CEFDINIR- cefdinir_capsule

CLINICAL PHARMACOLOGY
Oral Bioavailability: Effect of Food: max Cefdinir Capsules: Mean (+/-SD) Plasma Cefdinir Pharmacokinetic Parameter Values Following Administration of Capsules to Adult Subjects Dose C m a x ( mcg / mL ) t m a x ( hr ) AUC ( mcg. hr / mL ) 300 mg 1. 17) 600 mg 2. 87) Multiple Dosing: The mean volume of distribution (Vd area area Skin Blister: max Tonsil Tissue: Sinus Tissue: Lung Tissue: Middle Ear Fluid: CSF: Cefdinir is not appreciably metabolized. Activity is primarily due to parent drug. Cefdinir is eliminated principally via renal excretion with a mean plasma elimination half-life (t 1/2 Special Populations: Patients with Renal Insufficiency Because renal excretion is the predominant pathway of elimination, dosage should be adjusted in patients with markedly compromised renal function or who are undergoing hemodialysis (see DOSAGE AND ADMINISTRATION Patients with Renal Insufficiency: cr cr max 1/2 cr max 1/2 DOSAGE AND ADMINISTRATION Hemodialysis: 1/2 DOSAGE AND ADMINISTRATION Hepatic Disease: Geriatric Patients: max 1/2 Gender and Race: Mechanism of Action: As with other cephalosporins, bactericidal activity of cefdinir results from inhibition of cell wall synthesis. Cefdinir is stable in the presence of some, but not all, beta-lactamase enzymes. As a result, many organisms resistant to penicillins and some cephalosporins are susceptible to cefdinir. Mechanism of Resistance: Resistance to cefdinir is primarily through hydrolysis by some beta-lactamases, alteration of penicillin-binding proteins (PBPs) and decreased permeability. Cefdinir is inactive against most strains of Enterobacter Pseudomonas Enterococcus H. influenzae Antimicrobial Activity: Cefdinir has been shown to be active against most strains of the following microorganisms, both in vitro INDICATIONS AND USAGE Gram-Positive Bacteria: Staphylococcus aureus Streptococcus pneumoniae Streptococcus pyogenes Gram-Negative Bacteria: Haemophilus influenzae Haemophilus parainfluenzae Moraxella catarrhalis The following in vitro Cefdinir exhibits in vitro Gram-Positive Bacteria: Staphylococcus epidermidis Streptococcus agalactiae Viridans group streptococci Gram-Negative Bacteria: Citrobacter koseri Escherichia coli Klebsiella pneumoniae Proteus mirabilis Susceptibility Test Methods: For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.
Pharmacokinetics and Drug Metabolism:
Oral Bioavailability: Effect of Food: max Cefdinir Capsules: Mean (+/-SD) Plasma Cefdinir Pharmacokinetic Parameter Values Following Administration of Capsules to Adult Subjects Dose C m a x ( mcg / mL ) t m a x ( hr ) AUC ( mcg. hr / mL ) 300 mg 1. 17) 600 mg 2. 87) Multiple Dosing: The mean volume of distribution (Vd area area Skin Blister: max Tonsil Tissue: Sinus Tissue: Lung Tissue: Middle Ear Fluid: CSF: Cefdinir is not appreciably metabolized. Activity is primarily due to parent drug. Cefdinir is eliminated principally via renal excretion with a mean plasma elimination half-life (t 1/2 Special Populations: Patients with Renal Insufficiency Because renal excretion is the predominant pathway of elimination, dosage should be adjusted in patients with markedly compromised renal function or who are undergoing hemodialysis (see DOSAGE AND ADMINISTRATION Patients with Renal Insufficiency: cr cr max 1/2 cr max 1/2 DOSAGE AND ADMINISTRATION Hemodialysis: 1/2 DOSAGE AND ADMINISTRATION Hepatic Disease: Geriatric Patients: max 1/2 Gender and Race:.
Absorption:
Oral Bioavailability: Effect of Food: max Cefdinir Capsules: Mean (+/-SD) Plasma Cefdinir Pharmacokinetic Parameter Values Following Administration of Capsules to Adult Subjects Dose C m a x ( mcg / mL ) t m a x ( hr ) AUC ( mcg . hr / mL ) 300 mg 1.60(0.55) 2.9(0.89) 7.05(2.17) 600 mg 2.87(1.01) 3.0(0.66) 11.1(3.87) Multiple Dosing:
Distribution:
The mean volume of distribution (Vd area area Skin Blister: max Tonsil Tissue: Sinus Tissue: Lung Tissue: Middle Ear Fluid: CSF:
Metabolism and Excretion:
Cefdinir is not appreciably metabolized. Activity is primarily due to parent drug. Cefdinir is eliminated principally via renal excretion with a mean plasma elimination half-life (t 1/2 Special Populations: Patients with Renal Insufficiency Because renal excretion is the predominant pathway of elimination, dosage should be adjusted in patients with markedly compromised renal function or who are undergoing hemodialysis (see DOSAGE AND ADMINISTRATION
Microbiology:
Mechanism of Action: As with other cephalosporins, bactericidal activity of cefdinir results from inhibition of cell wall synthesis. Cefdinir is stable in the presence of some, but not all, beta-lactamase enzymes. As a result, many organisms resistant to penicillins and some cephalosporins are susceptible to cefdinir. Mechanism of Resistance: Resistance to cefdinir is primarily through hydrolysis by some beta-lactamases, alteration of penicillin-binding proteins (PBPs) and decreased permeability. Cefdinir is inactive against most strains of Enterobacter Pseudomonas Enterococcus H. influenzae Antimicrobial Activity: Cefdinir has been shown to be active against most strains of the following microorganisms, both in vitro INDICATIONS AND USAGE Gram-Positive Bacteria: Staphylococcus aureus Streptococcus pneumoniae Streptococcus pyogenes Gram-Negative Bacteria: Haemophilus influenzae Haemophilus parainfluenzae Moraxella catarrhalis The following in vitro Cefdinir exhibits in vitro Gram-Positive Bacteria: Staphylococcus epidermidis Streptococcus agalactiae Viridans group streptococci Gram-Negative Bacteria: Citrobacter koseri Escherichia coli Klebsiella pneumoniae Proteus mirabilis Susceptibility Test Methods: For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.fda.gov/STIC.

INDICATIONS AND 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. Caused by Haemophilus influenzae Haemophilus parainfluenzae Streptococcus pneumoniae Moraxella catarrhalis CLINICAL STUDIES Caused by Haemophilus influenzae Haemophilus parainfluenzae Streptococcus pneumoniae Moraxella catarrhalis Caused by Haemophilus influenzae Streptococcus pneumoniae Moraxella catarrhalis NOTE Pediatric Use DOSAGE AND ADMINISTRATION Caused by Streptococcus pyogenes CLINICAL STUDIES NOTE S. pyogenes Caused by Staphylococcus aureus Streptococcus pyogenes Caused by Haemophilus influenzae Streptococcus pneumoniae Moraxella catarrhalis Caused by Streptococcus pyogenes CLINICAL STUDIES NOTE S. pyogenes Caused by Staphylococcus aureus Streptococcus pyogenes.
Community-Acquired Pneumonia:
Caused by Haemophilus influenzae Haemophilus parainfluenzae Streptococcus pneumoniae Moraxella catarrhalis CLINICAL STUDIES
Acute Exacerbations of Chronic Bronchitis:
Caused by Haemophilus influenzae Haemophilus parainfluenzae Streptococcus pneumoniae Moraxella catarrhalis
Acute Maxillary Sinusitis:
Caused by Haemophilus influenzae Streptococcus pneumoniae Moraxella catarrhalis NOTE Pediatric Use DOSAGE AND ADMINISTRATION
Uncomplicated Skin and Skin Structure Infections:
Caused by Staphylococcus aureus Streptococcus pyogenes
Acute Bacterial Otitis Media:
Caused by Haemophilus influenzae Streptococcus pneumoniae Moraxella catarrhalis
Community-Acquired Bacterial Pneumonia:
In a controlled, double-blind study in adults and adolescents conducted in the US, cefdinir BID was compared with cefaclor 500 mg TID. Using strict evaluability and microbiologic/clinical response criteria 6 to 14 days posttherapy, the following clinical cure rates, presumptive microbiologic eradication rates, and statistical outcomes were obtained: US Community-Acquired Pneumonia Study Cefdinir vs Cefaclor Cefdinir BID Cefaclor TID Outcome Clinical Cure Rates Eradication Rates 150/187 (80%) 147/186 (79%) Cefdinir equivalent to control Overall 177/195 (91%) 184/200 (92%) Cefdinir equivalent to control S . pneumoniae 31/31 (100%) 35/35 (100%) H . influenzae 55/65 (85%) 60/72 (83%) M . catarrhalis 10/10 (100%) 11/11 (100%) H . parainfluenzae 81/89 (91%) 78/82 (95%) In a second controlled, investigator-blind study in adults and adolescents conducted primarily in Europe, cefdinir BID was compared with amoxicillin/clavulanate 500/125 mg TID. Using strict evaluability and clinical response criteria 6 to 14 days posttherapy, the following clinical cure rates, presumptive microbiologic eradication rates, and statistical outcomes were obtained: European Community-Acquired Pneumonia Study Cefdinir vs Amoxicillin/Clavulanate Cefdinir vs Cefaclor Cefdinir BID Amoxicillin / Clavulanate TID Outcome Clinical Cure Rates Eradication Rates 83/104 (80%) 86/97 (89%) Cefdinir not equivalent to control Overall 85/96 (89%) 84/90 (93%) Cefdinir equivalent to control S . pneumoniae 42/44 (95%) 43/44 (98%) H . influenzae 26/35 (74%) 21/26 (81%) M . catarrhalis 6/6 (100%) 8/8 (100%) H . parainfluenzae 11/11 (100%) 12/12 (100%)
Streptococcal Pharyngitis/Tonsillitis:
In four controlled studies conducted in the United States, cefdinir was compared with 10 days of penicillin in adult, adolescent, and pediatric patients. Two studies (one in adults and adolescents, the other in pediatric patients) compared 10 days of cefdinir QD or BID to penicillin 250 mg or 10 mg/kg QID. Using strict evaluability and microbiologic/clinical response criteria 5 to 10 days posttherapy, the following clinical cure rates, microbiologic eradication rates, and statistical outcomes were obtained: Pharyngitis/Tonsillitis Studies Cefdinir (10 days) vs Penicillin (10 days) Study Efficacy Parameter Cefdinir QD Cefdinir BID Penicillin QID Outcome Adults/ Adolescents Eradication of S . pyogenes 192/210 (91%) 199/217 (92%) 181/217 (83%) Cefdinir superior to control Clinical Cure Rates 199/210 (95%) 209/217 (96%) 193/217 (89%) Cefdinir superior to control Pediatric Patients Eradication of S . pyogenes 215/228 (94%) 214/227 (94%) 159/227 (70%) Cefdinir superior to control Clinical Cure Rates 222/228 (97%) 218/227 (96%) 196/227 (86%) Cefdinir superior to control Two studies (one in adults and adolescents, the other in pediatric patients) compared 5 days of cefdinir BID to 10 days of penicillin 250 mg or 10 mg/kg QID. Using strict evaluability and microbiologic/ clinical response criteria 4 to 10 days posttherapy, the following clinical cure rates, microbiologic eradication rates, and statistical outcomes were obtained: Pharyngitis/Tonsillitis Studies Cefdinir (5 days) vs Penicillin (10 days) Study Efficacy Parameter Cefdinir BID Penicillin QID Outcome Adults/ Adolescents Eradication of S . pyogenes 193/218 (89%) 176/214 (82%) Cefdinir equivalent to control Clinical Cure Rates 194/218 (89%) 181/214 (85%) Cefdinir equivalent to control Pediatric Patients Eradication of S . pyogenes 176/196 (90%) 135/193 (70%) Cefdinir superior to control Clinical Cure Rates 179/196 (91%) 173/193 (90%) Cefdinir equivalent to control

(see INDICATIONS AND USAGE 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 BID 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 5 to 10 days or Acute Maxillary Sinusitis 600 mg q24h 10 days 300 mg q12h 10 days or Pharyngitis/Tonsillitis 600 mg q24h 10 days 300 mg q12h 5 to 10 days or Uncomplicated Skin and Skin Structure Infections 600 mg q24h 10 days 300 mg q12h 10 days 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 (weight) (140 en dash age) Males: CL cr (72) (serum creatinine) Females: CL cr 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: body length or height CL cr serum creatinine where K = 0. 55 for pediatric patients older than 1 year 2 3 In the above equation, creatinine clearance is in mL/min/1. 73 m 2 For pediatric patients with a creatinine clearance of <30 mL/min/1. 73 m 2 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.

Pharyngitis/Tonsillitis:
Caused by Streptococcus pyogenes CLINICAL STUDIES NOTE S. pyogenes S. pyogenes
ADVERSE EVENTS
In clinical trials, 5093 adult and adolescent patients (3841 US and 1252 non-US) 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 US, 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 US TRIALS IN ADULT AND ADOLESCENT PATIENTS ( N = 3841 ) a a Incidence >=1% Diarrhea 15% Vaginal moniliasis 4% of women Nausea 3% Headache 2% Abdominal pain 1% Vaginitis 1% of women Incidence 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 US: LABORATORY VALUE CHANGES OBSERVED WITH CEFDINIR CAPSULES US TRIALS IN ADULT AND ADOLESCENT PATIENTS ( N = 3841 ) a Incidence >=1% up arrowUrine leukocytes 2% up arrowUrine protein 2% up arrowGamma-glutamyltransferase a 1% down arrowLymphocytes, up arrowLymphocytes 1%, 0. 2% up arrowMicrohematuria 1% Incidence 0. 1% up arrowGLucose a 0. 9% up arrowUrine glucose 0. 9% up arrowWhite blood cells, down arrowWhite blood cells 0. 7% up arrowAlanine aminotransferase (ALT) 0. 7% up arrowEosinophils 0. 7% up arrowUrine specific gravity, down arrowUrine specific gravity a 0. 2% down arrowBicarbonate a 0. 6% up arrowPhosphorus, down arrowPhosphorus a 0. 3% up arrowAspartate aminotransferase (AST) 0. 4% up arrowAlkaline phosphatase 0. 3% up arrowBlood urea nitrogen (BUN) 0. 3% down arrowHemoglobin 0. 3% up arrowPolymorphonuclear neutrophils (PMNs), down arrowPMNs 0. 2% up arrowBilirubin 0. 2% up arrowLactate dehydrogenase a 0. 2% up arrowPlatelets 0. 2% up arrowPotassium a 0. 2% up arrowUrine pH a 0. 2% 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. 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 OVERDOSAGE.
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 OVERDOSAGE

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

Special Populations:
Patients with Renal Insufficiency: cr cr max 1/2 cr max 1/2 DOSAGE AND ADMINISTRATION Hemodialysis: 1/2 DOSAGE AND ADMINISTRATION Hepatic Disease: Geriatric Patients: max 1/2 Gender and Race:
Adults and Adolescents:
Caused by Haemophilus influenzae Haemophilus parainfluenzae Streptococcus pneumoniae Moraxella catarrhalis CLINICAL STUDIES Caused by Haemophilus influenzae Haemophilus parainfluenzae Streptococcus pneumoniae Moraxella catarrhalis Caused by Haemophilus influenzae Streptococcus pneumoniae Moraxella catarrhalis NOTE Pediatric Use DOSAGE AND ADMINISTRATION Caused by Streptococcus pyogenes CLINICAL STUDIES NOTE S. pyogenes Caused by Staphylococcus aureus Streptococcus pyogenes.
Pediatric Patients:
Caused by Haemophilus influenzae Streptococcus pneumoniae Moraxella catarrhalis Caused by Streptococcus pyogenes CLINICAL STUDIES NOTE S. pyogenes Caused by Staphylococcus aureus Streptococcus pyogenes.
Pregnancy:
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 2 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.
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 2 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.
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
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 (weight) (140 en dash age) Males: CL cr (72) (serum creatinine) Females: CL cr 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: body length or height CL cr serum creatinine where K = 0.55 for pediatric patients older than 1 year 2 3 In the above equation, creatinine clearance is in mL/min/1.73 m 2 For pediatric patients with a creatinine clearance of <30 mL/min/1.73 m 2
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.

Drug Interactions:
Concomitant administration of 300 mg cefdinir capsules with 30 mL Maalox registered max max As with other beta-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 Concomitant administration of cefdinir with a therapeutic iron supplement containing 60 mg of elemental iron (as FeSO 4 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.
Antacids (Aluminum- or Magnesium-Containing):
Concomitant administration of 300 mg cefdinir capsules with 30 mL Maalox registered max max
Probenecid:
As with other beta-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 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.
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 registered registered registered

WARNINGS
BEFORE THERAPY WITH CEFDINIR 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 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 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 C. difficile C. difficile C. difficile If CDAD is suspected or confirmed, ongoing antibacterial use not directed against C. difficile C. difficile
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 vivo 2
Labor and Delivery:
Cefdinir has not been studied for use during labor and delivery.
Clinical Trials - (Adult and Adolescent Patients):
In clinical trials, 5093 adult and adolescent patients (3841 US and 1252 non-US) 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 US, 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 US TRIALS IN ADULT AND ADOLESCENT PATIENTS ( N = 3841 ) a a Incidence >=1% Diarrhea 15% Vaginal moniliasis 4% of women Nausea 3% Headache 2% Abdominal pain 1% Vaginitis 1% of women Incidence 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 US: LABORATORY VALUE CHANGES OBSERVED WITH CEFDINIR CAPSULES US TRIALS IN ADULT AND ADOLESCENT PATIENTS ( N = 3841 ) a Incidence >=1% up arrowUrine leukocytes 2% up arrowUrine protein 2% up arrowGamma-glutamyltransferase a 1% down arrowLymphocytes, up arrowLymphocytes 1%, 0.2% up arrowMicrohematuria 1% Incidence 0.1% up arrowGLucose a 0.9% up arrowUrine glucose 0.9% up arrowWhite blood cells, down arrowWhite blood cells 0.9%, 0.7% up arrowAlanine aminotransferase (ALT) 0.7% up arrowEosinophils 0.7% up arrowUrine specific gravity, down arrowUrine specific gravity a 0.6%, 0.2% down arrowBicarbonate a 0.6% up arrowPhosphorus, down arrowPhosphorus a 0.6%, 0.3% up arrowAspartate aminotransferase (AST) 0.4% up arrowAlkaline phosphatase 0.3% up arrowBlood urea nitrogen (BUN) 0.3% down arrowHemoglobin 0.3% up arrowPolymorphonuclear neutrophils (PMNs), down arrowPMNs 0.3%, 0.2% up arrowBilirubin 0.2% up arrowLactate dehydrogenase a 0.2% up arrowPlatelets 0.2% up arrowPotassium a 0.2% up arrowUrine pH a 0.2%
OVERDOSAGE
Information on cefdinir overdosage in humans is not available. In acute rodent toxicity studies, a single oral 5600 mg/kg dose produced no adverse effects. Toxic signs and symptoms following overdosage with other beta- lactam antibiotics have included nausea, vomiting, epigastric distress, diarrhea, and convulsions. Hemodialysis removes cefdinir from the body. This may be useful in the event of a serious toxic reaction from overdosage, particularly if renal function is compromised.
CLINICAL STUDIES
In a controlled, double-blind study in adults and adolescents conducted in the US, cefdinir BID was compared with cefaclor 500 mg TID. Using strict evaluability and microbiologic/clinical response criteria 6 to 14 days posttherapy, the following clinical cure rates, presumptive microbiologic eradication rates, and statistical outcomes were obtained: US Community-Acquired Pneumonia Study Cefdinir vs Cefaclor Cefdinir BID Cefaclor TID Outcome Clinical Cure Rates Eradication Rates 150/187 (80%) 147/186 (79%) Cefdinir equivalent to control Overall 177/195 (91%) 184/200 (92%) Cefdinir equivalent to control S. pneumoniae 31/31 (100%) 35/35 (100%) H. influenzae 55/65 (85%) 60/72 (83%) M. catarrhalis 10/10 (100%) 11/11 (100%) H. parainfluenzae 81/89 (91%) 78/82 (95%) In a second controlled, investigator-blind study in adults and adolescents conducted primarily in Europe, cefdinir BID was compared with amoxicillin/clavulanate 500/125 mg TID. Using strict evaluability and clinical response criteria 6 to 14 days posttherapy, the following clinical cure rates, presumptive microbiologic eradication rates, and statistical outcomes were obtained: European Community-Acquired Pneumonia Study Cefdinir vs Amoxicillin/Clavulanate Cefdinir vs Cefaclor Cefdinir BID Amoxicillin / Clavulanate TID Outcome Clinical Cure Rates Eradication Rates 83/104 (80%) 86/97 (89%) Cefdinir not equivalent to control Overall 85/96 (89%) 84/90 (93%) Cefdinir equivalent to control S. pneumoniae 42/44 (95%) 43/44 (98%) H. influenzae 26/35 (74%) 21/26 (81%) M. catarrhalis 6/6 (100%) 8/8 (100%) H. parainfluenzae 11/11 (100%) 12/12 (100%) In four controlled studies conducted in the United States, cefdinir was compared with 10 days of penicillin in adult, adolescent, and pediatric patients. Two studies (one in adults and adolescents, the other in pediatric patients) compared 10 days of cefdinir QD or BID to penicillin 250 mg or 10 mg/kg QID. Using strict evaluability and microbiologic/clinical response criteria 5 to 10 days posttherapy, the following clinical cure rates, microbiologic eradication rates, and statistical outcomes were obtained: Pharyngitis/Tonsillitis Studies Cefdinir (10 days) vs Penicillin (10 days) Study Efficacy Parameter Cefdinir QD Cefdinir BID Penicillin QID Outcome Adults/ Adolescents Eradication of S. pyogenes 192/210 (91%) 199/217 (92%) 181/217 (83%) Cefdinir superior to control Clinical Cure Rates 199/210 (95%) 209/217 (96%) 193/217 (89%) Cefdinir superior to control Pediatric Patients Eradication of S. pyogenes 215/228 (94%) 214/227 (94%) 159/227 (70%) Cefdinir superior to control Clinical Cure Rates 222/228 (97%) 218/227 (96%) 196/227 (86%) Cefdinir superior to control Two studies (one in adults and adolescents, the other in pediatric patients) compared 5 days of cefdinir BID to 10 days of penicillin 250 mg or 10 mg/kg QID. Using strict evaluability and microbiologic/ clinical response criteria 4 to 10 days posttherapy, the following clinical cure rates, microbiologic eradication rates, and statistical outcomes were obtained: Pharyngitis/Tonsillitis Studies Cefdinir (5 days) vs Penicillin (10 days) Study Efficacy Parameter Cefdinir BID Penicillin QID Outcome Adults/ Adolescents Eradication of S. pyogenes 193/218 (89%) 176/214 (82%) Cefdinir equivalent to control Clinical Cure Rates 194/218 (89%) 181/214 (85%) Cefdinir equivalent to control Pediatric Patients Eradication of S. pyogenes 176/196 (90%) 135/193 (70%) Cefdinir superior to control Clinical Cure Rates 179/196 (91%) 173/193 (90%) Cefdinir equivalent to control.
REFERENCES
Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976;16:31-41. Schwartz GJ, Haycock GB, Edelmann CM, Spitzer A. A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics 1976;58:259-63. Schwartz GJ, Feld LG, Langford DJ. A simple estimate of glomerular filtration rate in full-term infants during the first year of life. J Pediatrics 1984;104:849-54.

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