Nitrofurantoin and Keflex (Cephalexin) Interaction
There is no clinically significant drug interaction between nitrofurantoin and cephalexin (Keflex), and these antibiotics can be used sequentially or in combination without concern for direct pharmacological interactions. 1, 2
Evidence for Safety of Combined or Sequential Use
Clinical studies demonstrate safe sequential use: A 1975 study comparing long-term urinary tract infection treatment with either cephalexin or nitrofurantoin as single evening doses showed both agents were effective and well-tolerated, with no reported interactions when patients were switched between medications. 1
Real-world case reports confirm sequential safety: A 2023 case report documented a patient who received nitrofurantoin followed by cephalexin for persistent urinary frequency, and while the patient developed SIADH-related hyponatremia, this was attributed to nitrofurantoin alone rather than any interaction between the two drugs. 2
Pediatric data supports combination safety: A 1984 prospective study in children with lower urinary tract infections compared 3-day cephalexin therapy with 10-day nitrofurantoin therapy, showing comparable efficacy (90% vs 96% cure rates) and no adverse interactions or safety concerns. 3
Clinical Context for Use
Both antibiotics are commonly prescribed for urinary tract infections and may be used in the following scenarios:
Sequential therapy: When initial treatment with one agent fails or when switching based on culture results. 4
Different clinical indications: Nitrofurantoin is preferred for uncomplicated cystitis, while cephalexin may be used for other infections or when nitrofurantoin is contraindicated. 5, 6
Prophylactic regimens: Nitrofurantoin 100 mg daily is a standard prophylactic option for recurrent UTIs in women, while cephalexin is not typically used for this indication. 6
Important Safety Considerations (Not Related to Drug Interaction)
Nitrofurantoin-specific toxicities: Pulmonary and hepatic toxicity can occur with long-term use, and nitrofurantoin should be avoided in patients with eGFR <30 mL/min/1.73m². 6
Nitrofurantoin and SIADH: Rare cases of severe hyponatremia secondary to SIADH have been reported with nitrofurantoin use, which can present with seizures and requires immediate recognition. 2
Cephalexin considerations: First-generation cephalosporins like cephalexin are associated with lower antibiotic switch rates compared to other UTI antibiotics, suggesting good clinical effectiveness. 4
Practical Prescribing Guidance
When prescribing these medications together or sequentially:
Monitor for individual drug adverse effects rather than interaction-related complications, as no pharmacokinetic or pharmacodynamic interactions exist. 1, 2
Consider resistance patterns: Antibiotic selection should be based on local susceptibility data and previous culture results when available. 5, 6
Duration matters: For cystitis, nitrofurantoin is typically given for 5 days, while cephalexin may require 7 days for pyelonephritis. 5