lemented with 10 mg of elemental iron reduced extent of absorption by 80% and 31%, respectively. if iron supplements are required during cefdinir therapy, cefdinir should be taken at least 2 hours before or after the supplement. the effect of foods highly fortified with elemental iron (primarily iron-fortified breakfast cereals) on cefdinir absorption has not been studied. there have been reports of reddish stools in patients receiving cefdinir. in many cases, patients were also receiving iron-containing products. the reddish color is due to the formation of a nonabsorbable complex between cefdinir or its breakdown products and iron in the gastrointestinal tract.

sceptible 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 .

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.

adult patients with creatinine clearance <30 ml/min, the dose of cefdinir should be 300 mg given once daily. creatinine clearance is difficult to measure in outpatients. however, the following formula may be used to estimate creatinine clearance (cl cr ) in adult patients. for estimates to be valid, serum creatinine levels should reflect steady-state levels of renal function. (weight) (140 – age) males: cl cr = —————————— (72) (serum creatinine) females: cl cr = 0.85 x above value where creatinine clearance is in ml/min, age is in years, weight is in kilograms, and serum creatinine is in mg/dl 1 . the following formula may be used to estimate creatinine clearance in pediatric patients: body length or height cl cr = k x —————————— 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.

lemented with 10 mg of elemental iron reduced extent of absorption by 80% and 31%, respectively. if iron supplements are required during cefdinir therapy, cefdinir should be taken at least 2 hours before or after the supplement. the effect of foods highly fortified with elemental iron (primarily iron-fortified breakfast cereals) on cefdinir absorption has not been studied. there have been reports of reddish stools in patients receiving cefdinir. in many cases, patients were also receiving iron-containing products. the reddish color is due to the formation of a nonabsorbable complex between cefdinir or its breakdown products and iron in the gastrointestinal tract.

lasma concentrations and pharmacokinetic parameter values following administration of single 300 and 600 mg oral doses of cefdinir to adult subjects are presented in the following table: 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: 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 ) of cefdinir in adult subjects is 0.35 l/kg (±0.29); in pediatric subjects (age 6 months-12 years), cefdinir vd area is 0.67 l/kg (±0.38). cefdinir is 60% to 70% bound to plasma proteins in both adult and pediatric subjects; binding is independent of concentration. skin blister: in adult subjects, median (range) maximal blister fluid cefdinir concentrations of 0.65 (0.33-1.1) and 1.1 (0.49-1.9) mcg/ml were observed 4 to 5 hours following administration of 300 and 600 mg doses, respectively. mean (±sd) blister c max and auc (0-∞) values were 48% (±13) and 91% (±18) of corresponding plasma values. 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 0.25 (0.22-0.46) and 0.36 (0.22-0.80) mcg/g. 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 (<0.12-0.46) and 0.21 (<0.12-2.0) mcg/g. mean sinus tissue concentrations were 16% (±20) of corresponding plasma concentrations. 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 (<0.06-1.33) and 1.14 (<0.06-1.92) mcg/ml, and were 31% (±18) of corresponding plasma concentrations. respective median epithelial lining fluid concentrations were 0.29 (<0.3-4.73) and 0.49 (<0.3-0.59) 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 (<0.09-0.94) and 0.72 (0.14-1.42) 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 1/2 ) of 1.7 (±0.6) hours. in healthy subjects with normal renal function, renal clearance is 2.0 (±1.0) ml/min/kg, and apparent oral clearance is 11.6 (±6.0) and 15.5 (±5.4) ml/min/kg following doses of 300 and 600 mg, respectively. mean percent of dose recovered unchanged in the urine following 300 and 600 mg doses is 18.4% (±6.4) and 11.6% (±4.6), respectively. cefdinir clearance is reduced in patients with renal dysfunction (see 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 ). 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 ). as a result, plasma cefdinir concentrations were higher and persisted longer in subjects with renal impairment than in those without renal impairment. in subjects with cl cr between 30 and 60 ml/min, c max and t 1/2 increased by approximately 2-fold and auc by approximately 3-fold. in subjects with cl cr <30 ml/min, c max increased by approximately 2-fold, t 1/2 by approximately 5-fold, and auc by approximately 6-fold. dosage adjustment is recommended in patients with markedly compromised renal function (creatinine clearance <30 ml/min; see 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 1/2 from 16 (±3.5) to 3.2 (±1.2) hours. dosage adjustment is recommended in this patient population (see 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 by 44% and auc by 86%. this increase was due to a reduction in cefdinir clearance. the apparent volume of distribution was also reduced, thus no appreciable alterations in apparent elimination t 1/2 were observed (elderly: 2.2 ± 0.6 hours vs young: 1.8 ± 0.4 hours). since cefdinir clearance has been shown to be primarily related to changes in renal function rather than age, elderly patients do not require dosage adjustment unless they have markedly compromised renal function (creatinine clearance <30 ml/min, see patients with renal insufficiency, above). 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, β-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 β-lactamases, alteration of penicillin-binding proteins (pbps) and decreased permeability. cefdinir is inactive against most strains of enterobacter spp., pseudomonas spp., enterococcus spp., penicillin-resistant streptococci, and methicillin-resistant staphylococci. β-lactamase negative, ampicillin-resistant (blnar) h. influenzae strains are typically non-susceptible to cefdinir. antimicrobial activity: cefdinir has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections as described in indications and usage . gram-positive bacteria: staphylococcus aureus (methicillin-susceptible strains only) streptococcus pneumoniae (penicillin-susceptible strains only) streptococcus pyogenes gram-negative bacteria: haemophilus influenzae haemophilus parainfluenzae moraxella catarrhalis the following in vitro data are available, but their clinical significance is unknown. cefdinir exhibits in vitro minimum inhibitory concentrations (mics) of 1 mcg/ml or less against (≥ 90%) strains of the following microorganisms; however, the safety and effectiveness of cefdinir in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled clinical trials. gram-positive bacteria: staphylococcus epidermidis (methicillin-susceptible strains only) 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.

nd pharmacokinetic parameter values following administration of single 300 and 600 mg oral doses of cefdinir to adult subjects are presented in the following table: 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: 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 ) of cefdinir in adult subjects is 0.35 l/kg (±0.29); in pediatric subjects (age 6 months-12 years), cefdinir vd area is 0.67 l/kg (±0.38). cefdinir is 60% to 70% bound to plasma proteins in both adult and pediatric subjects; binding is independent of concentration. skin blister: in adult subjects, median (range) maximal blister fluid cefdinir concentrations of 0.65 (0.33-1.1) and 1.1 (0.49-1.9) mcg/ml were observed 4 to 5 hours following administration of 300 and 600 mg doses, respectively. mean (±sd) blister c max and auc (0-∞) values were 48% (±13) and 91% (±18) of corresponding plasma values. 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 0.25 (0.22-0.46) and 0.36 (0.22-0.80) mcg/g. 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 (<0.12-0.46) and 0.21 (<0.12-2.0) mcg/g. mean sinus tissue concentrations were 16% (±20) of corresponding plasma concentrations. 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 (<0.06-1.33) and 1.14 (<0.06-1.92) mcg/ml, and were 31% (±18) of corresponding plasma concentrations. respective median epithelial lining fluid concentrations were 0.29 (<0.3-4.73) and 0.49 (<0.3-0.59) 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 (<0.09-0.94) and 0.72 (0.14-1.42) 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 1/2 ) of 1.7 (±0.6) hours. in healthy subjects with normal renal function, renal clearance is 2.0 (±1.0) ml/min/kg, and apparent oral clearance is 11.6 (±6.0) and 15.5 (±5.4) ml/min/kg following doses of 300 and 600 mg, respectively. mean percent of dose recovered unchanged in the urine following 300 and 600 mg doses is 18.4% (±6.4) and 11.6% (±4.6), respectively. cefdinir clearance is reduced in patients with renal dysfunction (see 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 ). 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 ). as a result, plasma cefdinir concentrations were higher and persisted longer in subjects with renal impairment than in those without renal impairment. in subjects with cl cr between 30 and 60 ml/min, c max and t 1/2 increased by approximately 2-fold and auc by approximately 3-fold. in subjects with cl cr <30 ml/min, c max increased by approximately 2-fold, t 1/2 by approximately 5-fold, and auc by approximately 6-fold. dosage adjustment is recommended in patients with markedly compromised renal function (creatinine clearance <30 ml/min; see 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 1/2 from 16 (±3.5) to 3.2 (±1.2) hours. dosage adjustment is recommended in this patient population (see 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 by 44% and auc by 86%. this increase was due to a reduction in cefdinir clearance. the apparent volume of distribution was also reduced, thus no appreciable alterations in apparent elimination t 1/2 were observed (elderly: 2.2 ± 0.6 hours vs young: 1.8 ± 0.4 hours). since cefdinir clearance has been shown to be primarily related to changes in renal function rather than age, elderly patients do not require dosage adjustment unless they have markedly compromised renal function (creatinine clearance <30 ml/min, see patients with renal insufficiency, above). 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.

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

nterfere 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. 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.