CEFDINIR- cefdinir_powder, for suspension

CLINICAL PHARMACOLOGY
Absorption Oral Bioavailability Maximal plasma cefdinir concentrations occur 2 to 4 hours postdose following capsule or suspension administration. Plasma cefdinir concentrations increase with dose, but the increases are less than dose-proportional from 300 mg (7 mg/kg) to 600 mg (14 mg/kg). Following administration of suspension to healthy adults, cefdinir bioavailability is 120% relative to capsules. Estimated bioavailability of cefdinir suspension is 25%. Cefdinir oral suspension of 250 mg/5 mL strength was shown to be bioequivalent to the 125 mg/5 mL strength in healthy adults under fasting conditions. Effect of Food In adults given the 250 mg/5 mL oral suspension with a high-fat meal, the C max Cefdinir Suspension Cefdinir plasma concentrations and pharmacokinetic parameter values following administration of single 7 and 14 mg/kg oral doses of cefdinir to pediatric subjects (age 6 months to 12 years) are presented in the following table: Mean (+/- SD) Plasma Cefdinir Pharmacokinetic Parameter Values Following Administration of Suspension to Pediatric Subjects Dose C max t max AUC 7 mg/kg 2. 31 14 mg/kg 3. 4 Multiple Dosing Cefdinir does not accumulate in plasma following once- or twice-daily administration to subjects with normal renal function. Distribution The mean volume of distribution (Vd area area Skin Blister In adult subjects, median (range) maximal blister fluid cefdinir concentrations of 0. 9) mcg/mL were observed 4 to 5 hours following administration of 300 and 600 mg doses, respectively. Mean (+/- SD) blister C max (0-infinity) Tonsil Tissue In adult patients undergoing elective tonsillectomy, respective median tonsil tissue cefdinir concentrations 4 hours after administration of single 300 and 600 mg doses were 0. Mean tonsil tissue concentrations were 24% (+/- 8) of corresponding plasma concentrations. Sinus Tissue In adult patients undergoing elective maxillary and ethmoid sinus surgery, respective median sinus tissue cefdinir concentrations 4 hours after administration of single 300 and 600 mg doses were < 0. 12 to 2) mcg/g. Mean sinus tissue concentrations were 16% (+/- 20) of corresponding plasma concentrations. In adult patients undergoing diagnostic bronchoscopy, respective median bronchial mucosa cefdinir concentrations 4 hours after administration of single 300 and 600 mg doses were 0. 92) mcg/mL, and were 31% (+/- 18) of corresponding plasma concentrations. Respective median epithelial lining fluid concentrations were 0. 59) mcg/mL, and were 35% (+/- 83) of corresponding plasma concentrations. In 14 pediatric patients with acute bacterial otitis media, respective median middle ear fluid cefdinir concentrations 3 hours after administration of single 7 and 14 mg/kg doses were 0. Mean middle ear fluid concentrations were 15% (+/- 15) of corresponding plasma concentrations. Data on cefdinir penetration into human cerebrospinal fluid are not available. 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 ½ 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 Special Populations Patients with Renal Insufficiency Cefdinir pharmacokinetics were investigated in 21 adult subjects with varying degrees of renal function. Decreases in cefdinir elimination rate, apparent oral clearance (CL/F), and renal clearance were approximately proportional to the reduction in creatinine clearance (CL cr cr max ½ cr max ½ DOSAGE AND ADMINISTRATION Hemodialysis Cefdinir pharmacokinetics were studied in 8 adult subjects undergoing hemodialysis. Dialysis (4 hours duration) removed 63% of cefdinir from the body and reduced apparent elimination t ½ DOSAGE AND ADMINISTRATION Hepatic Disease Because cefdinir is predominantly renally eliminated and not appreciably metabolized, studies in patients with hepatic impairment were not conducted. It is not expected that dosage adjustment will be required in this population. Geriatric Patients The effect of age on cefdinir pharmacokinetics after a single 300 mg dose was evaluated in 32 subjects 19 to 91 years of age. Systemic exposure to cefdinir was substantially increased in older subjects (N = 16), C max ½ Patients with Renal Insufficiency Gender and Race The results of a meta-analysis of clinical pharmacokinetics (N = 217) indicated no significant impact of either gender or race on cefdinir pharmacokinetics. 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. 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 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 Testing 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
Absorption Oral Bioavailability Maximal plasma cefdinir concentrations occur 2 to 4 hours postdose following capsule or suspension administration. Plasma cefdinir concentrations increase with dose, but the increases are less than dose-proportional from 300 mg (7 mg/kg) to 600 mg (14 mg/kg). Following administration of suspension to healthy adults, cefdinir bioavailability is 120% relative to capsules. Estimated bioavailability of cefdinir suspension is 25%. Cefdinir oral suspension of 250 mg/5 mL strength was shown to be bioequivalent to the 125 mg/5 mL strength in healthy adults under fasting conditions. Effect of Food In adults given the 250 mg/5 mL oral suspension with a high-fat meal, the C max Cefdinir Suspension Cefdinir plasma concentrations and pharmacokinetic parameter values following administration of single 7 and 14 mg/kg oral doses of cefdinir to pediatric subjects (age 6 months to 12 years) are presented in the following table: Mean (+/- SD) Plasma Cefdinir Pharmacokinetic Parameter Values Following Administration of Suspension to Pediatric Subjects Dose C max t max AUC 7 mg/kg 2. 31 14 mg/kg 3. 4 Multiple Dosing Cefdinir does not accumulate in plasma following once- or twice-daily administration to subjects with normal renal function. Distribution The mean volume of distribution (Vd area area Skin Blister In adult subjects, median (range) maximal blister fluid cefdinir concentrations of 0. 9) mcg/mL were observed 4 to 5 hours following administration of 300 and 600 mg doses, respectively. Mean (+/- SD) blister C max (0-infinity) Tonsil Tissue In adult patients undergoing elective tonsillectomy, respective median tonsil tissue cefdinir concentrations 4 hours after administration of single 300 and 600 mg doses were 0. Mean tonsil tissue concentrations were 24% (+/- 8) of corresponding plasma concentrations. Sinus Tissue In adult patients undergoing elective maxillary and ethmoid sinus surgery, respective median sinus tissue cefdinir concentrations 4 hours after administration of single 300 and 600 mg doses were < 0. 12 to 2) mcg/g. Mean sinus tissue concentrations were 16% (+/- 20) of corresponding plasma concentrations. In adult patients undergoing diagnostic bronchoscopy, respective median bronchial mucosa cefdinir concentrations 4 hours after administration of single 300 and 600 mg doses were 0. 92) mcg/mL, and were 31% (+/- 18) of corresponding plasma concentrations. Respective median epithelial lining fluid concentrations were 0. 59) mcg/mL, and were 35% (+/- 83) of corresponding plasma concentrations. In 14 pediatric patients with acute bacterial otitis media, respective median middle ear fluid cefdinir concentrations 3 hours after administration of single 7 and 14 mg/kg doses were 0. Mean middle ear fluid concentrations were 15% (+/- 15) of corresponding plasma concentrations. Data on cefdinir penetration into human cerebrospinal fluid are not available. 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 ½ 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 Special Populations Patients with Renal Insufficiency Cefdinir pharmacokinetics were investigated in 21 adult subjects with varying degrees of renal function. Decreases in cefdinir elimination rate, apparent oral clearance (CL/F), and renal clearance were approximately proportional to the reduction in creatinine clearance (CL cr cr max ½ cr max ½ DOSAGE AND ADMINISTRATION Hemodialysis Cefdinir pharmacokinetics were studied in 8 adult subjects undergoing hemodialysis. Dialysis (4 hours duration) removed 63% of cefdinir from the body and reduced apparent elimination t ½ DOSAGE AND ADMINISTRATION Hepatic Disease Because cefdinir is predominantly renally eliminated and not appreciably metabolized, studies in patients with hepatic impairment were not conducted. It is not expected that dosage adjustment will be required in this population. Geriatric Patients The effect of age on cefdinir pharmacokinetics after a single 300 mg dose was evaluated in 32 subjects 19 to 91 years of age. Systemic exposure to cefdinir was substantially increased in older subjects (N = 16), C max ½ Patients with Renal Insufficiency Gender and Race The results of a meta-analysis of clinical pharmacokinetics (N = 217) indicated no significant impact of either gender or race on cefdinir pharmacokinetics.
Lung Tissue
In adult patients undergoing diagnostic bronchoscopy, respective median bronchial mucosa cefdinir concentrations 4 hours after administration of single 300 and 600 mg doses were 0.78 (< 0.06 to 1.33) and 1.14 (< 0.06 to 1.92) mcg/mL, and were 31% (+/- 18) of corresponding plasma concentrations. Respective median epithelial lining fluid concentrations were 0.29 (< 0.3 to 4.73) and 0.49 (< 0.3 to 0.59) mcg/mL, and were 35% (+/- 83) of corresponding plasma concentrations.
Middle Ear Fluid
In 14 pediatric patients with acute bacterial otitis media, respective median middle ear fluid cefdinir concentrations 3 hours after administration of single 7 and 14 mg/kg doses were 0.21 (< 0.09 to 0.94) and 0.72 (0.14 to 1.42) mcg/mL. Mean middle ear fluid concentrations were 15% (+/- 15) of corresponding plasma concentrations.
CSF
Data on cefdinir penetration into human cerebrospinal fluid are not available. 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 ½ 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 Special Populations Patients with Renal Insufficiency Cefdinir pharmacokinetics were investigated in 21 adult subjects with varying degrees of renal function. Decreases in cefdinir elimination rate, apparent oral clearance (CL/F), and renal clearance were approximately proportional to the reduction in creatinine clearance (CL cr cr max ½ cr max ½ DOSAGE AND ADMINISTRATION Hemodialysis Cefdinir pharmacokinetics were studied in 8 adult subjects undergoing hemodialysis. Dialysis (4 hours duration) removed 63% of cefdinir from the body and reduced apparent elimination t ½ DOSAGE AND ADMINISTRATION Hepatic Disease Because cefdinir is predominantly renally eliminated and not appreciably metabolized, studies in patients with hepatic impairment were not conducted. It is not expected that dosage adjustment will be required in this population. Geriatric Patients The effect of age on cefdinir pharmacokinetics after a single 300 mg dose was evaluated in 32 subjects 19 to 91 years of age. Systemic exposure to cefdinir was substantially increased in older subjects (N = 16), C max ½ Patients with Renal Insufficiency Gender and Race The results of a meta-analysis of clinical pharmacokinetics (N = 217) indicated no significant impact of either gender or race on cefdinir pharmacokinetics.
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. 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 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 Testing 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.

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. 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 Acute Bacterial Otitis Media 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
Community-Acquired Bacterial Pneumonia
In a controlled, double-blind study in adults and adolescents conducted in the U.S., cefdinir BID was compared with cefaclor 500 mg TID. Using strict evaluability and microbiologic/clinical response criteria 6 to 14 days post therapy, the following clinical cure rates, presumptive microbiologic eradication rates, and statistical outcomes were obtained: U.S. Community-Acquired Pneumonia Study Cefdinir vs Cefaclor Cefdinir BID Cefaclor TID Outcome Clinical Cure Rates 150/187 (80%) 147/186 (79%) Cefdinir equivalent to control Eradication Rates 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%) European Community-Acquired Pneumonia Study Cefdinir vs Amoxicillin/Clavulanate Cefdinir BID Amoxicillin/ Clavulanate TID Outcome Clinical Cure Rates 83/104 (80%) 86/97 (89%) Cefdinir not equivalent to control Eradication Rates 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 post therapy, 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 post therapy, 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

DOSAGE AND ADMINISTRATION
(See INDICATIONS AND USAGE 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 USP should be administered twice daily in this infection. Cefdinir for oral suspension USP 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 5 to 10 days or 14 mg/kg q24h 10 days Acute Maxillary Sinusitis 7 mg/kg q12h 10 days or 14 mg/kg q24h 10 days Pharyngitis/Tonsillitis 7 mg/kg q12h 5 to 10 days or 14 mg/kg q24h 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. 5mL q24h 36 kg/80 lbs 10 mL q12h or 20 mL q24h 5 mL q12h or 10 mL q24h >= 43 kg 1 12 mL q12h or 24 mL q24h 6 mL q12h or 12 mL q24h 1. 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 Males: CL cr (weight) (140 − age) (72) (serum creatinine) Females: CL cr 0. 85 × 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 body length or height 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. Directions for Mixing Cefdinir for Oral Suspension, USP Final Concentration Final Volume (mL) Amount of Water Directions 125 mg/5 mL 60 50 mL Tap bottle to loosen powder, then add water in 2 portions. Shake well after each aliquot. 100 80 mL 250 mg/5 mL 60 49 mL Tap bottle to loosen powder, then add water in 2 portions.
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 USP should be administered twice daily in this infection. Cefdinir for oral suspension USP 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 5 to 10 days or 14 mg/kg q24h 10 days Acute Maxillary Sinusitis 7 mg/kg q12h 10 days or 14 mg/kg q24h 10 days Pharyngitis/Tonsillitis 7 mg/kg q12h 5 to 10 days or 14 mg/kg q24h 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 7.5mL q24h 36 kg/80 lbs 10 mL q12h or 20 mL q24h 5 mL q12h or 10 mL q24h >= 43 kg 1 12 mL q12h or 24 mL q24h 6 mL q12h or 12 mL q24h 1.

Pharyngitis/Tonsillitis
Caused by Streptococcus pyogenes CLINICAL STUDIES NOTE S. pyogenes S. pyogenes
ADVERSE EVENTS
In clinical trials, 2289 pediatric patients (1783 U. and 506 non-U. ) 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. , 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. TRIALS IN PEDIATRIC PATIENTS (N = 1783) 1 Incidence >= 1% Diarrhea 8% Rash 3% Vomiting 1% Incidence 0. 1% Cutaneous moniliasis 0. 9% Abdominal pain 0. 8% Leukopenia 2 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 2 0. 2% Maculopapular rash 0. 2% Nausea 0. 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. : LABORATORY VALUE CHANGES OF POSSIBLE CLINICAL SIGNIFICANCE OBSERVED WITH CEFDINIR SUSPENSION U. TRIALS IN PEDIATRIC PATIENTS (N = 1783) Incidence >= 1% up arrowLymphocytes, down arrowLymphocytes 2%, 0. 8% up arrowAlkaline phosphatase 1% down arrowBicarbonate 1 1% up arrowEosinophils 1% up arrowLactate dehydrogenase 1% up arrowPlatelets 1% up arrowPMNs, down arrowPMNs 1%, 1% up arrowUrine protein 1% Incidence 0. 1% up arrowPhosphorus, down arrowPhosphorus 0. 4% up arrowUrine pH 0. 8% down arrowWhite blood cells, up arrowWhite blood cells 0. 3% down arrowCalcium 1 0. 5% down arrowHemoglobin 0. 5% up arrowUrine leukocytes 0. 5% up arrowMonocytes 0. 4% up arrowAST 0. 3% up arrowPotassium 1 0. 3% up arrowUrine specific gravity, down arrowUrine specific gravity 0. 1% down arrowHematocrit 1 0. 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 To report SUSPECTED ADVERSE REACTIONS, contact Teva at 1-888-838-2872 or FDA at 1-800-FDA-1088 or www. gov/medwatch.
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 To report SUSPECTED ADVERSE REACTIONS, contact Teva at 1-888-838-2872 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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

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
Acute Bacterial Otitis Media 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.
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 Males: CL cr (weight) (140 − age) (72) (serum creatinine) Females: CL cr 0.85 × 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 body length or height 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. Directions for Mixing Cefdinir for Oral Suspension, USP Final Concentration Final Volume (mL) Amount of Water Directions 125 mg/5 mL 60 50 mL Tap bottle to loosen powder, then add water in 2 portions. Shake well after each aliquot. 100 80 mL 250 mg/5 mL 60 49 mL Tap bottle to loosen powder, then add water in 2 portions. Shake well after each aliquot. 100 80 mL

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 ½ 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. 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.
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 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 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.
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

Store the unsuspended powder at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Once reconstituted, the oral suspension can be stored at controlled room temperature for 10 days.

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 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
Teratogenic Effects
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.
Labor and Delivery
Cefdinir has not been studied for use during labor and delivery.
Clinical Trials
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) 1 Incidence >= 1% Diarrhea 8% Rash 3% Vomiting 1% Incidence 0.1% Cutaneous moniliasis 0.9% Abdominal pain 0.8% Leukopenia 2 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 2 0.2% Maculopapular rash 0.2% Nausea 0.2% 1. 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) Incidence >= 1% up arrowLymphocytes, down arrowLymphocytes 2%, 0.8% up arrowAlkaline phosphatase 1% down arrowBicarbonate 1 1% up arrowEosinophils 1% up arrowLactate dehydrogenase 1% up arrowPlatelets 1% up arrowPMNs, down arrowPMNs 1%, 1% up arrowUrine protein 1% Incidence 0.1% up arrowPhosphorus, down arrowPhosphorus 0.9%, 0.4% up arrowUrine pH 0.8% down arrowWhite blood cells, up arrowWhite blood cells 0.7%, 0.3% down arrowCalcium 1 0.5% down arrowHemoglobin 0.5% up arrowUrine leukocytes 0.5% up arrowMonocytes 0.4% up arrowAST 0.3% up arrowPotassium 1 0.3% up arrowUrine specific gravity, down arrowUrine specific gravity 0.3%, 0.1% down arrowHematocrit 1 0.2% 1.
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 U. , cefdinir BID was compared with cefaclor 500 mg TID. Using strict evaluability and microbiologic/clinical response criteria 6 to 14 days post therapy, the following clinical cure rates, presumptive microbiologic eradication rates, and statistical outcomes were obtained: U. Community-Acquired Pneumonia Study Cefdinir vs Cefaclor Cefdinir BID Cefaclor TID Outcome Clinical Cure Rates 150/187 (80%) 147/186 (79%) Cefdinir equivalent to control Eradication Rates 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%) European Community-Acquired Pneumonia Study Cefdinir vs Amoxicillin/Clavulanate Cefdinir BID Amoxicillin/ Clavulanate TID Outcome Clinical Cure Rates 83/104 (80%) 86/97 (89%) Cefdinir not equivalent to control Eradication Rates 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 post therapy, 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 post therapy, 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. Brands listed are the trademarks of their respective owners. Manufactured For: Teva Pharmaceuticals Rev. J 2/2023

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