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 in the form of film-coated tablets, with each tablet containing cefpodoxime proxetil USP equivalent to either 100 mg or 200 mg of cefpodoxime activity. The film-coated tablets contain the following inactive ingredients: carboxymethyl cellulose calcium, colloidal silicon dioxide, crospovidone, FD&C Yellow No. 5, FD&C Yellow No. 6, hydroxypropyl cellulose, hypromellose, iron oxide red, lactose monohydrate, macrogol, magnesium stearate, sodium lauryl sulfate, 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), and 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 or 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), or 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) or 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, and 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, or Staphylococcus saprophyticus.

Limitations of Use No specific teratogenic or nonteratogenic effects are mentioned in the provided text.

Dosage and Administration

Cefpodoxime Proxetil Tablets, USP should be administered orally with food to enhance absorption.

For adults and adolescents aged 12 years and older, the recommended dosages are as follows:

Pharyngitis and/or Tonsillitis:

• Total Daily Dose: 200 mg

• Dose Frequency: 100 mg every 12 hours

• Duration: 5 to 10 days

Acute Community Acquired Pneumonia:

• Total Daily Dose: 400 mg

• Dose Frequency: 200 mg every 12 hours

• Duration: 14 days

Acute Bacterial Exacerbations of Chronic Bronchitis:

• Total Daily Dose: 400 mg

• Dose Frequency: 200 mg every 12 hours

• Duration: 10 days

Uncomplicated Gonorrhea (Men and Women) and Rectal Gonococcal Infections (Women):

• Total Daily Dose: 200 mg

• Dose Frequency: Single dose

• Duration: Not specified

Skin and Skin Structure Infections:

• Total Daily Dose: 800 mg

• Dose Frequency: 400 mg every 12 hours

• Duration: 7 to 14 days

Acute Maxillary Sinusitis:

• Total Daily Dose: 400 mg

• Dose Frequency: 200 mg every 12 hours

• Duration: 10 days

Uncomplicated Urinary Tract Infection:

• Total Daily Dose: 200 mg

• Dose Frequency: 100 mg every 12 hours

• Duration: 7 days

For patients with renal dysfunction, the following adjustments are recommended:

• In patients with severe renal impairment (creatinine clearance <30 mL/min), the dosing intervals should be increased to every 24 hours.

• In patients maintained on hemodialysis, the dose frequency should be administered three times per week after hemodialysis.

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 severe 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 urgent medical intervention, including the administration of epinephrine and other emergency measures such as oxygen therapy, 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. The use of antibacterial agents disrupts the normal colonic flora, leading to an overgrowth of C. difficile, which produces toxins A and B that contribute to CDAD. Hypertoxin-producing strains of C. difficile are associated with increased morbidity and mortality, as these infections may be resistant to standard antimicrobial therapy and could necessitate 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, it may be necessary to discontinue ongoing antibiotic therapy not targeting C. difficile. Management should include appropriate fluid and electrolyte replacement, protein supplementation, targeted antibiotic treatment for C. difficile, and surgical evaluation as clinically warranted. Monitoring for C. difficile in patients treated with cefpodoxime who develop diarrhea is crucial, given the increased incidence observed in clinical trials. Notably, C. difficile organisms or toxins were identified in 10% of cefpodoxime-treated adult patients with diarrhea, although no specific diagnosis of pseudomembranous colitis was established in these cases. Additionally, post-marketing reports from outside the United States have indicated occurrences of pseudomembranous colitis associated with cefpodoxime proxetil.

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 accordingly, as elevated and prolonged serum antibiotic concentrations may occur. Caution should also be exercised when administering cefpodoxime to patients receiving 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 therapy, appropriate measures should be implemented. 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

Adverse reactions associated with the use of cefpodoxime proxetil tablets have been observed in clinical trials and post-marketing experiences.

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, the incidence of diarrhea was dose-related, decreasing from 10.4% in patients receiving 800 mg per day to 5.7% in those receiving 200 mg per day. Among patients experiencing diarrhea, 10% tested positive for Clostridium difficile organism or toxin in their stool.

Adverse reactions occurring in less than 1% of subjects were categorized by body system. These included a range of reactions such as fungal infections, malaise, fatigue, chest pain, and various gastrointestinal disturbances. Cardiovascular events included congestive heart failure and palpitations. Neurological effects such as dizziness, insomnia, and anxiety were also reported. Skin reactions included urticaria and rash, while urogenital issues encompassed urinary tract infections and hematuria.

Post-marketing experiences have revealed serious adverse reactions, including allergic reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, and erythema multiforme. Other serious events included pseudomembranous colitis, which can manifest as bloody diarrhea with abdominal pain, and has been associated with a fatal outcome in one reported case. Additional serious reactions included anaphylactic shock, acute liver injury, and pulmonary infiltrate with eosinophilia.

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. The severity of CDAD can range from mild diarrhea to fatal colitis, and it should be considered in any patient presenting with diarrhea following antibiotic use. Careful medical history is essential, as CDAD may occur up to two months after the administration of antibacterial agents.

Furthermore, adverse reactions and altered laboratory tests associated with cephalosporin class antibiotics may include renal dysfunction, hepatic dysfunction, and hematological disorders such as aplastic anemia and hemolytic anemia. Seizures have also been reported, particularly in patients with renal impairment when dosages were not appropriately 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 impact 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.

Oral anti-cholinergics, including propantheline, have been shown to delay peak plasma levels, resulting in a 47% increase in Tmax, although they do not affect the overall extent of absorption (AUC).

In terms of pharmacokinetic interactions, probenecid inhibits the renal excretion of cefpodoxime, leading to an approximate 31% increase in AUC and a 20% increase in peak plasma levels of cefpodoxime.

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

Additionally, cephalosporins, including cefpodoxime proxetil, may occasionally induce a positive direct Coombs’ test, which should be considered 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 evaluated were aged 65 years and older, with 6% being 75 years and older. No significant differences in effectiveness or safety were noted between elderly patients and their younger counterparts.

In healthy geriatric subjects with normal renal function, the pharmacokinetics of cefpodoxime indicate 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. Other pharmacokinetic parameters remained consistent with those observed in healthy younger subjects.

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, given the variability in drug response that can occur with aging.

Pregnancy

Cefpodoxime proxetil is classified as a Pregnancy Category B medication. 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, equivalent to one to two 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. Given that animal reproduction studies are not always predictive of human response, cefpodoxime proxetil should be used during pregnancy only if clearly needed. Healthcare professionals are advised to weigh the potential benefits against the risks when considering the use of this medication in pregnant patients.

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 importance of the drug to the mother when making a decision to either discontinue nursing or discontinue the drug.

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

Long-term animal carcinogenesis studies of cefpodoxime proxetil have not been conducted. Comprehensive mutagenesis studies have been performed, including the Ames test, both with and without metabolic activation, as well as the chromosome aberration test, the unscheduled DNA synthesis assay, mitotic recombination and gene conversion, the forward gene mutation assay, and the in vivo micronucleus test. All of these studies yielded negative results.

In terms of reproductive toxicity, no adverse effects on fertility or reproduction were observed in rats administered cefpodoxime at doses of 100 mg/kg/day or less, which corresponds to twice 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, reports of pseudomembranous colitis linked to the use of cefpodoxime proxetil have been documented in postmarketing experience outside the United States.

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 lead to decreased effectiveness of the treatment and may increase the risk of bacteria developing resistance. This resistance could render cefpodoxime proxetil tablets, or other antibacterial drugs, ineffective in the future.

Patients should also be made aware that diarrhea is a common side effect associated with antibiotic use, typically resolving upon discontinuation of the medication. However, they should be informed that in some cases, they may experience watery and bloody stools, with or without accompanying stomach cramps and fever, even up to 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 accordance with the National Drug Code (NDC) specifications. It should be stored at a temperature range of 20° to 25°C (68° to 77°F), adhering to the guidelines set forth by the United States Pharmacopeia (USP) for Controlled Room Temperature.

To ensure product integrity, it is essential to replace the cap securely after each opening. Proper handling and storage conditions are critical for maintaining the quality and efficacy of the product.

Additional Clinical Information

Cephalosporins, including cefpodoxime proxetil, may occasionally induce a positive direct Coombs’ test. Cefpodoxime proxetil tablets should be administered orally with food to enhance absorption. Clinicians should counsel patients that antibacterial drugs, such as cefpodoxime proxetil, are effective only against bacterial infections and do not treat viral infections. Patients should be advised to adhere strictly to the prescribed regimen, as skipping doses or not completing 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, 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 Amici Pharmaceuticals, LLC.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)