AZORD

Cefdinir, also known as Omnicef, is a semi-synthetic, broad-spectrum antibiotic belonging to the third generation of the cephalosporin class.

It has been proven to be effective for the treatment of common bacterial infections in the ear, sinus, throat, lungs, and skin.

Cefdinir was approved by the

FDA in to treat a variety of mild to moderate infections and was initially marketed by Abbvie.

Because of its chemical structure, it is effective against organisms that are resistant to first-line cephalosporin therapy due to the production of beta-lactamase enzymes. 2, 3.

Cefdinir is indicated to treat acute bacterial otitis media, acute maxillary sinusitis, community-acquired (CA) pneumonia, acute bacterial exacerbations of chronic bronchitis, pharyngitis/tonsillitis, and uncomplicated skin and skin structure infections in children and adults. 14, 6 The organisms susceptible to cefdinir have been listed below in addition to their associated clinical condition that may be treated with cefdinir.

Various beta-lactamase producing organisms may be treated, as indicated in certain sections below.

Acute bacterial exacerbations of chronic bronchitis caused by Haemophilus influenzae, Haemophilus parainfluenzae, Streptococcus pneumoniae (penicillin-susceptible only), and Moraxella catarrhalis Community-acquired pneumonia caused by Haemophilus influenzae, Haemophilus parainfluenzae, Streptococcus pneumoniae (penicillin-susceptible only), and Moraxella catarrhalis Ear, nose, and throat Acute bacterial otitis media caused by Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae (penicillin-susceptible only) Tonsillitis caused by Streptococcus pyogenes Pharyngitis caused by Streptococcus pyogenes Acute maxillary sinusitis caused by Haemophilus pneumoniae and Streptococcus pneumoniae (penicillin-susceptible only), and Moraxella catarrhalis Skin and skin structure infections Uncomplicated skin and skin structure infections caused by Staphylococcus aureus and Streptococcus pyogenes

Cefdinir is a bactericidal agent that treats bacterial infections by interfering with cell wall synthesis.

Cefdinir exerts broad-spectrum activity against a variety of gram-positive and gram-negative bacterial infections.

It is effective against several beta-lactamase enzyme producing bacteria.

As a result, many organisms that are resistant to other cephalosporins may be susceptible to cefdinir. 3, 4, 17.

Probable peptidoglycan

D,D-transpeptidase PenA (Neisseria gonorrhoeae) Inhibitor Peptidoglycan D,D-transpeptidase FtsI (Haemophilus influenzae) Inhibitor.

Maximal plasma cefdinir concentration can be attained between 2-4 hours after an ingested dose.

The bioavailability of cefdinir depends on the formulation used.

The estimated bioavailability of cefdinir in the capsule form is approximately 16%-21%, depending on the dose.

Absolute bioavailability after the administration of a suspension of cefdinir is 25%. 2.

Cmax of cefdinir is 1.60 μg/mL after a 300 mg dose with an AUC of 7.05.

Cmax is 2.87 μg/mL after a 600 mg dose with an AUC of 11.

A meal high in fat can reduce the absorption of cefdinir by up to 15%, however, this is not a cause for clinically significant changes, therefore cefdinir may be taken with or without food.

When given with aluminum or magnesium-containing antacids or iron, cefdinir absorption may decrease.

It is recommended to allow 2 hours between cefdinir administration and the administration of these agents.

The average volume of distribution of cefdinir in adults is about 0.35 L/kg and 0.67 L/kg in children. 14, 18 Another resource estimates the volume of distribution in adults at 1.56–2.09 L/kg.

Cefdinir is found to be distributed in various tissues at clinically effective concentrations.

It may be found in the epithelial lining fluid, bronchial mucosa, tonsils, sinuses, skin blister fluid, as well as the middle ear fluid.

Third-generation cephalosporins such as cefdinir cross the blood-brain barrier and are found in high concentrations in the cerebrospinal fluid, unlike their first and second generation counterparts.

The wide tissue distribution of cefdinir allows it to treat a variety of infections throughout the body.

This drug is not significantly metabolized and its pharmacological actions are mainly attributed to the parent drug. 2, 14.

This drug is mainly excreted by the kidneys.

Dose adjustments may be required for patients with renal impairment or patients on dialysis.

Approximately 18.4% of a 300 mg dose of cefdinir was found unchanged in the urine after a 300 mg dose was administered during a pharmacokinetic study of 21 individuals.

A large proportion of the administered dose is excreted in the feces, although the majority is found in the urine.

The average plasma elimination half-life is about 1.7 hours in adults.

In children and healthy infants, plasma elimination half-life ranges from 1.2–1.5 hours.

The renal clearance in healthy adults in a pharmacokinetic study was 2.0 (± 1.0) mL/min/kg and the clearance in patients with renal failure was lower, decreasing in proportion to the degree of renal impairment.

Dose adjustment is required in patients with renal impairment.

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LD50 of cefdinir in the rat is >2000 mg/kg.

There are limited data regarding cefdinir overdose in the literature.

In studies of rodents, one 5600-mg/kg dose administered Oral did not lead to adverse effects.

Signs of toxicity and overdose caused by other beta-lactam antibiotics included nausea, vomiting, diarrhea, abdominal pain, and seizures.

β-LACTAM ANTIBIOTICS HAS BEEN CLEARLY DOCUMENTED AND MAY OCCUR IN UP TO 10% OF PATIENTS WITH A HISTORY OF PENICILLIN ALLERGY.

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.

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

See INDICATIONS AND USAGE for Indicated Pathogens 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 should be administered twice daily in this infection.

Cefdinir for oral suspension may be administered without regard to meals.

Patients (Age 6 Months Through 12 Years) Type of Infection Dosage Duration Acute Bacterial Otitis Media 7 mg/kg q12h or 14 mg/kg q24h to 10 days 10 days Acute Maxillary Sinusitis 7 mg/kg q12h or 14 mg/kg q24h 10 days 10 days Pharyngitis/Tonsillitis 7 mg/kg q12h or 14 mg/kg q24h to 10 days 10 days Uncomplicated Skin and Skin Structure.

Infections 7 mg/kg q12h 10 days CEFDINIR FOR ORAL SUSPENSION PEDIATRIC DOSAGE CHART a Pediatric patients who weigh ≥ 43 kg should receive the maximum daily dose of 600 mg. Weight 125 mg/5 mL 250 mg/5 mL 9 kg/20 lbs 2.5 mL q12h or 5 mL q24h Use 125 mg/5 mL product 18 kg/40 lbs 5 mL q12h or 10 mL q24h 2.5 mL q12h or 5 mL q24h 27 kg/60 lbs 7.5 mL q12h or 15 mL q24h 3.75 mL q12h or 7.5 mL q24h 36 kg/80 lbs 10 mL q12h or 20 mL q24h 5 mL q12h or 10 mL q24h ≥ 43 kg a /95 lbs 12 mL q12h or 24 mL q24h 6 mL q12h or 12 mL q24h 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.

CL cr = (weight) (140 – age) (serum creatinine) Females: CL cr = 0.85 x above value where creatinine clearance is in mL/min, age is in years, weight is in kilograms, and serum creatinine is in mg/dL.

The following formula may be used to estimate creatinine clearance in pediatric patients: CL cr = K x body length or height serum creatinine where K=0.55 for pediatric patients older than 1 year 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.

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 Final Concentration Final Volume (mL) Amount of Water Directions 125 mg/5 mL 60 100 38 mL 63 mL Tap bottle to loosen powder, then add water in 2 portions.

Shake well after each aliquot. 250 mg/5 mL 60 100 38 mL 63 mL Tap bottle to loosen powder, then add water in 2 portions.

Shake well after each aliquot.

After 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.

Suspension, USP 125 mg/5 mL is a off-white to yellowish — white colored granular powder, on constitution with water, forming an off-white to yellowish-white colored suspension with strawberry and cream flavors. 60 mL Bottle NDC 65862-218-60 100 mL Bottle NDC 65862-218-01 Cefdinir for Oral Suspension, USP 250 mg/5 mL is a off-white to yellowish — white colored granular powder, on constitution with water, forming an off-white to yellowish-white colored suspension with strawberry and cream flavors. 60 mL Bottle NDC 65862-219-60 100 mL Bottle NDC 65862-219-01 Store dry powder at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) .

Once reconstituted, the oral suspension can be stored at controlled room temperature for 10 days.

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.

Following administration of single 600 mg doses, cefdinir was not detected in human breast milk.

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.

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.