European Commission has granted marketing authorization for Vibativ ( Telavancin hydrochloride ), following the Committee for Human Medicinal Products' positive opinion in May 2011.

Vibativ is a bactericidal, once-daily injectable lipoglycopeptide antibacterial agent with a dual mechanism of action against gram-positive bacteria, including resistant pathogens such as Methicillin-Resistant Staphylococcus Aureus ( MRSA ).

The Vibativ marketing authorization from the European Commission is granted for treating adults with nosocomial pneumonia, including ventilator-associated pneumonia, known or suspected to be caused by MRSA when other alternatives are not suitable.

Vibativ is approved in the United States and in Canada for the treatment of adult patients with complicated skin and skin structure infections ( cSSSI ) caused by susceptible isolates of the following Gram-positive microorganisms: Staphylococcus aureus ( including Methicillin-susceptible and -resistant isolates ), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus anginosus group ( includes S. anginosus, S. intermedius and S. constellatus ) and Enterococcus faecalis ( Vancomycin-susceptible isolates only ).

Vibativ has not been approved for the treatment of patients with nosocomial pneumonia in the United States and Canada or complicated skin and soft tissue infections in Europe.

Patients with nosocomial pneumonia suspected or proven to be caused by Gram-positive bacteria were enrolled in the ATTAIN program. This included ATTAIN I and ATTAIN II, two large, multi-center, multinational, double-blind, randomized phase 3 clinical studies, in which 1,503 patients were enrolled and treated either with Telavancin 10 mg/kg IV once daily or Vancomycin 1 g IV every 12hr ( the protocols allowed Vancomycin dosage to be modified per site-specific guidelines ). For patients with suspected or proven polymicrobial infections involving Gram-negative and/or anaerobic bacteria in addition to the Gram-positive organisms for which study medication therapy was used, Aztreonam and Piperacillin - Tazobactam were allowed. The objective of each study was non-inferiority of Telavancin versus Vancomycin in clinical cure rate at the test-of-cure visit. Determination of clinical cure was based upon physician-judged resolution of clinical signs and symptoms of nosocomial pneumonia. In both studies, Telavancin achieved the objective of non-inferiority compared to Vancomycin.

Safety Information

Fetal Risk - Women of childbearing potential should have a serum pregnancy test prior to administration of Vibativ. Avoid use of Vibativ during pregnancy unless the potential benefit to the patient outweighs the potential risk to the fetus. Adverse developmental outcomes observed in three animal species at clinically relevant doses raise concerns about potential adverse developmental outcomes in humans. If not already pregnant, women of childbearing potential should use effective contraception during Vibativ treatment.

Nephrotoxicity - New onset or worsening renal impairment occurred in patients who received Vibativ. Renal adverse events were more likely to occur in patients with baseline comorbidities known to predispose patients to kidney dysfunction and in patients who received concomitant medications known to affect kidney function. Monitor renal function in all patients receiving Vibativ prior to initiation of treatment, during treatment, and at the end of therapy. If renal function decreases, the benefit of continuing Vibativ versus discontinuing and initiating therapy with an alternative agent should be assessed. Clinical cure rates in Telavancin-treated patients were lower in patients with baseline CrCl = 50 mL/min compared to those with CrCl greater than 50 mL/min. Consider these data when selecting antibacterial therapy for use in patients with baseline moderate/severe renal impairment.

Geriatric Use - Telavancin is substantially excreted by the kidney, and the risk of adverse reactions may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection in this age group.

Infusion related reactions - Vibativ is a lipoglycopeptide antibacterial agent and should be administered over a period of 60 minutes to reduce the risk of infusion-related reactions. Rapid intravenous infusions of the glycopeptide class of antimicrobial agents can cause red-man syndrome-like reactions including: flushing of the upper body, urticaria, pruritus, or rash.

Clostridium difficile-associated diarrea - Clostridium difficile-associated diarrhea ( CDAD ) has been reported with nearly all antibacterial agents and may range in severity from mild diarrhea to fatal colitis. CDAD must be considered in all patients who present with diarrhea following antibiotic use.

Development of drug resistant bacteria - Prescribing Vibativ 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. As with other antibacterial drugs, use of Vibativ may result in overgrowth of nonsusceptible organisms, including fungi.

QTc Prolongation - Caution is warranted when prescribing Vibativ to patients taking drugs known to prolong the QT interval. In a study involving healthy volunteers, Vibativ prolonged the QTc interval. Use of Vibativ should be avoided in patients with congenital long QT syndrome, known prolongation of the QTc interval, uncompensated heart failure, or severe left ventricular hypertrophy.

Coagulation test interference - Vibativ does not interfere with coagulation, but does interfere with certain tests used to monitor coagulation such as prothrombin time, international normalized ratio, activated partial thromboplastin time, activated clotting time, and coagulation based factor Xa tests. Blood samples for these coagulation tests should be collected as close as possible prior to a patient's next dose of Vibativ.

Adverse reactions - The most common adverse reactions ( equal to 10% of patients treated with Vibativ ) observed in the phase 3 cSSSI clinical trials were taste disturbance, nausea, vomiting, and foamy urine.
In the phase 3 cSSSI clinical trials, serious adverse events were reported in 7% of patients treated with Vibativ and most commonly included renal, respiratory, or cardiac events. Serious adverse events were reported in 5% of Vancomycin-treated patients, and most commonly included cardiac, respiratory, or infectious events.

Source: Astellas, 2011

XagenaMedicine2011


Link: Xapedia - Medical Encyclopedia