Cefalexin Other names: Cephalexin

Creatinine clearance 30 to 59 mL/min: No dose adjustment; maximum daily dose should not exceed 1 g.

Cefalexin should be administered with careful monitoring in the presence of renal impairment (creatinine clearance <30 mL/min, with or without dialysis). Under such conditions, careful clinical observation and laboratory studies renal function monitoring should be conducted because safe dosage may be lower than that usually recommended. Monitor patients longer for toxicity and drug interactions due to delayed clearance.

Recommended dose regimen for patients with severe renal impairment:

Hypokalaemia has been described in patient taking cytotoxic drugs for leukaemia when they were given gentamicin and cephalexin.

Cephalosporins may have an increased risk of nephrotoxicity in the presence of amphotericin, loop diuretics, aminoglycosides, capreomycin or vancomycin.

Administration of cefalexin with metformin results in increased plasma metformin concentrations and decreased renal clearance of metformin.

Careful patient monitoring and dose adjustment of metformin is recommended in patients concomitantly taking cefalexin and metformin.

In a single study of 12 healthy subjects given single 500 mg doses of cefalexin and metformin, plasma metformin C_max and AUC increased by an average of 34% and 24%, respectively, and metformin renal clearance decreased by an average of 14%. No side-effects were reported in the 12 healthy subjects in this study. No information is available about the interaction of cefalexin and metformin following multiple dose administration. The clinical significance of this study is unclear, particularly as no cases of “lactic acidosis” have been reported in association with concomitant metformin and cefalexin treatment.

As with other beta-lactam drugs, renal excretion of cefalexin is inhibited by probenecid. Probenecid causes reduced excretion of cefalexin leading to increased plasma concentrations. Co-administration of probenecid with cefalexin is not recommended.

Cephalosporins should be given with caution to penicillin-sensitive patients, as there is some evidence of partial cross-allergenicity between the penicillins and the cephalosporins. Patients have had severe reactions (including anaphylaxis) to both drugs.

Although laboratory and clinical studies have shown no evidence of teratogenicity, caution should be exercised when prescribing for the pregnant patient.

Risk Summary

Available data from published epidemiologic studies and pharmacovigilance case reports over several decades with cephalosporin use, including cefalexin use in pregnant women have not established drug-associated risks of major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Data).

Animal reproduction studies with mice and rats using oral doses of cefalexin that are 0.6- and 1.2-times the maximum recommended human dose (MRHD) based on body surface area during organogenesis revealed no evidence of harm to the fetus (see Data).

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Data

Human Data

While available studies cannot definitively establish the absence of risk, published data from epidemiologic studies and postmarketing case reports over several decades have not identified a consistent association with cephalosporin use, including cefalexin, during pregnancy, and major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Available studies have methodologic limitations, including small sample size, retrospective data collection, and inconsistent comparator groups.

Animal data

In animal reproduction studies, pregnant mice and rats administered oral cefalexin doses of 250 or 500 mg/kg/day (approximately 0.6 and 1.2 times the MRHD) based on body surface area, respectively during the period of organogenesis showed no adverse effects on embryofetal development.

In a pre- and post-natal developmental toxicity study, pregnant rats that received oral doses of 250 or 500 mg/kg/day of cefalexin from Day 15 of pregnancy to litter Day 21 showed no adverse effects on parturition, litter size, or growth of offspring.

Risk Summary

Data from a published clinical lactation study reports that cefalexin is present in human milk. The Relative Infant Dose (RID) is considered to be <l% of the maternal weight adjusted dose. There are no data on the effects of cefalexin on the breastfed child or on milk production.

The development of health benefits of breastfeeding should be considered along with the mother’s clinical need for cefalexin and any potential adverse effects on the breastfed child from cefalexin or from the underlying maternal condition.

Not relevant.

Gastro-intestinal: Symptoms of pseudomembranous colitis may appear either during or after antibiotic treatment. Nausea and vomiting have been reported rarely. The most frequent side-effect has been diarrhoea. It was very rarely severe enough to warrant cessation of therapy. Dyspepsia and abdominal pain have also occurred. As with some penicillins and some other cephalosporins, transient hepatitis and cholestatic jaundice have been reported rarely.

Hypersensitivity: Allergic reactions have been observed in the form of rash, urticaria, angiooedema, rarely erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis. These reactions usually subside upon discontinuation of the drug, although in some cases supportive therapy may be necessary. Anaphylaxis has also been reported.

Haemic and Lymphatic System: Eosinophilia, neutropenia, thrombocytopenia, haemolytic anaemia and positive Coombs' test have been reported.

Hepatic: As with some penicillins and some other cephalosporins, transient hepatitis and cholestatic jaundice have been reported rarely. Slight elevations of AST and ALT have been reported.

Skin and subcutaneous tissue disorders: Acute generalised exanthematous pustulosis (AGEP) has been reported with unknown frequency.

Other: These have included genital and anal pruritus, genital moniliasis, vaginitis and vaginal discharge, dizziness, fatigue, headache, agitation, confusion, hallucinations, fever, arthralgia, arthritis and joint disorder, acute generalised exanthematous pustulosis (AGEP), hyperactivity, nervousness, sleep disturbances and hypertonia. Reversible interstitial nephritis has been reported rarely Slight elevations in AST and ALT have been observed rarely.