cefpodoxime 100 MG Oral Tablet [Dermaceph]

INDICATIONS AND USAGE Cefpodoxime proxetil is indicated for the treatment of patients with mild to moderate infections caused by susceptible strains of the designated microorganisms in the conditions listed below. Recommended dosages, durations of therapy, and applicable patient populations vary among these infections. Please see DOSAGE AND ADMINISTRATION for specific recommendations. Acute otitis media caused by Streptococcus pneumoniae (excluding penicillin-resistant strains), Streptococcus pyogenes, Haemophilusinfluenzae (including beta-lactamase-producing strains), or Moraxella (Branhamella) catarrhalis (including beta-lactamase-producing strains). Pharyngitis and/or tonsillitis caused by Streptococcus pyogenes . NOTE: Only penicillin by the intramuscular route of administration has been shown to be effective in the prophylaxis of rheumatic fever. Cefpodoxime proxetil is generally effective in the eradication of streptococci from the oropharynx. However, data establishing the efficacy of cefpodoxime proxetil for the prophylaxis of subsequent rheumatic fever are not available. Community-acquired pneumonia caused by S. pneumoniae or H. Influenzae (including beta-lactamase-producing strains). Acute bacterial exacerbation of chronic bronchitis caused by S. pneumoniae, H. influenzae (non-beta-lactamase-producing strains only), or M. catarrhalis. Data are insufficient at this time to establish efficacy in patients with acute bacterial exacerbations of chronic bronchitis caused by beta-lactamase-producing strains of H. influenzae. 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). NOTE: The efficacy of cefpodoxime in treating male patients with rectal infections caused by N. gonorrhoeae has not been established. Data do not support the use of cefpodoxime proxetil in the treatment of pharyngeal infections due to N. gonorrhoeae in men or women. Uncomplicated skin and skin structure infections caused by Staphylococcus aureus (including penicillinase-producing strains) or Streptococcus pyogenes . Abscesses should be surgically drained as clinically indicated. NOTE: In clinical trials, successful treatment of uncomplicated skin and skin structure infections was dose-related. The effective therapeutic dose for skin infections was higher than those used in other recommended indications. (See DOSAGE AND ADMINISTRATION .) Acute maxillary sinusitis caused by Haemophilus influenzae (including beta-lactamase-producing strains), Streptococcus pneumoniae , and Moraxella catarrhalis. Uncomplicated urinary tract infections (cystitis) caused by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis , or Staphylococcus saprophyticus . NOTE: In considering the use of cefpodoxime proxetil in the treatment of cystitis, cefpodoxime proxetil's lower bacterial eradication rates should be weighed against the increased eradication rates and different safety profiles of some other classes of approved agents. (See CLINICAL STUDIES section.) Appropriate specimens for bacteriological examination should be obtained in order to isolate and identify causative organisms and to determine their susceptibility to cefpodoxime. Therapy may be instituted while awaiting the results of these studies. Once these results become available, antimicrobial therapy should be adjusted accordingly. To reduce the development of drug-resistant bacteria and maintain the effectiveness of cefpodoxime proxetil tablets, and other antibacterial drugs, cefpodoxime proxetil tablets should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

DOSAGE AND ADMINISTRATION (See INDICATIONS AND USAGE for indicated pathogens.) Cefpodoxime proxetil for oral suspension may be given without regard to food. The recommended dosages, durations of treatment, and applicable patient populations are as described in the following chart: Adults and Adolescents (age 12 years and older): Type of Infection Total Daily Dose Dose Frequency Duration Pharyngitis and/or tonsillitis 200 mg 100 mg Q 12 hours 5 to 10 days Acute community-acquired pneumonia 400 mg 200 mg Q 12 hours 14 days Uncomplicated gonorrhea (men and women) and rectal gonococcal infections (women) 200 mg single dose Skin and skin structure 800 mg 400 mg Q 12 hours 7 to 14 days Acute maxillary sinusitis 400 mg 200 mg Q 12 hours 10 days Uncomplicated urinary tract infection 200 mg 100 mg Q 12 hours 7 days Infants and Pediatric Patients (age 2 months through 12 years): Type of Infection Total Daily Dose Dose Frequency Duration Acute otitis media 10 mg/kg/day (Max 400 mg/day) 5 mg/kg Q 12 h (Max 200 mg/dose) 5 days Pharyngitis and/or tonsillitis 10 mg/kg/day (Max 200 mg/day) 5 mg/kg/dose Q 12 h (Max 100 mg/dose) 5 to 10 days Acute maxillary sinusitis 10 mg/kg/day (Max 400 mg/day) 5 mg/kg Q 12 hours (Max 200 mg/dose) 10 days Patients with Renal Dysfunction: For patients with severe renal impairment (<30 mL/min creatinine clearance), the dosing intervals should be increased to Q 24 hours. In patients maintained on hemodialysis, the dose frequency should be 3 times/week after hemodialysis. When only the serum creatinine level is available, the following formula (based on sex, weight, and age of the patient) may be used to estimate creatinine clearance (mL/min). For this estimate to be valid, the serum creatinine level should represent a steady state of renal function. Males: Weight (kg) x (140 - age) (mL/min) 72 x serum creatinine (mg/100 mL) Females: 0.85 x above value (mL/min) Patients with Cirrhosis: Cefpodoxime pharmacokinetics in cirrhotic patients (with or without ascites) are similar to those in healthy subjects. Dose adjustment is not necessary in this population. Directions for use: Before reconstitution, remove the desiccant capsule by pulling out two small rings, then discard. Preparation of Suspension: Constitution Directions For Oral Suspension Constituted Volume Final Concentration Directions 50 mL 50 mg per 5 mL Suspend in a total of 31 mL of distilled water. Method: First, shake the bottle to loosen granules. Then add the water in two approximately equal portions, shaking vigorously after each aliquot of water. 75 mL 50 mg per 5 mL Suspend in a total of 44 mL of distilled water. Method: First, shake the bottle to loosen granules. Then add the water in two approximately equal portions, shaking vigorously after each aliquot of water. 100 mL 50 mg per 5 mL Suspend in a total of 57 mL of distilled water. Method: First, shake the bottle to loosen granules. Then add the water in two approximately equal portions, shaking vigorously after each aliquot of water. 50 mL 100 mg per 5 mL Suspend in a total of 30 mL of distilled water. Method: First, shake the bottle to loosen granules. Then add the water in two approximately equal portions, shaking vigorously after each aliquot of water. 75 mL 100 mg per 5 mL Suspend in a total of 43 mL of distilled water. Method: First, shake the bottle to loosen granules. Then add the water in two approximately equal portions, shaking vigorously after each aliquot of water. 100 mL 100 mg per 5 mL Suspend in a total of 57 mL of distilled water. Method: First, shake the bottle to loosen granules. Then add the water in two approximately equal portions, shaking vigorously after each aliquot of water. After mixing, the suspension should be stored in a refrigerator, 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.

WARNINGS 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 BECAUSE CROSS HYPERSENSITIVITY AMONG BETA-LACTAM ANTIBIOTICS HAS BEEN CLEARLY DOCUMENTED AND MAY OCCUR IN UP TO 10% OF PATIENTS WITH A HISTORY OF PENICILLIN ALLERGY. IF AN ALLERGIC REACTION TO CEFPODOXIME PROXETIL OCCURS, DISCONTINUE THE DRUG. 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 use of nearly all antibacterial agents, including cefpodoxime proxetil tablets, USP, 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 . C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can 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. A concerted effort to monitor for C. difficile in cefpodoxime-treated patients with diarrhea was undertaken because of an increased incidence of diarrhea associated with C. difficile in early trials in normal subjects. C. difficile organisms or toxin was reported in 10% of the cefpodoxime treated adult patients with diarrhea; however, no specific diagnosis of pseudomembranous colitis was made in these patients. In post-marketing experience outside the United States, reports of pseudomembranous colitis associated with the use of cefpodoxime proxetil have been received.

CONTRAINDICATIONS Cefpodoxime proxetil is contraindicated in patients with a known allergy to cefpodoxime or to the cephalosporin group of antibiotics.

CLINICAL PHARMACOLOGY Absorption and Excretion: Cefpodoxime proxetil is a prodrug that is absorbed from the gastrointestinal tract and de-esterified to its active metabolite, cefpodoxime. Following oral administration of 100 mg of cefpodoxime proxetil to fasting subjects, approximately 50% of the administered cefpodoxime dose was absorbed systemically. Over the recommended dosing range (100 to 400 mg), approximately 29 to 33% of the administered cefpodoxime dose was excreted unchanged in the urine in 12 hours. There is minimal metabolism of cefpodoxime in vivo . Effects of Food: The extent of absorption (mean AUC) and the mean peak plasma concentration increased when film-coated tablets were administered with food. Following a 200 mg tablet dose taken with food, the AUC was 21 to 33% higher than under fasting conditions, and the peak plasma concentration averaged 3.1 mcg/mL in fed subjects versus 2.6 mcg/mL in fasted subjects. Time to peak concentration was not significantly different between fed and fasted subjects. When a 200 mg dose of the suspension was taken with food, the extent of absorption (mean AUC) and mean peak plasma concentration in fed subjects were not significantly different from fasted subjects, but the rate of absorption was slower with food (48% increase in T max ). Pharmacokinetics of Cefpodoxime Proxetil Film-coated Tablets: Over the recommended dosing range (100 to 400 mg), the rate and extent of cefpodoxime absorption exhibited dose-dependency; dose-normalized C max and AUC decreased by up to 32% with increasing dose. Over the recommended dosing range, the T max was approximately 2 to 3 hours and the T 1/2 ranged from 2.09 to 2.84 hours. Mean C max was 1.4 mcg/mL for the 100 mg dose, 2.3 mcg/mL for the 200 mg dose, and 3.9 mcg/mL for the 400 mg dose. In patients with normal renal function, neither accumulation nor significant changes in other pharmacokinetic parameters were noted following multiple oral doses of up to 400 mg Q 12 hours. CEFPODOXIME PLASMA LEVELS (mcg/mL) IN FASTED ADULTS AFTER FILM-COATED TABLET ADMINISTRATION (Single Dose) Dose (cefpodoxime equivalents) Time after oral ingestion 1hr 2hr 3hr 4hr 6hr 8hr 12hr 100 mg 0.98 1.4 1.3 1 0.59 0.29 0.08 200 mg 1.5 2.2 2.2 1.8 1.2 0.62 0.18 400 mg 2.2 3.7 3.8 3.3 2.3 1.3 0.38 Pharmacokinetics of Cefpodoxime Proxetil Suspension: In adult subjects, a 100 mg dose of oral suspension produced an average peak cefpodoxime concentration of approximately 1.5 mcg/mL (range: 1.1 to 2.1 mcg/mL), which is equivalent to that reported following administration of the 100 mg tablet. Time to peak plasma concentration and area under the plasma concentration-time curve (AUC) for the oral suspension were also equivalent to those produced with film-coated tablets in adults following a 100 mg oral dose. The pharmacokinetics of cefpodoxime were investigated in 29 patients aged 1 to 17 years. Each patient received a single, oral, 5 mg/kg dose of cefpodoxime oral suspension. Plasma and urine samples were collected for 12 hours after dosing. The plasma levels reported from this study are as follows: CEFPODOXIME PLASMA LEVELS (mcg/mL) IN FASTED PATIENTS (1 to 17 YEARS OF AGE) AFTER SUSPENSION ADMINISTRATION Dose (cefpodoxime equivalents) Time after oral ingestion 1 Dose did not exceed 200 mg. 1hr 2hr 3hr 4hr 6hr 8hr 12hr 5 mg/kg 1 1.4 2.1 2.1 1.7 0.9 0.4 0.09 Distribution Protein binding of cefpodoxime ranges from 22 to 33% in serum and from 21 to 29% in plasma. Skin Blister: Following multiple-dose administration every 12 hours for 5 days of 200 mg or 400 mg cefpodoxime proxetil, the mean maximum cefpodoxime concentration in skin blister fluid averaged 1.6 and 2.8 mcg/mL, respectively. Skin blister fluid cefpodoxime levels at 12 hours after dosing averaged 0.2 and 0.4 mcg/mL for the 200 mg and 400 mg multiple-dose regimens, respectively. Tonsil Tissue: Following a single, oral 100 mg cefpodoxime proxetil film-coated tablet, the mean maximum cefpodoxime concentration in tonsil tissue averaged 0.24 mcg/g at 4 hours post-dosing and 0.09 mcg/g at 7 hours post-dosing. Equilibrium was achieved between plasma and tonsil tissue within 4 hours of dosing. No detection of cefpodoxime in tonsillar tissue was reported 12 hours after dosing. These results demonstrated that concentrations of cefpodoxime exceeded the MIC 90 of S. pyogenes for at least 7 hours after dosing of 100 mg of cefpodoxime proxetil. Lung Tissue: Following a single, oral 200 mg cefpodoxime proxetil film-coated tablet, the mean maximum cefpodoxime concentration in lung tissue averaged 0.63 mcg/g at 3 hours post-dosing, 0.52 mcg/g at 6 hours post-dosing, and 0.19 mcg/g at 12 hours post-dosing. The results of this study indicated that cefpodoxime penetrated into lung tissue and produced sustained drug concentrations for at least 12 hours after dosing at levels that exceeded the MIC 90 for S. pneumoniae and H. influenzae. CSF: Adequate data on CSF levels of cefpodoxime are not available. Effects of Decreased Renal Function: Elimination of cefpodoxime is reduced in patients with moderate to severe renal impairment (<50 mL/min creatinine clearance). (See PRECAUTIONS and DOSAGE AND ADMINISTRATION .) In subjects with mild impairment of renal function (50 to 80 mL/min creatinine clearance), the average plasma half-life of cefpodoxime was 3.5 hours. In subjects with moderate (30 to 49 mL/min creatinine clearance) or severe renal impairment (5 to 29 mL/min creatinine clearance), the half-life increased to 5.9 and 9.8 hours, respectively. Approximately 23% of the administered dose was cleared from the body during a standard 3-hour hemodialysis procedure. Effect of Hepatic Impairment (cirrhosis): Absorption was somewhat diminished and elimination unchanged in patients with cirrhosis. The mean cefpodoxime T 1/2 and renal clearance in cirrhotic patients were similar to those derived in studies of healthy subjects. Ascites did not appear to affect values in cirrhotic subjects. No dosage adjustment is recommended in this patient population. Pharmacokinetics in Elderly Subjects: Elderly subjects do not require dosage adjustments unless they have diminished renal function. (See PRECAUTIONS .) In healthy geriatric subjects, cefpodoxime half-life in plasma averaged 4.2 hours (vs 3.3 in younger subjects) and urinary recovery averaged 21% after a 400 mg dose was administered every 12 hours. Other pharmacokinetic parameters (C max , AUC, and T max ) were unchanged relative to those observed in healthy young subjects. Microbiology: Mechanism of Action : Cefpodoxime is a bactericidal agent that acts by inhibition of bacterial cell wall synthesis. Cefpodoxime has activity in the presence of some beta-lactamases, both penicillinases and cephalosporinases, of Gram-negative and Gram-positive bacteria. Mechanism of Resistance : Resistance to cefpodoxime is primarily through hydrolysis by beta-lactamase, alteration of penicillin-binding proteins (PBPs), and decreased permeability. Cefpodoxime has been shown to be active against most isolates of the following bacteria, both in vitro and in clinical infections as described in the Indications and Usage (1) section: Gram-positive bacteria: Staphylococcus aureus (methicillin-susceptible strains, including those producing penicillinases) Staphylococcus saprophyticus Streptococcus pneumoniae (excluding penicillin-resistant isolates) Streptococcus pyogenes Gram-negative bacteria: Escherichia coli Klebsiella pneumoniae Proteus mirabilis Haemophilus influenzae (including beta-lactamase producing isolates) Moraxella catarrhalis Neisseria gonorrhoeae (including penicillinase-producing isolates) The following in vitro data are available, but their clinical significance is unknown. At least 90 percent of the following microorganisms exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for cefpodoxime. However, the efficacy of cefpodoxime in treating clinical infections due to th