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 functions 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 in the form of film-coated tablets, with each tablet containing cefpodoxime proxetil equivalent to either 100 mg or 200 mg of cefpodoxime activity. The film-coated tablets contain the following inactive ingredients: carboxymethylcellulose calcium, crospovidone, FD&C Yellow No. 6, hydroxypropyl cellulose, hypromellose, lactose monohydrate, magnesium stearate, sodium lauryl sulfate, talc, and titanium dioxide.

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 Cefpodoxime proxetil is indicated for the treatment of acute otitis media caused by:

• Streptococcus pneumoniae (excluding penicillin-resistant strains)

• Streptococcus pyogenes

• Haemophilus influenzae (including beta-lactamase-producing strains)

• Moraxella (Branhamella) catarrhalis (including beta-lactamase-producing strains)

Pharyngitis and/or Tonsillitis This drug is indicated for the treatment of pharyngitis and/or tonsillitis caused by:

• Streptococcus pyogenes

Community-Acquired Pneumonia Cefpodoxime proxetil is indicated for the treatment of community-acquired pneumonia caused by:

• Streptococcus pneumoniae

• Haemophilus influenzae (including beta-lactamase-producing strains)

Acute Bacterial Exacerbation of Chronic Bronchitis This drug is indicated for the treatment of acute bacterial exacerbation of chronic bronchitis caused by:

• Streptococcus pneumoniae

• Haemophilus influenzae (non-beta-lactamase-producing strains only)

• Moraxella catarrhalis

Acute, Uncomplicated Urethral and Cervical Gonorrhea Cefpodoxime proxetil is indicated for the treatment of acute, uncomplicated urethral and cervical gonorrhea caused by:

• Neisseria gonorrhoeae (including penicillinase-producing strains)

Acute, Uncomplicated Ano-Rectal Infections in Women This drug is indicated for the treatment of acute, uncomplicated ano-rectal infections in women due to:

• Neisseria gonorrhoeae (including penicillinase-producing strains)

Uncomplicated Skin and Skin Structure Infections Cefpodoxime proxetil is indicated for the treatment of uncomplicated skin and skin structure infections caused by:

• Staphylococcus aureus (including penicillinase-producing strains)

• Streptococcus pyogenes

Acute Maxillary Sinusitis This drug is indicated for the treatment of acute maxillary sinusitis caused by:

• Haemophilus influenzae (including beta-lactamase-producing strains)

• Streptococcus pneumoniae

• Moraxella catarrhalis

Uncomplicated Urinary Tract Infections (Cystitis) Cefpodoxime proxetil is indicated for the treatment of uncomplicated urinary tract infections (cystitis) caused by:

• Escherichia coli

• Klebsiella pneumoniae

• Proteus mirabilis

• Staphylococcus saprophyticus

Limitations of Use No specific teratogenic or nonteratogenic effects have been mentioned.

Dosage and Administration

Administer the medication orally with food to enhance absorption.

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

Pharyngitis and/or Tonsillitis: The total daily dose is 200 mg, administered as 100 mg every 12 hours for a duration of 5 to 10 days.

Acute Community-Acquired Pneumonia: The total daily dose is 400 mg, given as 200 mg every 12 hours for 14 days.

Acute Bacterial Exacerbations of Chronic Bronchitis: The total daily dose is 400 mg, administered as 200 mg every 12 hours for 10 days.

Uncomplicated Gonorrhea (Men and Women) and Rectal Gonococcal Infections (Women): The total daily dose is 200 mg, given as a single dose. Duration is not specified.

Skin and Skin Structure Infections: The total daily dose is 800 mg, administered as 400 mg every 12 hours for a duration of 7 to 14 days.

Acute Maxillary Sinusitis: The total daily dose is 400 mg, given as 200 mg every 12 hours for 10 days.

Uncomplicated Urinary Tract Infection: The total daily dose is 200 mg, administered as 100 mg every 12 hours for 7 days.

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

Contraindications

Cefpodoxime proxetil is contraindicated in patients with a known allergy to cefpodoxime or to any member of the cephalosporin class of antibiotics. Use in these patients may lead to serious allergic reactions.

Warnings and Precautions

Before initiating therapy with cefpodoxime proxetil, it is imperative to conduct a thorough assessment of the patient's medical history to identify any previous 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. In the event of an allergic reaction to cefpodoxime proxetil, the medication should be discontinued immediately. Serious acute hypersensitivity reactions may necessitate emergency interventions, including the administration of epinephrine, oxygen, intravenous fluids, intravenous antihistamines, and airway management as clinically indicated.

Clostridium difficile associated diarrhea (CDAD) has been reported with the use of nearly all antibacterial agents, including cefpodoxime proxetil. The severity of CDAD can range from mild diarrhea to life-threatening colitis, as the use of antibacterial agents disrupts the normal colonic flora, leading to C. difficile overgrowth. This organism produces toxins A and B, which are implicated in the development of CDAD. Hypertoxin-producing strains of C. difficile are associated with increased morbidity and mortality, and infections may be resistant to antimicrobial therapy, potentially requiring surgical intervention. Clinicians should consider CDAD in any patient presenting with diarrhea following antibiotic use, and a detailed medical history is essential, as CDAD can manifest up to two months post-antibiotic treatment. If CDAD is suspected or confirmed, ongoing antibiotic therapy not targeting C. difficile should be reconsidered, and appropriate management strategies, including fluid and electrolyte replacement, protein supplementation, and specific antibiotic treatment for C. difficile, should be implemented as clinically warranted.

Monitoring for C. difficile is particularly important in patients treated with cefpodoxime who develop diarrhea, as early trials indicated an increased incidence of C. difficile-associated diarrhea. In these trials, C. difficile organisms or toxins were detected in 10% of adult patients treated with cefpodoxime who experienced diarrhea, although no definitive diagnosis of pseudomembranous colitis was established. Additionally, post-marketing reports from outside the United States have indicated cases of pseudomembranous colitis associated with cefpodoxime proxetil use.

In patients with transient or persistent renal insufficiency leading to reduced urinary output, it is recommended that the total daily dose of cefpodoxime proxetil be adjusted to prevent high and prolonged serum concentrations of the antibiotic. Caution should also be exercised when administering cefpodoxime to patients receiving potent diuretics.

As with other antibiotics, prolonged use of cefpodoxime proxetil may result in the overgrowth of non-susceptible organisms. Continuous evaluation of the patient's condition is essential, and if superinfection occurs during therapy, appropriate measures should be taken. Prescribing cefpodoxime proxetil in the absence of a confirmed or strongly suspected bacterial infection, or for prophylactic purposes, is unlikely to benefit the patient and may increase the risk of developing drug-resistant bacteria.

Side Effects

Patients receiving treatment with cefpodoxime proxetil may experience a range of adverse reactions. The following sections summarize the adverse reactions observed in clinical trials and post-marketing experiences, organized by incidence and seriousness.

In clinical trials, the most common adverse reactions occurring in more than 1% of participants included diarrhea (7%), nausea (3.3%), vaginal fungal infections (1%), vulvovaginal infections (1.3%), abdominal pain (1.2%), and headache (1%). Notably, diarrhea was dose-related, with an incidence of 10.4% at a dosage of 800 mg/day compared to 5.7% at 200 mg/day. Among patients experiencing diarrhea, 10% tested positive for C. difficile organism or toxin in their stool.

Adverse reactions occurring in less than 1% of subjects were categorized by body system and included a variety of symptoms. These encompassed fungal infections, malaise, fatigue, chest pain, and generalized pain under the body system category. Cardiovascular reactions included congestive heart failure, palpitations, and hypertension. Digestive system reactions featured vomiting, dyspepsia, and oral moniliasis. Other notable reactions included dizziness and insomnia in the nervous system category, urticaria and rash in the skin category, and hematuria and urinary tract infections in the urogenital category.

Post-marketing experiences have revealed serious adverse reactions, including allergic reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, and anaphylactic shock. Other serious events reported include pseudomembranous colitis, bloody diarrhea with abdominal pain, and acute liver injury. One death has been attributed to pseudomembranous colitis and disseminated intravascular coagulation.

It is important to note that C. difficile associated diarrhea (CDAD) has been reported with the use of nearly all antibacterial agents, including cefpodoxime proxetil. The severity of CDAD can range from mild diarrhea to fatal colitis, and it 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, hepatic dysfunction, aplastic anemia, and seizures, particularly in patients with renal impairment if the dosage is not adjusted. If seizures occur, discontinuation of the drug is recommended.

Drug Interactions

Concomitant administration of high doses of antacids, such as sodium bicarbonate and aluminum hydroxide, or H2 blockers may significantly affect the pharmacokinetics of cefpodoxime proxetil. Specifically, these agents can reduce peak plasma levels by 24% to 42% and the extent of absorption by 27% to 32%. However, the rate of absorption remains unchanged. Additionally, oral anti-cholinergics, such as propantheline, may delay peak plasma levels, resulting in a 47% increase in Tmax, while not affecting the overall extent of absorption (AUC).

Pharmacokinetic interactions are also observed with probenecid, which inhibits the renal excretion of cefpodoxime. This interaction leads to an approximate 31% increase in AUC and a 20% increase in peak plasma levels of cefpodoxime.

While nephrotoxicity has not been reported with cefpodoxime proxetil when administered alone, it is advisable to closely monitor renal function when this antibiotic is used in conjunction with other compounds known to have nephrotoxic potential.

Furthermore, it is important to note that cephalosporins, including cefpodoxime proxetil, may occasionally induce a positive direct Coombs’ test. This should be considered when interpreting laboratory results in patients receiving this medication.

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 3338 patients enrolled were aged 65 years and older, and 6% were aged 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 were found to be comparable to those observed in younger individuals. Specifically, the average half-life of cefpodoxime in plasma was 4.2 hours, with urinary recovery averaging 21% following a 400 mg dose administered every 12 hours over a 15-day period.

Importantly, dose adjustments for elderly patients with normal renal function are not necessary. However, healthcare providers should continue to monitor geriatric patients for any potential adverse effects, as individual responses may vary.

Pregnancy

Cefpodoxime proxetil has been evaluated in animal studies, where it was found to be neither teratogenic nor embryocidal when administered to rats during organogenesis at doses up to 100 mg/kg/day (approximately two times the human dose based on mg/m²) and to rabbits at doses up to 30 mg/kg/day (approximately 1 to 2 times the human dose based on mg/m²). However, 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 outcomes, cefpodoxime proxetil should be used during pregnancy only if clearly needed.

Additionally, cefpodoxime proxetil has not been studied for use during labor and delivery. Therefore, treatment with this medication should only be considered if clearly necessary, weighing the potential benefits against any possible risks to the fetus.

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 was evaluated for teratogenic and embryocidal effects in rats and rabbits. In rats, administration during organogenesis at doses up to 100 mg/kg/day, which is two times the human dose based on mg/m², did not result in teratogenicity or embryocidal effects. Similarly, in rabbits, doses up to 30 mg/kg/day, corresponding to one to two times the human dose based on mg/m², also showed no evidence of teratogenic effects. However, it is important to note that there are no adequate and well-controlled studies of cefpodoxime proxetil in pregnant women. Given that animal reproduction studies may not reliably predict human responses, the use of this drug during pregnancy should be considered only when clearly necessary.

Long-term carcinogenicity studies of cefpodoxime proxetil have not been conducted. In terms of mutagenicity, a series of 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.

Furthermore, no adverse effects on fertility or reproduction were observed in rats administered cefpodoxime proxetil at doses of 100 mg/kg/day or less, which is two times the human dose based on mg/m².

Postmarketing Experience

Serious adverse experiences reported in the postmarketing setting 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 of pseudomembranous colitis linked to the use of cefpodoxime proxetil.

Patient Counseling

Patients should be counseled that antibacterial drugs, including cefpodoxime proxetil tablets, are indicated solely for the treatment of bacterial infections and are ineffective against viral infections, such as the common cold.

When cefpodoxime proxetil tablets are prescribed, it is important for patients to understand that while they may begin to feel better early in the treatment course, the medication must be taken exactly as directed. Healthcare providers should emphasize that skipping doses or failing to complete the full course of therapy can diminish the effectiveness of the treatment and increase the risk of bacteria developing resistance, potentially rendering cefpodoxime proxetil tablets and other antibacterial drugs ineffective in the future.

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

Storage and Handling

The product is supplied in a configuration that includes specific NDC numbers, which should be referenced for accurate identification. It is essential to store the product at a temperature range of 20° to 25°C (68° to 77°F), in accordance with USP Controlled Room Temperature guidelines.

After each use, the cap must be replaced securely to maintain the integrity of the product. Additionally, it is crucial to keep the product out of the reach of children to ensure safety.

Additional Clinical Information

Cephalosporins, including cefpodoxime proxetil, may occasionally induce a positive direct Coombs’ test. For optimal absorption, cefpodoxime proxetil tablets should be administered orally with food. 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 may reduce treatment effectiveness and increase the risk of bacterial resistance.

Patients should also be informed about the potential for antibiotic-associated diarrhea, which typically resolves upon discontinuation of the medication. However, if they experience watery or bloody stools, with or without abdominal cramps and fever, even weeks after completing treatment, they should seek medical attention promptly. Postmarketing reports have indicated serious adverse events associated with cefpodoxime proxetil, including allergic reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis), pseudomembranous colitis, and other severe conditions. 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 Sandoz Inc. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)