Cefdinir

Description

DESCRIPTION Cefdinir capsules contain the active ingredient cefdinir, 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 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 empirical 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 capsules contain 300 mg cefdinir and the following inactive ingredients: carboxymethylcellulose calcium, colloidal silicone dioxide, magnesium stearate, and polyoxyl 40 stearate. The capsule shells contain FD&C Blue #2; gelatin, titanium dioxide. The printing ink ingredients are shellac, propylene glycol, black iron oxide, ammonia hydroxide, and potassium hydroxide. cefdinir-chemical-structure

What Is Cefdinir Used For?

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 capsules are 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 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...

Dosage and Administration

DOSAGE AND ADMINISTRATION (see INDICATIONS AND USAGE for Indicated Pathogens) The recommended dosage and duration of treatment for infections in adults and adolescents are described in the following chart; the total daily dose for all infections is 600 mg. Once-daily dosing for 10 days is as effective as b.i.d. dosing. Once-daily dosing has not been studied in pneumonia or skin infections; therefore, cefdinir capsules should be administered twice daily in these infections. Cefdinir capsules may be taken without regard to meals. Adults and Adolescents (Age 13 Years and Older) Type of Infection Dosage Duration Community-Acquired Pneumonia 300 mg q12h 10 days Acute Exacerbations of Chronic Bronchitis 300 mg q12h or 600 mg q24h 5 to 10 days 10 days Acute Maxillary Sinusitis 300 mg q12h or 600 mg q24h 10 days 10 days Pharyngitis/Tonsillitis 300 mg q12h or 600 mg q24h 5 to 10 days 10 days Uncomplicated Skin and Skin Structure Infections 300 mg q12h 10 days 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. 4 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 5 and 0.45 for infants (up to 1 year). 6 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.

Side Effects (Adverse Reactions)

ADVERSE EVENTS Clinical Trials Cefdinir Capsules (Adult and Adolescent Patients) In clinical trials, 5093 adult and adolescent patients (3841 U.S. and 1252 non-U.S.) were treated with the recommended dose of cefdinir capsules (600 mg/day). Most adverse events were mild and self-limiting. No deaths or permanent disabilities were attributed to cefdinir. One hundred forty-seven of 5093 (3%) 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, usually diarrhea or nausea. Nineteen of 5093 (0.4%) 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 capsules in multiple-dose clinical trials (N=3841 cefdinir-treated patients): Adverse Events Associated with Cefdinir Capsules U.S. Trials in Adult and Adolescent Patients (N=3841) 1733 males, 2108 females Incidence ≥ 1% Diarrhea 15% Vaginal moniliasis 4% of women Nausea 3% Headache 2% Abdominal pain 1% Vaginitis 1% of women Incidence < 1% but > 0.1% Rash 0.9% Dyspepsia 0.7% Flatulence 0.7% Vomiting 0.7% Abnormal stools 0.3% Anorexia 0.3% Constipation 0.3% Dizziness 0.3% Dry mouth 0.3% Asthenia 0.2% Insomnia 0.2% Leukorrhea 0.2% of women Moniliasis 0.2% Pruritus 0.2% Somnolence 0.2% 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 Observed with Cefdinir Capsules U.S. Trials in Adult and Adolescent Patients (N=3841) Incidence ≥ 1% ↑Urine leukocytes 2% ↑Urine protein 2% ↑Gamma-glutamyltransferase N < 3841 for these parameters 1% ↓Lymphocytes, ↑Lymphocytes 1%, 0.2% ↑Microhematuria 1% Incidence < 1% but > 0.1% ↑Glucose 0.9% ↑Urine glucose 0.9% ↑White blood cells, ↓White blood cells 0.9%, 0.7% ↑Alanine aminotransferase (ALT) 0.7% ↑Eosinophils 0.7% ↑Urine specific gravity, ↓Urine specific gravity 0.6%, 0.2% ↓Bicarbonate 0.6% ↑Phosphorus, ↓Phosphorus 0.6%, 0.3% ↑Aspartate aminotransferase (AST) 0.4% ↑Alkaline phosphatase 0.3% ↑Blood urea nitrogen (BUN) 0.3% ↓Hemoglobin 0.3% ↑Polymorphonuclear neutrophils (PMNs), ↓PMNs 0.3%, 0.2% ↑Bilirubin 0.2% ↑Lactate dehydrogenase 0.2% ↑Platelets 0.2% ↑Potassium 0.2% ↑Urine pH 0.2%

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 1/2 . 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. 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.

Contraindications

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

Pregnancy and Breastfeeding

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.

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

Overdosage

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.

How Supplied

HOW SUPPLIED Cefdinir capsules, containing 300 mg cefdinir, are blue, opaque hard gelatin capsules imprinted with “Sandoz 663” and are supplied as follows: NDC 0781-2176-60 in bottles of 60 capsules NDC 0781-2176-01 in bottles of 100 capsules NDC 0781-2176-64 in unit dose cartons of 10 (1 x 10) capsule-blisters - 3 cartons packed in 1 unit dose carton of 30 (3 x 10) NDC 0781-2176-69 in unit dose cartons of 50 (5 x 10) capsule-blisters Store at 20°-25°C (68°-77°F) [See USP Controlled Room Temperature].