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 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. Cefpodoxime proxetil tablets, USP, contain cefpodoxime proxetil USP equivalent to either 100 mg or 200 mg of cefpodoxime activity. The tablets 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 Cefpodoxime proxetil is not indicated for the treatment of infections caused by penicillin-resistant strains of Streptococcus pneumoniae or non-beta-lactamase-producing strains of Haemophilus influenzae in the context of acute bacterial exacerbation of chronic bronchitis.

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 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: for those with severe renal impairment (creatinine clearance <30 mL/min), increase the dosing intervals 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 in the absence of a proven or strongly suspected bacterial infection, or for prophylactic purposes, 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.

In the event of an allergic reaction to cefpodoxime proxetil, the medication should be discontinued immediately. Serious acute hypersensitivity reactions may necessitate emergency interventions, including the administration of epinephrine, oxygen, 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. It is essential to consider CDAD in any patient presenting with diarrhea following antibiotic therapy, as cases have been documented to occur up to two months post-treatment. If CDAD is suspected or confirmed, it may be necessary to discontinue ongoing antibiotic therapy not targeting C. difficile. Clinicians should implement appropriate fluid and electrolyte management, protein supplementation, and consider antibiotic treatment for C. difficile, along with surgical evaluation as clinically warranted.

In patients experiencing transient or persistent reductions in urinary output due to renal insufficiency, the total daily dose of cefpodoxime proxetil should be adjusted to prevent high and prolonged serum concentrations of the antibiotic. Caution is also advised when cefpodoxime is prescribed concurrently with 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 taken. 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 involving film-coated tablets, the most common adverse reactions occurring in more than 1% of participants included diarrhea (7%), nausea (3.3%), vaginal fungal infections (1%), vulvovaginal infections (1.3%), abdominal pain (1.2%), and headache (1%). Less frequent adverse reactions, occurring in less than 1% of subjects, encompassed a wide range of body systems. These included various fungal infections, abdominal distention, malaise, fatigue, asthenia, fever, chest pain, back pain, chills, generalized pain, and abnormal microbiological tests. Cardiovascular events such as congestive heart failure, migraine, palpitations, vasodilation, hematoma, hypertension, and hypotension were also noted.

Gastrointestinal disturbances were reported, including vomiting, dyspepsia, dry mouth, flatulence, decreased appetite, constipation, and oral moniliasis, among others. Hematological reactions included anemia, while metabolic and nutritional issues such as dehydration, gout, and peripheral edema were observed. Musculoskeletal complaints included myalgia, and nervous system effects included dizziness, insomnia, somnolence, anxiety, and confusion. Respiratory adverse reactions comprised asthma, cough, epistaxis, and pneumonia. Dermatological reactions included urticaria, rash, pruritus, and various skin conditions. Urogenital issues such as hematuria and urinary tract infections were also reported.

In trials involving granules for oral suspension, the most common adverse reactions occurring in more than 1% of participants included diarrhea (6%, with a higher incidence of 12.8% in infants and toddlers), diaper rash/fungal skin rash (2%, including moniliasis, with 8.5% in infants and toddlers), other skin rashes (1.8%), and vomiting (2.3%). Less than 1% of subjects experienced localized abdominal pain, headache, nausea, and various hematological changes such as thrombocythemia and leukopenia.

For single-dose film-coated tablets, the most common adverse reactions were nausea (1.4%) and diarrhea (1.2%), with less frequent reports of dizziness, headache, syncope, rash, vaginitis, and anxiety.

Post-marketing experiences have revealed serious adverse reactions, including allergic reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, and serum sickness-like reactions. Other serious events included pseudomembranous colitis, bloody diarrhea with abdominal pain, ulcerative colitis, anaphylactic shock, acute liver injury, and purpuric nephritis. Notably, one death was attributed to pseudomembranous colitis and disseminated intravascular coagulation.

Adverse reactions associated with cephalosporin class antibiotics, which may be relevant, include renal dysfunction, toxic nephropathy, hepatic dysfunction, aplastic anemia, hemolytic anemia, and seizures, particularly in patients with renal impairment when dosage adjustments were not made.

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. Therefore, it is advisable to monitor the therapeutic effectiveness of cefpodoxime proxetil when used alongside these agents.

Oral anti-cholinergics, including propantheline, have been shown to delay the peak plasma levels of cefpodoxime proxetil, resulting in a 47% increase in Tmax, although they do not affect the extent of absorption (AUC). Clinicians should consider this interaction when prescribing cefpodoxime proxetil in conjunction with anti-cholinergics.

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. It is recommended that dosage adjustments be considered when these medications are used together to avoid potential toxicity.

While nephrotoxicity has not been observed with cefpodoxime proxetil when administered alone, close monitoring of renal function is advised when it is given concurrently with compounds known to have nephrotoxic potential.

Additionally, cephalosporins, including cefpodoxime proxetil, may occasionally induce a positive direct Coombs’ test. This interaction should be taken into account 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, 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. 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 (1 to 2 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 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 no specific information regarding dosage adjustments, special monitoring, or safety considerations provided in the text. Therefore, healthcare professionals should exercise caution and consider individual patient factors when prescribing to this population. Regular assessment of renal function may be warranted to ensure safe and effective use of the medication in patients with reduced kidney function.

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.

Healthcare providers should be vigilant for symptoms associated with an overdose of beta-lactam antibiotics. Potential toxic symptoms may include nausea, vomiting, epigastric distress, and diarrhea. Monitoring and supportive care should be initiated promptly to manage these symptoms effectively.

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, this drug should be used during pregnancy only if clearly needed.

In terms of non-teratogenic effects, no adverse effects on fertility or reproduction were observed when cefpodoxime proxetil was administered orally to rats at doses of 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 in animals 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.

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. When cefpodoxime proxetil is 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 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 in the future.

Additionally, patients should 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 instruct patients to monitor for the development of watery and bloody stools, which may occur even two months after completing the antibiotic course, and to contact their physician immediately if such symptoms arise.

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, which is important for clinicians to consider during laboratory evaluations. Patients should be counseled that antibacterial drugs, such as cefpodoxime proxetil, are effective only against bacterial infections and do not treat viral infections like the common cold. It is crucial for patients to adhere to the prescribed regimen, as skipping doses or failing to complete the full course can 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 accompanying symptoms such as stomach cramps and fever, they should seek medical attention promptly. Postmarketing reports have indicated serious adverse events associated with cefpodoxime proxetil, including severe allergic reactions, pseudomembranous colitis, and other significant conditions, with one reported death 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 Cronus Pharma LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)