Cefpodoxime Drug Information

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 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 associated with drug therapy occur, the drug should be discontinued. Anticonvulsant therapy can be given if clinically indicated.

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.

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 times the human dose based on mg/m2) or to rabbits at doses up to 30 mg/kg/day (1 to 2 times the human dose based on mg/m2). There are, however, no adequate and well-controlled studies of cefpodoxime proxetil use in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Pediatric Use Safety and efficacy in infants less than 2 months of age have not been established.

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

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.