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.

Cefpodoxime proxetil functions as a prodrug, with its active metabolite being cefpodoxime. All dosages of cefpodoxime proxetil mentioned in this insert are expressed in terms of the active cefpodoxime moiety. The drug is supplied as flavored granules for oral suspension. Each 5 mL of cefpodoxime proxetil for oral suspension USP contains cefpodoxime proxetil USP equivalent to 50 mg or 100 mg of cefpodoxime activity after constitution. The formulation includes the following inactive ingredients: lactose monohydrate, corn starch, croscarmellose sodium, ferric oxide yellow, hydroxypropyl cellulose, microcrystalline cellulose, carboxymethyl cellulose sodium, colloidal silicon dioxide, citric acid anhydrous, sodium citrate, sodium benzoate, sucrose, and citron & vanille flavorings.

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 is treatable with cefpodoxime proxetil for infections 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 caused by Streptococcus pyogenes is also an indication for this drug.

Cefpodoxime proxetil is indicated for community-acquired pneumonia due to S. pneumoniae and H. influenzae (including beta-lactamase-producing strains).

The drug is effective in treating acute bacterial exacerbation of chronic bronchitis caused by S. pneumoniae, H. influenzae (non-beta-lactamase-producing strains only), and M. catarrhalis.

Cefpodoxime proxetil is indicated for the treatment of acute, uncomplicated urethral and cervical gonorrhea caused by Neisseria gonorrhoeae (including penicillinase-producing strains), as well as acute, uncomplicated ano-rectal infections in women due to the same organism.

Uncomplicated skin and skin structure infections caused by Staphylococcus aureus (including penicillinase-producing strains) and Streptococcus pyogenes are also treatable with this medication.

Acute maxillary sinusitis caused by Haemophilus influenzae (including beta-lactamase-producing strains), Streptococcus pneumoniae, and Moraxella catarrhalis is another indication for cefpodoxime proxetil.

Lastly, uncomplicated urinary tract infections (cystitis) caused by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Staphylococcus saprophyticus are included in the indications for this drug.

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

Dosage and Administration

Cefpodoxime proxetil for oral suspension may be administered 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.

• Uncomplicated Gonorrhea (men and women) and Rectal Gonococcal Infections (women): Administer a total daily dose of 200 mg as a single dose. Duration is not specified.

• 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 severe renal impairment (creatinine clearance <30 mL/min), dosing intervals should be adjusted to every 24 hours. In patients maintained on hemodialysis, the dose frequency should be three times per week following 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 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.

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. Clinicians should consider CDAD in any patient presenting with diarrhea following antibiotic therapy, as this condition can arise even two months post-administration of antibacterial agents. 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 indicated.

In patients experiencing transient or persistent reductions in urinary output due to renal insufficiency, it is recommended that the total daily dose of cefpodoxime proxetil be adjusted downward. This adjustment is crucial to avoid the risk of elevated and prolonged serum antibiotic concentrations that can occur with standard dosing in these individuals. Additionally, caution should 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. It is also important to note that prescribing cefpodoxime proxetil in the absence of a confirmed or strongly suspected bacterial infection, or for prophylactic purposes, is unlikely to benefit the patient and may increase the risk of developing drug-resistant bacteria.

Side Effects

In clinical trials, the most commonly reported adverse reactions with an incidence greater than 1% included diarrhea (6%), vomiting (2.3%), and diaper rash or fungal skin rash (2%), with the incidence of diarrhea in infants and toddlers (ages 1 month to 2 years) reported at 12.8% and diaper rash at 8.5%. Other skin rashes were observed in 1.8% of participants.

Adverse reactions with an incidence of less than 1% encompassed a variety of body systems. Notable reactions included localized abdominal pain, abdominal cramp, headache, generalized abdominal pain, asthenia, fever, and fungal infections. Digestive system reactions included nausea, anorexia, dry mouth, stomatitis, and pseudomembranous colitis. Hematological reactions reported were thrombocythemia, positive direct Coombs’ test, eosinophilia, leukocytosis, leukopenia, prolonged partial thromboplastin time, and thrombocytopenic purpura. Metabolic and nutritional changes included increased SGPT levels. Musculoskeletal reactions such as myalgia, nervous system effects including hallucination, hyperkinesia, nervousness, and somnolence, as well as respiratory issues like epistaxis and rhinitis were also noted. Skin reactions included skin moniliasis, urticaria, fungal dermatitis, acne, exfoliative dermatitis, and maculopapular rash. Additionally, taste perversion was reported under special senses.

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, rectorrhagia with hypotension, anaphylactic shock, acute liver injury, miscarriage due to in utero exposure, purpuric nephritis, pulmonary infiltrate with eosinophilia, and eyelid dermatitis. Notably, one death was 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, and may range in severity from mild diarrhea to fatal colitis. CDAD should be considered in all patients presenting with diarrhea following antibiotic use.

Adverse reactions and abnormal laboratory tests associated with cephalosporin class antibiotics include renal dysfunction, toxic nephropathy, hepatic dysfunction (including cholestasis), aplastic anemia, hemolytic anemia, serum sickness-like reactions, hemorrhage, agranulocytosis, and pancytopenia. Additionally, several cephalosporins have been implicated in triggering seizures, particularly in patients with renal impairment when the dosage was not appropriately reduced.

Drug Interactions

Antacids, specifically those containing sodium bicarbonate and aluminum hydroxide, have been shown to reduce the peak plasma levels of cefpodoxime proxetil by 24% to 42% and decrease the extent of absorption by 27% to 32%. However, these antacids do not alter the rate of absorption. Therefore, it is advisable to separate the administration of cefpodoxime proxetil and antacids to minimize the impact on drug levels.

Oral anti-cholinergics, such as propantheline, may delay the peak plasma levels of cefpodoxime proxetil, resulting in a 47% increase in time to reach maximum concentration (T max). Nonetheless, these agents do not affect the overall extent of absorption (AUC). Clinicians should consider this interaction when prescribing cefpodoxime proxetil alongside oral anti-cholinergics.

Probenecid is known to inhibit the renal excretion of cefpodoxime proxetil, leading to an approximate 31% increase in AUC and a 20% increase in peak plasma levels. When these medications are used together, careful monitoring of the patient's response and potential side effects is recommended.

Additionally, close monitoring of renal function is advised when cefpodoxime proxetil is administered with compounds that have known nephrotoxic potential to mitigate the risk of renal impairment.

It is important to note that cephalosporins, including cefpodoxime proxetil, may occasionally induce a positive direct Coombs’ test. This interaction should be considered when interpreting laboratory results in patients receiving cefpodoxime proxetil.

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. The data indicate that there are no overall differences in effectiveness or safety between elderly patients and their younger counterparts.

In healthy geriatric subjects with normal renal function, the pharmacokinetics of cefpodoxime were found to be comparable to those observed in younger individuals. Specifically, the average half-life of cefpodoxime in plasma was 4.2 hours, with urinary recovery averaging 21% following a 400 mg dose administered every 12 hours over a 15-day period.

Importantly, dose adjustments for elderly patients with normal renal function are not necessary. However, healthcare providers should continue to monitor geriatric patients for any potential adverse effects, as individual responses 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, 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 have not been established for use during labor and delivery, 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 not been specifically addressed in the available data regarding dosage adjustments, special monitoring, or safety considerations. Therefore, healthcare professionals should exercise caution when prescribing this medication to patients with reduced kidney function, as the lack of information necessitates careful clinical judgment and monitoring.

Hepatic Impairment

Patients with hepatic impairment have not been specifically studied in relation to the use of this medication. Consequently, there are no established dosage adjustments, special monitoring requirements, or precautions for individuals with compromised liver function. It is recommended that healthcare providers exercise caution when prescribing this medication to patients with hepatic impairment, given the lack of data on its safety and efficacy in this population. Regular monitoring of liver function may be prudent in these cases, although specific parameters are not defined in the available information.

Overdosage

In acute rodent toxicity studies, administration of a single oral dose of 5 g/kg did not result in any adverse effects. This finding suggests a relatively high threshold for toxicity in this model.

In cases of serious toxic reactions due to overdosage, it is recommended that healthcare professionals consider hemodialysis or peritoneal dialysis as potential interventions. These procedures may facilitate the removal of cefpodoxime from the body, especially in patients with compromised renal function.

Symptoms associated with an overdose of beta-lactam antibiotics, including cefpodoxime, may manifest as nausea, vomiting, epigastric distress, and diarrhea. Healthcare providers should monitor for these symptoms and manage them accordingly to ensure patient safety and comfort.

Nonclinical Toxicology

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, no teratogenic effects were observed at doses up to 30 mg/kg/day, corresponding to 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, the use of this drug during pregnancy should be considered only when clearly necessary.

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

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 linking pseudomembranous colitis to the use of cefpodoxime proxetil.

Patient Counseling

Patients should be counseled that antibacterial drugs, including cefpodoxime proxetil, are indicated solely for the treatment of bacterial infections and are ineffective against viral infections, such as the common cold. It is important for patients to understand that even if they begin to feel better early in the course of therapy, 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 made aware 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 informed 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 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, especially if accompanied by stomach cramps and fever.

Storage and Handling

Unsuspended granules are supplied in containers that 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). After the granules are mixed, the resulting suspension must be stored in a refrigerator at a temperature of 2° to 8°C (36° to 46°F). It is essential to shake the container well before each use and to keep it tightly closed when not in use. The mixed suspension is stable for up to 14 days; any unused portion should be discarded after this period to ensure safety and efficacy.

Additional Clinical Information

Cephalosporins, including cefpodoxime proxetil, may occasionally induce a positive direct Coombs’ test. Clinicians should counsel patients that antibacterial drugs, such as cefpodoxime proxetil, are effective only against bacterial infections and do not treat viral infections, like the common cold. Patients should be advised to adhere strictly to the prescribed regimen, as skipping doses or failing to complete the full course can reduce treatment effectiveness and increase the risk of bacterial resistance. Additionally, patients should be informed about the potential for antibiotic-associated diarrhea, which may manifest as watery and bloody stools, and to seek medical attention if such symptoms occur, even weeks after completing therapy.

Postmarketing experience has revealed serious adverse events associated with cefpodoxime proxetil, including allergic reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis), pseudomembranous colitis, and other severe gastrointestinal and systemic reactions. 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)