Cefpodoxime proxetil

Description

Cefpodoxime proxetil is an orally administered, extended spectrum, semi-synthetic antibiotic belonging to the cephalosporin class. The chemical name is (RS)-1(isopropoxycarbonyloxy) ethyl (+)-(6R,7R)-7-2-(2-amino-4-thiazolyl)-2-{(Z)methoxyimino}acetamido-3-methoxymethyl-8-oxo-5-thia-1-azabicyclo 4.2.0oct-2-ene-2-carboxylate. Its molecular formula is C21H27N5O9S2, and it has a molecular weight of 557.6. Cefpodoxime proxetil acts as a prodrug, with its active metabolite being cefpodoxime. All doses of cefpodoxime proxetil mentioned in this insert are expressed in terms of the active cefpodoxime moiety.

The drug is supplied as flavored granules for oral suspension. Each 5 mL of cefpodoxime proxetil for oral suspension USP contains cefpodoxime proxetil USP equivalent to 50 mg or 100 mg of cefpodoxime activity after constitution. The formulation includes the following inactive ingredients: lactose monohydrate, corn starch, croscarmellose sodium, ferric oxide yellow, hydroxypropyl cellulose, microcrystalline cellulose, carboxymethyl cellulose sodium, colloidal silicon dioxide, citric acid anhydrous, sodium citrate, sodium benzoate, sucrose, and citron & vanille flavorings.

Uses and Indications

Cefpodoxime proxetil is indicated for the treatment of patients with mild to moderate infections caused by susceptible strains of designated microorganisms in the following conditions:

Acute otitis media is indicated for treatment caused by Streptococcus pneumoniae (excluding penicillin-resistant strains), Streptococcus pyogenes, Haemophilus influenzae (including beta-lactamase-producing strains), and Moraxella (Branhamella) catarrhalis (including beta-lactamase-producing strains).

Pharyngitis and/or tonsillitis is indicated for treatment caused by Streptococcus pyogenes.

Community-acquired pneumonia is indicated for treatment caused by S. pneumoniae and H. influenzae (including beta-lactamase-producing strains).

Acute bacterial exacerbation of chronic bronchitis is indicated for treatment caused by S. pneumoniae, H. influenzae (non-beta-lactamase-producing strains only), and M. catarrhalis.

Acute, uncomplicated urethral and cervical gonorrhea is indicated for treatment caused by Neisseria gonorrhoeae (including penicillinase-producing strains).

Acute, uncomplicated ano-rectal infections in women are indicated for treatment caused by Neisseria gonorrhoeae (including penicillinase-producing strains).

Uncomplicated skin and skin structure infections are indicated for treatment caused by Staphylococcus aureus (including penicillinase-producing strains) and Streptococcus pyogenes.

Acute maxillary sinusitis is indicated for treatment caused by Haemophilus influenzae (including beta-lactamase-producing strains), Streptococcus pneumoniae, and Moraxella catarrhalis.

Uncomplicated urinary tract infections (cystitis) are indicated for treatment caused by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Staphylococcus saprophyticus.

Limitations of use include the exclusion of penicillin-resistant strains in the treatment of acute otitis media and the restriction of non-beta-lactamase-producing strains in the treatment of acute bacterial exacerbation of chronic bronchitis.

Dosage and Administration

Cefpodoxime proxetil for oral suspension may be administered without regard to food.

For adults and adolescents aged 12 years and older, the following dosing regimens are recommended:

• Pharyngitis and/or tonsillitis: Administer a total daily dose of 200 mg, with a frequency of 100 mg every 12 hours for a duration of 5 to 10 days.

• Acute community-acquired pneumonia: Administer a total daily dose of 400 mg, with a frequency of 200 mg every 12 hours for a duration of 14 days.

• Uncomplicated gonorrhea (men and women) and rectal gonococcal infections (women): Administer a total daily dose of 200 mg as a single dose.

• Skin and skin structure infections: Administer a total daily dose of 800 mg, with a frequency of 400 mg every 12 hours for a duration of 7 to 14 days.

• Acute maxillary sinusitis: Administer a total daily dose of 400 mg, with a frequency of 200 mg every 12 hours for a duration of 10 days.

• Uncomplicated urinary tract infection: Administer a total daily dose of 200 mg, with a frequency of 100 mg every 12 hours for a duration of 7 days.

For infants and pediatric patients aged 2 months through 12 years, the following dosing regimens are recommended:

• Acute otitis media: Administer a total daily dose of 10 mg/kg/day (maximum 400 mg/day), with a frequency of 5 mg/kg every 12 hours (maximum 200 mg/dose) for a duration of 5 days.

• Pharyngitis and/or tonsillitis: Administer a total daily dose of 10 mg/kg/day (maximum 200 mg/day), with a frequency of 5 mg/kg/dose every 12 hours (maximum 100 mg/dose) for a duration of 5 to 10 days.

• Acute maxillary sinusitis: Administer a total daily dose of 10 mg/kg/day (maximum 400 mg/day), with a frequency of 5 mg/kg every 12 hours (maximum 200 mg/dose) for a duration of 10 days.

For patients with severe renal impairment (creatinine clearance <30 mL/min), dosing intervals should be increased to every 24 hours. In patients maintained on hemodialysis, the dose frequency should be adjusted to three times per week following hemodialysis.

Contraindications

Cefpodoxime proxetil is contraindicated in patients with a known allergy to cefpodoxime or to the cephalosporin group of antibiotics. Additionally, prescribing cefpodoxime proxetil in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is contraindicated, as it is unlikely to provide benefit and may increase the risk of developing drug-resistant bacteria.

Warnings and Precautions

Before initiating therapy with cefpodoxime proxetil, it is imperative to conduct a thorough assessment to ascertain any history of hypersensitivity reactions to cefpodoxime, other cephalosporins, penicillins, or related medications. Caution is particularly warranted when administering cefpodoxime to patients with a known penicillin allergy, as cross-reactivity among beta-lactam antibiotics has been documented, potentially affecting up to 10% of individuals with a history of penicillin hypersensitivity. Should an allergic reaction to cefpodoxime proxetil manifest, the medication must be discontinued immediately.

In cases of serious acute hypersensitivity reactions, prompt medical intervention is essential. Treatment may necessitate the administration of epinephrine and other emergency measures, including oxygen therapy, intravenous fluids, intravenous antihistamines, and airway management, as clinically indicated.

Cefpodoxime proxetil has been associated with Clostridium difficile-associated diarrhea (CDAD), which can range from mild diarrhea to severe, potentially fatal colitis. Clinicians should consider CDAD in any patient presenting with diarrhea following antibiotic therapy. A detailed medical history is crucial, as CDAD may occur up to two months post-administration of antibacterial agents. If CDAD is suspected or confirmed, it may be necessary to discontinue ongoing antibiotic therapy not targeting C. difficile. Management should include appropriate fluid and electrolyte replacement, protein supplementation, antibiotic treatment for C. difficile, and surgical evaluation if warranted.

Reports of pseudomembranous colitis linked to cefpodoxime proxetil have emerged from post-marketing experiences outside the United States, further emphasizing the need for vigilance in monitoring gastrointestinal symptoms.

In patients experiencing transient or persistent reductions in urinary output due to renal insufficiency, it is recommended that the total daily dose of cefpodoxime proxetil be adjusted downward. This adjustment is crucial to avoid elevated and prolonged serum antibiotic concentrations that may occur with standard dosing in these individuals. Caution is also advised when cefpodoxime is prescribed alongside potent diuretics.

As with other antibiotics, prolonged use of cefpodoxime proxetil may lead to the overgrowth of non-susceptible organisms. Continuous evaluation of the patient's condition is essential, and if superinfection occurs during treatment, appropriate measures should be implemented. Prescribing cefpodoxime proxetil in the absence of a confirmed or strongly suspected bacterial infection, or without a prophylactic indication, is unlikely to benefit the patient and may increase the risk of developing drug-resistant bacteria.

Side Effects

In clinical trials, the most commonly reported adverse reactions with an incidence greater than 1% included diarrhea (6%), vomiting (2.3%), and diaper rash or fungal skin rash (2%), with the incidence of diarrhea in infants and toddlers (ages 1 month to 2 years) reported at 12.8% and diaper rash at 8.5%. Other skin rashes occurred in 1.8% of participants.

Adverse reactions with an incidence of less than 1% encompassed a variety of body systems. Notable reactions included localized abdominal pain, abdominal cramp, headache, monilia, generalized abdominal pain, asthenia, fever, and fungal infection. Digestive system reactions included nausea, anorexia, dry mouth, stomatitis, and pseudomembranous colitis. Hematological reactions reported were thrombocythemia, positive direct Coombs’ test, eosinophilia, leukocytosis, leukopenia, prolonged partial thromboplastin time, and thrombocytopenic purpura. Metabolic and nutritional changes included increased SGPT levels. Musculoskeletal reactions such as myalgia, nervous system effects including hallucination, hyperkinesia, nervousness, and somnolence, as well as respiratory issues like epistaxis and rhinitis were also noted. Skin reactions included skin moniliasis, urticaria, fungal dermatitis, acne, exfoliative dermatitis, and maculopapular rash. Additionally, taste perversion was reported among the special senses.

Post-marketing experiences have revealed serious adverse reactions, including allergic reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, and serum sickness-like reactions. Other serious conditions reported include pseudomembranous colitis, bloody diarrhea with abdominal pain, ulcerative colitis, rectorrhagia with hypotension, anaphylactic shock, acute liver injury, miscarriage due to in utero exposure, purpuric nephritis, pulmonary infiltrate with eosinophilia, and eyelid dermatitis. Notably, one death was attributed to pseudomembranous colitis and disseminated intravascular coagulation.

It is important to note that Clostridium difficile-associated diarrhea (CDAD) has been reported with the use of nearly all antibacterial agents, including cefpodoxime proxetil, and may range in severity from mild diarrhea to fatal colitis. CDAD should be considered in all patients presenting with diarrhea following antibiotic use.

Additionally, adverse reactions and altered laboratory tests associated with cephalosporin class antibiotics may include renal dysfunction, toxic nephropathy, hepatic dysfunction (including cholestasis), aplastic anemia, hemolytic anemia, serum sickness-like reactions, hemorrhage, agranulocytosis, and pancytopenia. Several cephalosporins have been implicated in triggering seizures, particularly in patients with renal impairment when dosages were not adjusted. In cases of seizures associated with drug therapy, discontinuation of the drug is recommended, and anticonvulsant therapy may be administered if clinically indicated.

Drug Interactions

Concomitant administration of certain medications may influence the pharmacokinetics and pharmacodynamics of cefpodoxime proxetil.

Antacids and H2 Blockers The use of high doses of antacids, such as sodium bicarbonate and aluminum hydroxide, or H2 blockers has been shown to reduce peak plasma levels of cefpodoxime proxetil by 24% to 42% and the extent of absorption by 27% to 32%. However, these agents do not alter the rate of absorption. It is advisable to separate the administration of cefpodoxime proxetil and these medications to minimize the impact on drug levels.

Oral Anti-cholinergics Oral anti-cholinergics, including propantheline, may delay the peak plasma levels of cefpodoxime proxetil, resulting in a 47% increase in Tmax. Nonetheless, these agents do not affect the overall extent of absorption (AUC). Monitoring for therapeutic efficacy may be warranted when these medications are used concurrently.

Probenecid Co-administration of probenecid inhibits the renal excretion of cefpodoxime proxetil, leading to an approximate 31% increase in AUC and a 20% increase in peak plasma levels. Dosage adjustments may be necessary to avoid potential toxicity, and careful monitoring of patient response is recommended.

Nephrotoxic Drugs When cefpodoxime proxetil is administered alongside nephrotoxic drugs, close monitoring of renal function is advised due to the potential for increased risk of renal impairment.

Laboratory Test Interactions Cefpodoxime proxetil, as a member of the cephalosporin class, may occasionally induce a positive direct Coombs’ test. Clinicians should be aware of this potential interaction when interpreting laboratory results.

Packaging & NDC

The table below lists all NDC Code configurations of Cefpodoxime Proxetil, the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

Safety and efficacy in pediatric patients less than 2 months of age have not been established. Therefore, caution is advised when considering treatment in this age group.

Geriatric Use

In clinical studies involving cefpodoxime proxetil film-coated tablets, 16% of the 3,338 patients enrolled were aged 65 years and older, with 6% being 75 years and older. The data indicate that there are no overall differences in effectiveness or safety between elderly patients and their younger counterparts.

In healthy geriatric subjects with normal renal function, the pharmacokinetics of cefpodoxime reveal a plasma half-life averaging 4.2 hours, with urinary recovery averaging 21% following a 400 mg dose administered every 12 hours over a 15-day period. Notably, other pharmacokinetic parameters remained consistent with those observed in healthy younger subjects.

Given these findings, dose adjustment for elderly patients with normal renal function is not necessary. However, healthcare providers should continue to monitor geriatric patients closely, considering the potential for altered pharmacodynamics and the presence of comorbidities that may affect treatment outcomes.

Pregnancy

Cefpodoxime proxetil is classified as Pregnancy Category B. Animal studies have demonstrated that cefpodoxime proxetil was neither teratogenic nor embryocidal when administered to rats during organogenesis at doses up to 100 mg/kg/day, which is approximately two times the human dose based on mg/m². Similarly, in rabbits, doses up to 30 mg/kg/day (1 to 2 times the human dose based on mg/m²) did not show teratogenic effects.

However, there are no adequate and well-controlled studies of cefpodoxime proxetil in pregnant women. Therefore, due to the limitations of animal reproduction studies in predicting human response, cefpodoxime proxetil should be used during pregnancy only if clearly needed. Additionally, the safety and efficacy of cefpodoxime proxetil have not been established for use during labor and delivery, and treatment should be administered only when clearly indicated.

Lactation

Cefpodoxime is excreted in human milk. In a study involving three lactating women, the levels of cefpodoxime in human milk were found to be 0%, 2%, and 6% of concomitant serum levels at 4 hours following a 200 mg oral dose of cefpodoxime proxetil. At 6 hours post-dosing, the levels increased to 0%, 9%, and 16% of concomitant serum levels.

Due to the potential for serious reactions in breastfed infants, healthcare professionals should consider the risks and benefits when advising lactating mothers. A decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Renal Impairment

Patients with renal impairment have not been specifically addressed in the available data regarding dosage adjustments, special monitoring, or safety considerations. Therefore, healthcare professionals should exercise caution when prescribing this medication to patients with reduced kidney function, as the lack of information necessitates careful clinical judgment and monitoring.

Hepatic Impairment

Patients with hepatic impairment have not been specifically studied in relation to the use of this medication. Consequently, there are no established dosage adjustments, special monitoring requirements, or precautions outlined for individuals with compromised liver function. It is recommended that healthcare providers exercise caution when prescribing this medication to patients with hepatic impairment, given the lack of data on its safety and efficacy in this population. Regular monitoring of liver function may be prudent in these cases, although specific parameters are not defined in the available information.

Overdosage

In acute rodent toxicity studies, administration of a single oral dose of 5 g/kg did not result in any adverse effects. This finding suggests a relatively high threshold for toxicity in this model.

In cases of serious toxic reactions due to overdosage, it is recommended that healthcare professionals consider hemodialysis or peritoneal dialysis as potential interventions. These procedures may facilitate the removal of cefpodoxime from the body, especially in patients with compromised renal function.

Symptoms associated with an overdose of beta-lactam antibiotics, including cefpodoxime, may manifest as nausea, vomiting, epigastric distress, and diarrhea. Healthcare providers should monitor for these symptoms and manage them accordingly to ensure patient safety and comfort.

Nonclinical Toxicology

Cefpodoxime proxetil is classified as Pregnancy Category B. In nonclinical studies, it was determined that cefpodoxime proxetil was neither teratogenic nor embryocidal when administered to rats during organogenesis at doses up to 100 mg/kg/day, which is equivalent to two times the human dose based on mg/m². Similarly, in rabbits, doses up to 30 mg/kg/day, corresponding to one to two times the human dose based on mg/m², did not demonstrate teratogenic effects. However, it is important to note that there are no adequate and well-controlled studies of cefpodoxime proxetil in pregnant women. Due to the limitations of animal reproduction studies in predicting human responses, the use of this drug during pregnancy should be considered only when clearly necessary.

In terms of non-teratogenic effects, no adverse effects on fertility or reproduction were observed in rats administered 100 mg/kg/day or less, which is also two times the human dose based on mg/m².

Long-term carcinogenicity studies of cefpodoxime proxetil have not been conducted. However, mutagenicity studies, including the Ames test (both with and without metabolic activation), chromosome aberration tests, unscheduled DNA synthesis assays, mitotic recombination and gene conversion assessments, forward gene mutation assays, and in vivo micronucleus tests, yielded negative results.

Postmarketing Experience

Serious adverse experiences reported in postmarketing surveillance include allergic reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, and serum sickness-like reactions. Additional events include pseudomembranous colitis, bloody diarrhea accompanied by abdominal pain, ulcerative colitis, rectorrhagia with hypotension, anaphylactic shock, acute liver injury, in utero exposure resulting in miscarriage, purpuric nephritis, pulmonary infiltrate with eosinophilia, and eyelid dermatitis.

One fatality has been associated with pseudomembranous colitis and disseminated intravascular coagulation. Furthermore, outside the United States, there have been reports linking pseudomembranous colitis to the use of cefpodoxime proxetil.

Patient Counseling

Patients should be counseled that antibacterial drugs, including cefpodoxime proxetil, are indicated solely for the treatment of bacterial infections and are ineffective against viral infections, such as the common cold. It is important for patients to understand that even if they begin to feel better early in the course of therapy, they must take the medication exactly as directed.

Healthcare providers should emphasize that skipping doses or failing to complete the full course of therapy can lead to decreased effectiveness of the treatment and may increase the risk of bacteria developing resistance. This resistance could render cefpodoxime proxetil or other antibacterial drugs ineffective for future infections.

Patients should also be informed that diarrhea is a common side effect associated with antibiotic use, which typically resolves upon discontinuation of the medication. However, they should be made aware that in some cases, they may experience watery and bloody stools, with or without accompanying stomach cramps and fever, even weeks after completing the antibiotic course. If such symptoms occur, patients should be advised to contact their physician promptly.

Storage and Handling

Unsuspended granules are supplied in containers that should be stored at a temperature range of 20° to 25°C (68° to 77°F), with permissible excursions between 15° to 30°C (59° to 86°F). After the granules are mixed, the resulting suspension must be stored in a refrigerator at a temperature of 2° to 8°C (36° to 46°F). It is essential to shake the container well before each use and to keep it tightly closed when not in use. The mixed suspension is stable for up to 14 days; any unused portion should be discarded after this period to ensure safety and efficacy.

Additional Clinical Information

Cephalosporins, including cefpodoxime proxetil, may occasionally induce a positive direct Coombs’ test. Clinicians should counsel patients that antibacterial drugs, such as cefpodoxime proxetil, are effective only against bacterial infections and do not treat viral infections, like the common cold. Patients should be advised to adhere strictly to the prescribed regimen, as skipping doses or failing to complete the full course can reduce treatment effectiveness and increase the risk of bacterial resistance. Additionally, patients should be informed about the potential for antibiotic-associated diarrhea, which may occur even weeks after treatment has ended. If patients experience watery or bloody stools, they should seek medical attention promptly.

Postmarketing surveillance has identified serious adverse events associated with cefpodoxime proxetil, including allergic reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis), pseudomembranous colitis, and other severe gastrointestinal and systemic reactions. Notably, one death has been linked to pseudomembranous colitis and disseminated intravascular coagulation.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Cefpodoxime Proxetil as submitted by Aurobindo Pharma Limited. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)