CEFDINIR

Cefdinir capsules, USP contain the active ingredient cefdinir, an extended-spectrum, semisynthetic cephalosporin, for oral administration. Chemically, cefdinir is [6R-[6α,7β (Z)]]-7-[[(2-amino-4 thiazolyl)(hydroxyimino)acetyl]amino]-3-ethenyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2- carboxylic acid. Cefdinir is a white to slightly brownish-yellow solid. It is slightly soluble in dilute hydrochloric acid and sparingly soluble in 0.1 M pH 7.0 phosphate buffer. The empirical formula is C 14 H 13 N 5 O 5 S 2 and the molecular weight is 395.42. Cefdinir has the structural formula shown below: Cefdinir capsules, USP contain 300 mg cefdinir and the following inactive ingredients: carboxymethylcellulose calcium, polyoxyl 40 stearate, colloidal silicone dioxide and magnesium stearate. The capsule shells contain FD&C Blue #2; gelatin, titanium dioxide, gelatin and water. Imprinting ink components shellac, Black Iron Oxide and potassium hydroxide Structural Formula

INDICATIONS & USAGE To reduce the development of drug-resistant bacteria and maintain the effectiveness of cefdinir capsules and other antibacterial drugs, Cefdinir capsules 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. Cefdinir capsules are indicated for the treatment of patients with mild to moderate infections caused by susceptible strains of the designated microorganisms in the conditions listed below. Adults and Adolescents Community-Acquired Pneumonia Caused by Haemophilus influenzae (including β-lactamase producing strains), Haemophilus parainfluenzae (including β-lactamase producing strains), Streptococcus pneumoniae (penicillin-susceptible strains only), and Moraxella catarrhalis (including β-lactamase producing strains) (see CLINICAL STUDIES ). Acute Exacerbations of Chronic Bronchitis Caused by Haemophilus influenzae (including β-lactamase producing strains), Haemophilus parainfluenzae (including β-lactamase producing strains), Streptococcus pneumoniae (penicillin-susceptible strains only), and Moraxella catarrhalis (including β-lactamase producing strains). Acute Maxillary Sinusitis Caused by Haemophilus influenzae (including β-lactamase producing strains), Streptococcus pneumonia (penicillin-susceptible strains only), and Moraxella catarrhalis (including β-lactamase producing strains). NOTE: For information on use in pediatric patients, see Pediatric Use and DOSAGE AND ADMINISTRATION . Pharyngitis/Tonsillitis Caused by Streptococcus pyogenes (see CLINICAL STUDIES ). NOTE: Cefdinir is effective in the eradication of S. pyogenes from the oropharynx. Cefdinir has not, however, been studied for the prevention of rheumatic fever following S. pyogenes pharyngitis/tonsillitis. Only intramuscular penicillin has been demonstrated to be effective for the prevention of rheumatic fever. Uncomplicated Skin and Skin Structure Infections Caused by Staphylococcus aureus (including β-lactamase producing strains) and Streptococcus pyogenes . Pediatric Patients Acute Bacterial Otitis Media Caused by Haemophilus influenzae (including β-lactamase producing strains), Streptococcus pneumonia (penicillin-susceptible strains only), and Moraxella catarrhalis (including β-lactamase producing strains). Pharyngitis/Tonsillitis Caused by Streptococcus pyogenes (see CLINICAL STUDIES ). NOTE: Cefdinir is effective in the eradication of S. pyogenes from the oropharynx. Cefdinir has not, however, been studied for the prevention of rheumatic fever following S. pyogenes pharyngitis/tonsillitis. Only intramuscular penicillin has been demonstrated to be effective for the prevention of rheumatic fever. Uncomplicated Skin and Skin Structure Infections Caused by Staphylococcus aureus (including β-lactamase producing strains) and Streptococcus pyogenes

DOSAGE & ADMINISTRATION (see INDICATIONS AND USAGE for Indicated Pathogens) The recommended dosage and duration of treatment for infections in adults and adolescents are described in the following chart; the total daily dose for all infections is 600 mg. Once-daily dosing for 10 days is as effective as b.i.d. dosing. Once-daily dosing has not been studied in pneumonia or skin infections; therefore, cefdinir capsules should be administered twice daily in these infections. Cefdinir capsules may be taken without regard to meals. Adults and Adolescents (Age 13 Years and Older) Type of Infection Dosage Duration Community-Acquired Pneumonia 300 mg q12h 10 days Acute Exacerbations of Chronic Bronchitis 300 mg q12h or 600 mg q24h 5 to 10 days 10 days Acute Maxillary Sinusitis 300 mg q12h or 600 mg q24h 10 days 10 days Pharyngitis/Tonsillitis 300 mg q12h or 600 mg q24h 5 to 10 days 10 days Uncomplicated Skin and Skin Structure Infections 300 mg q12h 10 days Patients with Renal Insufficiency For adult patients with creatinine clearance < 30 mL/min, the dose of cefdinir should be 300 mg given once daily. Creatinine clearance is difficult to measure in outpatients. However, the following formula may be used to estimate creatinine clearance (CL cr ) in adult patients. For estimates to be valid, serum creatinine levels should reflect steady-state levels of renal function. Males: CL cr = (weight) (140 – age) (72) (serum creatinine) Females: CL cr = 0.85 x above value where creatinine clearance is in mL/min, age is in years, weight is in kilograms, and serum creatinine is in mg/dL. 1 The following formula may be used to estimate creatinine clearance in pediatric patients: CL cr = K x body length or height serum creatinine where K=0.55 for pediatric patients older than 1 year 2 and 0.45 for infants (up to 1 year). 3 In the above equation, creatinine clearance is in mL/min/1.73 m 2 , body length or height is in centimeters, and serum creatinine is in mg/dL. For pediatric patients with a creatinine clearance of < 30 mL/min/1.73 m 2 , the dose of cefdinir should be 7 mg/kg (up to 300 mg) given once daily. Patients on Hemodialysis Hemodialysis removes cefdinir from the body. In patients maintained on chronic hemodialysis, the recommended initial dosage regimen is a 300 mg or 7 mg/kg dose every other day. At the conclusion of each hemodialysis session, 300 mg (or 7 mg/kg) should be given. Subsequent doses (300 mg or 7 mg/kg) are then administered every other day.

Cefdinir is contraindicated in patients with known allergy to the cephalosporin class of antibiotics

ADVERSE EVENTS Clinical Trials Cefdinir Capsules (Adult and Adolescent Patients) In clinical trials, 5093 adult and adolescent patients (3841 U.S. and 1252 non-U.S.) were treated with the recommended dose of cefdinir capsules (600 mg/day). Most adverse events were mild and self-limiting. No deaths or permanent disabilities were attributed to cefdinir. One hundred forty-seven of 5093 (3%) patients discontinued medication due to adverse events thought by the investigators to be possibly, probably, or definitely associated with cefdinir therapy. The discontinuations were primarily for gastrointestinal disturbances, usually diarrhea or nausea. Nineteen of 5093 (0.4%) patients were discontinued due to rash thought related to cefdinir administration. In the U.S., the following adverse events were thought by investigators to be possibly, probably, or definitely related to cefdinir capsules in multiple-dose clinical trials (N=3841 cefdinir-treated patients): Adverse Events Associated with Cefdinir Capsules U.S. Trials in Adult and Adolescent Patients (N=3841) 1733 males, 2108 females Incidence ≥1% Diarrhea 15% Vaginal moniliasis 4 % of women Nausea 3% Headache 2% Abdominal pain 1% Vaginitis 1% of women Incidence < 1% but > 0:1% Rash 0.9% Dyspepsia 0.7% Flatulence 0.7% Vomiting 0.7% Abnormal stools 0.3% Anorexia 0.3% Constipation 0.3% Dizziness 0.3% Dry mouth 0.3% Asthenia 0.2% Insomnia 0.2% Leukorrhea 0.2% of women Moniliasis 0.2% Pruritus 0.2% Somnolence 0.2% The following laboratory value changes of possible clinical significance, irrespective of relationship to therapy with cefdinir, were seen during clinical trials conducted in the U.S.: Laboratory Value Changes Observed with Cefdinir Capsules U.S. Trials in Adult and Adolescent Patients (N=3841) Incidence ≥1% ↑Urine leukocytes 2% ↑Urine protein 2% ↑Gamma-glutamyltransferase N < 3841 for these parameters 1% ↓Lymphocytes, ↑Lymphocytes 1%, 0.2% ↑Microhematuria 1% Incidence < 1% but > 0.1% ↑Glucose 0.9% ↑Urine glucose 0.9% ↑White blood cells, ↓White blood cells 0.9%, 0.7% ↑Alanine aminotransferase (ALT) 0.7% ↑Eosinophils 0.7% ↑Urine specific gravity, ↓Urine specific gravity 0.6%, 0.2% ↓Bicarbonate 0.6% ↑Phosphorus, ↓Phosphorus 0.6%, 0.3% ↑Aspartate aminotransferase (AST) 0.4% ↑Alkaline phosphatase 0.3% ↑Blood urea nitrogen (BUN) 0.3% ↓Hemoglobin 0.3% ↑Polymorphonuclear neutrophils (PMNs), ↓PMNs 0.3%, 0.2% ↑Bilirubin 0.2% ↑Lactate dehydrogenase 0.2% ↑Platelets 0.2% ↑Potassium 0.2% ↑Urine pH 0.2% Postmarketing Experience The following adverse experiences and altered laboratory tests, regardless of their relationship to cefdinir, have been reported during extensive postmarketing experience, beginning with approval in Japan in 1991: shock, anaphylaxis with rare cases of fatality, facial and laryngeal edema, feeling of suffocation, serum sickness-like reactions, conjunctivitis, stomatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis, erythema multiforme, erythema nodosum, acute hepatitis, cholestasis, fulminant hepatitis, hepatic failure, jaundice, increased amylase, acute enterocolitis, bloody diarrhea, hemorrhagic colitis, melena, pseudomembranous colitis, pancytopenia, granulocytopenia, leukopenia, thrombocytopenia, idiopathic thrombocytopenic purpura, hemolytic anemia, acute respiratory failure, asthmatic attack, drug-induced pneumonia, eosinophilic pneumonia, idiopathic interstitial pneumonia, fever, acute renal failure, nephropathy, bleeding tendency, coagulation disorder, disseminated intravascular coagulation, upper GI bleed, peptic ulcer, ileus, loss of consciousness, allergic vasculitis, possible cefdinir-diclofenac interaction, cardiac failure, chest pain, myocardial infarction, hypertension, involuntary movements, and rhabdomyolysis. Cephalosporin Class Adverse Events The following adverse events and altered laboratory tests have been reported for cephalosporin-class antibiotics in general: Allergic reactions, anaphylaxis, Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, renal dysfunction, toxic nephropathy, hepatic dysfunction including cholestasis, aplastic anemia, hemolytic anemia, hemorrhage, false-positive test for urinary glucose, neutropenia, pancytopenia, and agranulocytosis. Pseudomembranous colitis symptoms may begin during or after antibiotic treatment (see WARNINGS ). 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

Antacids (Aluminum- or Magnesium-Containing) Concomitant administration of 300 mg cefdinir capsules with 30 mL Maalox ® TC suspension reduces the rate (C max ) and extent (AUC) of absorption by approximately 40%. Time to reach C max is also prolonged by 1 hour. There are no significant effects on cefdinir pharmacokinetics if the antacid is administered 2 hours before or 2 hours after cefdinir. If antacids are required during cefdinir capsule therapy, cefdinir should be taken at least 2 hours before or after the antacid. Probenecid As with other β-lactam antibiotics, probenecid inhibits the renal excretion of cefdinir, resulting in an approximate doubling in AUC, a 54% increase in peak cefdinir plasma levels, and a 50% prolongation in the apparent elimination t 1/2 . Iron Supplements and Foods Fortified With Iron Concomitant administration of cefdinir with a therapeutic iron supplement containing 60 mg of elemental iron (as FeSO 4 ) or vitamins supplemented with 10 mg of elemental iron reduced extent of absorption by 80% and 31%, respectively. If iron supplements are required during cefdinir therapy, cefdinir should be taken at least 2 hours before or after the supplement. The effect of foods highly fortified with elemental iron (primarily iron-fortified breakfast cereals) on cefdinir absorption has not been studied. There have been reports of reddish stools in patients receiving cefdinir. In many cases, patients were also receiving iron-containing products. The reddish color is due to the formation of a nonabsorbable complex between cefdinir or its breakdown products and iron in the gastrointestinal tract.