CEFDINIR

General Administration Information
For storage information, see the specific product information within the How Supplied section.

Route-Specific Administration

Oral Administration
-If antacids or iron supplements are necessary during cefdinir therapy, cefdinir should be given at least 2 hours before or after the antacid or iron supplement. Iron-fortified infant formulas do not significantly alter the absorption of cefdinir.
Oral Solid Formulations
-Cefdinir capsules may be administered without regard to meals.

Oral Liquid Formulations
-Cefdinir oral suspension may be administered without regard to meals.
-Shake well prior to each use.
-For accurate dosage, measure using a calibrated oral syringe, spoon or cup.

Suspension Reconstitution:
-Tap the bottle to loosen the powder. The water should be added in 2 portions; shake well after each aliquot.
-See manufacturer's specific instructions regarding reconstitution volumes needed.
-Storage: After reconstitution, the suspension can be stored at controlled room temperature for 10 days. The container should be kept tightly closed when not in use.

In clinical trials, 5093 adult and adolescent patients (3841 US and 1252 non-US) were treated with the recommended dose of cefdinir capsules (600 mg/day) and 2289 pediatric patients (1783 US and 506 non-US) were treated with the recommended dose of cefdinir suspension (14 mg/kg/day). Most adverse events were mild and self-limiting. One hundred forty-seven (3%) adult/adolescent patients and 40 (2%) pediatric patients discontinued medication due to adverse events thought by the investigators to be possibly, probably, or definitely associated with cefdinir therapy. The discontinuations were primarily for gastrointestinal disturbances. Nineteen (0.4%) adult/adolescent patients and five (0.2%) pediatric patients were discontinued due to rash thought related to cefdinir administration.

Hypersensitivity or allergic reactions have occurred in patients receiving beta-lactam antibiotics, including cefdinir. Rash (unspecified) has been reported in 3% of pediatric patients and 0.9% of adolescents. Rash (primarily diaper dermatitis) was reported in 8% of patients <= 2 years old and in 1% of pediatric patients > 2 years old. Pruritus has been reported in 0.2% of patients. Other reactions noted in post-marketing reports include anaphylactoid reactions and anaphylactic shock with rare cases of fatality, facial edema (angioedema), laryngeal edema, erythema multiforme, erythema nodosum, exfoliative dermatitis, maculopapular rash, serum sickness, Stevens-Johnson syndrome, toxic epidermal necrolysis, and allergic vasculitis. If an allergic reaction occurs, cefdinir therapy should be discontinued and appropriate therapy instigated.

In clinical trials, gastrointestinal disturbances were the most commonly reported reasons for cefdinir discontinuation. Diarrhea was reported in 8% of pediatric patients and in 15% of adults and adolescents. In pediatric patients <= 2 years old, the incidence of diarrhea was 17% compared to 4% in patients > 2 years old. Other adverse events included nausea (0.2-3%), abdominal pain (0.8-1%), vomiting (0.7-1%), dyspepsia (0.2-0.7%), abnormal stools (0.2-3%), anorexia (0.3%), flatulence (0.7%), constipation (0.3%), and xerostomia (0.3%). Acute enterocolitis, bloody diarrhea, hemorrhagic colitis, melena, peptic ulcer, stomatitis, and ileus have been noted in post-marketing reports.

Microbial overgrowth and superinfection can occur with antibiotic use. C. difficile-associated diarrhea (CDAD) or pseudomembranous colitis has been reported with cefdinir. If pseudomembranous colitis is suspected or confirmed, ongoing antibacterial therapy not directed against C. difficile may need to be discontinued. Institute appropriate fluid and electrolyte management, protein supplementation, C. difficile-directed antibacterial therapy, and surgical evaluation as clinically appropriate. Candidiasis (unspecified) has been reported in 0.2% of patients. Candidiasis (unspecified) has been reported in 0.2% of patients. Cutaneous candidiasis has been reported in 0.9% of pediatric patients, while vaginal candidiasis and vaginitis have each been noted in 0.3% of pediatric patients.

Cefdinir may cause nonbloody, reddish stool discoloration in infants being treated with cefdinir who are also receiving iron-fortified infant formulas. There have been reports of reddish stools in patients of all ages receiving cefdinir. In many cases, patients were also receiving iron-containing products. The reddish color, which is not harmful, is due to the formation of a nonabsorbable complex between cefdinir or its breakdown products and iron in the gastrointestinal tract.

Seizures are a rare but serious complication of cephalosporin therapy. Seizures have been reported in < 1% of patients receiving cephalosporins. More commonly associated with penicillins, the epileptogenic properties of both penicillins and cephalosporins are believed to be related to their beta-lactam ring. High doses and renal impairment are associated with an increased risk of seizures. Post-marketing reports have included cases of seizures during cefdinir therapy. Although not reported specifically in pediatric trials (infants and children), headache was reported in 2% of adolescent and adult patients receiving cefdinir. Dizziness (0.3%), insomnia (0.2%), and somnolence/drowsiness (0.2%) were also reported. Loss of consciousness was noted in post-marketing reports.

Hematologic adverse events have been noted with the use of cefdinir. Increased lymphocytes have been reported in <= 2% of cefdinir patients. Adverse events reported in <= 1% of patients include increased and decreased white blood cells, eosinophilia, decreased lymphocytes, increased platelets, increased or decreased PMNs, increased monocytes, decreased hematocrit, and decreased hemoglobin. Post-marketing adverse events reported include pancytopenia, granulocytopenia, leukopenia, thrombocytopenia, idiopathic thrombotic thrombocytopenic purpura (TTP), hemolytic anemia, bleeding tendency, coagulation disorders, disseminated intravascular coagulation (DIC), and upper GI bleeding. Aplastic anemia, neutropenia, and agranulocytosis have been noted with the cephalosporin class.

Elevated hepatic enzymes (AST, ALT, alkaline phosphatase, GGT) and hyperbilirubinemia were noted in <= 1% of patients receiving cefdinir. Hepatic adverse events noted in post-marketing reports include acute hepatitis, cholestasis, fulminant hepatitis, hepatic failure, and jaundice.

Hyperkinesis (0.2%) and asthenia (0.2%) have both been reported with cefdinir use. Other adverse events noted in post-marketing reports include involuntary movements and rhabdomyolysis.

Abnormal urinary laboratory values including increased urine leukocytes (0.5-2%), increased micro-hematuria (1%), and increased urine protein/proteinuria (1-2%) have been reported with cefdinir therapy. Other abnormal laboratory values that occurred in < 1% of patients include increased urine glucose/glycosuria, increased or decreased urine specific gravity, increased urine pH, and increased BUN/azotemia. Acute renal failure (unspecified) and nephropathy were noted in post-marketing reports.

Abnormal laboratory values that have been reported in <= 1% of patients with the use of cefdinir include decreased bicarbonate, elevated lactate dehydrogenase, hyperphosphatemia, hypophosphatemia, hypocalcemia, hyperglycemia, and hyperkalemia. Hyperamylasemia has been noted in post-marketing reports.

General adverse events noted in post-marketing reports with cefdinir include a feeling of suffocation, conjunctivitis, and fever.

Respiratory system adverse events noted in post-marketing reports with cefdinir include acute respiratory failure (respiratory arrest), asthmatic attack, drug-induced pneumonia, eosinophilic pneumonia, and idiopathic interstitial pneumonia.

Cardiovascular adverse events noted in post-marketing reports with cefdinir include heart failure, chest pain (unspecified), myocardial infarction, and hypertension.

A false-positive reaction for glucose in the urine has been observed in patients receiving cefdinir (any formulation) and using Benedict's solution, Fehling's solution, or Clinitest tablets. However, this reaction has not been observed with glucose tests based on enzymatic glucose oxidase reactions (e.g., Clinistix or Tes-tape).

A positive direct Coombs test may develop in some patients. In hematologic studies or in transfusion cross-matching procedures when antiglobulin tests are performed on the minor side or in Coombs' testing of newborns whose mothers received cefdinir before delivery, clinicians should keep in mind that a positive Coombs' test may be due to the drug.

In patients taking cefdinir, a false-positive reaction for ketones in the urine may occur with tests using nitroprusside, but not with those using nitroferricyanide.

Cefdinir is contraindicated in patients with a known history of cephalosporin hypersensitivity or cephamycin hypersensitivity. Cefdinir should be used cautiously in patients with hypersensitivity to penicillin. The structural similarity between cefdinir and penicillin means cross-reactivity can occur. Penicillins can cause a variety of hypersensitivity reactions ranging from mild rash to fatal anaphylaxis. Patients who have experienced severe penicillin hypersensitivity should not receive cefdinir. The incidence of cephalosporin hypersensitivity is approximately 3-7% among patients with a documented history of penicillin hypersensitivity. Cefdinir should be used with caution in patients who have had a delayed-type reaction to penicillin or related drugs.

In patients with transient or persistent renal impairment (creatinine clearance less than 30 mL/minute/1.73 m2) or renal failure, the total daily dose of cefdinir should be reduced because high and prolonged plasma concentrations of cefdinir can result after recommended doses. Cephalosporins have been associated with precipitating seizures, especially in patients with renal impairment when the dosage was not reduced. In patients receiving dialysis, additional dosage adjustments are needed to ensure therapeutic effect because cefdinir is removed from the body by hemodialysis.

Consider pseudomembranous colitis in patients presenting with diarrhea after antibacterial use. Careful medical history is necessary as pseudomembranous colitis has been reported to occur over 2 months after the administration of antibacterial agents. Almost all antibacterial agents, including cefdinir, have been associated with pseudomembranous colitis or C. difficile-associated diarrhea (CDAD) which may range in severity from mild to life-threatening. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

All cephalosporins, including cefdinir, can rarely cause hypoprothrombinemia and have the potential to cause bleeding. Cephalosporins, which contain the methylthiotetrazole (MTT) side chain (e.g., cefoperazone, cefamandole, cefotetan), have been associated with an increased risk for bleeding. Cephalosporins should be used cautiously in patients with a preexisting coagulopathy (e.g., vitamin K deficiency) because these patients are at a higher risk for developing bleeding complications.

In patients with diabetes mellitus, it should be noted that cefdinir oral suspension contains sucrose (1.37 to 2.94 grams per teaspoon, the exact amount differs by manufacturer), which may be a concern in patients whose blood glucose is very sensitive to carbohydrate intake.

Description: Cefdinir is an oral extended-spectrum, semisynthetic, cephalosporin. It is generally classified as a third-generation cephalosporin with activity similar to cefpodoxime and cefixime. Because it can be dosed once or twice daily and the oral suspension is relatively palatable compared to some other antibiotics, cefdinir has become a useful option for pediatric patients requiring oral therapy. Cefdinir is indicated for treatment of skin infections and a variety of upper respiratory infections including chronic bronchitis, otitis media, pharyngitis, pneumonia, sinusitis, and tonsillitis. However, third-generation oral cephalosporins, such as cefdinir, are not recommended by the Infectious Disease Society of America (IDSA) for empiric monotherapy of acute bacterial sinusitis due to highly variable activity against Streptococcus pneumoniae. Cefdinir is FDA-approved for use in pediatric patients as young as 6 months of age.

Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: Citrobacter koseri, Escherichia coli, Haemophilus influenzae (beta-lactamase negative), Haemophilus influenzae (beta-lactamase positive), Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Proteus mirabilis, Staphylococcus aureus (MSSA), Staphylococcus epidermidis, Streptococcus agalactiae (group B streptococci), Streptococcus pneumoniae, Streptococcus pyogenes (group A beta-hemolytic streptococci), Viridans streptococci
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.

For the treatment of acute otitis media:
Oral dosage:
Infants 2 to 5 months*: 7 mg/kg/dose PO every 12 hours or 14 mg/kg/dose PO every 24 hours for 10 days. Guidelines recommend cefdinir as an alternative to high-dose amoxicillin or high-dose amoxicillin; clavulanate in penicillin allergic patients.
Infants and Children 6 to 23 months: 7 mg/kg/dose (Max: 300 mg/dose) PO every 12 hours or 14 mg/kg/dose (Max: 600 mg/dose) PO every 24 hours for 10 days. Guidelines recommend cefdinir as an alternative to high-dose amoxicillin or high-dose amoxicillin; clavulanate in penicillin allergic patients.
Children 2 to 5 years: 7 mg/kg/dose (Max: 300 mg/dose) PO every 12 hours or 14 mg/kg/dose (Max: 600 mg/dose) PO every 24 hours for 7 days for mild to moderate disease and 10 days for severe disease. Guidelines recommend cefdinir as an alternative to high-dose amoxicillin or high-dose amoxicillin; clavulanate in penicillin allergic patients.
Children 6 years and older: 7 mg/kg/dose (Max: 300 mg/dose) PO every 12 hours or 14 mg/kg/dose (Max: 600 mg/dose) PO every 24 hours for 5 to 7 days for mild to moderate disease and 10 days for severe disease. Guidelines recommend cefdinir as an alternative to high-dose amoxicillin or high-dose amoxicillin; clavulanate in penicillin allergic patients.

For the treatment of pharyngitis or tonsillitis:
Oral dosage:
Infants 6 months and older and Children: 7 mg/kg/dose PO every 12 hours (Max: 300 mg/dose) for 5 to 10 days or 14 mg/kg/dose PO every 24 hours (Max: 600 mg/dose) for 10 days. Guidelines do not recommend cefdinir Group A Streptococcal pharyngitis to prevent rheumatic fever.
Adolescents: 300 mg PO every 12 hours for 5 to 10 days or 600 mg PO every 24 hours for 10 days. Guidelines do not recommend cefdinir for Group A Streptococcal pharyngitis to prevent rheumatic fever.

For the treatment of acute maxillary sinusitis:
Oral dosage:
Infants >= 6 months and Children: 7 mg/kg/dose PO every 12 hours (Max: 300 mg/dose) or 14 mg/kg/dose PO every 24 hours (Max: 600 mg/dose) for 10 days is the FDA-approved dosage. Third-generation oral cephalosporins, such as cefdinir, are not recommended by the Infectious Disease Society of America (IDSA) for empiric monotherapy of acute bacterial sinusitis due to variable rates of Streptococcus pneumoniae resistance. Amoxicillin/clavulanate is recommended as the first-line empiric treatment.
Adolescents: 300 mg PO every 12 hours or 600 mg PO every 24 hours for 10 days is the FDA-approved dosage. Third-generation oral cephalosporins, such as cefdinir, are not recommended by the Infectious Disease Society of America (IDSA) for empiric monotherapy of acute bacterial sinusitis due to variable rates of Streptococcus pneumoniae resistance. Amoxicillin/clavulanate is recommended as the first-line empiric treatment.

For the treatment of community-acquired pneumonia (CAP):
Oral dosage:
Infants and Children 4 months to 12 years*: 7 mg/kg/dose (Max: 300 mg/dose) PO every 12 hours for 10 days. Guidelines recommend cefdinir as an alternative to amoxicillin or amoxicillin; clavulanate for infections due to H. influenzae.
Adolescents: 300 mg PO every 12 hours for 10 days. Guidelines recommend cefdinir as an alternative to amoxicillin or amoxicillin; clavulanate for infections due to H. influenzae.

For the treatment of uncomplicated skin and skin structure infections:
Oral dosage:
Infants >= 6 months and Children: 7 mg/kg/dose PO every 12 hours (Max: 300 mg/dose) for 10 days.
Adolescents: 300 mg PO every 12 hours for 10 days.

For the treatment of acute exacerbations of chronic bronchitis:
Oral dosage:
Adolescents: 300 mg PO every 12 hours for 5 to 10 days or 600 mg PO every 24 hours for 10 days.

Maximum Dosage Limits:
-Neonates
Safety and efficacy have not been established.
-Infants
1 to 5 months: Safety and efficacy have not been established; however, 14 mg/kg/day PO has been used off-label.
6 months and older: 14 mg/kg/day PO.
-Children
14 mg/kg/day PO (Max: 600 mg/day).
-Adolescents
600 mg/day PO.

Patients with Hepatic Impairment Dosing
Dosage adjustment is not necessary.

Patients with Renal Impairment Dosing
CrCl 30 mL/minute/1.73 m2 or more: No dosage adjustment needed.
CrCl less than 30 mL/minute/1.73 m2: 7 mg/kg/dose PO once daily (Max: 300 mg/dose).

Intermittent hemodialysis
Hemodialysis removes cefdinir from the body. In pediatric patients maintained on chronic hemodialysis, the recommended initial dosage regimen is 7 mg/kg/dose PO every other day. At the conclusion of each hemodialysis session, 7 mg/kg/dose should be given, followed by subsequent doses of 7 mg/kg/dose administered every other day. The maximum recommended dose should not exceed 300 mg.

*non-FDA-approved indication

Monograph content under development

Mechanism of Action: Cefdinir is a beta-lactam antibiotic like the penicillins and is mainly bactericidal. Cefdinir inhibits the third and final stage of bacterial cell wall synthesis by preferentially binding to specific penicillin-binding proteins (PBPs) that are located inside the bacterial cell wall. Penicillin-binding proteins are responsible for several steps in the synthesis of the cell wall and are found in quantities of several hundred to several thousand molecules per bacterial cell. Penicillin-binding proteins vary among different bacterial species. Thus, the intrinsic activity of cefdinir as well as the other cephalosporins and penicillins against a particular organism depends on their ability to gain access to and bind with the necessary PBP. Like all beta-lactam antibiotics, the ability of cefdinir to interfere with PBP-mediated cell wall synthesis ultimately leads to cell lysis. Lysis is mediated by bacterial cell wall autolytic enzymes (i.e., autolysins). The relationship between PBPs and autolysins is unclear, but it is possible that the beta-lactam antibiotic interferes with an autolysin inhibitor. Bacterial resistance to cefdinir occurs as a result of hydrolysis by some beta-lactamases, alteration of the PBP, and decreased drug permeability.

Pharmacokinetics: Cefdinir is administered orally. Once in the systemic circulation, cefdinir is 60-73% bound to plasma proteins; protein binding is independent of concentration. Widely distributed to various sites including the lungs, middle ear fluid, sinuses, skin blister, and tonsils. Volume of distribution in children is approximately 0.67 L/kg, compared to 0.35 L/kg in adults. Data on cefdinir penetration into human cerebrospinal fluid (CSF) are not available. Cefdinir is not appreciably metabolized and activity is primarily due to the parent drug. Excretion is principally via renal excretion of unchanged drug. In children, fractional elimination of unchanged drug is less compared with adults (2.7-12.7% vs. 12.7-23%). Elimination half-life in children with normal renal function is approximately 1.5 hours, which is similar to that of adults, and is prolonged in patients with renal impairment.

Affected cytochrome P450 isoenzymes: none


-Route-Specific Pharmacokinetics
Oral Route
Peak concentrations occur approximately 2 hours after suspension administration and 3 hours after capsule administration. Bioavailability is approximately 25% and 16-21% for the suspension and capsules, respectively. Food does not significantly affect cefdinir absorption.


-Special Populations
Pediatrics
Infants and Children
Clearance is higher in younger children (< 3 years of age) compared with older children (3-12 years of age). Elimination half-life has been reported to be 1.3 and 1.6 hours, respectively.

Hepatic Impairment
Pharmacokinetic data are not available in patients with hepatic impairment. However, cefdinir is not appreciably metabolized and no differences in the pharmacokinetics of cefdinir are expected in patients with hepatic impairment.

Renal Impairment
Pharmacokinetic data in pediatric patients with renal impairment are not available. However, in a pharmacokinetic study in 21 adult patients with renal impairment, cefdinir peak concentrations (Cmax) and elimination half-life were increased by approximately 2-fold and the area under the curve (AUC) was increased by approximately 3-fold in patients with a CrCl of 30-60 ml/min. In patients with a CrCl < 30 ml/min, Cmax was increased by approximately 2-fold, elimination half-life was increased by approximately 5-fold, and AUC was increased by approximately 6-fold. Decreases in cefdinir clearance were proportional to the decrease in CrCl. Dosage adjustment is recommended in patients with renal impairment (CrCl < 30 ml/min).

Hemodialysis
Pharmacokinetic data in pediatric patients undergoing hemodialysis are not available. In 8 adult patients undergoing hemodialysis (4 hours duration), 63% of cefdinir was eliminated from the body and elimination half-life was decreased from 16 (+/- 3.5) to 3.2 (+/- 1.2) hours.

Continuous Ambulatory Peritoneal Dialysis (CAPD)
A minimal amount of cefdinir is removed during CAPD.