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Cefpodoxime
Cefpodoxime
Cefpodoxime
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Cefpodoxime
Clinical data
Trade namesVantin, others
Other namesCefpodoxime proxetil
AHFS/Drugs.comMonograph
MedlinePlusa698024
Pregnancy
category
  • AU: B1
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability50%
Protein binding21% to 29%
MetabolismNegligible. Cefpodoxime proxetil is metabolized to cefpodoxime by the liver
Elimination half-life2 hours
ExcretionKidney, unchanged
Identifiers
  • (6R,7R)-7-{[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyimino-acetyl]amino}-3-(methoxymethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.210.871 Edit this at Wikidata
Chemical and physical data
FormulaC15H17N5O6S2
Molar mass427.45 g·mol−1
3D model (JSmol)
  • O=C2N1/C(=C(\CS[C@@H]1[C@@H]2NC(=O)C(=N\OC)/c3nc(sc3)N)COC)C(=O)O
  • InChI=1S/C15H17N5O6S2/c1-25-3-6-4-27-13-9(12(22)20(13)10(6)14(23)24)18-11(21)8(19-26-2)7-5-28-15(16)17-7/h5,9,13H,3-4H2,1-2H3,(H2,16,17)(H,18,21)(H,23,24)/b19-8-/t9-,13-/m1/s1 checkY
  • Key:WYUSVOMTXWRGEK-HBWVYFAYSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Cefpodoxime is an oral, third-generation cephalosporin antibiotic available in various generic preparations. It is active against both Gram-positive and Gram-negative organisms with notable exceptions including Pseudomonas aeruginosa, Enterococcus, and Bacteroides fragilis. It is typically used to treat acute otitis media, pharyngitis, sinusitis, and gonorrhea. It also finds use as oral continuation therapy when intravenous cephalosporins (such as ceftriaxone) are no longer necessary for continued treatment.

Cefpodoxime inhibits peptidoglycan synthesis in bacterial cell walls. It has an oral bioavailability of approximately 50%, which is increased when taken with food. It has an elimination half-life of 2-3 hours in adults, which is prolonged in renal failure. Approved indications include community acquired pneumonia, uncomplicated skin and skin structure infections, and uncomplicated urinary tract infections.

It was patented in 1980 and approved for medical use in 1989.[1]

Spectrum of bacterial susceptibility and resistance

[edit]

Cefpodoxime has been used to treat gonorrhoea, tonsillitis, pneumonia, and bronchitis. The following minimum inhibitory concentrations have been reported:[2]

  • Haemophilus influenzae: ≤0.03 – 1 μg/ml
  • Neisseria gonorrhoeae: 0.004 – 0.06 μg/ml
  • Streptococcus pyogenes: ≤0.004 – 2 μg/ml

Brand names

[edit]

Zoetis markets cefpodoxime proxetil under the trade name Simplicef for veterinary use, and Finecure in India markets the drug as Cefpo.[3][4]

Vantin (by Pfizer)[5] in suspension or tablet form.

Toraxim (by Delta Pharma Ltd., Bangladesh)

Trucef (by Renata Limited, Bangladesh)

Tricef (by Alkaloid Skopje, North Macedonia)

Orelox (by Sanofi-Aventis)[6]

MAPDOX-CV: Combination cefpodoxime–clavulanic acid[by whom?]

MONOTAX O (cefpodoxime)/MONOTAX CV (cefpodoxime–clavulanic acid) by Zydus Healthcare Ltd.

ACXIME 200/CV (by Allencia Biosciences, India)

POSTPOD-50 (cefpodoxime 50mg/5ml) by Laafon Galaxy Pharmaceuticals[7]

References

[edit]
[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Cefpodoxime

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from Grokipedia
Cefpodoxime is an oral third-generation used to treat mild to moderate bacterial infections, administered as the cefpodoxime proxetil which is de-esterified in the gut to the active form. Developed by Sankyo Co., Ltd. in , cefpodoxime proxetil received FDA approval on August 7, 1992, under the brand name Vantin (now discontinued; available as generic) for indications including acute and . Its chemical name is (6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-3-(methoxymethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, with a molecular formula of C₁₅H₁₇N₅O₆S₂ and molecular weight of 427.5 g/mol. Cefpodoxime works by inhibiting bacterial synthesis through binding to , particularly protein 3, and is stable against many plasmid-mediated beta-lactamases produced by . It exhibits a broad antibacterial spectrum effective against most Gram-positive and Gram-negative organisms, including , , and , but lacks activity against Pseudomonas aeruginosa, enterococci, and . Common indications include acute , acute bacterial exacerbations of chronic bronchitis, skin and soft tissue infections, and urinary tract infections caused by susceptible strains. It is typically dosed every 12 hours for 5 to 14 days and is available as film-coated tablets or oral suspension. The drug's show good oral , a of approximately 2 to 3 hours, and primary renal , with dosage adjustments recommended for patients with impaired function. Precautions include avoiding use in individuals with to cephalosporins or penicillins due to risk, and caution in those with gastrointestinal disorders or on estrogen-based contraceptives, as it may reduce their efficacy. Like other antibiotics, cefpodoxime should only be used for confirmed or suspected bacterial infections to minimize resistance development.

Medical uses

Indications

Cefpodoxime is approved for the treatment of mild to moderate bacterial infections caused by susceptible strains of designated microorganisms, including acute due to Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae, or Moraxella catarrhalis; and due to S. pyogenes; due to S. pneumoniae or H. influenzae; acute bacterial exacerbations of chronic due to S. pneumoniae, H. influenzae (non-beta-lactamase-producing strains), or M. catarrhalis; acute uncomplicated (urethral, cervical, or anorectal in women) due to Neisseria gonorrhoeae; uncomplicated skin and skin structure infections due to Staphylococcus aureus or S. pyogenes; acute maxillary due to H. influenzae, S. pneumoniae, or M. catarrhalis; and uncomplicated urinary tract infections (cystitis) due to Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, or Staphylococcus saprophyticus. The drug is indicated for use in adults and pediatric patients aged 2 months and older, with safety and efficacy established in children 2 months through 12 years for acute , /, and acute maxillary , though not for infants under 2 months. In , cefpodoxime is classified as Category B, indicating no of in but insufficient controlled in humans, and it should be used only if clearly needed. It is also considered compatible with , as low concentrations appear in with no reported adverse effects in nursing infants. Clinical trials have demonstrated high efficacy for respiratory tract infections, with success rates of 92% to 100% in pediatric pharyngotonsillitis, 84% to 97% in bronchial infections, and 81.8% to 100% in . For acute , controlled studies reported clinical success rates of approximately 67% to 92%, with bacterial eradication rates varying by (e.g., 72% for S. pneumoniae). In uncomplicated cystitis, bacterial eradication rates reached 82% at 5 to 9 days post-therapy. Off-label, cefpodoxime is commonly used as oral step-down following intravenous cephalosporins for mild infections or in patients with penicillin allergy, particularly after initial parenteral treatment for conditions like or urinary tract infections, though it is not recommended for bacteremic infections due to limited serum bioavailability.

Dosage and administration

Cefpodoxime proxetil is administered orally as tablets or suspension for treating bacterial infections such as upper and lower infections, urinary tract infections, skin and skin structure infections, and acute . In adults and adolescents aged 12 years and older, the standard dosing range is 100 to 400 mg every 12 hours, adjusted based on the infection's severity and site; for example, 200 mg every 12 hours for 14 days is recommended for , while 400 mg every 12 hours for 7 to 14 days is used for skin and skin structure infections. For uncomplicated , a single 200 mg dose is given. Treatment durations typically range from 5 to 14 days depending on the indication. For pediatric patients aged 2 months to 12 years, the recommended dose is 5 mg/kg body weight every 12 hours, with a maximum of 200 mg per dose and 400 mg daily; for instance, this applies to (5 days duration) and (10 days duration). In children with or , the maximum is 100 mg per dose and 200 mg daily for 5 to 10 days. Dose adjustments are required in renal impairment; for creatinine clearance less than 30 mL/min, the dosing interval should be extended to every 24 hours, and for patients on , the usual dose is given three times weekly following dialysis. No dosage adjustment is necessary in hepatic impairment or . Cefpodoxime proxetil is formulated as an oral to improve , available as 100 mg or 200 mg tablets or as an oral suspension (50 mg/5 mL or 100 mg/5 mL after reconstitution). Tablets should be taken with to enhance absorption, while the suspension may be taken with or without ; shake the suspension well before use and store reconstituted suspension in the refrigerator, discarding after 14 days.

Contraindications and precautions

Contraindications

Cefpodoxime is contraindicated in patients with known to the drug itself or to other antibiotics, as severe allergic reactions, including , may occur. Additionally, individuals with a history of anaphylactic reactions to beta-lactam antibiotics, such as penicillins, should avoid cefpodoxime due to the risk of cross-, which occurs in approximately 2% or less of patients with confirmed IgE-mediated penicillin . Relative contraindications include severe renal impairment, where dosage adjustment is essential to prevent accumulation and potential ; in patients with clearance <30 mL/min, the dosing interval should be extended to every 24 hours. For patients undergoing hemodialysis, the recommended dose is administered three times per week following dialysis. Patients with a history of colitis or Clostridium difficile-associated infection require caution, as cefpodoxime use may precipitate or exacerbate pseudomembranous colitis, a potentially life-threatening condition. Furthermore, the oral suspension form is contraindicated in patients with phenylketonuria (PKU) because it contains aspartame, which metabolizes to phenylalanine and can elevate blood phenylalanine levels in susceptible individuals. In special populations, cefpodoxime should be avoided in neonates and infants younger than 2 months of age, as safety and efficacy have not been established in this group. Prior to initiating therapy, a thorough assessment of allergy history is mandatory to identify any prior hypersensitivity reactions, and baseline renal function tests are recommended, particularly in patients with risk factors for impairment, to guide dosing and monitor for adjustments. Pregnancy and lactation: Cefpodoxime is classified as pregnancy category B; it has not been associated with adverse effects in animal reproduction studies, but there are no adequate and well-controlled studies in pregnant women. The drug crosses the placenta. It is excreted in human milk in low concentrations; caution is advised when administering to nursing mothers, and consideration should be given to temporary discontinuation of nursing or the drug.

Drug interactions

Cefpodoxime exhibits several significant drug interactions that can alter its pharmacokinetics and increase the risk of adverse effects. Probenecid inhibits the renal excretion of cefpodoxime, leading to an approximately 31% increase in area under the curve (AUC) and a 20% increase in peak plasma levels. Concomitant administration of high doses of antacids, such as those containing sodium bicarbonate and aluminum hydroxide, H2-receptor antagonists like ranitidine, or proton pump inhibitors such as omeprazole reduces peak plasma levels of cefpodoxime by 24% to 42% and the extent of absorption by 27% to 40%; these agents increase gastric pH, leading to decreased dissolution and bioavailability of cefpodoxime proxetil, which may decrease its efficacy against infections. It is recommended to avoid coadministration or consider alternative antibiotics; where separation is feasible, these should be separated by at least two hours to minimize interference. Moderate interactions include those with nephrotoxic agents, such as aminoglycosides, which may potentiate renal toxicity when co-administered with cefpodoxime; close monitoring of renal function is recommended in such cases. Additionally, cefpodoxime may reduce the efficacy of oral contraceptives through gastrointestinal effects that alter absorption, necessitating the use of alternative contraception methods during treatment. Food interactions enhance cefpodoxime bioavailability, with meals increasing AUC by 21% to 33% and peak concentrations from 2.6 mcg/mL (fasting) to 3.1 mcg/mL; administration with food is advised to optimize absorption. Concurrent use with iron supplements or multivitamins containing minerals like aluminum, magnesium, or calcium should be avoided or timed at least two hours apart, as these can chelate cefpodoxime and reduce its absorption. Laboratory test interactions with cefpodoxime include occasional false-positive results for urine glucose using copper reduction methods, such as Benedict's or Fehling's solutions, though enzymatic tests remain unaffected. Cephalosporins like cefpodoxime may also induce a positive direct Coombs' test.

Adverse effects

Common side effects

The most common side effects of cefpodoxime are mild and primarily affect the gastrointestinal tract, occurring in more than 1% of patients across clinical trials. Diarrhea is the most frequent, reported in up to 15% of pediatric patients (particularly infants and toddlers) and 5.7% to 10.4% of adults depending on dose, often linked to disruption of gut flora by the drug's broad-spectrum antibacterial activity. Nausea affects 3% to 5% of patients, vomiting 2% to 4%, and abdominal pain about 2%. Other common side effects include headache in 1% to 2% of patients and rash in approximately 1%. In females, vaginitis or vulvovaginal infections occur in about 1%. In clinical trials for respiratory tract infections, overall gastrointestinal complaints were reported in around 11% of patients treated with cefpodoxime. These effects are typically self-limiting and managed symptomatically with hydration or antidiarrheal agents if needed; most resolve without discontinuing the medication.

Serious adverse effects

Serious adverse effects associated with cefpodoxime are uncommon but can be severe, potentially requiring hospitalization or immediate intervention, and are primarily identified through post-marketing surveillance. Allergic reactions represent a critical concern, including anaphylaxis that may demand epinephrine and other emergency measures, as well as severe dermatologic manifestations such as Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, and serum sickness-like reactions; these occur with an incidence of less than 0.1%. Patients with prior penicillin hypersensitivity face a higher risk of cross-reactivity with cefpodoxime. Gastrointestinal complications include Clostridium difficile-associated diarrhea (CDAD), which can range from mild to fatal pseudomembranous colitis and may manifest up to two months following treatment cessation due to overgrowth of toxin-producing C. difficile strains. Hematologic effects, though rare with an incidence below 1%, encompass thrombocytopenia, leukopenia, and prolonged prothrombin time, alongside class-wide risks like hemolytic anemia and agranulocytosis observed in cephalosporin use. Other serious reactions involve seizures, particularly in patients with renal impairment where dosage adjustment is inadequate; hepatotoxicity manifesting as acute liver injury; and interstitial nephritis, including purpuric forms leading to renal dysfunction. These events are tracked via FDA post-marketing surveillance to monitor ongoing safety.

Pharmacology

Mechanism of action

Cefpodoxime, a third-generation cephalosporin, functions as a beta-lactam antibiotic by covalently binding to penicillin-binding proteins (PBPs), which are transpeptidase enzymes essential for bacterial cell wall synthesis. This binding inhibits the cross-linking of peptidoglycan strands in the cell wall, disrupting the structural integrity required for bacterial survival. Primarily, cefpodoxime targets PBP-3 in Gram-negative bacteria, such as Escherichia coli, with high affinity (I50 of 1 mg/L), leading to filamentation and eventual . The inhibition of cross-linking by cefpodoxime triggers the activation of autolytic enzymes in susceptible bacteria, resulting in bactericidal activity through . This mechanism is time-dependent, with efficacy optimized when the drug concentration exceeds the for a significant portion of the dosing interval. Unlike bacteriostatic agents, cefpodoxime's action directly causes bacterial death in actively growing cells. Cefpodoxime demonstrates stability against hydrolysis by some chromosomal beta-lactamases, including those produced by certain like Neisseria and Haemophilus species, allowing it to retain activity against beta-lactamase-producing strains that resist earlier cephalosporins. However, it is hydrolyzed by extended-spectrum beta-lactamases (ESBLs), limiting its utility against organisms expressing these enzymes. The enhanced Gram-negative spectrum of cefpodoxime compared to first-generation cephalosporins stems from its superior affinity for PBPs in these organisms and partial resistance to their beta-lactamases, enabling broader coverage without compromising core bactericidal effects.

Pharmacokinetics

Cefpodoxime proxetil, the oral form of cefpodoxime, exhibits approximately 50% absolute in fasting adults following oral administration. It is hydrolyzed by intestinal esterases to the active cefpodoxime during absorption. The presence of food enhances absorption, increasing the area under the curve (AUC) by 21-33% and peak plasma concentrations (C_max) by about 20-30%, while time to maximum concentration (T_max) occurs 2-3 hours post-dose. The volume of distribution for cefpodoxime is approximately 0.3-0.4 L/kg, reflecting limited distribution primarily to . It penetrates well into tissues, such as parenchyma (concentrations up to 0.63 mcg/g), tonsillar tissue (0.24 mcg/g), and blister (penetration ratios of 67-104%), as well as achieving high urinary concentrations due to renal excretion. However, penetration into (CSF) is poor, with CSF/plasma ratios averaging about 5%. Cefpodoxime undergoes minimal hepatic metabolism and is primarily excreted unchanged. Approximately 29-33% of the administered dose is eliminated renally via glomerular filtration within 12 hours, with the remainder excreted in feces as unabsorbed prodrug or metabolites. The elimination half-life is 2-3 hours in individuals with normal renal function but prolongs to 5-10 hours in those with moderate to severe renal impairment. Plasma protein binding of cefpodoxime ranges from 21-29%. This relatively low binding contributes to its favorable tissue penetration in accessible sites.

Spectrum of activity

Susceptible organisms

Cefpodoxime demonstrates significant and clinical activity against a range of , particularly streptococci. It is highly effective against , with minimum inhibitory concentrations (MICs) typically ranging from ≤0.03 to 1 μg/mL for susceptible strains. Similarly, shows excellent susceptibility, with MICs of ≤0.004 to 0.12 μg/mL. For methicillin-sensitive , cefpodoxime exhibits moderate activity, with MICs generally in the range of 1 to 4 μg/mL. Among gram-negative organisms, cefpodoxime is active against several respiratory and uropathogens, including beta-lactamase-producing strains. Haemophilus influenzae is highly susceptible, with MICs of ≤0.03 to 1 μg/mL, even among beta-lactamase producers. Neisseria gonorrhoeae displays strong sensitivity, with MICs ranging from 0.004 to 0.06 μg/mL. Moraxella catarrhalis is consistently susceptible, as is Escherichia coli in community-acquired infections, where MICs for quality control strains fall between 0.25 and 1 μg/mL (note: this is a QC range for ATCC 25922, not clinical isolates). Cefpodoxime has limited activity against anaerobes, with variable inhibition of species at concentrations of 0.25 to 8 μg/mL. As of 2014, clinical susceptibility was guided by FDA-recognized breakpoints: for , susceptible at ≤2 μg/mL; for Haemophilus influenzae, susceptible at ≤2 μg/mL; for Streptococcus pneumoniae, susceptible at ≤0.5 μg/mL; and for , susceptible at ≤0.5 μg/mL. However, CLSI has removed specific breakpoints for cefpodoxime since 2010, and current testing often relies on pharmacokinetic/pharmacodynamic (PK/PD) data or surrogate markers (e.g., penicillin MIC ≤0.06 μg/mL predicts cefpodoxime susceptibility in S. pneumoniae). For , USCAST recommends susceptible at ≤1 μg/mL for high-dose regimens (400 mg every 12 hours) as of 2025. These reflect cefpodoxime's bactericidal action via inhibition of synthesis in susceptible pathogens.
OrganismRepresentative MIC Range (μg/mL)Source
Streptococcus pneumoniae≤0.03–1FDA Label (2014)
≤0.004–0.12PubMed Study
Methicillin-sensitive Staphylococcus aureus1–4AAC Journal
(incl. β-lactamase+)≤0.03–1FDA Label (2014)
0.004–0.06FDA Label (2014)
(QC strain)0.25–1FDA Label (2014)
spp.0.25–8 (limited)PubMed Study

Resistance mechanisms

Bacterial resistance to cefpodoxime, a third-generation , primarily arises through several well-characterized mechanisms that undermine its bactericidal action by targeting (PBPs) in the . One predominant mechanism is the production of beta-lactamases, enzymes that hydrolyze the beta-lactam ring essential for the drug's activity. Extended-spectrum beta-lactamases (ESBLs), such as those encoded by CTX-M or TEM variants, effectively degrade cefpodoxime, rendering it ineffective against producing strains. This resistance is particularly common in like Escherichia coli and Klebsiella pneumoniae, where ESBL production correlates with cefpodoxime minimum inhibitory concentrations (MICs) ≥2 mg/L, serving as a reliable phenotypic screen for ESBL detection. Another key resistance pathway involves alterations in PBPs, which reduce the drug's affinity for these essential enzymes. In , penicillin-resistant strains often exhibit mutations in PBPs 1A, 2B, and 2X, leading to decreased binding not only to penicillins but also to cephalosporins like cefpodoxime. These modifications elevate MICs above 2 μg/mL, classifying strains as intermediate or resistant and complicating treatment of community-acquired respiratory infections. In , additional barriers include efflux pumps and loss of outer membrane porins, which limit intracellular drug accumulation. Multidrug resistance efflux systems, such as MexAB-OprM in , actively expel cefpodoxime, contributing to intrinsic resistance in this pathogen, while porin mutations further decrease permeability. These mechanisms often combine with production, amplifying resistance. P. aeruginosa remains inherently resistant to cefpodoxime due to these factors, highlighting its unsuitability for pseudomonal infections. Resistance prevalence is rising in community settings, driven by selective pressure from antibiotic overuse. For instance, as of 2024, approximately 35% of Haemophilus influenzae isolates globally produce s, conferring resistance to earlier cephalosporins but variable susceptibility to cefpodoxime, which retains activity against many non-ESBL producers (though -negative ampicillin-resistant [BLNAR] strains may show reduced susceptibility due to PBP alterations). To counter this trend, with inhibitors or alternative agents is increasingly employed for suspected resistant infections. Routine susceptibility testing is strongly recommended prior to cefpodoxime initiation to guide therapy and mitigate treatment failure, as per established antimicrobial stewardship guidelines.

Chemistry and pharmacology

Chemical structure

Cefpodoxime is classified as a third-generation antibiotic, belonging to the beta-lactam class of compounds characterized by a core beta-lactam ring fused to a six-membered dihydrothiazine ring, forming the cephem nucleus. The molecular of the active form of cefpodoxime is C₁₅H₁₇N₅O₆S₂, while its , cefpodoxime proxetil, has the C₂₁H₂₇N₅O₉S₂. The IUPAC name for cefpodoxime is (6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-3-(methoxymethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid. A distinguishing structural feature is the side chain at the C-7 position, consisting of a (2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl group, which contributes to enhanced activity against and improved stability against beta-lactamases compared to earlier generations. The C-3 position bears a methoxymethyl , further defining its cephem framework. Cefpodoxime is produced through semisynthetic modification, starting from C, a isolated from of the Acremonium chrysogenum, via intermediate compounds like 7-aminocephalosporanic acid to attach the specific side chains.

Physical properties

Cefpodoxime proxetil appears as a white to off-white crystalline . It is sparingly soluble in , with reported solubility values around 0.4 mg/mL, and exhibits greater solubility in organic solvents such as and dehydrated alcohol. The compound is stable when stored at under controlled (25 °C/60% RH), but it degrades under acidic and basic conditions, highlighting its susceptibility to pH variations. As a , cefpodoxime proxetil enhances oral by masking the active moiety, which is otherwise prone to degradation in the gastric environment. The pKa values for cefpodoxime proxetil are approximately 3.73 for the strongest acidic group, while the computed logP is 0.6, indicating moderate that aids membrane permeation. These physicochemical properties influence its , particularly absorption, which is improved when taken with food due to better dissolution in the intestinal milieu. Formulation strategies account for its low aqueous and instability, employing film-coated tablets to protect the in the gastric environment and oral suspensions suitable for pediatric administration.

History and development

Discovery and patent

Cefpodoxime, a third-generation antibiotic, was discovered through collaborative research efforts by Sankyo Co., Ltd. and Ube Industries, Ltd. in during the late 1970s. This development occurred as part of broader investigations into oxime-based cephalosporins aimed at enhancing oral and expanding coverage against , addressing limitations of earlier oral agents like first- and second-generation cephalosporins. The focus on the methoxyiminoacetyl side chain at the 7-position contributed to improved stability against β-lactamases and potent activity against pathogens such as . Key inventors included Hideo Nakao, Koichi Fujimoto, Sadao Ishihara, Shinichi Sugawara, and Isamu Igarashi from Sankyo Co., Ltd., who synthesized the core compound and its ester to facilitate gastrointestinal absorption. The active form, cefpodoxime (R-3746), was first derived from modifications to existing scaffolds, with the proxetil ester (CS-807) designed as an orally active that hydrolyzes to release the parent acid. Preclinical evaluation began shortly after initial synthesis, demonstrating the compound's promise in the late 1970s. Early in vitro studies revealed cefpodoxime's broad-spectrum activity, inhibiting over 90% of tested H. influenzae strains (including β-lactamase producers) at MICs of ≤0.025 µg/ml, outperforming cefaclor (MIC₉₀ typically 1–4 µg/ml) against this respiratory pathogen. In vivo assessments in murine models of systemic infections, such as those caused by Staphylococcus aureus, Escherichia coli, and β-lactamase-positive H. influenzae, confirmed superior efficacy with oral CS-807 administration, achieving protective doses (ED₅₀) as low as 0.24–2.6 mg/kg against H. influenzae, compared to higher requirements for cefaclor. These results highlighted cefpodoxime's potential for treating community-acquired infections, particularly those involving Gram-negative organisms resistant to older oral cephalosporins. The invention was protected by U.S. Patent 4,486,425, filed on September 30, 1980, by Sankyo Co., Ltd., and issued on December 4, 1984. This patent specifically covers the synthesis and use of 7-[2-(2-aminothiazol-4-yl)-2-(syn)-methoxyiminoacetamido]-3-methoxymethyl-3-cephem-4-carboxylic acid esters, including the 1-(ethoxycarbonyloxy)ethyl (proxetil) form, emphasizing its role as an orally absorbable prodrug with enhanced pharmacokinetic properties over the free acid. The filing marked a key milestone, securing intellectual property for the prodrug innovation that enabled clinical advancement.

Regulatory approval

Cefpodoxime proxetil, marketed as Vantin by (later ), received initial U.S. (FDA) approval on August 7, 1992, for oral treatment of mild to moderate infections including acute , acute bacterial exacerbations of chronic bronchitis, uncomplicated (cervical/urethral), acute uncomplicated cystitis, and structure infections, and /. In , cefpodoxime was approved in the early under the brand name Orelox by , with indications encompassing respiratory tract infections, urinary tract infections, , and skin and soft tissue infections. The drug was first approved in in 1989 for similar bacterial infections. Approval followed in in 1992 for oral use in treating susceptible bacterial infections. For veterinary applications, the FDA approved cefpodoxime proxetil tablets (Simplicef) in July 2004 for treating skin infections, including wounds and abscesses, in dogs caused by susceptible strains of and . In November 2025, the FDA approved a new formulation of cefpodoxime proxetil tablets for veterinary use by Felixvet. Subsequent regulatory updates included FDA label revisions in , which incorporated enhanced warnings on mechanisms, such as beta-lactamase hydrolysis and alterations in , to guide appropriate use and mitigate resistance development. Post-approval studies have further evaluated its and in pediatric populations, confirming tolerability for conditions like acute with primarily gastrointestinal and dermatological adverse events. No major withdrawals or restrictions have occurred, though ongoing regulatory monitoring for resistance has been emphasized since the early due to increasing production in clinical isolates.

Society and culture

Brand names

Cefpodoxime is marketed under several brand names for human use in various regions. In the United States, it was originally sold as Vantin by , though the brand has been discontinued and replaced by generics. In , the primary brand is Orelox, produced by . In , it is available as Banan from Company. In , Podom is a common brand. Generic versions of cefpodoxime proxetil have been widely available since the original U.S. expired in 2006, allowing multiple manufacturers to produce the drug. For veterinary applications, cefpodoxime is marketed as Simplicef in the United States by , primarily for use in dogs. Generic versions for veterinary use are also available, including a approved by the FDA on October 30, 2025, by Felixvet. Cefpodoxime is available only by prescription worldwide, with over 50 generic manufacturers producing it globally, particularly in and other emerging markets. In the United States, generic 200 mg tablets cost approximately $0.50 to $1.00 per dose as of 2025 pricing.

Veterinary use

Cefpodoxime proxetil, marketed as Simplicef, received FDA approval on July 22, 2004, for use in dogs to treat skin infections, including wounds and abscesses caused by susceptible strains of and . It is not FDA-approved for cats due to insufficient safety data, though occurs under veterinary supervision. The drug's in veterinary applications mirrors its human profile, offering activity against select gram-positive and gram-negative bacteria, but therapeutic focus remains on prevalent canine pathogens like staphylococci and streptococci. The standard dosing regimen for dogs is 5–10 mg/kg body weight administered orally once daily, with treatment durations ranging from 5 to 28 days depending on severity and response. In dogs with renal impairment, caution is advised, and dose adjustments may be required to prevent accumulation, as cefpodoxime is primarily excreted by the kidneys. Clinical trials have demonstrated high efficacy, with cefpodoxime achieving an 88.7% success rate in resolving skin infections such as wounds and abscesses in dogs, comparable to standard therapies like cephalexin. Safety profiles in dogs are generally favorable at recommended doses, though gastrointestinal upset, including and , is the most common adverse effect. Cefpodoxime should be avoided in rabbits and rodents, as cephalosporins can disrupt and intestinal microflora, potentially causing severe toxicity or death.

References

  1. https://pubchem.ncbi.nlm.nih.gov/compound/Cefpodoxime
  2. https://medlineplus.gov/druginfo/meds/a698024.html
  3. https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/50675-S14_Vantin_medr_P1.pdf
  4. https://pubmed.ncbi.nlm.nih.gov/1280571/
  5. https://pubmed.ncbi.nlm.nih.gov/39120118/
  6. https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/050674s014%2C050675s017lbl.pdf
  7. https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050674s015%2C050675s018lbl.pdf
  8. https://doi.org/10.1016/S0011-393X(96)80107-X
  9. https://publications.aap.org/pediatriccare/drug-monograph/18/5231/Cefpodoxime
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