Cefpodoxime Proxetil 100 mg/5mL Granule, For Suspension — NDC 64980-403-10 (Billing 64980-0403-10)

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, 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.

ADVERSE REACTIONS Clinical Trials: 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 in multiple dose clinical trials (N=2128 patients treated with cefpodoxime) were: Incidence Greater Than 1%: Diarrhea 6 % The incidence of diarrhea in infants and toddlers (age 1 month to 2 years) was 12.8%. Diaper rash/Fungal skin rash 2 % (includes moniliasis) The incidence of diaper rash in infants and toddlers was 8.5%.

Other skin rashes 1.8% Vomiting 2.3% Incidence Less Than 1%: Body: Localized abdominal pain, abdominal cramp, headache, monilia, generalized abdominal pain, asthenia, fever, fungal infection. Digestive: Nausea, monilia, anorexia, dry mouth, stomatitis, pseudomembranous colitis. Hemic & Lymphatic: Thrombocythemia, positive direct Coombs’ test, eosinophilia, leukocytosis, leukopenia, prolonged partial thromboplastin time, thrombocytopenic purpura.

Metabolic & Nutritional: Increased SGPT. Musculo-Skeletal: Myalgia. Nervous: Hallucination, hyperkinesia, nervousness, somnolence.

Respiratory: Epistaxis, rhinitis. Skin: Skin moniliasis, urticaria, fungal dermatitis, acne, exfoliative dermatitis, maculopapular rash. Special Senses: Taste perversion.

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 hypotension, anaphylactic shock, acute liver injury, in utero exposure with miscarriage, purpuric nephritis, pulmonary infiltrate with eosinophilia, and eyelid dermatitis. One death was attributed to pseudomembranous colitis and disseminated intravascular coagulation.

Cephalosporin Class Labeling: In addition to the adverse reactions listed above which have been observed in patients treated with cefpodoxime proxetil, the following adverse reactions and altered laboratory tests have been reported for cephalosporin class antibiotics: Adverse Reactions and Abnormal Laboratory Tests : Renal dysfunction, toxic nephropathy, hepatic dysfunction including cholestasis, aplastic anemia, hemolytic anemia, serum sickness-like reaction, hemorrhage, agranulocytosis, and pancytopenia. Several cephalosporins have been implicated in triggering seizures, particularly in patients with renal impairment when the dosage was not reduced.

(See DOSAGE AND ADMINISTRATION and OVERDOSAGE .) If seizures ass… [Excerpted — this section continues on DailyMed.]

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.

Drug/Laboratory Test Interactions: Cephalosporins, including cefpodoxime proxetil, are known to occasionally induce a positive direct Coombs’ test.

PRECAUTIONS General: In patients with transient or persistent reduction in urinary output due to renal insufficiency, the total daily dose of cefpodoxime proxetil should be reduced because 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. (See DOSAGE AND ADMINISTRATION .) 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. 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.

Information for Patients: Patients should be counseled that antibacterial drugs including cefpodoxime proxetil should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When cefpodoxime proxetil is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed.

Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by cefpodoxime proxetil or other antibacterial drugs in the future. Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic.

If this occurs, patients should contact their physician as soon as possible. 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.

Drug/Laboratory Test Interactions: Cephalosporins, including cefpodoxime proxetil, are known to occasionally induce a positive direct Coombs’ test. Carcinogenesis, Mutagenesis, Impairment of Fertility: Long-term animal carcinogenesis studies of cefpodoxime proxetil have not been performed. 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, were all negative.

No untoward effects on fertility or reproduction were noted when 100 mg/kg/day or less (2 times the human dose based on mg/m 2 ) was administered orally to rats. Pregnancy - Teratogenic Effects: Pregnancy Category B Cefpodoxime proxetil was neither teratogenic nor embryocidal when administered to rats during organogenesis at doses up to 100 mg/kg/day (2 time… [Excerpted — this section continues on DailyMed.]