Adverse Events
Clinical Trials - OMNICEF Capsules (Adult and Adolescent Patients)
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 |
|
a 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 US:
LABORATORY VALUE CHANGES OBSERVED WITH CEFDINIR CAPSULES
US TRIALS IN ADULT AND ADOLESCENT PATIENTS
(N = 3841) |
|
a N < 3841 for these parameters
|
| Incidence ≥ 1% | ↑Urine leukocytes | 2% |
| ↑Urine protein | 2% |
| ↑Gamma-glutamyltransferasea | 1% |
| ↓Lymphocytes, ↑Lymphocytes | 1%, 0.2% |
| ↑Microhematuria | 1% |
| Incidence < 1% but > 0.1% | ↑Glucosea | 0.9% |
| ↑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 gravitya | 0.6%, 0.2% |
| ↓Bicarbonatea | 0.6% |
| ↑Phosphorus, ↓Phosphorusa | 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 dehydrogenasea | 0.2% |
| ↑Platelets | 0.2% |
| ↑Potassiuma | 0.2% |
| ↑Urine pHa | 0.2% |
Clinical Trials - OMNICEF for Oral Suspension (Pediatric Patients)
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 cefdinir-treated patients):
ADVERSE EVENTS ASSOCIATED WITH CEFDINIR SUSPENSION
US TRIALS IN PEDIATRIC PATIENTS
(N = 1783)a |
|
a 977 males, 806 females
b Laboratory changes were occasionally reported as adverse events.
|
| Incidence ≥ 1% | Diarrhea | 8% |
| Rash | 3% |
| Vomiting
| 1%
|
| Incidence < 1% but > 0.1% | Cutaneous moniliasis | 0.9% |
| Abdominal pain | 0.8% |
| Leukopeniab | 0.3% |
| Vaginal moniliasis | 0.3% of girls |
| Vaginitis | 0.3% of girls |
| Abnormal stools | 0.2% |
| Dyspepsia | 0.2% |
| Hyperkinesia | 0.2% |
| Increased ASTb | 0.2% |
| Maculopapular rash | 0.2% |
| Nausea | 0.2% |
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) |
|
a N=1387 for these parameters
|
| 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 | 0.8% |
| ↓White blood cells, ↑White blood cells | 0.7%, 0.3% |
| ↓Calciuma | 0.5% |
| ↓Hemoglobin | 0.5% |
| ↑Urine leukocytes | 0.5% |
| ↑Monocytes | 0.4% |
| ↑AST | 0.3% |
| ↑Potassiuma | 0.3% |
| ↑Urine specific gravity, ↓Urine specific gravity | 0.3%, 0.1% |
| ↓Hematocrita | 0.2% |
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.
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