Cefpodoxime proxetil

Uses and Indications

Cefpodoxime proxetil is indicated for the treatment of patients with mild to moderate infections caused by susceptible strains of the designated microorganisms in the following conditions:

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

• Caused by:

  • Streptococcus pyogenes

Community-Acquired Pneumonia

• Caused by:

  • Streptococcus pneumoniae

  • Haemophilus influenzae (including beta-lactamase-producing strains)

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

• Caused by:

  • Neisseria gonorrhoeae (including penicillinase-producing strains)

Acute, Uncomplicated Ano-Rectal Infections in Women

• Due to:

  • Neisseria gonorrhoeae (including penicillinase-producing strains)

Uncomplicated Skin and Skin Structure Infections

• Caused by:

  • Staphylococcus aureus (including penicillinase-producing strains)

  • Streptococcus pyogenes

Acute Maxillary Sinusitis

• Caused by:

  • Haemophilus influenzae (including beta-lactamase-producing strains)

  • Streptococcus pneumoniae

  • Moraxella catarrhalis

Uncomplicated Urinary Tract Infections (Cystitis)

• Caused by:

  • Escherichia coli

  • Klebsiella pneumoniae

  • Proteus mirabilis

  • Staphylococcus saprophyticus

Limitations of Use

• No specific teratogenic or nonteratogenic effects are mentioned in the provided text.

Dosage and Administration

Cefpodoxime proxetil is available in two formulations: film-coated tablets and granules for oral suspension. The route of administration is oral, with specific instructions for each formulation regarding food intake.

Film-Coated Tablets:Cefpodoxime proxetil tablets should be administered orally with food to enhance absorption.

Granules for Oral Suspension:Cefpodoxime proxetil for oral suspension may be given without regard to food.

Recommended Dosages for Adults and Adolescents (age 12 years and older):

• Pharyngitis and/or tonsillitis:

  • Total Daily Dose: 200 mg

  • Dose Frequency: 100 mg Q 12 hours

  • Duration: 5 to 10 days

• Acute community-acquired pneumonia:

  • Total Daily Dose: 400 mg

  • Dose Frequency: 200 mg Q 12 hours

  • Duration: 14 days

• Acute bacterial exacerbations of chronic bronchitis:

  • Total Daily Dose: 400 mg

  • Dose Frequency: 200 mg Q 12 hours

  • Duration: 10 days

• Uncomplicated gonorrhea (men and women) and rectal gonococcal infections (women):

  • Total Daily Dose: 200 mg

  • Dose Frequency: single dose

• Skin and skin structure infections:

  • Total Daily Dose: 800 mg

  • Dose Frequency: 400 mg Q 12 hours

  • Duration: 7 to 14 days

• Acute maxillary sinusitis:

  • Total Daily Dose: 400 mg

  • Dose Frequency: 200 mg Q 12 hours

  • Duration: 10 days

• Uncomplicated urinary tract infection:

  • Total Daily Dose: 200 mg

  • Dose Frequency: 100 mg Q 12 hours

  • Duration: 7 days

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

• Acute otitis media:

  • Total Daily Dose: 10 mg/kg/day (Max 400 mg/day)

  • Dose Frequency: 5 mg/kg Q 12 hours (Max 200 mg/dose)

  • Duration: 5 days

• Pharyngitis and/or tonsillitis:

  • Total Daily Dose: 10 mg/kg/day (Max 200 mg/day)

  • Dose Frequency: 5 mg/kg/dose Q 12 hours (Max 100 mg/dose)

  • Duration: 5 to 10 days

• Acute maxillary sinusitis:

  • Total Daily Dose: 10 mg/kg/day (Max 400 mg/day)

  • Dose Frequency: 5 mg/kg Q 12 hours (Max 200 mg/dose)

  • Duration: 10 days

Renal Impairment Considerations:For patients with severe renal impairment (creatinine clearance <30 mL/min), the dosing intervals should be increased to Q 24 hours. In patients maintained on hemodialysis, the dose frequency should be adjusted to three times per week after hemodialysis.

Preparation of Suspension:For the granules for oral suspension, the following preparation instructions apply:

• 50 mL: Suspend in a total of 31 mL of distilled water.

• 75 mL: Suspend in a total of 44 mL of distilled water.

• 100 mL: 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 and discard any unused portion after 14 days.

Contraindications

Cefpodoxime proxetil is contraindicated in patients with a known allergy to cefpodoxime or to the cephalosporin group of antibiotics. Additionally, prescribing cefpodoxime proxetil in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Warnings and Precautions

Before therapy with cefpodoxime proxetil is instituted, careful inquiry should be made to determine whether the patient has had previous hypersensitivity reactions to cefpodoxime, other cephalosporins, penicillins, or other drugs. If cefpodoxime is to be administered to penicillin-sensitive patients, caution should be exercised due to the documented risk of cross-hypersensitivity among beta-lactam antibiotics, which may occur in up to 10% of patients with a history of penicillin allergy. If an allergic reaction to cefpodoxime proxetil occurs, the drug should be discontinued immediately.

Serious Warnings

Serious acute hypersensitivity reactions may require treatment with epinephrine and other emergency measures, including oxygen, intravenous fluids, intravenous antihistamine, 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, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon, leading to overgrowth of C. difficile, which produces toxins A and B contributing to the development of CDAD. Hypertoxin-producing strains of C. difficile can cause increased morbidity and mortality, as these infections may be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

General Precautions

In patients with transient or persistent reduction in urinary output due to renal insufficiency, the total daily dose of cefpodoxime proxetil should be reduced, as high and prolonged serum antibiotic concentrations can occur in such individuals following usual doses. Cefpodoxime, like other cephalosporins, should be administered with caution to patients receiving concurrent treatment with potent diuretics. As with other antibiotics, prolonged use of cefpodoxime proxetil may result in overgrowth of non-susceptible organisms. Repeated evaluation of the patient’s condition is essential, and if superinfection occurs during therapy, appropriate measures should be taken. Prescribing cefpodoxime proxetil in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Laboratory Tests

No specific laboratory tests are mentioned.

Get Emergency Medical Help Instructions

Serious acute hypersensitivity reactions may require treatment with epinephrine and other emergency measures, including oxygen, intravenous fluids, intravenous antihistamine, and airway management, as clinically indicated.

Stop Taking and Call Your Doctor Instructions

If an allergic reaction to cefpodoxime proxetil occurs, the drug should be discontinued immediately.

Side Effects

Adverse Reactions

In clinical trials, the most commonly reported adverse reactions (incidence greater than 1%) for cefpodoxime proxetil include:

• Diarrhea: 7% (dose-related; 10.4% at 800 mg/day to 5.7% at 200 mg/day; 10% of patients with diarrhea had C. difficile organism or toxin in stool)

• Nausea: 3.3%

• Vaginal Fungal Infections: 1%

• Vulvovaginal Infections: 1.3%

• Abdominal Pain: 1.2%

• Headache: 1%

Adverse reactions with an incidence of less than 1% are categorized by body system as follows:

• Body: fungal infections, abdominal distention, malaise, fatigue, asthenia, fever, chest pain, back pain, chills, generalized pain, abnormal microbiological tests, moniliasis, abscess, allergic reaction, facial edema, bacterial infections, parasitic infections, localized edema, localized pain.

• Cardiovascular: congestive heart failure, migraine, palpitations, vasodilation, hematoma, hypertension, hypotension.

• Digestive: vomiting, dyspepsia, dry mouth, flatulence, decreased appetite, constipation, oral moniliasis, anorexia, eructation, gastritis, mouth ulcers, gastrointestinal disorders, rectal disorders, tongue disorders, tooth disorders, increased thirst, oral lesions, tenesmus, dry throat, toothache.

• Hemic and Lymphatic: anemia.

• Metabolic and Nutritional: dehydration, gout, peripheral edema, weight increase.

• Musculo-skeletal: myalgia.

• Nervous: dizziness, insomnia, somnolence, anxiety, shakiness, nervousness, cerebral infarction, change in dreams, impaired concentration, confusion, nightmares, paresthesia, vertigo.

• Respiratory: asthma, cough, epistaxis, rhinitis, wheezing, bronchitis, dyspnea, pleural effusion, pneumonia, sinusitis.

• Skin: urticaria, rash, pruritus non-application site, diaphoresis, maculopapular rash, fungal dermatitis, desquamation, dry skin non-application site, hair loss, vesiculobullous rash, sunburn.

• Special Senses: taste alterations, eye irritation, taste loss, tinnitus.

• Urogenital: hematuria, urinary tract infections, metrorrhagia, dysuria, urinary frequency, nocturia, penile infection, proteinuria, vaginal pain.

Post-marketing Experience Serious adverse experiences reported include:

• Allergic reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, and serum sickness-like reactions.

• Pseudomembranous colitis, bloody diarrhea with abdominal pain, ulcerative colitis, rectorrhagia with hypotension, anaphylactic shock, acute liver injury, in utero exposure with miscarriage, purpuric nephritis, pulmonary infiltrate with eosinophilia, and eyelid dermatitis.

• One death attributed to pseudomembranous colitis and disseminated intravascular coagulation.

Warnings

• 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 must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

Cephalosporin Class Labeling Adverse reactions and altered laboratory tests reported for cephalosporin class antibiotics include:

• Renal dysfunction, toxic nephropathy, hepatic dysfunction including cholestasis, aplastic anemia, hemolytic anemia, serum sickness-like reaction, hemorrhage, agranulocytosis, and pancytopenia.

• Seizures have been reported, particularly in patients with renal impairment when dosage was not reduced. If seizures associated with drug therapy occur, the drug should be discontinued.

Drug Interactions

Concomitant administration of high doses of antacids, such as sodium bicarbonate and aluminum hydroxide, or H2 blockers, has been shown to reduce peak plasma levels of cefpodoxime proxetil by 24% to 42% and the extent of absorption by 27% to 32%. However, the rate of absorption remains unaffected by these medications. Additionally, oral anti-cholinergics, such as propantheline, may delay peak plasma levels, resulting in a 47% increase in Tmax, while not altering the extent of absorption (AUC).

Probenecid, a known inhibitor of renal excretion, can significantly affect cefpodoxime levels. The co-administration of probenecid leads to an approximately 31% increase in AUC and a 20% increase in peak plasma levels of cefpodoxime.

When cefpodoxime proxetil is administered alongside nephrotoxic drugs, close monitoring of renal function is advised, despite the absence of noted nephrotoxicity when cefpodoxime is given alone.

Furthermore, cephalosporins, including cefpodoxime proxetil, are known to occasionally induce a positive direct Coombs’ test, which may affect laboratory test results.

Pediatric Use

Safety and efficacy of Cefpodoxime Proxetil have not been established in pediatric patients, specifically in infants less than 2 months of age. This applies to all formulations, including tablets (film-coated) and granules for suspension. Caution is advised when considering the use of this medication in this age group.

Geriatric Use

In multiple-dose clinical studies of cefpodoxime proxetil, 16% of the 3338 patients were aged 65 and over, and 6% were aged 75 and over. No overall differences in effectiveness or safety were observed between elderly patients and younger patients. In healthy geriatric subjects with normal renal function, the half-life of cefpodoxime in plasma averaged 4.2 hours, with urinary recovery averaging 21% after a 400 mg dose administered every 12 hours for 15 days. Other pharmacokinetic parameters remained unchanged compared to those observed in healthy younger subjects. Therefore, dose adjustment in elderly patients with normal renal function is not necessary.

Pregnancy

Cefpodoxime proxetil is classified as Pregnancy Category B. Animal studies have shown that it is neither teratogenic nor embryocidal when administered to rats during organogenesis at doses up to 100 mg/kg/day (approximately two times the human dose based on mg/m²) or to rabbits at doses up to 30 mg/kg/day (approximately one to two times the human dose based on mg/m²). However, there are no adequate and well-controlled studies of cefpodoxime proxetil in pregnant women.

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 drug has not been studied for use during labor and delivery, and treatment should only be administered if clearly necessary.

Lactation

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

Due to the potential for serious reactions in breastfed infants, healthcare providers should carefully consider whether to discontinue breastfeeding or to discontinue the medication, weighing the importance of the drug to the mother against the potential risks to the nursing infant.

Renal Impairment

Patients with renal impairment have not been specifically addressed in the available labeling for Cefpodoxime Proxetil, regardless of the formulation (tablet or granule for suspension). There is no information provided regarding necessary dosage adjustments, special monitoring, or safety considerations for this patient population. Consequently, healthcare professionals should exercise caution and consider individual patient factors when prescribing this medication to patients with reduced kidney function, as the lack of specific guidance necessitates careful clinical judgment.

Hepatic Impairment

Patients with hepatic impairment do not require specific dosage adjustments, special monitoring, or precautions when using Cefpodoxime Proxetil in any of its formulations, including tablets and granules for suspension. The available data does not provide any additional information regarding the management of these patients. Therefore, standard dosing may be applied without modification for those with liver problems.

Overdosage

In cases of overdose with cefpodoxime proxetil, acute rodent toxicity studies indicate that a single oral dose of 5 g/kg did not produce adverse effects. However, in the event of a serious toxic reaction, it is recommended that hemodialysis or peritoneal dialysis be considered to facilitate the removal of cefpodoxime from the body, especially if renal function is compromised.

Symptoms associated with an overdose of beta-lactam antibiotics, including cefpodoxime, may manifest as nausea, vomiting, epigastric distress, and diarrhea. Monitoring for these symptoms is advised, and appropriate supportive care should be provided as necessary.

Nonclinical Toxicology

Teratogenic Effects

Cefpodoxime proxetil is classified as Pregnancy Category B. In studies conducted on rats during organogenesis, cefpodoxime proxetil was neither teratogenic nor embryocidal at doses up to 100 mg/kg/day, which is approximately two times the human dose based on mg/m². Similarly, no teratogenic effects were observed in rabbits at doses up to 30 mg/kg/day, equivalent 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, this drug should be used during pregnancy only if clearly needed, as animal reproduction studies are not always predictive of human response.

Impairment of Fertility

No adverse effects on fertility or reproduction were noted in rats administered cefpodoxime proxetil at doses of 100 mg/kg/day or less, which corresponds to approximately two times the human dose based on mg/m².

Carcinogenesis and Mutagenesis

Long-term animal carcinogenesis studies of cefpodoxime proxetil have not been performed. However, mutagenesis studies, including the Ames test (both with and without metabolic activation), chromosome aberration tests, unscheduled DNA synthesis assays, mitotic recombination and gene conversion tests, forward gene mutation assays, and in vivo micronucleus tests, have all yielded negative results.

Storage and Handling

Cefpodoxime Proxetil is available in the following forms:

• Tablet, Film Coated

  • Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) see USP Controlled Room Temperature.

  • Dispense in a tight, light-resistant container.

  • Replace cap securely after each opening.

  • Keep out of the reach of children.

• Granule, for Suspension

  • Store unsuspended granules at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F).

  • After mixing, store the suspension in a refrigerator at 2° to 8°C (36° to 46°F).

  • Shake well before using.

  • Keep container tightly closed.

  • The mixture may be used for 14 days; discard unused portion after 14 days.