Cefpodoxime

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 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 tr

DOSAGE AND ADMINISTRATION (See INDICATIONS AND USAGE for indicated pathogens.) Film-coated Tablets Cefpodoxime Proxetil Tablets, USP 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 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) × (140 - age) (mL/min) 72 × serum creatinine (mg/100 mL) Females: 0.85 × 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.

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. Film-coated Tablets (Single dose) In clinical trials using a single dose of cefpodoxime proxetil film-coated tablets, 509 patients were treated with the recommended dosage of cefpodoxime (200 mg). There were no deaths or permanent disabilities thought related to drug toxicity in these studies. Adverse events thought possibly or probably related to cefpodoxime in single-dose clinical trials conducted in the United States were: Incidence Greater Than 1% Nausea 1.4 % Diarrhea 1.2 % Incidence Less Than 1 % Central Nervous System: Dizziness, headache, syncope. Dermatologic: Rash. Genital: Vaginitis. Gastrointestinal: Abdominal pain. Psychiatric: Anxiety. Laboratory Changes Significant laboratory changes that have been reported in adult and pediatric patients in clinical trials of cefpodoxime proxetil, without regard to drug relationship, were: Hepatic: Transient increases in AST (SGOT), ALT (SGPT), GGT, alkaline phosphatase, bilirubin, and LDH. Hematologic: Eosinophilia, leukocytosis, lymphocytosis, granulocytosis, basophilia, monocytosis, thrombocytosis, decreased hemoglobin, decreased hematocrit, leukopenia, neutropenia, lymphocytopenia, thrombocytopenia, thrombocythemia, positive Coombs’ test, and prolonged PT, and PTT. Serum Chemistry: Hyperglycemia, hypoglycemia, hypoalbuminemia, hypoproteinemia, hyperkalemia, and hyponatremia. Renal: Increases in BUN and creatinine. Most of these abnormalities were transient and not clinically significant. Post-marketing Experience The following serious adverse experiences have been reported: allergic reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme and serum sickness-like reactions, pseudomembranous colitis, bloody diarrhea with abdominal pain, ulcerative colitis, rectorrhagia with hypote

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 Tmax), 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.