CEFDINIR: 1,627 Adverse Event Reports & Safety Profile

DESCRIPTION Cefdinir Capsules USP contain the active ingredient cefdinir, USP an extended-spectrum, semisynthetic cephalosporin, for oral administration. Chemically, cefdinir is (6 R ,7 R )-7-[[(2Z)-(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,USP is a white to light yellow crystalline powder. Its solubility is 19.56 mg/mL in 0.1 M pH 7.0 phosphate buffer. Cefdinir has the structural formula shown below: C 14 H 13 N 5 O 5 S 2 M.W.

395.41 Cefdinir Capsules USP contain 300 mg cefdinir, USP and the following inactive ingredients: carboxymethylcellulose calcium, colloidal silicon dioxide, croscarmellose sodium, D&C red #28, D&C yellow #10, D&C yellow #10 aluminum lake, FD&C blue #1, FD&C blue #1 aluminum lake, FD&C blue #2 aluminum lake, FD&C green #3, FD&C red #40, FD&C red #40 aluminum lake, gelatin, iron oxide black, magnesium stearate, polyoxyl 40 stearate, propylene glycol, shellac glaze, sodium lauryl sulfate, and titanium dioxide.

Chemical

Structure for cefdinir

INDICATIONS AND USAGE To reduce the development of drug-resistant bacteria and maintain the effectiveness of cefdinir for oral suspension, USP and other antibacterial drugs, cefdinir for oral suspension, USP 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 for oral suspension, USP 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. 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 pneumoniae (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 pneumoniae (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) Powder for Oral Suspension The recommended dosage and duration of treatment for infections in pediatric patients are described in the following chart; the total daily dose for all infections is 14 mg/kg, up to a maximum dose of 600 mg per day. Once-daily dosing for 10 days is as effective as BID. dosing. Once-daily dosing has not been studied in skin infections; therefore, cefdinir for oral suspension should be administered twice daily in this infection. Cefdinir for oral suspension may be administered without regard to meals.

Pediatric

Patients (Age 6 Months Through 12 Years) Type of Infection Dosage Duration Acute Bacterial Otitis Media 7 mg/kg q12h or 14 mg/kg q24h 5 to 10 days 10 days Acute Maxillary Sinusitis 7 mg/kg q12h or 14 mg/kg q24h 10 days 10 days Pharyngitis/Tonsillitis 7 mg/kg q12h or 14 mg/kg q24h 5 to 10 days 10 days Uncomplicated Skin and Skin Structure Infections 7 mg/kg q12h 10 days CEFDINIR FOR ORAL SUSPENSION PEDIATRIC DOSAGE CHART Weight 125 mg/5 mL 250 mg/5 mL 9 kg/20 lbs 2.5 mL q12h or 5 mL q24h Use 125 mg/5 mL product 18 kg/40 lbs 5 mL q12h or 10 mL q24h 2.5 mL q12h or 5 mL q24h 27 kg/60 lbs 7.5 mL q12h or 15 mL q24h 3.75 mL q12h or 7.5 mL q24h 36 kg/80 lbs 10 mL q12h or 20 mL q24h 5 mL q12h or 10 mL q24h ≥43 kg* /95 lbs 12 mL q12h or 24 mL q24h 6 mL q12h or 12 mL q24h * Pediatric patients who weigh ≥ 4 3 kg should receive the maximum daily dose of 600 mg. 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 (CLcr) in adult patients. For estimates to be valid, serum creatinine levels should reflect steady-state levels of renal function. Males: CLcr = (weight) (140 – age) (72) (serum creatinine) Females: CLcr = 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: CLcr = 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. Directions for Mixing Cefdinir for Oral Suspension Final Concentration Final Volume(mL) Amount of Water Directions 125 mg/5 mL 60 100 40 mL 64 mL Tap bottle to loosen powder, then add water in 2 portions. Shake well after each aliquot. 250 mg/5 mL 60 100 40 mL 64 mL Tap bottle to loosen powder, then add water in 2 portions. Shake well after each aliquot. After mixing, the suspension can be stored at controlled room temperature (20 ° to 25 ° C/68 ° to 77 ° F). The container should be kept tightly closed, and the suspension should be shaken well before each administration. The suspension may be used for 10 days, after which any unused portion must be discarded.

CONTRAINDICATIONS Cefdinir for oral suspension 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) a a 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) a N <3841 for these parameters Incidence ≥1% ↑Urine leukocytes 2% ↑Urine protein 2% ↑Gamma-glutamyltransferase a 1% ↓Lymphocytes, ↑Lymphocytes 1%, 0.2% ↑Microhematuria 1% Incidence <1% but >0.1% ↑Glucose a 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 a 0.6%, 0.2% ↓Bicarbonate a 0.6% ↑Phosphorus, ↓Phosphorus a 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 a 0.2% ↑Platelets 0.2% ↑Potassium a 0.2% ↑Urine pH a 0.2% Clinical Trials - Cefdinir for Oral Suspension (Pediatric Patients) In clinical trials, 2289 pediatric patients (1783 U.S. and 506 non-U.S.) were treated with the recommended dose of cefdinir suspension (14 mg/kg/day). Most adverse events were mild and self-limiting. No deaths or permanent disabilities were attributed to cefdinir. Forty of 2289 (2%) patients discontinued medication due to adverse events considered by the investigators to be possibly, probably, or definitely associated with cefdinir therapy. Discontinuations were primarily for gastrointestinal disturbances, usually diarrhea. Five of 2289 (0.2%) 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 suspension in multiple-dose clinical trials (N = 1783 cefdinir-treated patients): ADVERSE EVENTS ASSOCIATED WITH CEFDINIR SUSPENSION U.S. TRIALS IN PEDIATRIC PATIENTS (N = 1783) a a 977 males, 806 females b Laboratory changes were occasionally reported as adverse events. Incidence ≥ 1% Diarrhea 8% Rash 3% Vomiting 1% Incidence <1% but >0.1% Cutaneous moniliasis 0.9% Abdominal pain 0.8% Leukopenia b 0.3% Vaginal moniliasis 0.3% of girls Vaginitis 0.3% of girls Abnormal stools 0.2% Dyspepsia 0.2% Hyperkinesia 0.2% Increased AST b 0.2% Maculopapular rash 0.2% Nausea 0.2% NOTE: In both cefdinir- and control-treated patients, rates of diarrhea and rash were higher in the youngest pediatric patients. The incidence of diarrhea in cefdinir-treated patients ≤2 years of age was 17% (95/557) compared with 4% (51/1226) in those >2 years old. The incidence of rash (primarily diaper rash in the younger patients) was 8% (43/557) in patients ≤2 years of age compared with 1% (8/1226) in those >2 years old. 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 OF POSSIBLE CLINICAL SIGNIFICANCE OBSERVED WITH CEFDINIR SUSPENSION U.S. TRIALS IN PEDIATRIC PATIENTS (N = 1783) a N = 1387 for these parameters Incidence ≥1% ↑Lymphocytes, ↓Lymphocytes 2%, 0.8% ↑Alkaline phosphatase 1% ↓Bicarbonate a 1% ↑Eosinophils 1% ↑Lactate dehydrogenase 1% ↑Platelets 1% ↑PMNs, ↓PMNs 1%, 1% ↑Urine protein 1% Incidence <1% but >0.1% ↑Phosphorus, ↓Phosphorus 0.9%, 0.4% ↑Urine pH 0.8% ↓White blood cells, ↑White blood cells 0.7%, 0.3% ↓Calcium a 0.5% ↓Hemoglobin 0.5% ↑Urine leukocytes 0.5% ↑Monocytes 0.4% ↑AST 0.3% ↑Potassium a 0.3% ↑Urine specific gravity, ↓Urine specific gravity 0.3%, 0.1% ↓Hematocrit a 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.

WARNINGS BEFORE THERAPY WITH CEFDINIR FOR ORAL SUSPENSION IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE TO DETERMINE WHETHER THE PATIENT HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO CEFDINIR, OTHER CEPHALOSPORINS, PENICILLINS, OR OTHER DRUGS. IF CEFDINIR IS TO BE GIVEN TO PENICILLIN-SENSITIVE PATIENTS, CAUTION SHOULD BE EXERCISED BECAUSE CROSS-HYPERSENSITIVITY AMONG β-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 CEFDINIR OCCURS, THE DRUG SHOULD BE DISCONTINUED. SERIOUS ACUTE HYPERSENSITIVITY REACTIONS MAY REQUIRE TREATMENT WITH EPINEPHRINE AND OTHER EMERGENCY MEASURES, INCLUDING OXYGEN, INTRAVENOUS FLUIDS, INTRAVENOUS ANTIHISTAMINES, CORTICOSTEROIDS, PRESSOR AMINES, AND AIRWAY MANAGEMENT, AS CLINICALLY INDICATED. Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including cefdinir, 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 antibacterial 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 antibacterial use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile , and surgical evaluation should be instituted as clinically indicated.

PRECAUTIONS General: Prescribing cefdinir for oral suspension 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. As with other broad-spectrum antibiotics, prolonged treatment may result in the possible emergence and overgrowth of resistant organisms. Careful observation of the patient is essential. If superinfection occurs during therapy, appropriate alternative therapy should be administered. Cefdinir, as with other broad-spectrum antimicrobials (antibiotics), should be prescribed with caution in individuals with a history of colitis. In patients with transient or persistent renal insufficiency (creatinine clearance <30 mL/min), the total daily dose of cefdinir should be reduced because high and prolonged plasma concentrations of cefdinir can result following recommended doses (see DOSAGE AND ADMINISTRATION ). Information for Patients: Patients should be counseled that antibacterial drugs including cefdinir for oral suspension should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When cefdinir for oral suspension 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 cefdinir for oral suspension or other antibacterial drugs in the future. Antacids containing magnesium or aluminum interfere with the absorption of cefdinir. If this type of antacid is required during cefdinir therapy, cefdinir should be taken at least 2 hours before or after the antacid. Iron supplements, including multivitamins that contain iron, interfere with the absorption of cefdinir. If iron supplements are required during cefdinir therapy, cefdinir should be taken at least 2 hours before or after the supplement. Iron-fortified infant formula does not significantly interfere with the absorption of cefdinir. Therefore, cefdinir can be administered with iron-fortified infant formula. Diabetic patients and caregivers should be aware that the oral suspension contains 2.86 g of sucrose per teaspoon. 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 (Aluminum- or Magnesium-Containing): If antacids are required during cefdinir 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. Concomitantly administered iron-fortified infant formula (2.2 mg elemental iron/6 oz) has no significant effect on cefdinir pharmacokinetics. Therefore, cefdinir can be administered with iron-fortified infant formula. 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.

Drug/Laboratory

Test Interactions: A false-positive reaction for ketones in the urine may occur with tests using nitroprusside, but not with those using nitroferricyanide. The administration of cefdinir may result in a false-positive reaction for glucose in urine using Clinitest ® , Benedict's solution, or Fehling's solution. It is recommended that glucose tests based on enzymatic glucose oxidase reactions (such as Clinistix ® or Tes-Tape ® ) be used. Cephalosporins are known to occasionally induce a positive direct Coombs' test. Carcinogenesis, Mutagenesis, Impairment of Fertility: The carcinogenic potential of cefdinir has not been evaluated. No mutagenic effects were seen in the bacterial reverse mutation assay (Ames) or point mutation assay at the hypoxanthine-guanine phosphoribosyltransferase locus (HGPRT) in V79 Chinese hamster lung cells. No clastogenic effects were observed in vitro in the structural chromosome aberration assay in V79 Chinese hamster lung cells or in vivo in the micronucleus assay in mouse bone marrow. In rats, fertility and reproductive performance were not affected by cefdinir at oral doses up to 1000 mg/kg/day (70 times the human dose based on mg/kg/day, 11 times based on mg/m 2 /day). Pregnancy : Teratogenic Effects: Pregnancy Category B. Cefdinir was not teratogenic in rats at oral doses up to 1000 mg/kg/day (70 times the human dose based on mg/kg/day, 11 times based on mg/m 2 /day) or in rabbits at oral doses up to 10 mg/kg/ day (0.7 times the human dose based on mg/kg/day, 0.23 times based on mg/m 2 /day). Maternal toxicity (decreased body weight gain) was observed in rabbits at the maximum tolerated dose of 10 mg/kg/day without adverse effects on offspring. Decreased body weight occurred in rat fetuses at ≥100 mg/kg/day, and in rat offspring at ≥32 mg/kg/day. No effects were observed on maternal reproductive parameters or offspring survival, development, behavior, or reproductive function. There are, however, no adequate and well-controlled studies 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. Labor and Delivery: Cefdinir has not been studied for use during labor and delivery.

Nursing

Mothers: Following administration of single 600 mg doses, cefdinir was not detected in human breast milk.

Pediatric

Use: Safety and efficacy in neonates and infants less than 6 months of age have not been established. Use of cefdinir for the treatment of acute maxillary sinusitis in pediatric patients (age 6 months through 12 years) is supported by evidence from adequate and well-controlled studies in adults and adolescents, the similar pathophysiology of acute sinusitis in adult and pediatric patients, and comparative pharmacokinetic data in the pediatric population.

Geriatric

Use: Efficacy is comparable in geriatric patients and younger adults. While cefdinir has been well-tolerated in all age groups, in clinical trials geriatric patients experienced a lower rate of adverse events, including diarrhea, than younger adults. Dose adjustment in elderly patients is not necessary unless renal function is markedly compromised (see DOSAGE AND ADMINISTRATION ).

Adverse Events

Clinical Trials - (Pediatric Patients): In clinical trials, 2289 pediatric patients (1783 US and 506 non-US) were treated with the recommended dose of cefdinir suspension (14 mg/kg/day). Most adverse events were mild and self-limiting. No deaths or permanent disabilities were attributed to cefdinir. Forty of 2289 (2%) patients discontinued medication due to adverse events considered by the investigators to be possibly, probably, or definitely associated with cefdinir therapy. Discontinuations were primarily for gastrointestinal disturbances, usually diarrhea. Five of 2289 (0.2%) patients were discontinued due to rash thought related to cefdinir administration. In the US, the following adverse events were thought by investigators to be possibly, probably, or definitely related to cefdinir suspension in multiple-dose clinical trials (N=1783 cefdinir-treated patients): ADVERSE EVENTS ASSOCIATED WITH CEFDINIR SUSPENSION U . S . TRIALS IN PEDIATRIC PATIENTS ( N = 1783 ) a a 977 males, 806 females b Laboratory changes were occasionally reported as adverse events. Incidence ≥1% Diarrhea 8% Rash 3% Vomiting 1% Incidence <1% but >0.1% Cutaneous moniliasis 0.9% Abdominal pain 0.8% Leukopenia b 0.3% Vaginal moniliasis 0.3% of girls Vaginitis 0.3% of girls Abnormal stools 0.2% Dyspepsia 0.2% Hyperkinesia 0.2% Increased AST b 0.2% Maculopapular rash 0.2% Nausea 0.2% NOTE: In both cefdinir- and control-treated patients, rates of diarrhea and rash were higher in the youngest pediatric patients. The incidence of diarrhea in cefdinir-treated patients ≤2 years of age was 17% (95/557) compared with 4% (51/1226) in those >2 years old. The incidence of rash (primarily diaper rash in the younger patients) was 8% (43/557) in patients ≤2 years of age compared with 1% (8/1226) in those >2 years old. The following laboratory value changes of possible clinical significance, irrespective of relationship to therapy with cefdinir, were seen during clinical trials conducted in the US: LABORATORY VALUE CHANGES OF POSSIBLE CLINICAL SIGNIFICANCE OBSERVED WITH CEFDINIR SUSPENSION U . S . TRIALS IN PEDIATRIC PATIENTS ( N = 1783 ) a N = 1387 for these parameters. Incidence ≥1% ↑Lymphocytes,↓Lymphocytes 2%, 0.8% ↑Alkaline phosphatase 1% ↓Bicarbonate a 1% ↑Eosinophils 1% ↑Lactate dehydrogenase 1% ↑Platelets 1% ↑PMNs, ↓PMNs 1%, 1% ↑Urine protein 1% Incidence <1% but >0.1% ↑Phosphorus, ↓Phosphorus 0.9%, 0.4% ↑Urine pH 0.8% ↓White blood cells, ↑White blood cells 0.7%, 0.3% ↓Calcium a 0.5% ↓Hemoglobin 0.5% ↑Urine leukocytes 0.5% ↑Monocytes 0.4% ↑AST 0.3% ↑Potassium a 0.3% ↑Urine specific gravity, ↓Urine specific gravity 0.3%, 0.1% ↓Hematocrit a 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.

Drug Interactions 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 for oral suspension therapy, cefdinir for oral suspension 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 ½ .

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 for oral suspension therapy, cefdinir for oral suspension 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. Concomitantly administered iron-fortified infant formula (2.2 mg elemental iron/6 oz) has no significant effect on cefdinir pharmacokinetics. Therefore, cefdinir for oral suspension can be administered with iron-fortified infant formula. 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.