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 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 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. 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 (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 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

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 history regarding hypersensitivity reactions to cefpodoxime, other cephalosporins, penicillins, or any other drugs. 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 allergy. 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 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 over two months post-antibiotic treatment.

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 as clinically warranted. Monitoring for C. difficile in patients treated with cefpodoxime who develop diarrhea is crucial, given the increased incidence observed in early 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 downward, as elevated and prolonged serum antibiotic concentrations may occur following standard dosing. Caution should also be exercised when administering cefpodoxime to patients concurrently 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 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 (7%), nausea (3.3%), vaginal fungal infections (1%), vulvovaginal infections (1.3%), abdominal pain (1.2%), and headache (1%).

Adverse reactions occurring with an incidence of less than 1% were categorized by body system. Notable reactions included fungal infections, abdominal distention, malaise, fatigue, asthenia, fever, chest pain, back pain, chills, generalized pain, and abnormal microbiological tests within the body system. Cardiovascular reactions included congestive heart failure, migraine, palpitations, vasodilation, hematoma, hypertension, and hypotension. Digestive system reactions comprised 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 reactions included anemia, while metabolic and nutritional reactions encompassed dehydration, gout, peripheral edema, and weight increase. Musculoskeletal reactions were primarily myalgia. Nervous system reactions included dizziness, insomnia, somnolence, anxiety, shakiness, nervousness, cerebral infarction, changes in dreams, impaired concentration, confusion, nightmares, paresthesia, and vertigo. Respiratory reactions included asthma, cough, epistaxis, rhinitis, wheezing, bronchitis, dyspnea, pleural effusion, pneumonia, and sinusitis. Skin reactions included 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 reactions included taste alterations, eye irritation, taste loss, and tinnitus. Urogenital reactions included hematuria, urinary tract infections, metrorrhagia, dysuria, urinary frequency, nocturia, penile infection, proteinuria, and vaginal pain.

Post-marketing experience has 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 with miscarriage, purpuric nephritis, pulmonary infiltrate with eosinophilia, and eyelid dermatitis. One death has been 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 tablets, and may range in severity from mild diarrhea to fatal colitis. CDAD should be considered in all patients presenting with diarrhea following antibiotic use.

Additional adverse reactions and altered laboratory tests reported for cephalosporin class antibiotics 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 the dosage was not reduced. If seizures associated with drug therapy occur, the drug should be discontinued.

Drug Interactions

Concomitant administration of certain medications may influence the pharmacokinetics and clinical effects 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 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 based on the increased exposure when these medications are used together.

Nephrotoxic Drugs While nephrotoxicity has not been observed with cefpodoxime proxetil alone, it is recommended to closely monitor renal function when this antibiotic is administered alongside drugs known for their nephrotoxic potential.

Laboratory Test Interactions Cefpodoxime proxetil, as a member of the cephalosporin class, may occasionally induce a positive direct Coombs’ test. This should be taken into account when interpreting laboratory results during treatment.

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 were consistent with those observed in younger individuals. The average half-life of cefpodoxime in plasma was approximately 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 required. However, healthcare providers should continue to monitor renal function and overall health status in geriatric patients, as individual responses to medication may vary.

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 (approximately two times the human dose based on mg/m²) and to rabbits at doses up to 30 mg/kg/day (approximately one to two times the human dose based on mg/m²).

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; treatment should be administered only if 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

There is no specific information regarding dosage adjustments, special monitoring, or safety considerations for patients with renal impairment. Healthcare professionals should exercise caution when prescribing to patients with reduced kidney function, as the absence of detailed guidance necessitates careful clinical judgment. Regular monitoring of renal function may be advisable in this patient population.

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 and consider the overall clinical context when prescribing this medication to patients with hepatic impairment.

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.

Mutagenesis studies of cefpodoxime, 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 when cefpodoxime was administered orally to rats 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 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 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, rendering cefpodoxime proxetil tablets, USP and potentially 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 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 ensure that the cap is replaced 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. Patients should be informed that these antibacterial drugs are effective only against bacterial infections and do not treat viral infections, such as the common cold. It is crucial for patients to adhere 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 made aware of 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 contact their physician immediately. Postmarketing reports have indicated serious adverse reactions, including allergic responses such as Stevens-Johnson syndrome and toxic epidermal necrolysis, as well as gastrointestinal issues like pseudomembranous colitis, which has been associated with severe outcomes, including one reported death.

FDA Insert (PDF)

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

View full prescribing information (PDF)