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 empirical 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 include the following inactive ingredients: carboxymethyl cellulose calcium, colloidal silicon dioxide, crospovidone, 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 (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 have been mentioned.

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 applicable

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 adjusted to 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 tablets is contraindicated in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication, as this may not provide therapeutic benefit and could 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.

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.

Cefpodoxime proxetil has been associated with Clostridium difficile-associated diarrhea (CDAD), which can range from mild diarrhea to severe, potentially fatal 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 particularly concerning due to their association with increased morbidity and mortality, as these infections may be resistant to standard antimicrobial therapy and could necessitate surgical intervention. Clinicians should maintain a high index of suspicion for CDAD in any patient presenting with diarrhea following antibiotic treatment, as cases have been reported to occur up to two months post-therapy.

If CDAD is suspected or confirmed, it may be necessary to discontinue ongoing antibiotic therapy not directed against C. difficile. Management should include appropriate fluid and electrolyte replacement, protein supplementation, targeted antibiotic treatment for C. difficile, and surgical evaluation when clinically warranted. Monitoring for C. difficile in patients treated with cefpodoxime who develop diarrhea is essential, 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 definitive 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 concentrations of the antibiotic 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 crucial, 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 without a prophylactic indication, is unlikely to benefit the patient and may increase the risk of developing drug-resistant bacteria.

Side Effects

Patients receiving treatment may experience a range of adverse reactions. The following outlines 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 greater 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%). Adverse reactions with an incidence of less than 1% were reported across various body systems, including:

• Body: Fungal infections, abdominal distention, malaise, fatigue, asthenia, fever, chest pain, back pain, chills, generalized pain, abnormal microbiological tests, moniliasis, abscess, allergic reactions, facial edema, bacterial infections, parasitic infections, localized edema, and localized pain.

• Cardiovascular: Congestive heart failure, migraine, palpitations, vasodilation, hematoma, hypertension, and hypotension.

• Digestive: Vomiting, dyspepsia, dry mouth, flatulence, decreased appetite, constipation, oral moniliasis, anorexia, eructation, gastritis, mouth ulcers, gastrointestinal disorders, rectal disorders, tongue disorders, tooth disorders, increased thirst, oral lesions, tenesmus, dry throat, and toothache.

• Hemic and Lymphatic: Anemia.

• Metabolic and Nutritional: Dehydration, gout, peripheral edema, and weight increase.

• Musculoskeletal: Myalgia.

• Nervous: Dizziness, insomnia, somnolence, anxiety, shakiness, nervousness, cerebral infarction, change in dreams, impaired concentration, confusion, nightmares, paresthesia, and vertigo.

• Respiratory: Asthma, cough, epistaxis, rhinitis, wheezing, bronchitis, dyspnea, pleural effusion, pneumonia, and sinusitis.

• Skin: Urticaria, rash, pruritus (non-application site), diaphoresis, maculopapular rash, fungal dermatitis, desquamation, dry skin (non-application site), hair loss, vesiculobullous rash, and sunburn.

• Special Senses: Taste alterations, eye irritation, taste loss, and tinnitus.

• Urogenital: Hematuria, urinary tract infections, metrorrhagia, dysuria, urinary frequency, nocturia, penile infection, proteinuria, and vaginal pain.

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

Clinicians should be aware of the risk of Clostridium difficile-associated diarrhea (CDAD), which has been reported with the use of nearly all antibacterial agents, including cefpodoxime proxetil tablets. 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.

Additional adverse reactions 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. Seizures may also occur, particularly in patients with renal impairment if the dosage is not appropriately reduced. In cases where seizures associated with drug therapy 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 reduce the peak plasma levels of cefpodoxime proxetil by 24% to 42% and the extent of absorption by 27% to 32%. However, these medications do not alter the rate of absorption. It is advisable to monitor the timing of administration to optimize therapeutic outcomes.

Oral anti-cholinergics, including propantheline, have been shown to delay the peak plasma levels of cefpodoxime proxetil, resulting in a 47% increase in Tmax, while not affecting the extent of absorption (AUC). Clinicians should consider this interaction when prescribing these agents concurrently.

As with other beta-lactam antibiotics, the renal excretion of cefpodoxime proxetil can be inhibited by probenecid, leading to an approximate 31% increase in AUC and a 20% increase in peak plasma levels. Dosage adjustments may be necessary, and careful monitoring of the patient's response is recommended.

Although nephrotoxicity has not been observed when cefpodoxime proxetil is administered alone, it is prudent to closely monitor renal function when it is given in conjunction with compounds known to have nephrotoxic potential.

Cephalosporins, including cefpodoxime proxetil, may occasionally induce a positive direct Coombs’ test. This interaction 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 3338 patients enrolled were aged 65 years and older, and 6% were aged 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 inherent variability in drug response among this population.

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 of these patients.

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 tablets, USP, are indicated solely for the treatment of bacterial infections and are ineffective against viral infections, such as the common cold.

When cefpodoxime proxetil tablets, USP 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, USP, or other antibacterial drugs ineffective for future infections.

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, 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 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 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), in compliance with USP Controlled Room Temperature guidelines. It is essential to replace the cap securely after each opening to maintain product integrity and prevent contamination.

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 these antibacterial drugs are effective only against bacterial infections and do not treat viral infections, such as the common cold. Patients are advised to adhere strictly to the prescribed regimen, as skipping doses or failing to complete the course may 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 discontinuation of the medication. If patients experience watery or bloody stools, they should seek medical attention promptly.

Postmarketing experience has revealed serious adverse events associated with cefpodoxime proxetil, including allergic reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis, as well as gastrointestinal issues like pseudomembranous colitis and bloody diarrhea. Other reported serious reactions include 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 Golden State Medical Supply, Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)