Current Therapeutic Research (Dec 2015)
Chemical Stability of Telavancin in Elastomeric Pumps
Abstract
Background: VIBATIV is a once-daily, injectable lipoglycopeptide antibiotic approved in the U.S. for the treatment of hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) caused by susceptible isolates of Staphylococcus aureus when alternative treatments are not suitable. In addition, VIBATIV is approved in the U.S. for the treatment of adult patients with complicated skin & skin structure infections (cSSSI) caused by susceptible isolates of Gram-positive bacteria, including Staphylococcus aureus, both methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) strains. Objective: To evaluate the chemical stability of telavancin (Vibativ; Theravance Biopharma US, Inc, Northbrook, Illinois), a lipoglycopeptide antibiotic with activity against methicillin-resistant Staphylococcus aureus, in 2 types of elastomeric pumps, the Intermate Infusion System (Baxter International Inc) and the Homepump Eclipse (I-Flow Corporation). Methods: Different sizes of the Baxter (Ontario, Canada) (105 mL and 275 mL) and I-Flow (Stoughton, Massachusetts) (100 mL and 250 mL) pumps were compared with glass controls. The telavancin drug product was reconstituted and diluted to concentrations of 0.6 mg/mL and 8.0 mg/mL using either 0.9% saline, 5% dextrose in water, or sterilized water for injection (0.6 mg/mL telavancin) or saline (8.0 mg/mL telavancin) followed by Ringer’s Lactate solution. Pumps were filled and stored at 2°C to 8°C, protected from light. Aliquots from both pump types and for all telavancin reconstitution/dilution schemes and concentrations were taken over a period of 8 days and analyzed for appearance, pH, telavancin concentration and purity, and degradation products. Results: The pH of all pump solutions remained consistent throughout the 8-day analysis period, within a range of 4.6 to 5.7 for the 0.6 mg/mL and 4.4 to 4.9 for the 8.0 mg/mL telavancin solutions. There was no significant change in the chromatographic purity for any of the pump solutions examined. All decreases in telavancin concentration were ≤2.7%. Comparison of each test sample solution to the corresponding glass control indicated no loss of active drug due to absorption by the elastomeric material of the pumps. The greatest increase in the amount of total degradants observed over the 8-day period was ~0.7 w/w%. Conclusions: The results of this study indicate that telavancin remains chemically stable when diluted in the Intermate Infusion System and the Homepump Eclipse elastomeric pumps and stored at 2°C to 8°C for up to 8 days protected from light at the concentration range and dilution schemes evaluated.
Keywords
