is there any evidence for bone marrow suppresion from cefpodoxime

Background

A 2021 narrative review of β-lactam-associated neutropenia reported that neutropenia is a well-documented class adverse reaction, occurring most often after approximately 2 to 3 weeks of parenteral therapy; both direct toxic and immune-mediated mechanisms have been implicated. Orally administered β-lactams were excluded because associated neutropenia was described as remarkably rare. Cefpodoxime was mentioned only as sharing an R1 side chain with ceftriaxone, cefotaxime, and cefepime; the review presented no cefpodoxime-specific cases or clinical data demonstrating neutropenia or broader bone marrow suppression. Therefore, this review provides class-level evidence for β-lactam–associated neutropenia but no direct evidence specific to cefpodoxime. [1]

Relevant Prescribing Information

ADVERSE REACTIONS [2]
Laboratory Changes - Significant laboratory changes that have been reported in adult and pediatric patients in clinical trials of cefpodoxime proxetil, without regard to drug relationship, were:

Hepatic: Transient increases in AST (SGOT), ALT (SGPT), GGT, alkaline phosphatase, bilirubin, and LDH.

Hematologic: Eosinophilia, leukocytosis, lymphocytosis, granulocytosis, basophilia, monocytosis, thrombocytosis, decreased hemoglobin, decreased hematocrit, leukopenia, neutropenia, lymphocytopenia, thrombocytopenia, thrombocythemia, positive Coombs’ test, and prolonged PT, and PTT.

Serum Chemistry: Hyperglycemia, hypoglycemia, hypoalbuminemia, hypoproteinemia, hyperkalemia, and hyponatremia.

Renal: Increases in BUN and creatinine.

Most of these abnormalities were transient and not clinically significant.

Literature Review

A search of the published medical literature revealed 1 study investigating the researchable question:

is there an evidence for bone marrow suppresion from cefpodoxime

Level of evidence

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Review of Clinical Experience in the United States with Cefpodoxime Proxetil in Adults with Uncomplicated Urinary Tract Infections
Design	Review reporting 2 previously unpublished, prospective, multicenter, double-blind, randomized, parallel-group, comparative phase 3 trials N= 1137
Objective	To compare the safety and efficacy of cefpodoxime proxetil with cefaclor and amoxicillin in patients with uncomplicated urinary tract infections (UTIs)
Study Groups	Cefpodoxime proxetil (n= 762) Cefaclor (n= 190) Amoxicillin (n= 185)
Inclusion Criteria	Male or female patients aged 12 years or older with bacteriuria and pyuria, and at least 1 sign or symptom typical of UTIs
Exclusion Criteria	Patients who were asymptomatic, had complicated UTIs, or had a history of allergy to cephalosporins, cephamycins, or penicillins. Also excluded were those with significant hepatic or renal dysfunction, impaired immunological function, or a history of antibiotic-associated colitis
Methods	Patients were randomized 2:1 to cefpodoxime proxetil or a comparator. In one trial, cefpodoxime proxetil was compared with cefaclor; in the second, it was compared with amoxicillin. Clinical adverse experiences were assessed at every visit and classified by intensity and relationship to study medication. Hematology, blood chemistry, and urinalysis were performed before and at the end of therapy. Laboratory adverse experiences were defined as changes from baseline judged by the investigator to be clinically important, irrespective of drug-relatedness. Safety analyses included all patients exposed to study medication.
Duration	7 days treatment with follow-up 4 to 6 weeks after the last dose
Outcome Measures	Bacteriological cure rate; clinical cure rate; overall bacteriological eradication; clinically important changes from baseline in hematologic laboratory values, including hemoglobin, hematocrit, white blood cell count, and polymorphonuclear leukocyte count
Baseline Characteristics		Cefpodoxime proxetil (n= 188)	Cefaclor (n= 99)
	Mean age, years	38.4 ± 18.25	33 ± 15.34
	Female	179 (95%)	98 (99%)
	Race White Black Other	144 (77%) 40 (21%) 4 (2%)	80 (81%) 16 (16%) 3 (3%)
	Mean duration of UTI, days	4.5 ± 6.77	4.9 ± 5.73
	The cefpodoxime and cefaclor groups differed significantly in mean age (p= 0.012); the remaining listed comparisons were not reported as statistically significant.
Results		Cefpodoxime proxetil (n= 307)	Cefaclor (n= 99)	Amoxicillin (n= 57)
	Bacteriological cure	247 (80%)	81 (82%)	40/ (70%)
	Clinical cure	242 (79%)	78 (79%)	41 (72%)
	Overall bacteriological eradication	200 (79%)	61 (81%)	33 (69%)
	Among 762 cefpodoxime-treated patients, clinically important laboratory changes occurred in 6 of 378 (1.6%) patients in the cefaclor-controlled trial and 12 of 384 (3%) patients in the amoxicillin-controlled trial. Reported hematologic changes included hemoglobin and hematocrit abnormalities and decreases below normal limits in white blood cell or polymorphonuclear leukocyte counts; however, the number of patients experiencing each specific abnormality was not reported. Overall adverse events occurred in 234 of 762 (31%) cefpodoxime recipients, including moderate drug-related events in 52 (7%), severe drug-related events in 5 (<1%), and adverse events resulting in discontinuation in 12 (2%). No serious hematologic adverse events were reported.
Adverse Events	Cefpodoxime proxetil was well tolerated with no significant difference in the overall incidence of adverse experiences compared to cefaclor and amoxicillin. Common adverse events included gastrointestinal issues such as diarrhea and nausea, and genital tract issues such as candidiasis/vaginitis.
Study Author Conclusions	The type, severity, and incidence of adverse events observed in patients treated with cefpodoxime proxetil were typical of those associated with β-lactam antibacterial therapy. Thus, cefpodoxime proxetil has been shown to be a clinically useful therapeutic agent and is an effective alternative in the treatment of patients with uncomplicated urinary tract infections.
Critique	The large randomized safety population and protocol-specified pre- and post-treatment hematology testing identified clinically important decreases in hemoglobin, hematocrit, WBC count, and polymorphonuclear leukocytes among laboratory abnormalities observed with cefpodoxime. However, the authors reported only aggregate numbers for all laboratory abnormalities and did not provide event-specific incidence, magnitude, timing, reversibility, or evidence of impaired marrow production; consequently, the findings indicate hematologic laboratory changes but do not establish cefpodoxime-induced bone marrow suppression.

Table 1 References:
[3] Cox CE, Graveline JF, Luongo JM. Review of clinical experience in the United States with cefpodoxime proxetil in adults with uncomplicated urinary tract infections. Drugs. 1991;42(suppl 3):41-50.