uding DALVANCE, with severity ranging from mild diarrhea to fatal colitis. Treatment with antibacterial agents can alter the normal flora of the colon, and may permit 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 antibacterial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial use. Careful medical history is necessary because CDAD has been reported to occur more than 2 months after the administration of antibacterial agents.
If CDAD is suspected or confirmed, ongoing antibacterial use not directed against C. difficile should be discontinued, if possible. Appropriate measures such as fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile, and surgical eva luation should be instituted as clinically indicated.
5.5 Development of Drug-Resistant BacteriaPrescribing DALVANCE in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
6 ADVERSE REACTIONS
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of DALVANCE cannot be directly compared to rates in the clinical trials of another drug and may not reflect rates observed in practice.
6.1 Adverse Reactions in Clinical TrialsAdverse reactions were eva luated for 1778 patients treated with DALVANCE and 1224 patients treated with comparator antibacterial drugs in seven Phase 2 and Phase 3 clinical trials. A causal relationship between study drug and adverse reactions was not always established. The median age of patients treated with DALVANCE was 47 years, ranging between 16 and 93 years old. Patients treated with DALVANCE were predominantly male (60%) and Caucasian (78%).
Serious Adverse Reactions and Adverse Reactions Leading to Discontinuation
Serious adverse reactions occurred in 109/1778 (6.1%) of patients treated with DALVANCE and in 80/1224 (6.5%) of patients treated with comparator. DALVANCE was discontinued due to an adverse reaction in 53/1778 (3%) patients and the comparator was discontinued due to an adverse reaction in 35/1224 (2.8%) patients.
Most Common Adverse Reactions
The most common adverse reactions in patients treated with DALVANCE were nausea (5.5%), headache (4.7%), and diarrhea (4.4%). The median duration of adverse reactions was 4.0 days in both treatment groups.
Table 1 lists selected adverse reactions occurring in more than 2% of patients treated with DALVANCE in clinical trials.
Table1. Selected Adverse Reactions in Phase 2/3 Trials
(Number (%) of Patients)
Dalbavancin Comparator*
(N = 1778) (N = 1224)
Nausea
98 (5.5)
78 (6.4)
Vomiting
50 (2.8)
37 (3)
Diarrhea
79 (4.4)
72 (5.9)
Headache
83 (4.7)
59 (4.8)
Rash
48 (2.7)
30 (2.4)
Pruritus
38 (2.1)
41 (3.3)
* Comparators included linezolid, cefazolin, cephalexin, and vancomycin.
The following selected adverse reactions were reported in DA |
