NDC 70518-2076 Cefdinir

Cefdinir

NDC Product Code 70518-2076

NDC 70518-2076-0

Package Description: 100 mL in 1 BOTTLE

NDC Product Information

Cefdinir with NDC 70518-2076 is a a human prescription drug product labeled by Remedyrepack Inc.. The generic name of Cefdinir is cefdinir. The product's dosage form is powder, for suspension and is administered via oral form.

Labeler Name: Remedyrepack Inc.

Dosage Form: Powder, For Suspension - An intimate mixture of dry, finely divided drugs and/or chemicals, which, upon the addition of suitable vehicles, yields a suspension (a liquid preparation containing the solid particles dispersed in the liquid vehicle).

Product Type: Human Prescription Drug What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Cefdinir Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.

  • CEFDINIR MONOHYDRATE 250 mg/5mL

Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • ANHYDROUS CITRIC ACID (UNII: XF417D3PSL)
  • SILICON DIOXIDE (UNII: ETJ7Z6XBU4)
  • GUAR GUM (UNII: E89I1637KE)
  • MAGNESIUM STEARATE (UNII: 70097M6I30)
  • SODIUM BENZOATE (UNII: OJ245FE5EU)
  • ANHYDROUS TRISODIUM CITRATE (UNII: RS7A450LGA)
  • SUCROSE (UNII: C151H8M554)
  • XANTHAN GUM (UNII: TTV12P4NEE)

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Oral - Administration to or by way of the mouth.

Pharmacological Class(es)

What is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • Cephalosporin Antibacterial - [EPC] (Established Pharmacologic Class)
  • Cephalosporins - [CS]

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Remedyrepack Inc.
Labeler Code: 70518
FDA Application Number: ANDA065332 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: ANDA - A product marketed under an approved Abbreviated New Drug Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 05-13-2019 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2020 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA’s requests for correction to deficient or non-compliant submissions. Values = ‘Y’ or ‘N’.

* Please review the disclaimer below.

Cefdinir Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

Description

Cefdinir for Oral Suspension USP contains the active ingredient cefdinir monohydrate, USP, an extended-spectrum, semisynthetic cephalosporin, for oral administration. Chemically, cefdinir monohydrate, USP is (6


R,7


R)-7-[[(2Z)-(2-amino-4-thiazolyl)(hydroxyimino)acetyl]amino]-3-ethenyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid monohydrate. Cefdinir monohydrate, USP is a white to light yellow crystalline powder. Its solubility is 19.56 mg/mL in 0.1 M pH 7 phosphate buffer. Cefdinir monohydrate, USP has the structural formula shown below:


C


14H


13N


5O


5S


2•H


2O M.W. 413.44


Cefdinir for Oral Suspension USP, after reconstitution, contains 125 mg or 250 mg cefdinir per 5 mL and the following inactive ingredients: artificial cherry-mixed fruit flavor, anhydrous citric acid, colloidal silicon dioxide, guar gum, magnesium stearate, sodium benzoate, sodium citrate (anhydrous), sucrose, and xanthan gum.

Pharmacokinetics And Drug Metabolism

AbsorptionOral BioavailabilityMaximal 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 FoodIn adults given the 250 mg/5 mL oral suspension with a high-fat meal, the C


max and AUC of cefdinir are reduced by 44% and 33%, respectively. The magnitude of these reductions is not likely to be clinically significant because the safety and efficacy studies of oral suspension in pediatric patients were conducted without regard to food intake. Therefore, cefdinir may be taken without regard to food.


Cefdinir SuspensionCefdinir 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 SubjectsDoseC


max(mcg/mL)


t


max(hr)


AUC


(mcg•hr/mL)


7 mg/kg2.30


(0.65)


2.2


(0.6)


8.31


(2.50)


14 mg/kg3.86


(0.62)


1.8


(0.4)


13.4


(2.64)


Multiple DosingCefdinir does not accumulate in plasma following once- or twice-daily administration to subjects with normal renal function.DistributionThe mean volume of distribution (Vd


area) of cefdinir in adult subjects is 0.35 L/kg (± 0.29); in pediatric subjects (age 6 months to 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 BlisterIn adult subjects, median (range) maximal blister fluid cefdinir concentrations of 0.65 (0.33 to 1.1) and 1.1 (0.49 to 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 TissueIn 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 to 0.46) and 0.36 (0.22 to 0.80) mcg/g. Mean tonsil tissue concentrations were 24% (± 8) of corresponding plasma concentrations.Sinus TissueIn 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 to 0.46) and 0.21 (< 0.12 to 2) 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 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 ExcretionCefdinir 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) of 1.7 (± 0.6) hours. In healthy subjects with normal renal function, renal clearance is 2 (± 1) mL/min/kg, and apparent oral clearance is 11.6 (± 6) 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 PopulationsPatients with Renal InsufficiencyCefdinir 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


½ 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


½ 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).


HemodialysisCefdinir 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 from 16 (± 3.5) to 3.2 (± 1.2) hours. Dosage adjustment is recommended in this patient population (see


DOSAGE AND ADMINISTRATION).


Hepatic DiseaseBecause 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 PatientsThe 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


½ 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 RaceThe 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 ActionAs 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.ResistanceResistance 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 ActivityCefdinir 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 pyogenesGram-Negative BacteriaHaemophilus influenzaeHaemophilus parainfluenzaeMoraxella catarrhalisThe 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 BacteriaStaphylococcus epidermidis (methicillin-susceptible strains only)


Streptococcus agalactiae Viridans group streptococciGram-Negative BacteriaCitrobacter koseri Escherichia coli Klebsiella pneumoniae Proteus mirabilisSusceptibility 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.fda.gov/STIC.

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.

Community-Acquired Pneumonia

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) (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.

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.

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).

Contraindications

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

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 β-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 associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including cefdinir, and may range in severity from mild diarrhea to fatal 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.

General

Prescribing cefdinir for oral suspension in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.As with other broad-spectrum antibiotics, prolonged treatment may result in the possible emergence and overgrowth of resistant organisms. Careful observation of the patient is essential. If superinfection occurs during therapy, appropriate alternative therapy should be administered.Cefdinir, as with other broad-spectrum antimicrobials (antibiotics), should be prescribed with caution in individuals with a history of colitis.In patients with transient or persistent renal insufficiency (creatinine clearance < 30 mL/min), the total daily dose of cefdinir should be reduced because high and prolonged plasma concentrations of cefdinir can result following recommended doses (see


DOSAGE AND ADMINISTRATION).

Information For Patients

Patients should be counseled that antibacterial drugs including cefdinir for oral suspension should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When cefdinir for oral suspension is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by cefdinir for oral suspension or other antibacterial drugs in the future.Antacids containing magnesium or aluminum interfere with the absorption of cefdinir. If this type of antacid is required during cefdinir for oral suspension therapy, cefdinir for oral suspension should be taken at least 2 hours before or after the antacid.Iron supplements, including multivitamins that contain iron, interfere with the absorption of cefdinir. If iron supplements are required during cefdinir for oral suspension therapy, cefdinir for oral suspension should be taken at least 2 hours before or after the supplement.Iron-fortified infant formula does not significantly interfere with the absorption of cefdinir. Therefore, cefdinir for oral suspension can be administered with iron-fortified infant formula.Diabetic patients and caregivers should be aware that the oral suspension, 250 mg/5 mL contains 1.37 g of sucrose per teaspoon and 125 mg/5 mL contains 1.50 g of sucrose per teaspoon.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.

Antacids (Aluminum- Or Magnesium-Containing)

Concomitant administration of 300 mg cefdinir capsules with 30 mL Maalox


® TC suspension reduces the rate (C


max) and extent (AUC) of absorption by approximately 40%. Time to reach C


max is also prolonged by 1 hour. There are no significant effects on cefdinir pharmacokinetics if the antacid is administered 2 hours before or 2 hours after cefdinir. If antacids are required during cefdinir for oral suspension therapy, cefdinir for oral suspension should be taken at least 2 hours before or after the antacid.

Probenecid

As with other β-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) or vitamins supplemented with 10 mg of elemental iron reduced extent of absorption by 80% and 31%, respectively. If iron supplements are required during cefdinir for oral suspension therapy, cefdinir for oral suspension 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.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


®, Benedict’s solution, or Fehling’s solution. It is recommended that glucose tests based on enzymatic glucose oxidase reactions (such as Clinistix


® or Tes-Tape


®) be used. Cephalosporins are known to occasionally induce a positive direct Coombs’ test.

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 the structural chromosome aberration assay in V79 Chinese hamster lung cells or


in vivo in the micronucleus assay in mouse bone marrow. In rats, fertility and reproductive performance were not affected by cefdinir 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/day).

Pregnancy Category B

Cefdinir was not teratogenic in rats at oral doses up to 1000 mg/kg/day (70 times the human dose based on mg/kg/day, 11 times based on mg/m


2/day) or in rabbits at oral doses up to 10 mg/kg/day (0.7 times the human dose based on mg/kg/day, 0.23 times based on mg/m


2/day). Maternal toxicity (decreased body weight gain) was observed in rabbits at the maximum tolerated dose of 10 mg/kg/day without adverse effects on offspring. Decreased body weight occurred in rat fetuses at ≥ 100 mg/kg/day, and in rat offspring at ≥ 32 mg/kg/day. No effects were observed on maternal reproductive parameters or offspring survival, development, behavior, or reproductive function.


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.

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).

Cefdinir For Oral Suspension (Pediatric Patients)

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)


1Incidence ≥ 1%Diarrhea8%Rash3%Vomiting1%Incidence < 1% but > 0.1%Cutaneous moniliasis0.9%Abdominal pain0.8%Leukopenia


20.3%Vaginal moniliasis0.3% of girlsVaginitis0.3% of girlsAbnormal stools0.2%Dyspepsia0.2%Hyperkinesia0.2%Increased AST


20.2%Maculopapular rash0.2%Nausea0.2%1. 977 males, 806 females


2. Laboratory changes were occasionally reported as adverse events. 


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%↑Lymphocytes, ↓Lymphocytes2%, 0.8%↑Alkaline phosphatase1%↓Bicarbonate


11%↑Eosinophils1%↑Lactate dehydrogenase1%↑Platelets1%↑PMNs, ↓PMNs1%, 1%↑Urine protein1%Incidence < 1% but > 0.1%↑Phosphorus, ↓Phosphorus0.9%, 0.4%↑Urine pH0.8%↓White blood cells, ↑White blood cells0.7%, 0.3%↓Calcium


10.5%↓Hemoglobin0.5%↑Urine leukocytes0.5%↑Monocytes0.4%↑AST0.3%↑Potassium


10.3%↑Urine specific gravity, ↓Urine specific gravity0.3%, 0.1%↓Hematocrit


10.2% 


1. N = 1387 for these parameters

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 and


OVERDOSAGE). If seizures associated with drug therapy occur, the drug should be discontinued. Anticonvulsant therapy can be given if clinically indicated.

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 β-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.

Dosage And Administration

(See


INDICATIONS AND USAGE for Indicated Pathogens.)

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 InfectionDosageDurationAcute Bacterial Otitis Media7 mg/kg q12h5 to 10 daysor14 mg/kg q24h10 daysAcute Maxillary Sinusitis7 mg/kg q12h10 daysor14 mg/kg q24h10 daysPharyngitis/Tonsillitis7 mg/kg q12h5 to 10 daysor14 mg/kg q24h10 daysUncomplicated Skin and Skin Structure Infections7 mg/kg q12h10 daysCEFDINIR FOR ORAL SUSPENSION PEDIATRIC DOSAGE CHARTWeight125 mg/5 mL250 mg/5 mL9 kg/20 lbs2.5 mL q12h or 5 mL q24hUse 125 mg/5 mL product18 kg/40 lbs5 mL q12h or 10 mL q24h2.5 mL q12h or 5 mL q24h27 kg/60 lbs 7.5 mL q12h or 15 mL q24h 3.75 mL q12h or 7.5mL q24h 36 kg/80 lbs10 mL q12h or 20 mL q24h5 mL q12h or 10 mL q24h≥ 43 kg


1/95 lbs


12 mL q12h or 24 mL q24h6 mL q12h or 12 mL q24h1. Pediatric patient who weigh ≥43 kg should receive the maximum daily dose of 600 mg.

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) in adult patients. For estimates to be valid, serum creatinine levels should reflect steady-state levels of renal function.


Males:CL


cr =


(weight) (140 − age)(72) (serum creatinine)Females:CL


cr =


0.85 × above valuewhere creatinine clearance is in mL/min, age is in years, weight is in kilograms, and serum creatinine is in mg/dL.


1The following formula may be used to estimate creatinine clearance in pediatric patients:CL


cr = K ×


body length or heightserum creatininewhere 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.Directions for Mixing Cefdinir for Oral Suspension USPFinal 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. 10080 mLAfter mixing, the suspension can be stored at room temperature (25°C/77°F). The container should be kept tightly closed, and the suspension should be shaken well before each administration. The suspension may be used for 10 days, after which any unused portion must be discarded.

How Supplied

Cefdinir for Oral Suspension USP is a white to off-white powder formulation that, when reconstituted as directed, contains either 125 mg cefdinir/5 mL or 250 mg cefdinir/5 mL. The reconstituted suspension has a white to off-white color and cherry flavor. The powder is available as follows:125 mg/5 mL – in bottles of 60 mL (NDC 0093-4136-64) and 100 mL (NDC 0093-4136-73).250 mg/5 mL – in bottles of 60 mL (NDC 0093-4137-64) and 100 mL (NDC 0093-4137-73).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.KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.

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 RatesOverall 177/195 (91%) 184/200 (92%) Cefdinir equivalent to control S. pneumoniae 31/31 (100%) 35/35 (100%) H. influenzae 55/65 (85%) 60/72 (83%) M. catarrhalis 10/10 (100%) 11/11 (100%) H. parainfluenzae 81/89 (91%) 78/82 (95%) In a second controlled, investigator-blind study in adults and adolescents conducted primarily in Europe, cefdinir BID was compared with amoxicillin/clavulanate 500/125 mg TID. Using strict evaluability and clinical response criteria 6 to 14 days post therapy, the following clinical cure rates, presumptive microbiologic eradication rates, and statistical outcomes were obtained:


European Community-Acquired Pneumonia Study Cefdinir vs Amoxicillin/ClavulanateCefdinir BIDAmoxicillin/ Clavulanate TIDOutcomeClinical Cure Rates83/104 (80%)86/97 (89%)Cefdinir not equivalent to controlEradication RatesOverall85/96 (89%)84/90 (93%)Cefdinir equivalent to controlS. pneumoniae42/44 (95%)43/44 (98%)H. influenzae26/35 (74%)21/26 (81%)M. catarrhalis6/6 (100%)8/8 (100%)H. parainfluenzae11/11 (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)StudyEfficacy ParameterCefdinir QDCefdinir BIDPenicillin QIDOutcomeAdults/ AdolescentsEradication of


 S. pyogenes192/210 (91%)199/217 (92%)181/217 (83%)Cefdinir superior to controlClinical Cure Rates199/210 (95%)209/217 (96%)193/217 (89%)Cefdinir superior to controlPediatric PatientsEradication of


 S. pyogenes215/228 (94%)214/227 (94%)159/227 (70%)Cefdinir superior to controlClinical Cure Rates222/228 (97%)218/227 (96%)196/227 (86%)Cefdinir superior to controlTwo 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)StudyEfficacy ParameterCefdinir BIDPenicillin QIDOutcomeAdults/ AdolescentsEradication of


S. pyogenes 193/218 (89%)176/214 (82%)Cefdinir equivalent to controlClinical Cure Rates194/218 (89%)181/214 (85%)Cefdinir equivalent to controlPediatric PatientsEradication of


S. pyogenes 176/196 (90%)135/193 (70%)Cefdinir superior to controlClinical Cure Rates179/196 (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. All brand names listed are the registered trademarks of their respective owners and are not trademarks of Teva Pharmaceuticals USA, Inc.

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