Adults: 500 mg PO every 6 hours for 5 to 14 days.
Infants*, Children, and Adolescents: 25 to 50 mg/kg/day PO in 4 divided doses (Max: 2 g/day) for 5 to 14 days.
-for the treatment of purulent skin infections, such as furunculosis, carbuncle, and skin abscesses:
Oral dosage:
Adults: 500 mg PO every 6 hours for 5 to 10 day plus incision and drainage.
Infants*, Children, and Adolescents: 25 to 50 mg/kg/day PO in 4 divided doses (Max: 2 g/day) for 5 to 10 days plus incision and drainage.
-for the treatment of mild diabetic foot ulcer*:
Oral dosage:
Adults: 500 mg PO every 6 hours for 7 to 14 days. Up to 4 g/day may be used. Continue treatment for up to 28 days if infection is improving but is extensive and resolving slower than expected or if patient has severe peripheral artery disease.
-for the treatment of surgical incision site infections:
Oral dosage:
Adults: 500 mg PO every 6 hours for incisional surgical site infections of the trunk or extremity away from the axilla or perineum.
For the treatment of otitis media:
Oral dosage:
Children and Adolescents: 75 to 100 mg/kg/day PO in 3 to 4 divided doses (Max: 2 to 4 g/day). Although cephalexin is FDA-approved for the treatment of otitis media, it is not recommended as a treatment option in guidelines. Second- or third-generation oral cephalosporins (i.e., cefdinir, cefuroxime, and cefpodoxime) are the recommended agents for patients allergic to amoxicillin.
For bacterial endocarditis prophylaxis*:
Oral dosage:
Adults: 2 g PO as a single dose given 30 to 60 minutes before procedure as an alternative for patients allergic to penicillin. Prophylaxis is recommended for at-risk cardiac patients who are undergoing dental procedures that involve manipulation of gingival tissue, manipulation of the periapical region of teeth, or perforation of the oral mucosa.
Children and Adolescents: 50 mg/kg/dose (Max: 2 g/dose) PO as a single dose given 30 to 60 minutes before procedure as an alternative for patients allergic to penicillin. Prophylaxis is recommended for at-risk cardiac patients who are undergoing dental procedures that involve manipulation of gingival tissue, manipulation of the periapical region of teeth, or perforation of the oral mucosa.
For the treatment of bone and joint infections, including osteomyelitis, infectious arthritis*, infectious bursitis*, and orthopedic device-related infection*:
-for the treatment of osteomyelitis including as step-down therapy after initial IV therapy:
Oral dosage:
Adults: 500 mg to 1 g PO every 6 to 12 hours for 4 to 6 weeks.
Children and Adolescents: 75 to 150 mg/kg/day (Max: 6 g/day) PO in 3 to 4 divided doses. Treat for a total duration of 3 to 4 weeks (parenteral plus oral) for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for severe or complicated infections.
Infants 3 to 11 months*: 75 to 150 mg/kg/day PO in 3 to 4 divided doses. Treat for a total duration of 3 to 4 weeks (parenteral plus oral) for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for severe or complicated infections.
Infants 1 to 2 months*: 75 to 150 mg/kg/day PO in 3 to 4 divided doses. Treat for a total duration of 4 to 6 weeks (parenteral plus oral). A longer course (several months) may be needed for severe or complicated infections.
-for step-down therapy for infectious arthritis* after initial IV therapy:
Oral dosage:
Adults: 500 mg to 1 g PO every 6 to 12 hours. Treat for a total duration of 3 to 6 weeks (parenteral plus oral).
Children and Adolescents: 75 to 150 mg/kg/day (Max: 6 g/day) PO in 3 to 4 divided doses. Treat for a total duration of 2 to 3 weeks (parenteral plus oral) for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for septic hip arthritis or severe or complicated infections.
Infants 3 to 11 months: 75 to 150 mg/kg/day PO in 3 to 4 divided doses. Treat for a total duration of 2 to 3 weeks (parenteral plus oral) for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for septic hip arthritis or severe or complicated infections.
Infants 1 to 2 months: 75 to 150 mg/kg/day PO in 3 to 4 divided doses. Treat for a total duration of 4 to 6 weeks (parenteral plus oral). A longer course (several months) may be needed for severe or complicated infections.
-for the treatment of infectious bursitis*:
Oral dosage:
Adults: 500 mg to 1 g PO every 6 to 12 hours for 2 to 3 weeks. Generally, 2 weeks is appropriate for most patients; immunocompromised patients may require a longer duration.
Children and Adolescents: 75 to 150 mg/kg/day (Max: 6 g/day) PO in 3 to 4 divided doses for 2 to 3 weeks. Generally, 2 weeks is appropriate for most patients; immunocompromised patients may require a longer duration.
-for step-down therapy for the treatment of prosthetic joint infections* after initial IV therapy:
Oral dosage:
Adults: 500 mg PO every 6 to 8 hours in combination with rifampin for 3 to 6 months, which may be followed by long-term suppressive therapy if needed.
-for long-term suppressive therapy of prosthetic joint infections*:
Oral dosage:
Adults: 500 mg PO every 6 to 8 hours.
For the treatment of asymptomatic bacteriuria* and urinary tract infection (UTI), including cystitis, prostatitis, pyelonephritis, and catheter-associated urinary tract infection:
-for the treatment of asymptomatic bacteriuria*:
Oral dosage:
Adults: 500 mg PO every 6 hours for 3 to 5 days or 500 mg PO every 12 hours for 7 days.
-for the treatment of nonspecific UTI:
Oral dosage:
Adults: 1 to 4 g/day PO divided in 2 to 4 doses for 7 to 14 days. Usual dose: 250 mg PO every 6 hours or 500 mg PO every 12 hours.
Children and Adolescents 3 to 17 years: 25 to 50 mg/kg/day (Max: 2 g/day) PO in 2 to 4 divided doses. For severe infections, 50 to 100 mg/kg/day (Max: 4 g/day) PO in 3 to 4 divided doses may be used. Treat for 7 to 14 days.
Children 1 to 2 years: 50 to 100 mg/kg/day PO in 4 divided doses for 7 to 14 days. The FDA-approved dosage is 25 to 50 mg/kg/day PO in 2 to 4 divided doses. For severe infections, 50 to 100 mg/kg/day PO in 3 to 4 divided doses may be used.
-for the treatment of acute uncomplicated cystitis:
Oral dosage:
Nonpregnant Adults: 250 mg PO every 6 hours or 500 mg PO every 12 hours for 3 days.
Pregnant Persons: 500 mg PO every 12 hours for 7 days.
-for the treatment of acute uncomplicated lower UTI in pediatric patients:
Oral dosage:
Children and Adolescents 3 to 17 years: 25 to 50 mg/kg/day (Max: 2 g/day) PO in 2 to 4 divided doses for 3 to 5 days.
Children 1 to 2 years: 50 to 100 mg/kg/day PO in 4 divided doses for 3 to 5 days.
Infants 2 to 11 months*: 50 to 100 mg/kg/day PO in 4 divided doses for 3 to 5 days.
-for the treatment of severe UTI, including pyelonephritis:
Oral dosage:
Adults: 500 mg PO every 8 to 12 hours up to 1.5 g PO every 6 to 8 hours for 7 to 14 days. Consider an initial dose of a long-acting IV antibiotic prior to use.
Children and Adolescents 12 to 17 years: 50 to 100 mg/kg/day (Max: 6 g/day) PO in 3 to 4 divided doses for 7 to 14 days.
Children 1 to 11 years: 50 to 100 mg/kg/day (Max: 4 g/day) PO in 3 to 4 divided doses for 7 to 14 days.
Infants 2 to 11 months*: 50 to 100 mg/kg/day PO in 4 divided doses for 7 to 14 days.
-for the treatment of catheter-associated UTI:
Oral dosage:
Adults: 500 mg PO every 8 to 12 hours up to 1.5 g PO every 6 to 8 hours for 7 to 14 days.
Children and Adolescents 12 to 17 years: 50 to 100 mg/kg/day (Max: 6 g/day) PO in 3 to 4 divided doses for 7 to 14 days.
Children 1 to 11 years: 50 to 100 mg/kg/day (Max: 4 g/day) PO in 3 to 4 divided doses for 7 to 14 days.
Infants 2 to 11 months*: 50 to 100 mg/kg/day PO in 4 divided doses for 7 to 14 days.
For urinary tract infection (UTI) prophylaxis*:
-for continuous, long-term UTI prophylaxis* for recurrent infections:
Oral dosage:
Adults: 125 or 250 mg PO every 24 hours. The duration of prophylaxis is variable and should be assessed routinely. Generally 3 to 12 months is suggested; however, longer durations have been used.
-for intermittent, pre- or post-coital UTI prophylaxis* for recurrent infections:
Oral dosage:
Adults: 250 mg as a single dose as needed.
-for UTI prophylaxis* in infants with hydronephrosis or vesicoureteral reflux:
NOTE: Routine antimicrobial prophylaxis for patients aged 2 to 24 months with vesicoureteral reflux is not supported by currently available data; however, antimicrobial prophylaxis is still utilized and has biological plausibility.
Oral dosage:
Infants 1 month: 10 to 15 mg/kg/dose PO every 24 hours. Guidelines recommend antibiotic prophylaxis for all grades of vesicoureteral reflux in all patients younger than 1 year.
Neonates: 10 to 15 mg/kg/dose PO every 24 hours. Guidelines recommend antibiotic prophylaxis for all grades of vesicoureteral reflux in all children younger than 1 year.
For the treatment of mastitis:
Oral dosage:
Adults: 250 to 500 mg PO every 6 hours for 10 to 14 days.
For the treatment of peritoneal dialysis catheter-related infection*:
Oral dosage:
Adults: 500 mg PO every 8 to 12 hours for at least 14 days to 21 days.
Infants, Children, and Adolescents: 10 to 20 mg/kg/day PO divided every 12 to 24 hours (Max: 1 g/day) for at least 14 to 28 days.
Maximum Dosage Limits:
-Adults
4 g/day PO.
-Geriatric
4 g/day PO.
-Adolescents
100 mg/kg/day (Max: 4 g/day) PO is FDA-approved maximum; however, doses up to 150 mg/kg/day (Max: 6 g/day) PO have been used off-label.
-Children
100 mg/kg/day (Max: 4 g/day) PO is FDA-approved maximum; however, doses up to 150 mg/kg/day (Max: 6 g/day) PO have been used off-label.
-Infants
100 mg/kg/day PO is FDA-approved maximum; however, doses up to 150 mg/kg/day PO have been used off-label.
-Neonates
Safety and efficacy have not been established; however, doses up to 15 mg/kg/day PO have been used for UTI prophylaxis.
Patients with Hepatic Impairment Dosing
No dosage adjustment is necessary.
Patients with Renal Impairment Dosing
FDA-approved dosage adjustments (adults and adolescents at least 15 years of age)
CrCl 60 mL/minute or greater: No dosage adjustment is needed.
CrCl 30 to 59 mL/minute: No dosage adjustment is needed; maximum daily dose not to exceed 1 gram/day.
CrCl 15 to 29 mL/minute: 250 mg PO every 8 to 12 hours.
CrCl 5 to 14 mL/minute and not on dialysis: 250 mg PO every 24 hours.
CrCl 1 to 4 mL/minute and not on dialysis: 250 mg PO every 48 to 60 hours.
Pediatric renal dosage adjustments based on a usual dose in pediatric patients of 25 to 50 mg/kg/day PO divided every 6 hours
CrCl greater than 50 mL/minute/1.73 m2: No dosage adjustment needed.
CrCl 30 to 50 mL/minute/1.73 m2: 5 to 10 mg/kg/dose PO every 8 hours.
CrCl 10 to 29 mL/minute/1.73 m2: 5 to 10 mg/kg/dose PO every 12 hours.
CrCl less than 10 mL/minute/1.73 m2: 5 to 10 mg/kg/dose PO every 24 hours.
Intermittent hemodialysis
Adults: For patients receiving intermittent hemodialysis, dose after dialysis.
Pediatric patients: 5 to 10 mg/kg/dose PO every 24 hours, after hemodialysis.
Peritoneal dialysis
For mild infections (adults): 250 to 500 mg PO every 12 to 24 hours.
For mild infections (pediatric patients): 5 to 10 mg/kg/dose PO every 24 hours.
For exit-site and tunnel infections (adults): 500 mg PO every 8 to 12 hours.
For exit-site and tunnel infections (pediatric patients): 10 to 20 mg/kg/day given in 1 or 2 doses (Max: 1 gram/day).
*non-FDA-approved indication
Alogliptin; Metformin: (Moderate) Monitor for metformin-related adverse reactions during concomitant cephalexin use; a metformin dosage adjustment may be necessary. Concomitant use results in increased serum metformin concentrations and decreased renal clearance of metformin. In healthy subjects given single cephalexin 500 mg doses and metformin, serum metformin mean Cmax and AUC increased by an average of 34% and 24%, respectively, and metformin mean renal clearance decreased by 14%.
Bumetanide: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
Canagliflozin; Metformin: (Moderate) Monitor for metformin-related adverse reactions during concomitant cephalexin use; a metformin dosage adjustment may be necessary. Concomitant use results in increased serum metformin concentrations and decreased renal clearance of metformin. In healthy subjects given single cephalexin 500 mg doses and metformin, serum metformin mean Cmax and AUC increased by an average of 34% and 24%, respectively, and metformin mean renal clearance decreased by 14%.
Chlorpheniramine; Pseudoephedrine: (Minor) Caution may be warranted with coadminstration of cephalexin and zinc salts as zinc may decrease the absorption of cephalexin. In a randomized, single-dose, four-way crossover study (n = 12), patients received cephalexin alone, in combination with zinc sulfate (250 mg), 3 hours after zinc sulfate, or 3 hours before zinc sulfate. When administered in combination with zinc, the cephalexin Cmax decreased from 18.07 +/- 4.27 mcg/ml to 12.46 +/- 2.73 mcg/ml (p < 0.05) and the AUC decreased from 41.97 +/- 6.04 mcg x h/ml to 30.47 +/- 3.52 mcg x h/ml (p < 0.05). When cephalexin was administered 3 hours after zinc, the Cmax and AUC were 16 +/- 4.06 mcg/ml (p < 0.05) and 34.37 +/- 1.58 mcg x h/mL (p < 0.05), respectively. When cephalexin was administered 3 hours before zinc, there were no significant differences in the cephalexin Cmax or AUC. One in vitro study suggested that zinc is a competitive inhibitor of the intestinal peptide transporter, PEPT1, which may inhibit the uptake of oral cephalosporins. An additional in vitro study suggested that trace elements may have an antagonistic effect on cephalosporins.
Cholestyramine: (Minor) Caution may be warranted with coadministration of cephalexin and cholestyramine as cephalexin absorption may be decreased. In a study comparing patients receiving cephalexin alone with cephalexin plus cholestyramine, cephalexin mean and peak plasma concentrations were significantly reduced in patients with malabsorption syndromes.
Dapagliflozin; Metformin: (Moderate) Monitor for metformin-related adverse reactions during concomitant cephalexin use; a metformin dosage adjustment may be necessary. Concomitant use results in increased serum metformin concentrations and decreased renal clearance of metformin. In healthy subjects given single cephalexin 500 mg doses and metformin, serum metformin mean Cmax and AUC increased by an average of 34% and 24%, respectively, and metformin mean renal clearance decreased by 14%.
Desogestrel; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Dienogest; Estradiol valerate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Drospirenone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Drospirenone; Estetrol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Drospirenone; Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Drospirenone; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Elagolix; Estradiol; Norethindrone acetate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Empagliflozin; Linagliptin; Metformin: (Moderate) Monitor for metformin-related adverse reactions during concomitant cephalexin use; a metformin dosage adjustment may be necessary. Concomitant use results in increased serum metformin concentrations and decreased renal clearance of metformin. In healthy subjects given single cephalexin 500 mg doses and metformin, serum metformin mean Cmax and AUC increased by an average of 34% and 24%, respectively, and metformin mean renal clearance decreased by 14%.
Empagliflozin; Metformin: (Moderate) Monitor for metformin-related adverse reactions during concomitant cephalexin use; a metformin dosage adjustment may be necessary. Concomitant use results in increased serum metformin concentrations and decreased renal clearance of metformin. In healthy subjects given single cephalexin 500 mg doses and metformin, serum metformin mean Cmax and AUC increased by an average of 34% and 24%, respectively, and metformin mean renal clearance decreased by 14%.
Ertugliflozin; Metformin: (Moderate) Monitor for metformin-related adverse reactions during concomitant cephalexin use; a metformin dosage adjustment may be necessary. Concomitant use results in increased serum metformin concentrations and decreased renal clearance of metformin. In healthy subjects given single cephalexin 500 mg doses and metformin, serum metformin mean Cmax and AUC increased by an average of 34% and 24%, respectively, and metformin mean renal clearance decreased by 14%.
Estradiol; Levonorgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Estradiol; Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Estradiol; Norgestimate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Ethacrynic Acid: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
Ethinyl Estradiol; Norelgestromin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Ethinyl Estradiol; Norethindrone Acetate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Ethinyl Estradiol; Norgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Ethynodiol Diacetate; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Etonogestrel; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Furosemide: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
Glipizide; Metformin: (Moderate) Monitor for metformin-related adverse reactions during concomitant cephalexin use; a metformin dosage adjustment may be necessary. Concomitant use results in increased serum metformin concentrations and decreased renal clearance of metformin. In healthy subjects given single cephalexin 500 mg doses and metformin, serum metformin mean Cmax and AUC increased by an average of 34% and 24%, respectively, and metformin mean renal clearance decreased by 14%.
Glyburide; Metformin: (Moderate) Monitor for metformin-related adverse reactions during concomitant cephalexin use; a metformin dosage adjustment may be necessary. Concomitant use results in increased serum metformin concentrations and decreased renal clearance of metformin. In healthy subjects given single cephalexin 500 mg doses and metformin, serum metformin mean Cmax and AUC increased by an average of 34% and 24%, respectively, and metformin mean renal clearance decreased by 14%.
Iron Sucrose, Sucroferric Oxyhydroxide: (Moderate) Administer cephalexin at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide. Oral iron salts may reduce the bioavailability of cephalexin, leading to decreased absorption.
Leuprolide; Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Levonorgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Levonorgestrel; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Linagliptin; Metformin: (Moderate) Monitor for metformin-related adverse reactions during concomitant cephalexin use; a metformin dosage adjustment may be necessary. Concomitant use results in increased serum metformin concentrations and decreased renal clearance of metformin. In healthy subjects given single cephalexin 500 mg doses and metformin, serum metformin mean Cmax and AUC increased by an average of 34% and 24%, respectively, and metformin mean renal clearance decreased by 14%.
Loop diuretics: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
Metformin: (Moderate) Monitor for metformin-related adverse reactions during concomitant cephalexin use; a metformin dosage adjustment may be necessary. Concomitant use results in increased serum metformin concentrations and decreased renal clearance of metformin. In healthy subjects given single cephalexin 500 mg doses and metformin, serum metformin mean Cmax and AUC increased by an average of 34% and 24%, respectively, and metformin mean renal clearance decreased by 14%.
Metformin; Repaglinide: (Moderate) Monitor for metformin-related adverse reactions during concomitant cephalexin use; a metformin dosage adjustment may be necessary. Concomitant use results in increased serum metformin concentrations and decreased renal clearance of metformin. In healthy subjects given single cephalexin 500 mg doses and metformin, serum metformin mean Cmax and AUC increased by an average of 34% and 24%, respectively, and metformin mean renal clearance decreased by 14%.
Metformin; Saxagliptin: (Moderate) Monitor for metformin-related adverse reactions during concomitant cephalexin use; a metformin dosage adjustment may be necessary. Concomitant use results in increased serum metformin concentrations and decreased renal clearance of metformin. In healthy subjects given single cephalexin 500 mg doses and metformin, serum metformin mean Cmax and AUC increased by an average of 34% and 24%, respectively, and metformin mean renal clearance decreased by 14%.
Metformin; Sitagliptin: (Moderate) Monitor for metformin-related adverse reactions during concomitant cephalexin use; a metformin dosage adjustment may be necessary. Concomitant use results in increased serum metformin concentrations and decreased renal clearance of metformin. In healthy subjects given single cephalexin 500 mg doses and metformin, serum metformin mean Cmax and AUC increased by an average of 34% and 24%, respectively, and metformin mean renal clearance decreased by 14%.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Norethindrone; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Norgestimate; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Norgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Oral Contraceptives: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Pioglitazone; Metformin: (Moderate) Monitor for metformin-related adverse reactions during concomitant cephalexin use; a metformin dosage adjustment may be necessary. Concomitant use results in increased serum metformin concentrations and decreased renal clearance of metformin. In healthy subjects given single cephalexin 500 mg doses and metformin, serum metformin mean Cmax and AUC increased by an average of 34% and 24%, respectively, and metformin mean renal clearance decreased by 14%.
Probenecid: (Minor) Probenecid competitively inhibits renal tubular secretion of cephalexin, causing higher, prolonged serum levels of the drug.
Probenecid; Colchicine: (Minor) Probenecid competitively inhibits renal tubular secretion of cephalexin, causing higher, prolonged serum levels of the drug.
Relugolix; Estradiol; Norethindrone acetate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Segesterone Acetate; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Sodium picosulfate; Magnesium oxide; Anhydrous citric acid: (Major) Prior or concomitant use of antibiotics with sodium picosulfate; magnesium oxide; anhydrous citric acid may reduce efficacy of the bowel preparation as conversion of sodium picosulfate to its active metabolite bis-(p-hydroxy-phenyl)-pyridyl-2-methane (BHPM) is mediated by colonic bacteria. If possible, avoid coadministration. Certain antibiotics (i.e., tetracyclines and quinolones) may chelate with the magnesium in sodium picosulfate; magnesium oxide; anhydrous citric acid solution. Therefore, these antibiotics should be taken at least 2 hours before and not less than 6 hours after the administration of sodium picosulfate; magnesium oxide; anhydrous citric acid solution.
Torsemide: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
Warfarin: (Moderate) The concomitant use of warfarin with many classes of antibiotics, including cephalosporins, may increase the INR thereby potentiating the risk for bleeding. Inhibition of vitamin K synthesis due to alterations in the intestinal flora may be a mechanism; however, concurrent infection is also a potential risk factor for elevated INR. Additionally, certain cephalosporins (cefotetan, cefoperazone, cefamandole) are associated with prolongation of the prothrombin time due to the methylthiotetrazole (MTT) side chain at the R2 position, which disturbs the synthesis of vitamin K-dependent clotting factors in the liver. Monitor patients for signs and symptoms of bleeding. Additionally, increased monitoring of the INR, especially during initiation and upon discontinuation of the antibiotic, may be necessary.
Zinc Salts: (Minor) Caution may be warranted with coadminstration of cephalexin and zinc salts as zinc may decrease the absorption of cephalexin. In a randomized, single-dose, four-way crossover study (n = 12), patients received cephalexin alone, in combination with zinc sulfate (250 mg), 3 hours after zinc sulfate, or 3 hours before zinc sulfate. When administered in combination with zinc, the cephalexin Cmax decreased from 18.07 +/- 4.27 mcg/ml to 12.46 +/- 2.73 mcg/ml (p < 0.05) and the AUC decreased from 41.97 +/- 6.04 mcg x h/ml to 30.47 +/- 3.52 mcg x h/ml (p < 0.05). When cephalexin was administered 3 hours after zinc, the Cmax and AUC were 16 +/- 4.06 mcg/ml (p < 0.05) and 34.37 +/- 1.58 mcg x h/mL (p < 0.05), respectively. When cephalexin was administered 3 hours before zinc, there were no significant differences in the cephalexin Cmax or AUC. One in vitro study suggested that zinc is a competitive inhibitor of the intestinal peptide transporter, PEPT1, which may inhibit the uptake of oral cephalosporins. An additional in vitro study suggested that trace elements may have an antagonistic effect on cephalosporins.
Zinc: (Minor) Caution may be warranted with coadminstration of cephalexin and zinc salts as zinc may decrease the absorption of cephalexin. In a randomized, single-dose, four-way crossover study (n = 12), patients received cephalexin alone, in combination with zinc sulfate (250 mg), 3 hours after zinc sulfate, or 3 hours before zinc sulfate. When administered in combination with zinc, the cephalexin Cmax decreased from 18.07 +/- 4.27 mcg/ml to 12.46 +/- 2.73 mcg/ml (p < 0.05) and the AUC decreased from 41.97 +/- 6.04 mcg x h/ml to 30.47 +/- 3.52 mcg x h/ml (p < 0.05). When cephalexin was administered 3 hours after zinc, the Cmax and AUC were 16 +/- 4.06 mcg/ml (p < 0.05) and 34.37 +/- 1.58 mcg x h/mL (p < 0.05), respectively. When cephalexin was administered 3 hours before zinc, there were no significant differences in the cephalexin Cmax or AUC. One in vitro study suggested that zinc is a competitive inhibitor of the intestinal peptide transporter, PEPT1, which may inhibit the uptake of oral cephalosporins. An additional in vitro study suggested that trace elements may have an antagonistic effect on cephalosporins.
Cephalexin, a beta-lactam antibiotic similar to penicillins, inhibits the third and final stage of bacterial cell wall synthesis by preferentially binding to specific penicillin-binding proteins (PBPs) that are located inside the bacterial cell wall. Penicillin-binding proteins are responsible for several steps in the synthesis of the cell wall and are found in quantities of several hundred to several thousand molecules per bacterial cell. Penicillin-binding proteins vary among different bacterial species. Thus, the intrinsic activity of cephalexin, as well as the other cephalosporins and penicillins, against a particular organism depends on its ability to gain access to and bind with the necessary PBP. Like all beta-lactam antibiotics, cephalexin's ability to interfere with PBP-mediated cell wall synthesis ultimately leads to cell lysis. Lysis is mediated by bacterial cell wall autolytic enzymes (i.e., autolysins). The relationship between PBPs and autolysins is unclear, but it is possible that the beta-lactam antibiotic interferes with an autolysin inhibitor.
Beta-lactams, including cephalexin, exhibit concentration-independent or time-dependent killing. In vitro and in vivo animal studies have demonstrated that the major pharmacodynamic parameter that determines efficacy for beta-lactams is the amount of time free (non-protein bound) drug concentrations exceed the minimum inhibitory concentration (MIC) of the organism (free T above the MIC). This microbiological killing pattern is due to the mechanism of action, which is acylation of PBPs. There is a maximum proportion of PBPs that can be acylated; therefore, once maximum acylation has occurred, killing rates cannot increase. Free beta-lactam concentrations do not have to remain above the MIC for the entire dosing interval. The percentage of time required for both bacteriostatic and maximal bactericidal activity is different for the various classes of beta-lactams. Cephalosporins require free drug concentrations to be above the MIC for 35% to 40% of the dosing interval for bacteriostatic activity and 60% to 70% of the dosing interval for bactericidal activity.
Considering site of infection and appropriate cephalexin dosing, oxacillin-susceptible Staphylococcus sp. can be considered susceptible to cephalexin. Breakpoints for cefazolin are used to predict results for cephalexin for treatment of uncomplicated urinary tract infections due to E. coli, K. pneumoniae, and P. mirabilis.
Cephalexin is administered orally. Approximately 10-15% of the circulating drug is protein-bound. Cephalexin is distributed into most body tissues and fluids but does not reach therapeutic levels within the CSF. It crosses the placenta. A small percentage is excreted in breast milk.
Cephalexin is not metabolized and largely excreted unchanged into the urine, which leads to high urinary concentrations. Approximately 50-60% of the dose appears unchanged in the urine during the first 2 hours and 80-100% of dose appears unchanged in the urine after 6-8 hours. One-third of plasma clearance is by glomerular filtration and the other two-thirds by tubular excretion. The elimination half-life is approximately 1 hour in patients with normal renal function.
Affected cytochrome P450 isoenzymes: none
-Route-Specific Pharmacokinetics
Oral Route
Cephalexin is acid-stable. It is rapidly absorbed in the upper intestine after oral administration. There may be a delay in absorption when cephalexin is administered with food resulting in lower peak concentrations as compared to a fasting state. However, serum concentrations are more prolonged resulting in similar areas under the curve. After 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.
-Special Populations
Hepatic Impairment
Cephalexin pharmacokinetics do not appear significantly altered by hepatic disease.
Renal Impairment
In adult patients with renal impairment, the elimination half-life of cephalexin is prolonged to 4-6 hours in patients with a CrCl of 15-30 mL/min, 6-10 hours in patients with a CrCl of 4-15 mL/min, and 30-40 hours in patients with a CrCl < 4 mL/min. Cephalexin is moderately dialyzable (20-50%). Cephalexin appears to be partially removed by peritoneal dialysis (approximately 20%).
Pediatrics
The elimination half-life of cephalexin in infants and children is approximately 1 hour which is similar to the half-life in adults.