Antibiotic
PREGNANCY RECOMMENDATION: No Human Data—Animal Data Suggest Low Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Potential Toxicity
PREGNANCY SUMMARY
No reports describing the use of telavancin, a synthetic derivative of vancomycin, in human pregnancy have been located. The manufacturer interpreted the animal reproduction data as showing risk of limb and skeletal malformations. However, a presentation by Anthony Scialli, MD, Tetra Tech Sciences, at a public meeting of the FDA Advisory Committee on Antimicrobial Drugs, November 2008, did not support that interpretation. Among 654 rat and 156 rabbit fetuses, shortened limbs were observed in only three fetuses: two rats (one of which was not confirmed) and a rabbit. In minipigs, polydactyly was observed in controls and in all drug groups except the high-dose group, so inclusion of these results is questionable. Nevertheless, a better reason for not using this drug, at least until human pregnancy data are available, is that it does not appear to offer a clear advantage for its indication over other available antibiotics that do have pregnancy experience. A pregnancy registry has been established by the manufacturer to monitor pregnancy outcomes in women exposed to telavancin. Either the physician or the patient herself can register by calling 1-888-658-4228 (1).
FETAL RISK SUMMARY
Telavancin is a lipoglycopeptide antibacterial that is a synthetic derivative of vancomycin. It is given as an IV infusion. Telavancin is indicated for the treatment of adult patients with complicated skin and skin structure infections 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 Streptococcus anginosus, Staphylococcus intermedius, and Streptococcus constellatus), or Enterococcus faecalis (vancomycin-susceptible isolates only). The drug is partially metabolized. Binding to plasma proteins, primarily to albumin, is about 90%, and the elimination half-life is about 8 hours. The drug is highly lipophilic (1).
Reproduction studies have been conducted in rats, rabbits, and minipigs. In these species, IV doses resulting in exposures that were about 1–2 times the human exposure (AUC) at the maximum recommended clinical dose showed a potential to cause limb and skeletal malformations that included brachymelia (rats, rabbits), syndactyly (rats, minipigs), adactyly (rabbits), and polydactyly (minipigs) (see also above Summary). Other findings were flexed front paw and absent ulna (rabbits), misshapen digits and deformed front leg (minipigs), and an increase in the number of stillborn pups and decreased fetal body weights (rats) (1).
Long-term carcinogenicity studies have not been conducted. The drug was not mutagenic or clastogenic in multiple assays. Telavancin did not impair fertility or reproductive performance in male and female rats. When the drug was given for longer periods in male rats at doses resulting in exposures similar to those in humans, reversible altered sperm parameters were observed (1).
It is not known if telavancin crosses the human placenta. The molecular weight (about 1756 for the free base) and moderately high plasma protein binding may partially inhibit placental crossing, but the high fat solubility and long elimination half-life suggest that the drug will cross to the embryo–fetus.
BREASTFEEDING SUMMARY
No reports describing the use of telavancin during human lactation have been located. The molecular weight (about 1756 for the free base) and moderately high plasma protein binding (about 90%) may partially inhibit excretion into breast milk, but the high fat solubility and long elimination half-life (8 hours) suggest that some drug will cross into milk. Because telavancin is a weak base, ion trapping in the more acidic milk may occur that results in a milk:plasma ratio >1. The effect of this exposure on a nursing infant is unknown, but three potential problems exist: modification of bowel flora, direct effects on the infant (e.g., allergic response), and interference with the interpretation of culture results if a fever workup is required.
Reference
1.Product information. Vibativ. Astellas Pharma US, 2009.