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.

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 inactive ingredients in the tablets include 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. All doses of cefpodoxime proxetil mentioned are expressed in terms of the active cefpodoxime moiety.

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 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

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

• Neisseria gonorrhoeae (including penicillinase-producing strains) It is also indicated for the treatment of acute, uncomplicated ano-rectal infections in women due to:

• Neisseria gonorrhoeae (including penicillinase-producing strains)

Skin and Skin Structure Infections This drug 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 Cefpodoxime proxetil 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 This drug is indicated for the treatment of uncomplicated urinary tract infections (cystitis) caused by:

• Escherichia coli

• Klebsiella pneumoniae

• Proteus mirabilis

• Staphylococcus saprophyticus

No specific teratogenic or nonteratogenic effects have been mentioned in the available data.

Dosage and Administration

Film-coated tablets and granules for oral suspension are administered orally. For optimal absorption, film-coated tablets should be taken with food.

Adults and Adolescents (age 12 years and older):

• Pharyngitis and/or Tonsillitis: 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: Total daily dose is 400 mg, administered as 200 mg every 12 hours for a duration of 14 days.

• Acute Bacterial Exacerbations of Chronic Bronchitis: Total daily dose is 400 mg, administered as 200 mg every 12 hours for a duration of 10 days.

• Uncomplicated Gonorrhea (men and women) and Rectal Gonococcal Infections (women): Total daily dose is 200 mg, administered as a single dose.

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

• Acute Maxillary Sinusitis: Total daily dose is 400 mg, administered as 200 mg every 12 hours for a duration of 10 days.

• Uncomplicated Urinary Tract Infection: Total daily dose is 200 mg, administered as 100 mg every 12 hours for a duration of 7 days.

Granules for Oral Suspension:

These may be given without regard to food.

• Adults and Adolescents (age 12 years and older): The dosing regimens are identical to those for film-coated tablets as outlined above.

• Infants and Pediatric Patients (age 2 months through 12 years):

  • Acute Otitis Media: Total daily dose is 10 mg/kg/day (maximum 400 mg/day), administered as 5 mg/kg every 12 hours (maximum 200 mg/dose) for a duration of 5 days.

  • Pharyngitis and/or Tonsillitis: Total daily dose is 10 mg/kg/day (maximum 200 mg/day), administered as 5 mg/kg/dose every 12 hours (maximum 100 mg/dose) for a duration of 5 to 10 days.

  • Acute Maxillary Sinusitis: Total daily dose is 10 mg/kg/day (maximum 400 mg/day), administered as 5 mg/kg every 12 hours (maximum 200 mg/dose) for a duration of 10 days.

Contraindications

Cefpodoxime proxetil is contraindicated in patients with a known allergy to cefpodoxime or to the cephalosporin class of 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 contraindicated due to the lack of therapeutic benefit and the increased 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.

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 can occur up to two months post-antibiotic administration. 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.

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 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 taken. It is important to note that 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

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%). For granules for oral suspension, common reactions included diarrhea (6%, with a higher incidence of 12.8% in infants and toddlers), diaper rash/fungal skin rash (2%, 8.5% in infants and toddlers), other skin rashes (1.8%), and vomiting (2.3%). In single-dose film-coated tablet studies, nausea (1.4%) and diarrhea (1.2%) were the most frequently reported adverse reactions.

Less common adverse reactions (incidence less than 1%) reported in the clinical trials for film-coated tablets encompassed a wide range of body systems. These included various body reactions such as fungal infections, malaise, fatigue, and chest pain; cardiovascular issues like congestive heart failure and palpitations; digestive complaints including vomiting and dyspepsia; and nervous system effects such as dizziness and insomnia. Other notable reactions included respiratory issues (e.g., asthma, cough), skin reactions (e.g., urticaria, rash), and urogenital symptoms (e.g., hematuria, urinary tract infections).

For the granules for oral suspension, less common reactions included localized abdominal pain, nausea, and various hematological changes such as thrombocythemia and leukopenia. Neurological effects such as hallucinations and nervousness were also noted.

Post-marketing experiences have revealed serious adverse reactions, including severe allergic reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis, as well as gastrointestinal complications like pseudomembranous colitis and bloody diarrhea. Other serious events included anaphylactic shock, acute liver injury, and renal dysfunction. Notably, one death was reported due to pseudomembranous colitis and disseminated intravascular coagulation.

Additionally, adverse reactions associated with the cephalosporin class of antibiotics, which may be relevant, include renal dysfunction, hepatic dysfunction, and hematological disorders such as aplastic anemia and agranulocytosis. Seizures have also been reported, particularly in patients with renal impairment when dosages were not appropriately adjusted.

Healthcare professionals should monitor patients for these adverse reactions and manage them accordingly.

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 efficacy.

Probenecid Probenecid has been observed to inhibit 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 co-administering probenecid.

Nephrotoxic Drugs While nephrotoxicity has not been reported with cefpodoxime proxetil when used 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.

Laboratory Test Interaction 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, 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 were consistent with those observed in younger individuals. Specifically, the average half-life of cefpodoxime in plasma was 4.2 hours, and urinary recovery was approximately 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 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. Additionally, the safety and efficacy of cefpodoxime proxetil during labor and delivery have not been established, and treatment should be administered only when 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

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 is classified as Pregnancy Category B. In nonclinical studies, it was determined that cefpodoxime proxetil was neither teratogenic nor embryocidal when administered to rats during organogenesis at doses up to 100 mg/kg/day, which is equivalent to two times the human dose based on mg/m². Similarly, in rabbits, doses up to 30 mg/kg/day, corresponding to one to two times the human dose based on mg/m², did not demonstrate 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, the use of this drug during pregnancy should be considered only if clearly needed.

In terms of non-teratogenic effects, no adverse effects on fertility or reproduction were observed in rats administered 100 mg/kg/day or less, which is also two times the human dose based on mg/m².

Long-term carcinogenicity studies of cefpodoxime proxetil have not been conducted. However, mutagenicity 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.

Overall, no adverse effects on fertility or reproduction were noted in animal studies when cefpodoxime proxetil was administered at doses of 100 mg/kg/day or less.

Postmarketing Experience

Post-marketing experience has revealed reports of pseudomembranous colitis associated with the use of cefpodoxime proxetil outside the United States. Serious adverse experiences reported include allergic reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, and serum sickness-like reactions. Additional serious events include 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. Furthermore, adverse reactions and altered laboratory tests associated with cephalosporin class antibiotics have included renal dysfunction, toxic nephropathy, hepatic dysfunction such as cholestasis, aplastic anemia, hemolytic anemia, serum sickness-like reactions, hemorrhage, agranulocytosis, and pancytopenia. It has also been noted that several cephalosporins may trigger seizures, particularly in patients with renal impairment when the dosage is not appropriately reduced.

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, cefpodoxime proxetil must be taken exactly as directed by their healthcare provider.

Healthcare providers should emphasize the importance of adhering to the prescribed dosing schedule and completing the full course of therapy. Patients should be informed that skipping doses or discontinuing treatment prematurely may reduce the effectiveness of the immediate treatment and increase the risk of bacterial resistance, potentially rendering cefpodoxime proxetil and other antibacterial drugs ineffective for future infections.

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, they should be advised to monitor for more serious gastrointestinal symptoms. If patients experience watery and bloody stools, with or without accompanying stomach cramps and fever, they should contact their physician promptly, as these symptoms may occur even two months or more after completing the antibiotic course.

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) in accordance with 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. 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 NorthStar Rx LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)