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 g/mol. 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. Cefpodoxime proxetil tablets, USP, contain cefpodoxime proxetil USP equivalent to either 100 mg or 200 mg of cefpodoxime activity. The tablets also include the following inactive ingredients: carboxy methyl cellulose calcium, lactose monohydrate, hydroxy propyl cellulose, sodium lauryl sulfate, crospovidone, corn starch, magnesium stearate, hypromellose, titanium dioxide, propylene glycol, and FD&C yellow #6 aluminum lake. Additionally, the 100 mg film-coated tablets contain iron oxide yellow, while the 200 mg film-coated tablets contain FD&C red #40 aluminum lake.

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

Cefpodoxime proxetil tablets should be administered orally with food to enhance absorption, while the oral suspension may be given 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.

• Acute Bacterial Exacerbations of Chronic Bronchitis: Administer a total daily dose of 400 mg, with a frequency of 200 mg every 12 hours for a duration of 10 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 renal dysfunction, the following adjustments are necessary:

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

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

Contraindications

Cefpodoxime proxetil is contraindicated in patients with a known allergy to cefpodoxime or to any cephalosporin antibiotics. Additionally, the use of cefpodoxime proxetil in the absence of a proven or strongly suspected bacterial infection, or in the absence of a prophylactic indication, is not recommended, as it does not provide therapeutic benefit and may contribute to the development of 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 necessary to prevent the risk of elevated and prolonged serum antibiotic concentrations. 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 for prophylactic purposes, is unlikely to benefit the patient and may increase the risk of developing drug-resistant bacteria.

Side Effects

Adverse reactions observed in clinical trials and post-marketing experiences have been categorized based on their incidence and seriousness.

In clinical trials involving film-coated tablets, the most common adverse reactions (incidence greater than 1%) included diarrhea (7%), nausea (3.3%), vaginal fungal infections (1%), vulvovaginal infections (1.3%), abdominal pain (1.2%), and headache (1%). Other reactions with an incidence of less than 1% encompassed a range of body, cardiovascular, digestive, hemic and lymphatic, metabolic and nutritional, musculoskeletal, nervous, respiratory, skin, special senses, and urogenital effects. Notably, participants reported fungal infections, malaise, fatigue, chest pain, dizziness, insomnia, and various skin reactions, among others.

For granules for oral suspension, the most frequently reported adverse reactions (incidence greater than 1%) were diarrhea (6%, with 12.8% in infants and toddlers), diaper rash/fungal skin rash (2%, with 8.5% in infants and toddlers), other skin rashes (1.8%), and vomiting (2.3%). Less common reactions included localized abdominal pain, nausea, and various hematological changes such as thrombocythemia and leukocytosis.

In single-dose trials of film-coated tablets, nausea (1.4%) and diarrhea (1.2%) were the most frequently reported adverse reactions, with less common reactions including dizziness, headache, and anxiety.

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 reported include pseudomembranous colitis, bloody diarrhea with abdominal pain, anaphylactic shock, acute liver injury, and renal dysfunction. One death has been attributed to pseudomembranous colitis and disseminated intravascular coagulation.

Additionally, adverse reactions associated with the cephalosporin class of antibiotics include renal dysfunction, hepatic dysfunction, aplastic anemia, and seizures, particularly in patients with renal impairment when dosage adjustments are not made.

Overall, healthcare professionals should monitor patients for these adverse reactions and manage them appropriately.

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 the 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. Additionally, oral anti-cholinergics, such as propantheline, may delay the peak plasma levels, resulting in a 47% increase in Tmax, while not affecting the overall extent of absorption (AUC). It is advisable to monitor the timing of administration of these agents to optimize cefpodoxime absorption.

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. Clinicians should consider dosage adjustments or increased monitoring of cefpodoxime levels when these drugs are used together.

Nephrotoxic Drugs While nephrotoxicity has not been observed with cefpodoxime proxetil alone, caution is warranted when it is administered alongside drugs known for their nephrotoxic potential. Close monitoring of renal function is recommended in such cases to ensure patient safety.

Drug/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, 521 out of 3338 patients (16%) were aged 65 years and older, and 214 patients (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 subjects. 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, given the inherent variability in drug response among this population.

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, 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. Therefore, due to the limitations of animal reproduction studies in predicting human response, cefpodoxime proxetil should be used during pregnancy only if clearly needed. Healthcare professionals should weigh the potential benefits against the risks when considering this medication for 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 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 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, including the Ames test both with and without metabolic activation, 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, yielded negative results.

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 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, 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

The product is supplied in a tight, light-resistant container to ensure its integrity and efficacy. It 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) as defined by USP Controlled Room Temperature guidelines.

Healthcare professionals are advised to securely replace the cap after each opening to maintain the product's quality and prevent contamination.

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 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 manifest as watery and bloody stools, and to seek medical attention if such symptoms occur, even weeks after completing therapy.

Postmarketing experience has revealed serious adverse events associated with cefpodoxime proxetil, including allergic reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, and serum sickness-like reactions. Other reported serious conditions include pseudomembranous colitis, bloody diarrhea, ulcerative colitis, anaphylactic shock, and acute liver injury. 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)