Telavancin clinical pharmacology: Difference between revisions
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==Clinical Pharmacology== | |||
===Mechanism of Action=== | |||
<ref name="dailymed.nlm.nih.gov">{{Cite web | last = | first = | title = VIBATIV (TELAVANCIN HYDROCHLORIDE) INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION [ASTELLAS PHARMA US INC.] | url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=5e7c066c-0950-47ce-899d-76881d80c492 | publisher = | date = | accessdate = }}</ref> | Telavancin is an antibacterial drug [see Clinical Pharmacology]. | ||
===Pharmacodynamics=== | |||
The antimicrobial activity of telavancin appears to best correlate with the ratio of area under the concentration-time curve to minimal inhibitory concentration (AUC/MIC) for [[Staphylococcus aureus]] based on animal models of infection. An exposure-response analysis of 2 cSSSI clinical trials supports the dose of 10 mg/kg every 24 hours. | |||
====Cardiac Electrophysiology==== | |||
The effect of telavancin on cardiac repolarization was assessed in a randomized, double-blind, multiple-dose, positive-controlled, and placebo-controlled, parallel study (n=160). Healthy subjects received VIBATIV 7.5 mg/kg, VIBATIV 15 mg/kg, positive control, or placebo infused over 60 minutes once daily for 3 days. Based on interpolation of the data from VIBATIV 7.5 mg/kg and 15 mg/kg, the mean maximum baseline-corrected, placebo-corrected QTc prolongation at the end of infusion was estimated to be 12-15 msec for VIBATIV 10 mg/kg and 22 msec for the positive control (Table 5). By 1 hour after infusion the maximum QTc prolongation was 6-9 msec for VIBATIV and 15 msec for the positive control. | |||
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ECGs were performed prior to and during the treatment period in patients receiving VIBATIV 10 mg/kg in 3 studies to monitor QTc intervals. In these trials, 214 of 1029 (21%) patients allocated to treatment with VIBATIV and 164 of 1033 (16%) allocated to [[vancomycin]] received concomitant medications known to prolong the QTc interval and are known to be associated with definite or possible risk of torsades de pointes. The incidence of QTc prolongation >60 msec was 1.5% (15 patients) in the VIBATIV group and 0.6% (6 patients) in the vancomycin group. Nine of the 15 VIBATIV patients received concomitant medications known to prolong the QTc interval and definitely or possibly associated with a risk of [[torsades de pointes]], compared with 1 of the 6 patients who received vancomycin. A similar number of patients in each treatment group (<1%) who did not receive a concomitant medication known to prolong the QTc interval experienced a prolongation >60 msec from baseline. In a separate analysis, 1 patient in the VIBATIV group and 2 patients in the vancomycin group experienced QTc >500 msec. No cardiac adverse events were ascribed to prolongation of the QTc interval.<ref name="dailymed.nlm.nih.gov">{{Cite web | last = | first = | title = VIBATIV (TELAVANCIN HYDROCHLORIDE) INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION [ASTELLAS PHARMA US INC.] | url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=5e7c066c-0950-47ce-899d-76881d80c492 | publisher = | date = | accessdate = }}</ref> | |||
Revision as of 23:06, 9 January 2014
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Chetan Lokhande, M.B.B.S [2]
Clinical Pharmacology
Mechanism of Action
Telavancin is an antibacterial drug [see Clinical Pharmacology].
Pharmacodynamics
The antimicrobial activity of telavancin appears to best correlate with the ratio of area under the concentration-time curve to minimal inhibitory concentration (AUC/MIC) for Staphylococcus aureus based on animal models of infection. An exposure-response analysis of 2 cSSSI clinical trials supports the dose of 10 mg/kg every 24 hours.
Cardiac Electrophysiology
The effect of telavancin on cardiac repolarization was assessed in a randomized, double-blind, multiple-dose, positive-controlled, and placebo-controlled, parallel study (n=160). Healthy subjects received VIBATIV 7.5 mg/kg, VIBATIV 15 mg/kg, positive control, or placebo infused over 60 minutes once daily for 3 days. Based on interpolation of the data from VIBATIV 7.5 mg/kg and 15 mg/kg, the mean maximum baseline-corrected, placebo-corrected QTc prolongation at the end of infusion was estimated to be 12-15 msec for VIBATIV 10 mg/kg and 22 msec for the positive control (Table 5). By 1 hour after infusion the maximum QTc prolongation was 6-9 msec for VIBATIV and 15 msec for the positive control.
| [[File:|800px|thumb]] |
ECGs were performed prior to and during the treatment period in patients receiving VIBATIV 10 mg/kg in 3 studies to monitor QTc intervals. In these trials, 214 of 1029 (21%) patients allocated to treatment with VIBATIV and 164 of 1033 (16%) allocated to vancomycin received concomitant medications known to prolong the QTc interval and are known to be associated with definite or possible risk of torsades de pointes. The incidence of QTc prolongation >60 msec was 1.5% (15 patients) in the VIBATIV group and 0.6% (6 patients) in the vancomycin group. Nine of the 15 VIBATIV patients received concomitant medications known to prolong the QTc interval and definitely or possibly associated with a risk of torsades de pointes, compared with 1 of the 6 patients who received vancomycin. A similar number of patients in each treatment group (<1%) who did not receive a concomitant medication known to prolong the QTc interval experienced a prolongation >60 msec from baseline. In a separate analysis, 1 patient in the VIBATIV group and 2 patients in the vancomycin group experienced QTc >500 msec. No cardiac adverse events were ascribed to prolongation of the QTc interval.[1]
References
Adapted from the FDA Package Insert.