DALVANCE SIDE EFFECTS

SIDE EFFECTS

Clinical Trials Experience

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.

Adverse reactions were evaluated for 2473 patients treated with DALVANCE: 1778 patients were treated with DALVANCE in seven Phase 2/3 trials comparing DALVANCE to comparator antibacterial drugs and 695 patients were treated with DALVANCE in one Phase 3 trial comparing DALVANCE single and two-dose regimens. A causal relationship between study drug and adverse reactions was not always established. The median age of patients treated with DALVANCE was 48 years, ranging between 16 and 93 years. Patients treated with DALVANCE were predominantly male (59.5%) and White (81.2%).

Serious Adverse Reactions and Adverse Reactions Leading to Discontinuation

Serious adverse reactions occurred in 121/2473 (4.9%) of patients treated with any regimen of DALVANCE. In the Phase 2/3 trials comparing DALVANCE to comparator, serious adverse reactions occurred in 109/1778 (6.1%) of patients in the DALVANCE group and 80/1224 (6.5%) of patients in the comparator group. In a Phase 3 trial comparing DALVANCE single and two-dose regimens, serious adverse reactions occurred in 7/349 (2.0%) of patients in the DALVANCE single dose group and 5/346 (1.4%) of patients in the DALVANCE two-dose group. DALVANCE was discontinued due to an adverse reaction in 64/2473 (2.6%) patients treated with any regimen of DALVANCE. In the Phase 2/3 trials comparing DALVANCE to comparator, DALVANCE was discontinued due to an adverse reaction in 53/1778 (3.0%) of patients in the DALVANCE group and 35/1224 (2.9%) of patients in the comparator group. In a Phase 3 trial comparing DALVANCE single and two-dose regimens, DALVANCE was discontinued due to an adverse reaction in 6/349 (1.7%) of patients in the DALVANCE single dose group and 5/346 (1.4%) of patients in the DALVANCE two-dose group.

Most Common Adverse Reactions

The most common adverse reactions in patients treated with DALVANCE were nausea (4.7%), headache (3.8%), and diarrhea (3.4%). The median duration of adverse reactions was 3.0 days in patients treated with DALVANCE. In the Phase 2/3 trials comparing DALVANCE to comparator, the median duration of adverse reactions was 3.0 days for patients in the DALVANCE group and 4.0 days in patients in the comparator group. In a Phase 3 trial comparing DALVANCE single and two-dose regimens, the median duration of adverse reactions was 3.0 days for patients in the DALVANCE single and two-dose group.

Table 1 lists selected adverse reactions occurring in 2% or more of patients treated with DALVANCE in Phase 2/3 clinical trials.

 Table 1: Selected Adverse Reactions Occurring in ≥ 2% of Patients Receiving DALVANCE in Phase 2/3 Trials (Number (%) of Patients)

In the Phase 3 trial comparing the single and two-dose regimen of DALVANCE, the adverse reaction that occurred in 2% or more of patients treated with DALVANCE was nausea (3.4% in the DALVANCE single dose group and 2% in the DALVANCE two-dose group).

The following selected adverse reactions were reported in DALVANCE treated patients at a rate of less than 2% in these clinical trials:

Blood and lymphatic system disorders: anemia, hemorrhagic anemia, leucopenia, neutropenia, thrombocytopenia, petechiae, eosinophilia, thrombocytosis

Gastrointestinal disorders: gastrointestinal hemorrhage, melena, hematochezia, abdominal pain

General disorders and administration site conditions: infusion-related reactions

Hepatobiliary disorders: hepatotoxicity

Immune system disorders: anaphylactic reaction

Infections and infestations: Clostridium difficile colitis, oral candidiasis, vulvovaginal mycotic infection

Investigations: hepatic transaminases increased, blood alkaline phosphatase increased, international normalized ratio increased, blood lactate dehydrogenase increased, gamma-glutamyl transferase increased

Metabolism and nutrition disorders: hypoglycemia

Nervous system disorders: dizziness

Respiratory, thoracic and mediastinal disorders: bronchospasm

Skin and subcutaneous tissue disorders: rash, pruritus, urticaria

Vascular disorders: flushing, phlebitis, wound hemorrhage, spontaneous hematoma

Alanine Aminotransferase (ALT) Elevations

Among patients with normal baseline ALT levels treated with DALVANCE 17 (0.8%) had post-baseline ALT elevations greater than 3 times the upper limit of normal (ULN) including five subjects with post-baseline ALT values greater than 10 times ULN. Among patients with normal baseline ALT levels treated with non-DALVANCE comparators 2 (0.2%) had post-baseline ALT elevations greater than 3 times the upper limit of normal. Fifteen of the 17 patients treated with DALVANCE and one comparator patient had underlying conditions which could affect liver enzymes, including chronic viral hepatitis, history of alcohol abuse and metabolic syndrome. In addition, one DALVANCE-treated subject in a Phase 1 trial had post-baseline ALT elevations greater than 20 times ULN. ALT elevations were reversible in all subjects with follow-up assessments. No comparator-treated subject with normal baseline transaminases had post-baseline ALT elevation greater than 10 times ULN.