"The European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended approval of dalbavancin 500 mg (Xydalba, Durata Therapeutics) for acute bacterial skin and skin structure infections (ABSSSI) in ad"...
The following serious adverse reactions are also discussed elsewhere in the labeling:
- Nephrotoxicity [See WARNINGS AND PRECAUTIONS]
- Infusion-related reactions [see WARNINGS AND PRECAUTIONS]
- Clostridium difficile-associated diarrhea [see WARNINGS AND PRECAUTIONS]
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Clinical Trials Experience
Complicated Skin and Skin Structure Infections
The two Phase 3 cSSSI clinical trials (Trial 1 and Trial 2) for VIBATIV included 929 adult patients treated with VIBATIV at 10 mg/kg IV once daily. The mean age of patients treated with VIBATIV was 49 years (range 18-96). There was a slight male predominance (56%) in patients treated with VIBATIV, and patients were predominantly Caucasian (78%).
In the cSSSI clinical trials, < 1% (8/929) patients who received VIBATIV died and < 1% (8/938) patients treated with vancomycin died. Serious adverse events were reported in 7% (69/929) of patients treated with VIBATIV and most commonly included renal, respiratory, or cardiac events. Serious adverse events were reported in 5% (43/938) of vancomycin-treated patients, and most commonly included cardiac, respiratory, or infectious events. Treatment discontinuations due to adverse events occurred in 8% (72/929) of patients treated with VIBATIV, the most common events being nausea and rash (~1% each). Treatment discontinuations due to adverse events occurred in 6% (53/938) of vancomycin-treated patients, the most common events being rash and pruritus (~1% each).
The most common adverse events occurring in ≥ 10% of VIBATIV-treated patients observed in the VIBATIV Phase 3 cSSSI trials were taste disturbance, nausea, vomiting, and foamy urine.
Table 4 displays the incidence of treatment-emergent adverse drug reactions reported in ≥ 2% of patients treated with VIBATIV possibly related to the drug.
Table 4: Incidence of Treatment-Emergent Adverse Drug
Reactions Reported in ≥ 2% of VIBATIV or Vancomycin Patients Treated in
cSSSI Trial 1 and Trial 2
|Body as a Whole|
|Metabolic and Nutritional|
|* Described as a metallic or soapy taste.|
Two randomized, double-blind Phase 3 trials (Trial 1 and Trial 2) for VIBATIV included 1,503 adult patients treated with VIBATIV at 10 mg/kg IV once daily or vancomycin at 1 g IV twice daily. The mean age of patients treated with VIBATIV was 62 years (range 18-100). In patients treated with VIBATIV, 69% of the patients were white and 65% were male. In the combined VIBATIV group, 29% were VAP and 71% were HAP patients.
Table 5 summarizes deaths using Kaplan-Meier estimates at Day 28 as stratified by baseline creatinine clearance categorized into four groups. Patients with pre-existing moderate/severe renal impairment (CrCl ≤ 50 mL/min) who were treated with VIBATIV for HABP/VABP had increased mortality observed versus vancomycin in both the trials.
Table 5: 28-Day Mortality (Kaplan-Meier Estimates)
Stratified by Baseline Creatinine Clearance — All-Treated Analysis Population
|CrCl (mL/min)||Trial 1||Trial 2|
|VIBATIV N (%)||Vancomycin N (%)||Difference (95% CI)||VIBATIV N (%)||Vancomycin N (%)||Difference (95% CI)|
|> 80||143 (12.2%)||152 (14.1%)||-1.8 (-9.6, 6.0)||181 (10.5%)||181 (18.7%)||-8.2 (-15.5, -0.9)|
|> 50-80||88 (27.4%)||88 (17.7%)||9.7 (-2.7, 22.1)||96 (25.6%)||90 (27.1%)||-1.5 (-14.4, 11.3)|
|30-50||80 (34.7%)||83 (23.1%)||11.5 (-2.5, 25.5)||62 (27.7%)||68 (23.7%)||4.0 (-11.1, 19.1)|
|< 30||61 (44.3%)||51 (37.3%)||7.0 (-11.2, 25.2)||38 (61.1%)||41(42.1%)||19.0 (-2.9, 40.8)|
Serious adverse events were reported in 31% of patients treated with VIBATIV and 26% of patients who received vancomycin. Treatment discontinuations due to adverse events occurred in 8% (60/751) of patients who received VIBATIV, the most common events being acute renal failure and electrocardiogram QTc interval prolonged (~1% each). Treatment discontinuations due to adverse events occurred in 5% (40/752) of vancomycin-patients, the most common events being septic shock and multi-organ failure ( < 1%).
Table 6 displays the incidence of treatment-emergent adverse drug reactions reported in ≥ 5% of HABP/VABP patients treated with VIBATIV possibly related to the drug.
Table 6: Incidence of Treatment-Emergent Adverse Drug
Reactions Reported in ≥ 5% of VIBATIV or Vancomycin Patients Treated in
HABP/VABP Trial 1 and Trial 2
|VIBATIV (N=751)||Vancomycin (N=752)|
|Renal Failure Acute||5%||4%|
Complicated Skin and Skin Structure Infections
In cSSSI trials, the incidence of renal adverse events indicative of renal impairment (increased serum creatinine, renal impairment, renal insufficiency, and/or renal failure) was 30/929 (3%) of VIBATIV-treated patients compared with 10/938 (1%) of vancomycin-treated patients. In 17 of the 30 VIBATIV-treated patients, these adverse events had not completely resolved by the end of the trials, compared with 6 of the 10 vancomycin-treated patients. Serious adverse events indicative of renal impairment occurred in 11/929 (1%) of VIBATIVtreated patients compared with 3/938 (0.3%) of vancomycin-treated patients. Twelve patients treated with VIBATIV discontinued treatment due to adverse events indicative of renal impairment compared with 2 patients treated with vancomycin.
Increases in serum creatinine to 1.5 times baseline occurred more frequently among VIBATIV-treated patients with normal baseline serum creatinine (15%) compared with vancomycin-treated patients with normal baseline serum creatinine (7%).
Fifteen of 174 (9%) VIBATIV-treated patients ≥ 65 years of age had adverse events indicative of renal impairment compared with 16 of 755 patients (2%) < 65 years of age [see Use In Specific Populations].
Hospital-Acquired and Ventilator-Associated Bacterial Pneumonia
In the HABP/VABP trials, the incidence of renal adverse events (increased serum creatinine, renal impairment, renal insufficiency, and/or renal failure) was 10% for VIBATIV vs. 8% for vancomycin. Of the patients who had at least one renal adverse event, 54% in each treatment group recovered completely, recovered with sequelae, or were improving from the renal AE at the last visit. Three percent of VIBATIV-treated patients and 2% of vancomycintreated patients experienced at least one serious renal adverse event. Renal adverse events resulted in discontinuation of study medication in 14 VIBATIV-treated patients (2%) and 7 vancomycin-treated patients (1%).
Increases in serum creatinine to 1.5 times baseline occurred more frequently among VIBATIV-treated patients (16%) compared with vancomycin-treated patients (10%).
Forty-four of 399 (11.0%) VIBATIV-treated patients ≥ 65 years of age had adverse events indicative of renal impairment compared with 30 of 352 patients (8%) < 65 years of age [see Use In Specific Populations].
The following adverse reactions have been identified during post-approval use of VIBATIV. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Serious hypersensitivity reactions have been reported after first or subsequent doses of VIBATIV, including anaphylactic reactions. It is unknown if patients with hypersensitivity reactions to vancomycin will experience cross-reactivity to telavancin. [see Hypersensitivity Reactions]
Read the Vibativ (telavancin for injection) Side Effects Center for a complete guide to possible side effects
Drug-Laboratory Test Interactions
Effects of Telavancin on Coagulation Test Parameters
Telavancin binds to the artificial phospholipid surfaces added to common anticoagulation ests, thereby interfering with the ability of the coagulation complexes to assemble on the surface of the phospholipids and promote clotting in vitro. These effects appear to depend on the type of reagents used in commercially available assays. Thus, when measured shortly after completion of an infusion of VIBATIV, increases in the PT, INR, aPTT, and ACT have been observed. These effects dissipate over time, as plasma concentrations of telavancin decrease.
Urine Protein Tests
Telavancin interferes with urine qualitative dipstick protein assays, as well as quantitative dye methods (e.g., pyrogallol red-molybdate). However, microalbumin assays are not affected and can be used to monitor urinary protein excretion during VIBATIV treatment.
Read the Vibativ Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 12/19/2014
This monograph has been modified to include the generic and brand name in many instances.
Additional Vibativ Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Find out what women really need.