B which contribute to the development of CDAD. Hypertoxinproducing strains of C. difficile may cause increased morbidity and mortality, as these infections canbe refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in allpatients who present with diarrhea following antibacterial drug use. Careful medical history isnecessary since CDAD has been reported to occur over two months after the administration of
antibacterial agents.
If CDAD is suspected or confirmed, antibacterial drug use not directed against C. difficile may need tobe discontinued. Appropriate fluid and electrolyte management, protein supplementation, specificantibiotic treatment of C. difficile, and/or surgical eva luation should be instituted as clinically indicated.
5.3 Development of Drug-Resistant Bacteria
Prescribing AEMCOLO in the absence of a proven or strongly suspected bacterial infection or aprophylactic indication is unlikely to provide benefit to the patient and increases the risk of thedevelopment of drug-resistant bacteria.
6 ADVERSE REACTIONS
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction ratesobserved in the clinical trials of a drug cannot be directly compared to rates in the clinical trials ofanother drug and may not reflect the rates observed in practice.
The safety of oral AEMCOLO 388 mg twice daily was assessed in 619 adults with travelers’ diarrheain two controlled clinical trials (Trial 1 and Trial 2) with 96% of patients receiving three or four days oftreatment. These patients had a mean age of 36.2 years (range 18 to 87 years) with 7% ≥ 65 yearsold; 49% were male, 84% were White, and 4% were Hispanic.
Discontinuation of AEMCOLO due to adverse reactions occurred in 1% of patients. The most frequentadverse reactions leading to discontinuation of AEMCOLO were abdominal pain (0.5%) and pyrexiaIn Trial 1 (placebo-controlled), the adverse reaction that occurred in at least 2% of AEMCOLO-treatedpatients (n = 199) and with an incidence higher than in the placebo group was constipation (3.5%AEMCOLO, 1.5% placebo)
In Trial 2 (active comparator), the adverse reaction that occurred in at least 2% of AEMCOLO-treatedpatients (n = 420) and with an incidence higher than in the ciprofloxacin group was headache (3.3%AEMCOLO, 1.9% ciprofloxacin)Adverse reactions reported in <2% of patients receiving AEMCOLO 388 mg twice daily with a higher
incidence than the comparator group was dyspepsia.
7 DRUG INTERACTIONS
No clinical Drug-Drug Interactions (DDIs) have been studied. Based on the minimal systemicrifamycin concentrations observed after the recommended dose of AEMCOLO, clinically relevantDDIs are not expected [see Clinical Pharmacology (12.3)]
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
There are no available data on AEMCOLO use in pregnant women to inform any drug associatedrisks for major birth defects, miscarriage, or adverse maternal or fetal outcomes. Systemic absorptionof AEMCOLO in humans is negligible following oral administration of the recommended dose ofAEMCOLO [see Clinical Pharmacology (12.3)].
Due to the negligible systemic exposure, it is notexpected that maternal use of AEMCOLO will result in fetal exposure to the drug.
In animal reproduction studies, no malformations were observed in pregnant rats or rabbits atexposures 25,000 and 500 times (based on AUC), respectively, the human exposure a |
