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. All doses 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 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. No specific teratogenic or nonteratogenic effects have been mentioned in the provided data.

Dosage and Administration

Cefpodoxime proxetil for oral suspension may be administered without regard to food.

Adults and Adolescents (age 12 years and older):

• Pharyngitis and/or Tonsillitis: The 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: The total daily dose is 400 mg, given as 200 mg every 12 hours for 14 days.

• Uncomplicated Gonorrhea (men and women) and Rectal Gonococcal Infections (women): A single dose of 200 mg is recommended. Duration is not specified.

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

• Acute Maxillary Sinusitis: The total daily dose is 400 mg, given as 200 mg every 12 hours for 10 days.

• Uncomplicated Urinary Tract Infection: The total daily dose is 200 mg, administered as 100 mg every 12 hours for 7 days.

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

• Acute Otitis Media: The total daily dose is 10 mg/kg/day (maximum 400 mg/day), given as 5 mg/kg every 12 hours (maximum 200 mg/dose) for 5 days.

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

• Acute Maxillary Sinusitis: The total daily dose is 10 mg/kg/day (maximum 400 mg/day), given as 5 mg/kg every 12 hours (maximum 200 mg/dose) for 10 days.

For Patients with Severe Renal Impairment (<30 mL/min Creatinine Clearance): Dosing intervals should be increased to every 24 hours. In patients maintained on hemodialysis, the dose frequency should be three times per week after hemodialysis.

Preparation of Suspension:

To prepare the suspension, the following volumes and directions should be followed:

• For a 50 mL suspension, suspend in a total of 31 mL of distilled water.

• For a 75 mL suspension, suspend in a total of 44 mL of distilled water.

• For a 100 mL suspension, suspend in a total of 57 mL of distilled water.

• For a 50 mL (100 mg/5 mL) suspension, suspend in a total of 30 mL of distilled water.

• For a 75 mL (100 mg/5 mL) suspension, suspend in a total of 43 mL of distilled water.

• For a 100 mL (100 mg/5 mL) suspension, suspend in a total of 57 mL of distilled water.

After mixing, the suspension should be stored in a refrigerator at 2° to 8°C (36° to 46°F). Shake well before use. The container should be kept tightly closed, and the mixture may be used for 14 days. Discard any unused portion after 14 days.

Contraindications

Cefpodoxime proxetil is contraindicated in patients with a known allergy to cefpodoxime or to any cephalosporin antibiotics.

Additionally, the use of cefpodoxime proxetil is not recommended in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication, as this may not benefit the patient and could contribute to the development of 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.

Reports from post-marketing experience outside the United States have indicated occurrences of pseudomembranous colitis associated with cefpodoxime proxetil use.

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. 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 occurring in more than 1% of participants 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 subjects.

Adverse reactions occurring in less than 1% of participants encompassed a range of body systems. Notable reactions included localized abdominal pain, abdominal cramp, headache, monilia, generalized abdominal pain, asthenia, fever, and fungal infection. Digestive system reactions included nausea, anorexia, dry mouth, stomatitis, and pseudomembranous colitis. Hematological reactions comprised thrombocythemia, positive direct Coombs’ test, eosinophilia, leukocytosis, leukopenia, prolonged partial thromboplastin time, and thrombocytopenic purpura. Metabolic and nutritional changes included increased SGPT levels, while musculoskeletal reactions involved myalgia. Nervous system effects included hallucination, hyperkinesia, nervousness, and somnolence. Respiratory reactions were noted as epistaxis and rhinitis, and skin reactions included skin moniliasis, urticaria, fungal dermatitis, acne, exfoliative dermatitis, and maculopapular rash. Additionally, taste perversion was reported among the special senses.

Post-marketing experience has 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.

Warnings regarding hypersensitivity reactions indicate that serious acute reactions may necessitate treatment with epinephrine and other emergency measures. Additionally, Clostridium difficile associated diarrhea (CDAD) has been reported with the use of nearly all antibacterial agents, including cefpodoxime proxetil, with severity ranging from mild diarrhea to fatal colitis.

It is important to note that adverse reactions and altered laboratory tests associated with cephalosporin class antibiotics may include renal dysfunction, toxic nephropathy, hepatic dysfunction (including cholestasis), aplastic anemia, hemolytic anemia, serum sickness-like reactions, hemorrhage, agranulocytosis, and pancytopenia. Furthermore, several cephalosporins have been implicated in triggering seizures, particularly in patients with renal impairment when dosages were not appropriately reduced.

Drug Interactions

Concomitant administration of antacids, specifically sodium bicarbonate and aluminum hydroxide, may significantly impact the pharmacokinetics of cefpodoxime proxetil. High doses of these antacids can reduce peak plasma levels by 24% to 42% and decrease the extent of absorption by 27% to 32%. However, the rate of absorption remains unaffected by these medications.

Oral anti-cholinergics, such as propantheline, have been shown to delay the peak plasma levels of cefpodoxime proxetil, resulting in a 47% increase in Tmax. Nonetheless, these agents do not alter the extent of absorption, as indicated by the area under the curve (AUC).

Probenecid is known to inhibit the renal excretion of cefpodoxime, leading to an approximate 31% increase in AUC and a 20% increase in peak plasma levels of cefpodoxime. Clinicians should consider dosage adjustments and monitor patients accordingly when these drugs are co-administered.

When cefpodoxime proxetil is used in conjunction with nephrotoxic drugs, it is essential to closely monitor renal function due to the potential for increased risk of nephrotoxicity.

Additionally, cephalosporins, including cefpodoxime proxetil, may occasionally induce a positive direct Coombs’ test, which 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 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 consistent with those observed in younger subjects. Specifically, the average half-life 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 necessary. However, healthcare providers should continue to monitor geriatric patients for any potential adverse effects, given the variability in individual responses to medication in 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. Healthcare professionals should weigh the potential benefits against the risks when considering this medication for pregnant patients.

Lactation

Cefpodoxime is excreted in human milk. In a study involving three lactating women, the levels of cefpodoxime in human milk were found to be 0%, 2%, and 6% of concomitant serum levels at 4 hours following a 200 mg oral dose of cefpodoxime proxetil. At 6 hours post-dosing, the levels increased to 0%, 9%, and 16% of concomitant serum levels.

Due to the potential for serious reactions in breastfed infants, healthcare professionals should consider the importance of the drug to the mother when making a decision to either discontinue nursing or discontinue the drug.

Renal Impairment

Patients with renal impairment have not been specifically addressed in the available data regarding dosage adjustments, special monitoring, or safety considerations. Therefore, healthcare professionals should exercise caution when prescribing this medication to patients with reduced kidney function, as the lack of information necessitates careful clinical judgment and monitoring.

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 resulting from 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 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 not only reduce the effectiveness of the immediate treatment but also increase the risk of bacteria developing resistance. This resistance could render cefpodoxime proxetil or other antibacterial drugs ineffective for future infections.

Additionally, patients should be informed that diarrhea is a common side effect associated with antibiotic use, which typically resolves upon discontinuation of the medication. However, healthcare providers should advise patients to be vigilant for the development of watery and bloody stools, which may occur even two months after completing the antibiotic course. If such symptoms arise, patients should be instructed to contact their physician promptly for further evaluation and management.

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 occur during or after treatment. If patients experience watery or bloody stools, they should seek medical attention promptly.

Postmarketing experience has revealed serious adverse events associated with cefpodoxime proxetil, including allergic reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, and erythema multiforme, as well as gastrointestinal issues like pseudomembranous colitis and ulcerative colitis. Other reported serious reactions include anaphylactic shock, acute liver injury, and purpuric nephritis. 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 Rising Pharma Holdings, Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)