cefdinir 50 MG/ML Oral Suspension

Details

Generic Name: CEFDINIR

Brand Name: Cefdinir

Substance Name(s):
CEFDINIR

WARNINGS

BEFORE THERAPY WITH CEFDINIR 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.

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.

DRUG INTERACTIONS

Drug Interactions 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 therapy, cefdinir 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 therapy, cefdinir should be taken at least 2 hours before or after the supplement.

The effect of foods highly fortified with elemental iron (primarily iron-fortified breakfast cereals) on cefdinir absorption has not been studied.

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.

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.

DESCRIPTION

Cefdinir for oral suspension, USP contains the active ingredient cefdinir USP, an extended-spectrum, semisynthetic cephalosporin, for oral administration.

Chemically, cefdinir is [6R-[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.

Cefdinir USP is a white to slightly brownish-yellow solid.

It is slightly soluble in dilute hydrochloric acid and sparingly soluble in 0.1 M pH 7.0 phosphate buffer.

The molecular formula is C 14 H 13 N 5 O 5 S 2 and the molecular weight is 395.42.

Cefdinir has the structural formula shown below: Cefdinir for oral suspension, USP after reconstitution, contains 125 mg cefdinir USP per 5 mL or 250 mg cefdinir USP per 5 mL and the following inactive ingredients: sucrose, sodium benzoate, colloidal silicone dioxide, xanthan gum, guar gum, citric acid (anhydrous), sodium citrate (dihydrate), strawberry flavour, fresh cream flavour and magnesium stearate.

Chemical Structure

CLINICAL STUDIES

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 posttherapy, 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 Rates Overall 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 posttherapy, the following clinical cure rates, presumptive microbiologic eradication rates, and statistical outcomes were obtained: European Community-Acquired Pneumonia Study Cefdinir vs Amoxicillin/Clavulanate Cefdinir BID Amoxicillin/ Clavulanate TID Outcome Clinical Cure Rates 83/104 (80%) 86/97(89%) Cefdinir not equivalent to control Eradication Rates Overall 85/96 (89%) 84/90 (93%) Cefdinir equivalent to control S.

pneumoniae 42/44 (95%) 43/44 (98%) H.

influenzae 26/35 (74%) 21/26 (81%) M.

catarrhalis 6/6 (100%) 8/8 (100%) H.

parainfluenzae 11/11 (100%) 12/12 (100%) Streptococcal Pharyngitis/Tonsillitis In four controlled studies conducted in the United States, cefdinir was compared with 10 days of penicillin in adult, adolescent, and pediatric patients.

Two studies (one in adults and adolescents, the other in pediatric patients) compared 10 days of cefdinir QD or BID to penicillin 250 mg or 10 mg/kg QID.

Using strict evaluability and microbiologic/clinical response criteria 5 to 10 days posttherapy, the following clinical cure rates, microbiologic eradication rates, and statistical outcomes were obtained: Pharyngitis/Tonsillitis Studies Cefdinir (10 days) vs Penicillin (10 days) Study Efficacy Parameter Cefdinir QD Cefdinir BID Penicillin QID Outcome Adults/ Adolescents Eradication of S.

pyogenes 192/210 (91%) 199/217 (92%) 181/217 (83%) Cefdinir superior to control Clinical Cure Rates 199/210 (95%) 209/217 (96%) 193/217 (89%) Cefdinir superior to control Pediatric Patients Eradication of S.

pyogenes 215/228 (94%) 214/227 (94%) 159/227 (70%) Cefdinir superior to control Clinical Cure Rates 222/228 (97%) 218/227 (96%) 196/227 (86%) Cefdinir superior to control Two studies (one in adults and adolescents, the other in pediatric patients) compared 5 days of cefdinir BID to 10 days of penicillin 250 mg or 10 mg/kg QID.

Using strict evaluability and microbiologic/clinical response criteria 4 to 10 days posttherapy, the following clinical cure rates, microbiologic eradication rates, and statistical outcomes were obtained: Pharyngitis/Tonsillitis Studies Cefdinir (5 days) vs Penicillin (10 days) Study Efficacy Parameter Cefdinir BID Penicillin QID Outcome Adults/ Adolescents Eradication of S.

pyogenes 193/218 (89%) 176/214 (82%) Cefdinir equivalent to control Clinical Cure Rates 194/218 (89%) 181/214 (85%) Cefdinir equivalent to control Pediatric Patients Eradication of S.

pyogenes 176/196 (90%) 135/193 (70%) Cefdinir superior to control Clinical Cure Rates 179/196 (91%) 173/193 (90%) Cefdinir equivalent to control

HOW SUPPLIED

Cefdinir for Oral 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) [see USP Controlled Room Temperature].

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

GERIATRIC USE

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 ).

INDICATIONS AND USAGE

To reduce the development of drug-resistant bacteria and maintain the effectiveness of cefdinir and other antibacterial drugs, cefdinir 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 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.

Adults and Adolescents 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 PRECAUTIONS, Pediatric Use and DOSAGE AND ADMINISTRATION .

Pharyngitis/Tonsillitis caused by Streptococcus pyogenes (see CLINICAL STUDIES ).

NOTE: Cefdinir is effective in the eradication of S.

pyogenes from the oropharynx.

Cefdinir has not, however, been studied for the prevention of rheumatic fever following S.

pyogenes pharyngitis/tonsillitis.

Only intramuscular penicillin has been demonstrated to be effective for the prevention of rheumatic fever.

Uncomplicated Skin and Skin Structure Infections caused by Staphylococcus aureus (including β-lactamase producing strains) and Streptococcus pyogenes .

Pediatric Patients Acute Bacterial Otitis Media caused by Haemophilus influenzae (including β-lactamase producing strains), Streptococcus pneumoniae (penicillin-susceptible strains only), and Moraxella catarrhalis (including β-lactamase producing strains).

Pharyngitis/Tonsillitis caused by Streptococcus pyogenes (see CLINICAL STUDIES ).

NOTE: Cefdinir is effective in the eradication of S.

pyogenes from the oropharynx.

Cefdinir has not, however, been studied for the prevention of rheumatic fever following S.

pyogenes pharyngitis/tonsillitis.

Only intramuscular penicillin has been demonstrated to be effective for the prevention of rheumatic fever.

Uncomplicated Skin and Skin Structure Infections caused by Staphylococcus aureus (including β-lactamase producing strains) and Streptococcus pyogenes .

PEDIATRIC USE

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.

PREGNANCY

Pregnancy Teratogenic Effects 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.

NUSRING MOTHERS

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

INFORMATION FOR PATIENTS

Information for Patients Patients should be counseled that antibacterial drugs including cefdinir should only be used to treat bacterial infections.

They do not treat viral infections (e.g., the common cold).

When cefdinir 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 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 therapy, cefdinir 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 therapy, cefdinir 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 125 mg/5 mL oral suspension contains 2.94 g of sucrose per teaspoon and the 250 mg/5 mL oral suspension contains 2.82 g of sucrose for 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.

DOSAGE AND ADMINISTRATION

(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.

Pediatric 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 5 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 5 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.

Males: CL cr = (weight) (140 – age) (72) (serum creatinine) Females: CL cr = 0.85 x above value where creatinine clearance is in mL/min, age is in years, weight is in kilograms, and serum creatinine is in mg/dL.

1 The following formula may be used to estimate creatinine clearance in pediatric patients: CL cr = K x body length or height serum creatinine where K=0.55 for pediatric patients older than 1 year 2 and 0.45 for infants (up to 1 year) 3 .

In the above equation, creatinine clearance is in mL/min/1.73 m 2 , body length or height is in centimeters, and serum creatinine is in mg/dL.

For pediatric patients with a creatinine clearance of <30 mL/min/1.73 m 2 , the dose of cefdinir should be 7 mg/kg (up to 300 mg) given once daily.

Patients on Hemodialysis Hemodialysis removes cefdinir from the body.

In patients maintained on chronic hemodialysis, the recommended initial dosage regimen is a 300 mg or 7 mg/kg dose every other day.

At the conclusion of each hemodialysis session, 300 mg (or 7 mg/kg) should be given.

Subsequent doses (300 mg or 7 mg/kg) are then administered every other day.

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.