CEPHALEXIN (cephalexin)

There are 2 contraindications. These drug combinations generally should not be dispensed or administered to the same patient. A manufacturer label warning that indicates the contraindication warrants inclusion of a drug combination in this category, regardless of clinical evidence or lack of clinical evidence to support the contraindication.

Drug Interaction	Drug Names
Live Typhoid Vaccine/Antimicrobials SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: The antimicrobial may be active against the organism in the live-vaccine. Antimicrobial therapy may prevent the vaccine organism from replicating enough to trigger an immune response.(1) CLINICAL EFFECTS: Vaccination may be ineffective. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Do not give oral typhoid vaccine until 72 hours after the last dose of antimicrobial. If possible, to optimize vaccine effectiveness, do not start antibacterial drugs for 72 hours after the last dose of oral typhoid vaccine. A longer interval should be considered for long-acting antimicrobials, such as azithromycin.(3) DISCUSSION: Because antimicrobial therapy may prevent sufficient vaccine-organism replication to generate an immune response, the manufacturer of live-attenuated typhoid vaccine and the Centers for Disease Control (CDC) state that the vaccine should not be administered to patients receiving antimicrobial therapy.(1-3)	VIVOTIF
Dofetilide/Cephalexin SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Dofetilide is primarily excreted in the urine via both glomerular filtration and active tubular secretion via the cation transport system. Cephalexin may inhibit the excretion of dofetilide by the renal cation transport system.(1) CLINICAL EFFECTS: Concurrent use of dofetilide with cephalexin may result in increased levels of and toxicities of dofetilide, including potentially life-threatening cardiac arrhythmias, like torsades de pointes (TdP).(1,2) PREDISPOSING FACTORS: Risk factors for QT prolongation include: cardiovascular disease (e.g. heart failure, recent myocardial infarction, history of torsades de pointes, congenital long QT syndrome), female sex, hypokalemia, hypomagnesemia, hypocalcemia, bradycardia, advanced age, and concurrent use of agents known to cause QT prolongation.(2) Concurrent use of more than one drug known to cause QT prolongation or higher systemic concentrations of either QT prolonging drug are additional risk factors for torsades de pointes. Factors which may increase systemic drug concentrations include rapid infusion of an intravenous dose or impaired metabolism or elimination of the drug (e.g. coadministration with an agent which inhibits its metabolism or elimination, genetic impairment in drug metabolism or elimination, and/or renal/hepatic dysfunction).(2) Renal impairment may increase risk for excessive QTc prolongation as dofetilide is primarily renally eliminated. To prevent increased serum levels and risk for ventricular arrhythmias, dofetilide must be dose adjusted for creatinine clearance < or = to 60 mL/min.(1) PATIENT MANAGEMENT: The manufacturer of dofetilide states that all renal cation transport inhibitors are contraindicated.(1) If dofetilide is to be discontinued, a washout of at least 2 days is recommended prior to starting cephalexin.(1) If concurrent therapy is warranted, consider obtaining serum calcium, magnesium, and potassium levels and monitoring ECG at baseline and at regular intervals. Correct any electrolyte abnormalities. Instruct patients to report any irregular heartbeat, dizziness, or fainting. DISCUSSION: While the combination of dofetilide and cephalexin has not been studied, clinical data is available for the combination of dofetilide with other renal transport inhibitors, and for cephalexin with other renal transport substrates. In a study, cephalexin 500 mg with metformin 500 mg increased the mean metformin concentration maximum (Cmax) and area-under-curve (AUC) by an average of 34% and 24%, respectively, and metformin mean renal clearance decreased by 14%. Metformin is a MATE and OCT2 substrate.(3) Dofetilide is primarily excreted in the urine via both glomerular filtration and active tubular secretion via the cation transport system. The concurrent administration of dofetilide (500 mcg twice daily) with cimetidine (a MATE and OCT2 inhibitor)(400 mg twice daily) resulted in an increase in dofetilide plasma levels by 58%. The concurrent administration of dofetilide (500 mcg single dose) with cimetidine (100 mg twice daily) resulted in an increase in dofetilide plasma levels by 13%.(1)	DOFETILIDE, TIKOSYN

Drug contraindication overview.

No enhanced Contraindications information available for this drug.

Adverse reaction overview.

No enhanced Common Adverse Effects information available for this drug.

No enhanced Pediatric Use information available for this drug.

Contraindicated

None

Severe Precaution

None

Management or Monitoring Precaution

None