VA Class:AM117

AHFS Class:

• Third Generation Cephalosporins 8:12.06.12

Generic Name(s):

• Cefdinir

Chemical Name:

• [6 R -[6α,7β( Z )]]-7-[[(2-amino-4-thiazolyl)(hydroxyimino)acetyl]amino]-3-ethenyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

Molecular Formula:

• C₁₄H₁₃N₅O₅S₂

Associated Monographs

• Cephalosporins General Statement

Cefdinir is a semisynthetic, third generation cephalosporin antibiotic.1,2,3,4,5,6,40

Cefdinir is used orally for the treatment of mild to moderate upper and lower respiratory tract infections (i.e., acute maxillary sinusitis, acute exacerbations of chronic bronchitis, community-acquired pneumonia) caused by susceptible bacteria.1,4,40 The drug also is used orally for the treatment of acute bacterial otitis media, streptococcal pharyngitis and tonsillitis, and mild to moderate, uncomplicated skin and skin structure infections caused by susceptible bacteria.1,5,6,7,12,40

Acute Otitis Media

Oral cefdinir is used in children 6 months of age or older for the treatment of acute otitis media (AOM) caused by Streptococcus pneumoniae (penicillin-susceptible strains only), Haemophilus influenzae (including β-lactamase-producing strains), or Moraxella catarrhalis (including β-lactamase-producing strains).1,12,37,40

When anti-infective therapy is indicated for the treatment of AOM, the American Academy of Pediatrics (AAP) recommends high-dose amoxicillin or amoxicillin and clavulanate potassium as the drugs of first choice for initial treatment.37 These experts recommend certain cephalosporins (cefdinir, cefuroxime, cefpodoxime, ceftriaxone) as alternatives for initial treatment in penicillin-allergic patients who do not have a history of severe and/or recent penicillin-allergic reactions.37

In a controlled study in children 6 months to 12 years of age with acute suppurative otitis media, a 10-day regimen of once-daily cefdinir (14 mg/kg as a single daily dose), twice-daily cefdinir (7 mg/kg twice daily), or amoxicillin and clavulanate potassium (13.3 mg/kg of amoxicillin 3 times daily) produced similar clinical and bacteriologic responses.12

For additional information regarding treatment of AOM, including information on diagnosis and management strategies, anti-infectives for initial treatment, duration of initial treatment, and anti-infectives after initial treatment failure, see Acute Otitis Media under Uses: Otitis Media, in the Cephalosporins General Statement 8:12.06.

Pharyngitis and Tonsillitis

Oral cefdinir is used for the treatment of pharyngitis and tonsillitis caused by susceptible S. pyogenes (group A β-hemolytic streptococci) in adults and children 6 months of age and older.1,6,25,40 Although cefdinir may effectively eradicate S. pyogenes from the nasopharynx, efficacy of the drug in the subsequent prevention of rheumatic fever has not been fully evaluated to date.1,16,40

Selection of an anti-infective for the treatment of S. pyogenes pharyngitis and tonsillitis should be based on the drug's spectrum of activity, bacteriologic and clinical efficacy, potential adverse effects, ease of administration, patient compliance, and cost.16,17,18,25 No regimen has been found to date that effectively eradicates group A β-hemolytic streptococci in 100% of patients.17

Because the drugs have a narrow spectrum of activity, are inexpensive, and generally are effective with a low frequency of adverse effects, the AAP,10 Infectious Diseases Society of America (IDSA),16 American Heart Association (AHA),17 and others11 recommend a penicillin regimen (i.e., 10 days of oral penicillin V or oral amoxicillin or single dose of IM penicillin G benzathine) as the treatment of choice for S. pyogenes pharyngitis and tonsillitis and prevention of initial attacks (primary prevention) of rheumatic fever. Other anti-infectives (e.g., oral cephalosporins, oral macrolides, oral clindamycin) are recommended as alternatives in penicillin-allergic individuals.10,11,16,17

If an oral cephalosporin is used for the treatment of S. pyogenes pharyngitis and tonsillitis, a 10-day regimen of a first generation cephalosporin (cefadroxil, cephalexin) is preferred instead of other cephalosporins with broader spectrums of activity (e.g., cefaclor, cefdinir, cefixime, cefpodoxime, cefuroxime).10,16,17

Although there is some evidence that a shorter duration of therapy with certain oral cephalosporins (e.g., a 5-day regimen of cefadroxil, cefdinir, cefixime, or cefpodoxime proxetil or a 4- or 5-day regimen of cefuroxime axetil) achieves bacteriologic and clinical cure rates equal to or greater than those achieved with the traditional 10-day oral penicillin V regimen,1,6,17,18,25,31,33,34,35,40 the IDSA and AHA state that use of cephalosporin regimens administered for 5 days or less for the treatment of S. pyogenes pharyngitis and tonsillitis cannot be recommended at this time.16,17

In double-blind, controlled studies in adults, adolescents, and children with streptococcal pharyngitis, the clinical and microbiologic response to a 10-day regimen of oral cefdinir was superior to that of a 10-day regimen of oral penicillin V1,40 and the clinical and microbiologic response to a 5-day regimen of oral cefdinir was similar to that of the 10-day regimen of oral penicillin V.1,6,25,40 In controlled comparative studies in adults, adolescents, and children, the bacterial eradication rate 4-10 days after completion of therapy was 91-94% in those who received cefdinir for 10 days, 89-90% in those who received cefdinir for 5 days, and 70-83% in those who received penicillin V for 10 days.1,6,25,40 The clinical cure rate 4-10 days after completion of therapy was about 95-97, 89-91, and 85-90%, respectively.1,6,25,40 When cefdinir is used in the treatment of pharyngitis and tonsillitis, a once-daily dosing regimen reportedly is as effective as a twice-daily dosing regimen.1,40

Respiratory Tract Infections

Acute Exacerbations of Chronic Bronchitis

Cefdinir is used in adults and adolescents 13 years of age or older for the treatment of acute exacerbations of chronic bronchitis caused by susceptible S. pneumoniae (penicillin-susceptible strains only) or β-lactamase- and non-β-lactamase-producing strains of H. influenzae , H. parainfluenzae , or M. catarrhalis .1,15,40 Although co-trimoxazole generally has been considered the drug of choice for the treatment of upper respiratory tract infections and bronchitis caused by susceptible H. influenzae or M. catarrhalis , second or third generation cephalosporins are considered by many clinicians to be alternative for the treatment of these infections.11

Acute Sinusitis

Cefdinir is used in adults and adolescents 13 years of age or older for the treatment of acute maxillary sinusitis caused by susceptible S. pneumoniae (penicillin-susceptible strains only), H. influenzae (including β-lactamase-producing strains), or M. catarrhalis (including β-lactamase-producing strains).1,7,40 While efficacy of cefdinir for the treatment of acute maxillary sinusitis in children 6 months through 12 years of age has not been fully established, use of the drug for the treatment of this infection in pediatric patients is supported by evidence from studies in adults and adolescents, the similar pathophysiology of acute sinusitis in adults and children, and data regarding the pharmacokinetics of cefdinir in children.1,40

When anti-infective therapy is indicated for the treatment of acute bacterial sinusitis, the IDSA recommends amoxicillin and clavulanate potassium and the AAP recommends either amoxicillin or amoxicillin and clavulanate potassium as the drug of choice for initial empiric treatment.43,44 Because of variable activity against S. pneumoniae and H. influenzae , the IDSA no longer recommends second or third generation oral cephalosporins for empiric monotherapy of sinusitis in adults or children.43 If an oral cephalosporin is used as an alternative for empiric treatment of acute bacterial sinusitis in children (e.g., in penicillin-allergic individuals), the IDSA and AAP recommend a combination regimen that includes a third generation cephalosporin (cefixime or cefpodoxime) and clindamycin (or linezolid).43,44

In controlled studies in patients 13 years of age or older with acute maxillary sinusitis, comparable clinical and bacteriologic responses were obtained with once-daily cefdinir (600 mg once daily), twice-daily cefdinir (300 mg twice daily), or amoxicillin and clavulanate potassium (500 mg of amoxicillin 3 times daily).7 When patients were subdivided based on the causative organism, the bacterial eradication rate in those with S. pneumoniae or M. catarrhalis infection was 89-100% with either drug; however, in those with H. influenzae infection, the eradication rate was 78% in those who received cefdinir and 57% in those who received amoxicillin and clavulanate potassium.7

Community-acquired Pneumonia

Cefdinir is used in adults and adolescents 13 years of age or older for the treatment of mild to moderate community-acquired pneumonia (CAP) caused by susceptible S. pneumoniae (penicillin-susceptible strains only) or β-lactamase- and non-β-lactamase-producing strains of H. influenzae , H. parainfluenzae , or M. catarrhalis .1,4,40

If an oral cephalosporin is used as an alternative to penicillin G or amoxicillin for treatment of CAP caused by penicillin-susceptible S. pneumoniae , the American Thoracic Society (ATS) and IDSA recommend cefdinir, cefditoren, cefpodoxime, cefprozil, or cefuroxime.39

Limited data in patients with CAP caused by organisms susceptible to the drugs indicate that the clinical response to cefdinir is similar to that reported with cefaclor,1,4,40 but may be inferior to that reported with amoxicillin and clavulanate potassium.1,40 In a double-blind, prospective, randomized study in adults and adolescents 13 years of age or older with CAP, a satisfactory clinical response (cure plus improvement) was achieved 6-14 days after completion of therapy in 89% of those who received cefdinir (300 mg twice daily for 10 days) and in 86% of those who received cefaclor (500 mg 3 times daily for 10 days).4 In another study conducted principally in Europe, the clinical cure rate 6-14 days after completion of therapy was 80% in those who received cefdinir (300 mg twice daily for 10 days) and 89% in those who received amoxicillin and clavulanate potassium (500 mg of amoxicillin 3 times daily for 10 days).1,40 In these studies, the bacteriologic eradication rate 6-14 days following completion of therapy was 89-92% in those who received cefdinir, 93% in those who received cefaclor, and 93% in those who received amoxicillin and clavulanate potassium.1,4,40 When patients were subdivided based on the causative organism, the presumptive bacteriologic eradication 6-14 days after completion of cefdinir therapy was 95-100% in those with S. pneumoniae infection, 74-85% in those with H. influenzae infection, 91-100% in those with H. parainfluenzae infection, and 100% in those with M. catarrhalis infection.1,4,40

For additional information on treatment of CAP, see Community-acquired Pneumonia under Uses: Respiratory Tract Infections, in the Cephalosporins General Statement 8:12.06.

Skin and Skin Structure Infections

Oral cefdinir is used in adults, adolescents, and children 6 months of age or older for the treatment of mild to moderate, uncomplicated skin and skin structure infections caused by S. aureus (including β-lactamase-producing strains) or S. pyogenes .1,5,24,40

In a comparative study in children 6 months to 12 years of age with mild to moderate bacterial skin and skin structure infections (e.g., impetigo, infected dermatitis, wound infection, cellulitis, paronychia, abscess), oral cefdinir (7 mg/kg twice daily for 10 days) was as effective as oral cephalexin (10 mg/kg 4 times daily for 10 days).5 In a comparative study in adults and adolescents 13 years of age or older, oral cefdinir (300 mg twice daily for 10 days) was as effective as oral cephalexin (500 mg 4 times daily for 10 days) for the treatment of bacterial skin and skin structure infections (e.g., abscess, wound infection, paronychia, infected dermatitis, impetigo, cellulitis).24

Reconstitution and Administration

Cefdinir is administered orally.1,4,5,6,7,12,15,24,40

Cefdinir may be given without regard to meals.1,40 (See Pharmacokinetics: Absorption.)

Oral iron preparations, including multivitamin and mineral preparations containing iron, may interfere with the absorption of oral cefdinir resulting in decreased plasma concentrations of the cephalosporin.1,8,40 If concomitant use is necessary, cefdinir doses should be given at least 2 hours before or after the oral iron preparation.1,8,40 Cefdinir oral suspension can be administered concomitantly with iron-fortified infant formula since concomitant administration with such formula (2.2 mg elemental iron/180 mL) does not alter absorption of the cephalosporin.1,40 The effect of iron-fortified food (e.g., iron-fortified breakfast cereal) on oral absorption of cefdinir has not been studied.1,40

While concomitant administration of antacids containing aluminum or magnesium interferes with the absorption of oral cefdinir, administration of aluminum- or magnesium-containing antacids 2 hours before or after a dose of cefdinir is not associated with clinically important changes in the pharmacokinetics of the cephalosporin.1,40 Therefore, doses of cefdinir should be given at least 2 hours before or after a dose of aluminum- or magnesium-containing antacid.1,40

Cefdinir may be administered as a single daily dose or in divided doses every 12 hours.1,4,5,6,7,12,15,24,40 Once- and twice-daily regimens are similarly effective for the treatment of acute bacterial exacerbations of chronic bronchitis, acute maxillary sinusitis, acute bacterial otitis media, and pharyngitis and tonsillitis caused by susceptible organisms and either regimen may be used in these infections.1,7,15,40 However, pending further study regarding the efficacy of once-daily cefdinir regimens in the treatment of community-acquired pneumonia and uncomplicated skin and skin structure infections, the manufacturer states that a twice-daily regimen should be used for these infections.1,24,40

Reconstitution

Cefdinir powder for oral suspension should be reconstituted at the time of dispensing by adding the amount of water specified on the container to provide a suspension containing 125 or 250 mg of cefdinir per 5 mL.40 The water should be added in 2 equal portions and the bottle inverted and shaken after each addition.40

The oral suspension should be shaken well prior to administration of each dose.40

Dosage

Adult Dosage

Pharyngitis and Tonsillitis

For the treatment of pharyngitis and tonsillitis, the usual dosage of cefdinir for adults and adolescents 13 years of age or older is 300 mg every 12 hours for 5-10 days or 600 mg once daily for 10 days.1

Cephalosporin regimens administered for 5 days or less are not recommended for the treatment of S. pyogenes pharyngitis and tonsillitis.16,17 (See Uses: Pharyngitis and Tonsillitis.)

Respiratory Tract Infections

For the treatment of acute exacerbations of chronic bronchitis, the usual dosage of cefdinir in adults and adolescents 13 years of age or older is 300 mg every 12 hours for 5-10 days or 600 mg once daily for 10 days.1

For the treatment of acute maxillary sinusitis in adults and adolescents 13 years of age or older, the usual dosage is 300 mg every 12 hours or 600 mg once daily for 10 days.1

Adult or adolescents 13 years of age or older should receive cefdinir in a dosage of 300 mg every 12 hours for 10 days for the treatment of community-acquired pneumonia (CAP).1

Skin and Skin Structure Infections

For the treatment of uncomplicated skin and skin structure infections caused by susceptible bacteria, the usual dosage of cefdinir for adults and adolescents 13 years of age or older is 300 mg every 12 hours for 10 days.1,24

Pediatric Dosage

Children 13 year of age or older or those weighing more than 43 kg may receive the usual adult dosage of cefdinir.1,40

General Pediatric Dosage

For pediatric patients beyond the neonatal period, the American Academy of Pediatrics (AAP) recommends a cefdinir dosage of 14 mg/kg daily in 1 or 2 equally divided doses for the treatment of mild or moderate infections.10 The AAP states that the drug is inappropriate for the treatment of severe infections.10

Acute Otitis Media

For the treatment acute bacterial otitis (AOM), children 6 months through 12 years of age should receive cefdinir in a dosage of 7 mg/kg every 12 hours for 5-10 days or 14 mg/kg once daily for 10 days.1,40

The AAP states that oral anti-infective regimens of less than 10 days' duration are not recommended for the treatment of AOM in children younger than 2 years of age or in patients with severe symptoms.37

Pharyngitis and Tonsillitis

For the treatment of pharyngitis and tonsillitis in children 6 months through 12 years of age, the usual dosage of cefdinir is 7 mg/kg every 12 hours for 5-10 days or 14 mg/kg once daily for 10 days.1,40

Cephalosporin regimens administered for 5 days or less are not recommended for the treatment of S. pyogenes pharyngitis and tonsillitis.16,17 (See Uses: Pharyngitis and Tonsillitis.)

Respiratory Tract Infections

The usual dosage of cefdinir for the treatment of acute maxillary sinusitis in children 6 months through 12 years of age is 7 mg/kg every 12 hours for 10 days or 14 mg/kg once daily for 10 days.1,40

Skin and Skin Structure Infections

For the treatment of mild to moderate, uncomplicated skin and skin structure infections in children 6 months through 12 years of age, the usual dosage of cefdinir is 7 mg/kg every 12 hours for 10 days.1,5,40

Dosage in Renal and Hepatic Impairment

Patients with creatinine clearances of 30 mL/minute or greater may receive the usual dosage of cefdinir.1

Adults with creatinine clearances less than 30 mL/minute should receive cefdinir in a dosage of 300 mg once daily and children with creatinine clearances less than 30 mL/minute per 1.73 m² should receive the drug in a dosage of 7 mg/kg (up to 300 mg) once daily.1,40

For patients maintained on long-term hemodialysis, the usual initial dosage of cefdinir is 300 mg every 48 hours for adults or 7 mg/kg (up to 300 mg) every 48 hours for children.1,40 Because cefdinir is partially removed by hemodialysis, a supplemental dose of cefdinir (300 mg in adults or 7 mg/kg in children) should be given at the end of each dialysis period and subsequent doses administered every 48 hours.1,40

While the pharmacokinetics of cefdinir have not been studied in patients with hepatic impairment, hepatic metabolism of the drug is negligible and the manufacturer states that dosage adjustments are not expected to be necessary in such patients.1,40

Adverse Effects

Adverse effects reported with cefdinir are similar to those reported with other oral cephalosporins.1,40 (See Cautions in the Cephalosporins General Statement 8:12.06.) Cefdinir generally is well tolerated.1,40 Diarrhea, the most frequent adverse effect, has been reported in 16% of adult or adolescent patients1,4,5,7,15,24 and in 8% of pediatric patients receiving usual dosages of the drug.1,5,6,12,40 Adverse effects usually are transient and mild in severity, but have been severe enough to require discontinuance of the drug in up to 3% of patients.4,5,6,7,15,24,40

Precautions and Contraindications

Cefdinir shares the toxic potentials of other cephalosporins, and the usual cautions, precautions, and contraindications associated with cephalosporin therapy should be observed.1,40 Prior to initiation of cefdinir therapy, careful inquiry should be made concerning previous hypersensitivity reactions to cephalosporins, penicillins, or other drugs.1,40 There is clinical and laboratory evidence of partial cross-allergenicity among cephalosporins and other β-lactam antibiotics, including penicillins and cephamycins.1,20,21,40 Cefdinir is contraindicated in patients who are hypersensitive to the drug or other cephalosporins and should be used with caution in patients with a history of hypersensitivity to penicillins.1,40 Use of cephalosporins should be avoided in patients who have had an immediate-type (anaphylactic) hypersensitivity reaction to penicillins.21 If an allergic reaction occurs during cefdinir therapy, the drug should be discontinued and the patient treated with appropriate therapy (e.g., epinephrine, corticosteroids, and maintenance of an adequate airway and oxygen) as indicated.1,40

To reduce development of drug-resistant bacteria and maintain effectiveness of cefdinir and other antibacterials, the drug should be used only for the treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.1,40 When selecting or modifying anti-infective therapy, results of culture and in vitro susceptibility testing should be used.1,40 In the absence of such data, local epidemiology and susceptibility patterns should be considered when selecting anti-infectives for empiric therapy.1,40

Patients should be advised that antibacterials (including cefdinir) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).1,40 Patients also should be advised about the importance of completing the full course of therapy, even if feeling better after a few days, and that skipping doses or not completing therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with cefdinir or other antibacterials in the future.1,40

Because Clostridium difficile infection (CDI) and C. difficile -associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) have been reported with nearly all anti-infectives, including cephalosporins, it should be considered in the differential diagnosis of patients who develop diarrhea during or after cefdinir therapy.1,40,42 Patients should be advised that diarrhea is a common problem caused by anti-infectives and usually ends when the drug is discontinued; however, they should contact a clinician if watery and bloody stools (with or without stomach cramps and fever) occur during or as late as 2 months or longer after the last dose.1,40

Individuals with diabetes mellitus and/or their caregivers should be informed that cefdinir oral suspension contains sucrose.40,41 Depending on the manufacturer, the reconstituted oral suspension contains 1.37-2.86 g of sucrose per 5 mL.40,41

For a more complete discussion of these and other precautions associated with the use of cefdinir, see Cautions: Precautions and Contraindications in the Cephalosporins General Statement 8:12.06.

Pediatric Precautions

Safety and efficacy of cefdinir in neonates and infants younger than 6 months of age have not been established.1,40

Although adverse effects reported in pediatric patients receiving cefdinir are similar to those reported in adults, the incidence of diarrhea and rash appears to be higher in pediatric patients 2 years of age or younger than in older pediatric patients.1,40 Diarrhea has been reported in 17% of those 2 years of age or younger and 4% of those older than 2 years of age.1,40 Rash (principally diaper rash in the younger patients) has been reported in 8% of those 2 years of age or younger and 1% of those older than 2 years of age.1,40

Geriatric Precautions

Cefdinir is well tolerated in geriatric patients, and the incidence of adverse effects (including diarrhea) reported in clinical trials generally has been lower in geriatric patients than in younger adults.1,40 Although single-dose studies indicate that peak plasma concentrations and the area under the plasma-concentration time curve (AUC) of cefdinir may be higher in older adults than in younger adults, no adjustments in cefdinir dosage appear to be necessary other than those related to renal impairment.1,40 (See Dosage and Administration: Dosage in Renal and Hepatic Impairment.)

Mutagenicity and Carcinogenicity

In vivo and in vitro studies evaluating cefdinir have not shown evidence of mutagenicity.1,40 Studies have not been performed to evaluate the carcinogenic potential of the drug.1,40

Pregnancy, Fertility, and Lactation

Pregnancy

Reproduction studies in rats or rabbits using oral cefdinir in dosages 70 or 0.7 times, respectively, the usual human dosage (based on mg/kg daily) have not revealed evidence of teratogenicity.1,40 There are no adequate and controlled studies using cefdinir in pregnant women or during labor and delivery, and the drug should be used during pregnancy only when clearly needed.1,40

Fertility

Studies in rats using oral cefdinir in dosages up to 70 times the usual human dosage (based on mg/kg daily) have not revealed evidence of impaired fertility.1,40

Lactation

Cefdinir was not detected in human milk following a single 600-mg oral dose of the drug.1,40

Spectrum

Based on its spectrum of activity, cefdinir is classified as a third generation cephalosporin.2,3,4,5,6 For information on the classification of cephalosporins and closely related β-lactam antibiotics based on spectra of activity, see Spectrum in the Cephalosporins General Statement 8:12.06.

Cefdinir is stable in the presence of a wide variety of β-lactamases produced by gram-negative and gram-positive bacteria but may be hydrolyzed by certain plasmid-mediated extended-spectrum β-lactamases.9,13,14,19 Like other currently available oral third generation cephalosporins (e.g., cefpodoxime proxetil, ceftibuten), cefdinir has an expanded spectrum of activity against aerobic gram-negative bacteria compared with first and second generation cephalosporins2,3,4,5,6,7,9,13,14 but is inactive against most strains of Enterobacter and Pseudomonas aeruginosa .2,3

In vitro on a weight basis, cefdinir is more active against susceptible staphylococci and streptococci than other currently available oral third generation cephalosporins (e.g., cefpodoxime proxetil, ceftibuten).2,9 Cefdinir is inactive against enterococci (e.g., Enterococcus faecalis ) and methicillin-resistant (oxacillin-resistant) staphylococci.1,2,3

In Vitro Susceptibility Testing

Strains of staphylococci resistant to penicillinase-resistant penicillins (methicillin-resistant [oxacillin-resistant] staphylococci) should be considered resistant to cefdinir, although results of in vitro susceptibility tests may indicate that the organisms are susceptible to the drug.38

For information on interpreting results of in vitro susceptibility testing (disk susceptibility tests, dilution susceptibility tests) when cefdinir susceptibility testing is performed according to the standards of the Clinical and Laboratory Standards Institute (CLSI; formerly National Committee for Clinical Laboratory Standards [NCCLS]), see Spectrum: In Vitro Susceptibility Testing, in the Cephalosporins General Statement 8:12.06.

Pharmacokinetics

Cefdinir exhibits nonlinear dose-dependent pharmacokinetics.1,23 The pharmacokinetics of cefdinir have been studied in adults and pediatric patients 6 months to 12 years of age.1,27,28,40 There is no evidence of gender- or race-related differences in the pharmacokinetics of the drug.1,40 Studies in adults with impaired renal function indicate that the pharmacokinetics of cefdinir are affected by the degree of renal impairment and that decreases in elimination rate, apparent oral clearance, and renal clearance are approximately proportional to reductions in creatinine clearance.1,40 Differences in the pharmacokinetics of the drug in geriatric individuals appear to be related to changes in renal function rather than age.1,40 Pharmacokinetics of cefdinir have not been studied in patients with hepatic impairment.1,40

Absorption

Following oral administration of cefdinir capsules or oral suspension, peak plasma concentrations are attained 2-4 hours after the dose.1,23,27,28,40 Relative bioavailability of cefdinir administered to adults as the commercially available oral suspension is 120% of that achieved following administration of commercially available capsules of the drug.1,40 When administered as capsules, estimated oral bioavailability of cefdinir is 21% following a 300-mg dose and 16% following a 600-mg dose;1 estimated absolute bioavailability is 25% following administration of the oral suspension.40

In healthy adults who received a single 300- or 600-mg oral dose of cefdinir as capsules, peak plasma concentrations about 3 hours after the dose were 1.6 or 2.87 mcg/mL, respectively.1 Results of a study in adults 19-91 years of age given a single 300-mg oral dose of cefdinir indicate that peak plasma concentrations may be 44% higher and the area under the plasma concentration-time curve (AUC) 86% higher in older adults compared with younger adults.1

In pediatric patients 6 months to 12 years of age who received a single 7-mg/kg oral dose of cefdinir as the suspension, peak plasma concentrations were attained 2.2 hours after the dose and averaged 2.3 mcg/mL.40 Single 14-mg/kg oral doses in these patients resulted in peak plasma concentrations averaging 3.86 mcg/mL at 1.8 hours after the dose.40

Compared with administration in the fasting state, concomitant administration of cefdinir capsules with a high-fat meal decreases peak plasma concentrations and AUC of oral cefdinir by 16 and 10%, respectively.1,28 When studied in adults, concomitant administration of cefdinir oral suspension with a high-fat meal decreased peak plasma concentrations and AUC of the drug by 44 and 33%, respectively.40

There is no evidence that cefdinir accumulates in plasma following multiple doses in patients with normal renal function receiving the drug once or twice daily.1,27,40

Distribution

The volume of distribution of cefdinir averages 0.35 L/kg in adults and 0.67 L/kg in children 6 months to 12 years of age.1,40

Following oral administration, cefdinir is distributed into blister fluid, middle ear fluid, tonsils, sinus tissue, and bronchial mucosa and epithelial lining fluid in concentrations ranging from 15-48% of concurrent plasma concentrations.1,22,23,40

In adults undergoing elective tonsillectomy who received single 300- or 600-mg oral doses of cefdinir, median concentrations of the drug in tonsils 4 hours after the dose were 0.25 or 0.36 mcg/g, respectively.1,40 In adults undergoing elective maxillary and ethmoid sinus surgery, median sinus tissue concentrations 4 hours after single 300- or 600-mg oral doses of the drug were less than 0.12 or 0.21 mcg/g, respectively.1,40 In adults undergoing diagnostic bronchoscopy who received single 300- or 600-mg oral doses of cefdinir, median bronchial mucosa concentrations 4 hours after the dose were 0.78 or 1.14 mcg/mL, respectively, and median epithelial lining fluid concentrations were 0.29 or 0.49 mcg/mL, respectively.1,22,40

In pediatric patients with acute bacterial otitis media who received single 7- or 14-mg/kg oral doses of cefdinir, median concentrations of the drug in middle ear fluid 3 hours after the dose were 0.21 or 0.72 mcg/mL, respectively.1,40

Median maximal concentrations of cefdinir in blister fluid 4-5 hours after single 300- or 600-mg oral doses of the drug were 0.65 or 1.1 mcg/mL, respectively.1,23,40

It is not known whether cefdinir is distributed into CSF following oral administration.1,40

Cefdinir was not detected in human milk following oral administration of single 600-mg doses of the drug.1,40

Cefdinir is 60-70% bound to plasma proteins in adults or children; binding is independent of drug concentration.1,23,40

Elimination

Cefdinir is not appreciably metabolized.1,40 The drug is eliminated principally by renal excretion.1,40 In adults with normal renal function, the mean plasma elimination half-life of cefdinir is 1.7-1.8 hours1,27 and renal clearance is 2 mL/minute per kg.1 Following oral administration of 300- or 600-mg of cefdinir, apparent oral clearance is 11.6 or 15.5 mL/minute per kg, respectively, and 18.4 or 11.6% of the dose, respectively, is eliminated unchanged in urine.1

Clearance of cefdinir is decreased in patients with impaired renal function.1,40 In patients with creatinine clearances of 30-60 mL/minute, peak plasma concentrations and plasma elimination half-life of the drug are increased approximately twofold and the AUC is increased approximately threefold.1,40 In patients with creatinine clearances less than 30 mL/minute, peak plasma concentrations are increased approximately twofold but plasma elimination half-life and AUC are increased approximately fivefold and sixfold, respectively.1,40

Cefdinir is removed by hemodialysis.1,40 A 4-hour period of dialysis removes approximately 63% of the drug and decreases the apparent elimination half-life of cefdinir in patients with substantial renal impairment from 16 to 3.2 hours.1,40

Chemistry and Stability

Chemistry

Cefdinir is a semisynthetic cephalosporin antibiotic.1,2,3,4,5,6,40 The drug is an oral aminothiazolyl hydroxyimino cephalosporin.2,9,13 Cefdinir is structurally similar to other oral (cefpodoxime proxetil, ceftibuten) or parenteral (cefepime, cefotaxime, ceftazidime, ceftriaxone) cephalosporins that contain an aminothiazolyl side chain at position 7 of the cephalosporin nucleus; however, cefdinir contains an unsubstituted oxime group rather than the methoxyimino group contained in many aminothiazolyl cephalosporins.13,14 The oxime group may contribute to improved activity against gram-positive bacteria.14,22 Like cefixime, cefdinir contains a vinyl moiety at position 3 of the cephalosporin nucleus which makes the drug suitable for oral administration.13

Cefdinir is a white to white to light yellow crystalline powder.1,40 Depending on the manufacturer, commercially available cefdinir powder for oral suspension occurs as a white to off-white cherry-flavored powder or cream-colored, strawberry-flavored powder.40,41 Following reconstitution, the oral suspension contains 125 or 250 mg of cefdinir per 5 mL.40,41

Stability

Cefdinir capsules and powder for oral suspension should be stored at 20-25°C, but may be exposed to temperatures ranging from 15-30°C.1,40

Following reconstitution, cefdinir oral suspension should be stored in a tight container at controlled room temperature; any unused suspension should be discarded after 10 days.40,41

Additional Information

For further information on chemistry, mechanism of action, spectrum, resistance, uses, cautions, acute toxicity, drug interactions, or laboratory test interferences of cefdinir, see the Cephalosporins General Statement 8:12.06.

1. Teva Pharmaceuticals USA. Cefdinir capsules prescribing information. Sellersville, PA; 2009 Dec.

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3. Marchese A, Saverino D, Debbia EA et al. Antistaphylococcal activity of cefdinir, a new oral third-generation cephalosporin, alone and in combination with other antibiotics, at supra- and sub-MIC levels. J Antimicrob Chemother . 1995; 35:53-66. [PubMed 7768782]

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5. Tack KJ, Keyserling CH, McCarty J et al et al. Study of use of cefdinir versus cephalexin in treatment of skin infections in pediatric patients. Antimicrob Agents Chemother . 1997; 41:739-42. [PubMedCentral][PubMed 9087480]

6. Tack KJ, Hedrick JA, Rothstein E et al. A study of 5-day cefdinir treatment for streptococcal pharyngitis in children. Arch Pediatr Adolesc Med . 1997; 151:45-9. [PubMed 9006528]

7. Gwaltney JM Jr, Savolainen S, Rivas P et al et al. Comparative effectiveness and safety of cefdinir and amoxicillin-clavulanate in treatment of acute community-acquired bacterial sinusitis. Antimicrob Agents Chemother . 1997; 41:1517-20. [PubMedCentral][PubMed 9210677]

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10. American Academy of Pediatrics. Red Book: 2012 Report of the Committee on Infectious Diseases. 29th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2012.

11. Anon. Drugs for bacterial infections. Med Lett Treat Guid . 2010; 8:43-52.

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13. Payne DJ, Amyes SGB. Stability of cefdinir (CI-983, FK482) to extended-spectrum plasmid-mediated β-lactamases. J Med Microbiol . 1993; 38:114-7. [PubMed 8429536]

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15. Sperling MJ, Puopolo A, Griffin TJ et al. Efficacy and safety of cefdinir in the treatment of patients with acute bronchitis. Clin Ther . 1996; 18:626-34. [PubMed 8879891]

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17. Gerber MA, Baltimore RS, Eaton CB et al. Prevention of rheumatic fever and diagnosis and treatment of acute Streptococcal pharyngitis: a scientific statement from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young, the Interdisciplinary Council on Functional Genomics and Translational Biology, and the Interdisciplinary Council on Quality of Care and Outcomes Research: endorsed by the American Academy of Pediatrics. Circulation . 2009; 119:1541-51. [PubMed 19246689]

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20. Kishiyam JL, Adelman DC. The cross-reactivity and immunology of β-lactam antibiotics. Drug Safety . 1994; 10:318-27. [PubMed 8018304]

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23. Richer M, Allard S, Manseau L et al. Suction-induced blister fluid penetration of cefdinir in healthy volunteers following ascending oral doses. Antimicrob Agents Chemother . 1995; 39:1082-6. [PubMedCentral][PubMed 7625793]

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27. Guttendorf RJ, Misiak PM, Koup JR et al. Safety, tolerance, and pharmacokinetics of cefdinir (CI-983, FK-482) after single and multiple doses. In: American Society for Microbiology. Program and abstracts of the 31st Interscience Conference on Antimicrobial Agents and Chemotherapy. Chicago, IL; 1991:415. Abstract No. 1535.

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40. Teva Pharmaceuticals. Cefdinir monohydrate powder for suspension prescribing information. Sellersville, PA; 2013 Jan.

41. Sandoz Inc. Cefdinir powder for suspension prescribing information. Princeton, NJ; 2011 Jul.

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