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.
Safdicure (cefdinir) is contraindicated in patients with known allergy to the cephalosporin class of antibiotics.
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). 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 US, 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 US TRIALS IN ADULT AND ADOLESCENT PATIENTS (N = 3841)a
| 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 | 0.90% |
| Dyspepsia | 0.70% | |
| Flatulence | 0.70% | |
| Vomiting | 0.70% | |
| Abnormal stools | 0.30% | |
| Anorexia | 0.30% | |
| Constipation | 0.30% | |
| Dizziness | 0.30% | |
| Dry mouth | 0.30% | |
| Asthenia | 0.20% | |
| Insomnia | 0.20% | |
| Leukorrhea | 0.2% of women | |
| Moniliasis | 0.20% | |
| Pruritus | 0.20% | |
| Somnolence | 0.20% | |
| a 1733 males, 2108 females |
The following laboratory value changes of possible clinical significance, irrespective of relationship to therapy with cefdinir, were seen during clinical trials conducted in the US:
LABORATORY VALUE CHANGES OBSERVED WITH CEFDINIR CAPSULES US TRIALS IN ADULT AND ADOLESCENT PATIENTS (N = 3841)
| Incidence ≥ 1% | ↑Urine leukocytes | 2% |
| ↑Urine protein | 2% | |
| ↑ Gamma-glutamyltransferasea | 1% | |
| ↓Lymphocytes, ↑Lymphocytes | 1%, 0.2% | |
| ↑Microhematuria | 1% | |
| Incidence < 1% but > 0.1% | ↑Glucosea | 0.90% |
| ↑Urine glucose | 0.90% | |
| ↑ White blood cells,↓White blood cells | 0.9%, 0.7% | |
| ↑ Alanine aminotransferase (ALT) | 0.70% | |
| ↑Eosinophils | 0.70% | |
| ↑Urine specific gravity,↓Urine specific gravitya | 0.6%, 0.2% | |
| ↓Bicarbonatea | 0.60% | |
| ↑Phosphorus,↓Phosphorusa | 0.6%, 0.3% | |
| ↑ Aspartate aminotransferase (AST) | 0.40% | |
| ↑ Alkaline phosphatase | 0.30% | |
| ↑ Blood urea nitrogen (BUN) | 0.30% | |
| ↓Hemoglobin | 0.30% | |
| ↑ Polymorphonuclear neutrophils (PMNs), ↓PMNs | 0.3%, 0.2% | |
| ↑Bilirubin | 0.20% | |
| ↑Lactate dehydrogenasea | 0.20% | |
| ↑Platelets | 0.20% | |
| ↑Potassiuma | 0.20% | |
| ↑Urine pHa | 0.20% | |
| a N < 3841 for these parameters |
In clinical trials, 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. 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 US, 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 cefdinirtreated patients):
ADVERSE EVENTS ASSOCIATED WITH CEFDINIR SUSPENSION US TRIALS IN PEDIATRIC PATIENTS (N = 1783)a
| Incidence ≥ 1% | Diarrhea | 8% |
| Rash | 3% | |
| Vomiting | 1% | |
| Incidence < 1% but > 0.1% | Cutaneous moniliasis | 0.90% |
| Abdominal pain | 0.80% | |
| Leukopeniab | 0.30% | |
| Vaginal moniliasis | 0.3% of girls | |
| Vaginitis | 0.3% of girls | |
| Abnormal stools | 0.20% | |
| Dyspepsia | 0.20% | |
| Hyperkinesia | 0.20% | |
| Increased ASTb | 0.20% | |
| Maculopapular rash | 0.20% | |
| Nausea | 0.20% | |
| a 977 males, 806 females b 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 US:
LABORATORY VALUE CHANGES OF POSSIBLE CLINICAL SIGNIFICANCE OBSERVED WITH CEFDINIR SUSPENSION US TRIALS IN PEDIATRIC PATIENTS (N = 1783)
| Incidence ≥ 1% | ↑Lymphocytes, ↓ Lymphocytes | 2%, 0.8% |
| ↑Alkaline phosphatase | 1% | |
| ↓Bicarbonatea | 1% | |
| ↑Eosinophils | 1% | |
| ↑Lactate dehydrogenase | 1% | |
| ↑Platelets | 1% | |
| ↑PMNs, ↓PMNs | 1%, 1% | |
| ↑Urine protein | 1% | |
| Incidence < 1% but > 0.1% | ↑Phosphorus, ↓Phosphorus | 0.9%, 0.4% |
| ↑Urine pH | 0.80% | |
| ↓White blood cells, ↑White blood cells | 0.7%, 0.3% | |
| ↓Calciuma | 0.50% | |
| ↓Hemoglobin | 0.50% | |
| ↑Urine leukocytes | 0.50% | |
| ↑Monocytes | 0.40% | |
| ↑AST | 0.30% | |
| ↑Potassiuma | 0.30% | |
| ↑Urine specific gravity, ↓Urine specific gravity | 0.3%, 0.1% | |
| ↓Hematocrita | 0.20% | |
| a N=1387 for these parameters |
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 EventsThe following adverse events and altered laboratory tests have been reported for cephalosporinclass 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.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Safdicure and other antibacterial drugs, Safdicure 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.
Safdicure (cefdinir) capsules and Safdicure (cefdinir) for oral suspension 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 Pneumoniacaused 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 Bronchitiscaused 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 Sinusitiscaused by Haemophilus influenzae (including β-lactamase producing strains), Streptococcus pneumoniae (penicillin-susceptible strains only), and Moraxella catarrhalis (including βlactamase producing strains).
NOTE: For information on use in pediatric patients, see Pediatric Use and DOSAGE AND ADMINISTRATION.
Pharyngitis/Tonsillitiscaused 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 Infectionscaused by Staphylococcus aureus (including β-lactamase producing strains) and Streptococcus pyogenes.
Pediatric PatientsAcute 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/Tonsillitiscaused 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 Infectionscaused by Staphylococcus aureus (including β-lactamase producing strains) and Streptococcus pyogenes.
BEFORE THERAPY WITH Safdicure (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 Safdicure, 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.
PRECAUTIONS GeneralPrescribing Safdicure 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 Safdicure should be reduced because high and prolonged plasma concentrations of cefdinir can result following recommended doses (see DOSAGE AND ADMINISTRATION).
Carcinogenesis, Mutagenesis, Impairment Of FertilityThe 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/m²/day).
Pregnancy Teratogenic EffectsPregnancy 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/m²/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/m²/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 DeliveryCefdinir has not been studied for use during labor and delivery.
Nursing MothersFollowing administration of single 600-mg doses, cefdinir was not detected in human breast milk.
Pediatric UseSafety 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 UseEfficacy 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).
(see INDICATIONS AND USAGE for Indicated Pathogens)
CapsulesThe 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 BID dosing. Once-daily dosing has not been studied in pneumonia or skin infections; therefore, Safdicure Capsules should be administered twice daily in these infections. Safdicure 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 |
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, Safdicure for Oral Suspension should be administered twice daily in this infection. Safdicure 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 |
Safdicure FOR ORAL SUSPENSION PEDIATRIC DOSAGE CHART
| 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 kga/95 lbs | 12 mL q12h or 24 mL q24h | 6 mL q12h or 12 mL q24h |
| a Pediatric patients who weigh > 43 kg should receive the maximum daily dose of 600 mg. |
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 (CLcr) in adult patients. For estimates to be valid, serum creatinine levels should reflect steady-state levels of renal function.
| Males: | (weight in kg) x (140 – age) |
| (72) x serum creatinine | |
| Females | CLcr =0.85 × 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:
CLcr = K × body length or height/ serum creatinine
where K = 0.55 for pediatric patients older than 1 year5 and 0.45 for infants (up to 1 year)6.
In the above equation, creatinine clearance is in mL/min/1.73 m², 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 m², the dose of cefdinir should be 7 mg/kg (up to 300 mg) given once daily.
Patients On HemodialysisHemodialysis 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 Safdicure 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.
