Cefpodoxime Proxetil

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 …

DOSAGE AND ADMINISTRATION (See INDICATIONS AND USAGE for indicated pathogens.) FILM-COATED TABLETS: Cefpodoxime proxetil tablets should be administered orally with food to enhance absorption. (See CLINICAL PHARMACOLOGY .) The recommended dosages, durations of treatment, and applicable patient population 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 Acute bacterial exacerbations of chronic bronchitis 400 mg 200 mg Q 12 hours 10 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 GRANULES FOR ORAL SUSPENSION: Cefpodoxime proxetil 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.

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

ADVERSE REACTIONS Clinical Trials: Film-coated Tablets (Multiple dose): In clinical trials using multiple doses of cefpodoxime proxetil film-coated tablets, 4696 patients were treated with the recommended dosages of cefpodoxime (100 to 400 mg Q 12 hours). There were no deaths or permanent disabilities thought related to drug toxicity. One-hundred twenty-nine (2.7%) patients discontinued medication due to adverse events thought possibly or probably related to drug toxicity. Ninety-three (52%) of the 178 patients who discontinued therapy (whether thought related to drug therapy or not) did so because of gastrointestinal disturbances, nausea, vomiting, or diarrhea. The percentage of cefpodoxime proxetil-treated patients who discontinued study drug because of adverse events was significantly greater at a dose of 800 mg daily than at a dose of 400 mg daily or at a dose of 200 mg daily. Adverse events thought possibly or probably related to cefpodoxime in multiple-dose clinical trials (N=4696 cefpodoxime-treated patients) were: Incidence Greater Than 1%: Diarrhea 7% Diarrhea or loose stools were dose-related: decreasing from 10.4% of patients receiving 800 mg per day to 5.7% for those receiving 200 mg per day. Of patients with diarrhea, 10% had C. difficile organism or toxin in the stool. (See WARNINGS .) Nausea 3.3% Vaginal Fungal Infections 1% Vulvovaginal Infections 1.3% Abdominal Pain 1.2% Headache 1% Incidence Less Than 1%: By body system in decreasing order: Clinical Studies Adverse events thought possibly or probably related to cefpodoxime proxetil that occurred in less than 1% of patients (N=4696) 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. Granules for Oral Suspension (Multiple dose): In clinical trials using multiple doses of cefpodoxime proxetil granules for oral suspension, 2128 pediatric patients (93% of whom were less than 12 years of age) were treated with the recommended dosages of cefpodoxime (10 mg/kg/day Q 24 hours or divided Q 12 hours to a maximum equivalent adult dose). There were no deaths or permanent disabilities in any of the patients in these studies. Twenty-four patients (1.1%) discontinued medication due to adverse events thought possibly or probably related to study drug. Primarily, these discontinuations were for gastrointestinal disturbances, usually diarrhea, vomiting, or rashes. Adverse events thought possibly or probably related, or of unknown relationship to cefpodoxime proxetil for oral suspension …

Drug Interactions: Antacids: Concomitant administration of high doses of antacids (sodium bicarbonate and aluminum hydroxide) or H 2 blockers reduces peak plasma levels by 24% to 42% and the extent of absorption by 27% to 32%, respectively. The rate of absorption is not altered by these concomitant medications. Oral anti-cholinergics (e.g., propantheline) delay peak plasma levels (47% increase in T max ), but do not affect the extent of absorption (AUC). Probenecid: As with other beta-lactam antibiotics, renal excretion of cefpodoxime was inhibited by probenecid and resulted in an approximately 31% increase in AUC and 20% increase in peak cefpodoxime plasma levels. Nephrotoxic drugs: Although nephrotoxicity has not been noted when cefpodoxime proxetil was given alone, close monitoring of renal function is advised when cefpodoxime proxetil is administered concomitantly with compounds of known nephrotoxic potential.

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.

DESCRIPTION Cefpodoxime proxetil is an orally administered, extended spectrum, semi-synthetic antibiotic of 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 [4.2.0]oct-2-ene- 2-carboxylate. Its molecular formula is C 21 H 27 N 5 O 9 S 2 and its structural formula is represented below: The molecular weight of cefpodoxime proxetil is 557.6. Cefpodoxime proxetil is a prodrug; its active metabolite is cefpodoxime. All doses of cefpodoxime proxetil in this insert are expressed in terms of the active cefpodoxime moiety. The drug is supplied as film-coated tablets. Cefpodoxime proxetil tablets, USP contain cefpodoxime proxetil USP equivalent to 100 mg or 200 mg of cefpodoxime activity and 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. In addition, the 100 mg film-coated tablets contain iron oxide yellow and the 200 mg film-coated tablets contain FD&C red #40 aluminum lake. Chemical Structure

OVERDOSAGE In acute rodent toxicity studies, a single 5 g/kg oral dose produced no adverse effects. In the event of serious toxic reaction from overdosage, hemodialysis or peritoneal dialysis may aid in the removal of cefpodoxime from the body, particularly if renal function is compromised. The toxic symptoms following an overdose of beta-lactam antibiotics may include nausea, vomiting, epigastric distress, and diarrhea.

HOW SUPPLIED Cefpodoxime Proxetil Tablets, USP 100 mg are light yellowish-orange, elliptical, film-coated tablets debossed with ‘C’ on one side and ‘61’ on the other side. Bottles of 20 NDC 65862-095-20 Bottles of 100 NDC 65862-095-01 Bottles of 250 NDC 65862-095-25 Bottles of 1,000 NDC 65862-095-99 Cefpodoxime Proxetil Tablets, USP 200 mg are coral red, elliptical, film-coated tablets debossed with ‘C’ on one side and ‘62’ on the other side. Bottles of 20 NDC 65862-096-20 Bottles of 100 NDC 65862-096-01 Bottles of 250 NDC 65862-096-25 Bottles of 1,000 NDC 65862-096-99 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 tight, light-resistant container. Replace cap securely after each opening.