Drug stability and compatibility in oncology care.
ABSTRACT Infusional chemotherapy has been increasingly used based upon the fact that most drugs have a relatively short half-life following bolus exposure, and increasing the available drug concentration over time may maximize the antitumor effect. As a practical matter, the application of infusional chemotherapy especially in an ambulatory setting, absolutely requires that the individual antineoplastic agents be stable in solution at room temperature (or at body temperature for implanted pump systems) and that the drugs in the infusion (including antiemetics) be compatible. The capacity to mix antineoplastic agents and antiemetics (also colony-stimulating factors) in a single solution facilitates infusional combination chemotherapy. Technologic advances are on the horizon which will provide the capability of administration of multiple drugs through a single access site to allow one to utilize a single delivery source obviating the need for admixtures of drugs. However, in the interim, admixtures represent the optimal method for the delivery of multi-agent chemotherapy in the setting in which continuous infusional drug delivery for 24 hours or more is employed. The goal of continuous infusion cancer chemotherapy is to ensure delivery of an unaltered cytotoxic drug, avoiding situations that could affect the stability of the infusion admixture. With cancer chemotherapy infusion therapy being administered through oncology clinics without the benefits of a pharmacist, the nurse plays a pivotal role in the preparation of the infusion, supervision of the patient, and when applicable in providing counseling on the proper storage, handling of the cytotoxic drugs, and disposal of contaminated infusion materials. Thus, by optimizing the integrity of the chemotherapeutic infusion, the patient achieves maximum benefits of cancer chemotherapy and the level of success anticipated with oncology care. The nurse may also be involved with clinical studies involving the preparation of other combinations of infusional chemotherapy including antiemetics and colony-stimulating factors, requiring integrity of the infusion to incompatibility and instability. In order to avoid failure of the infusion through improper preparation or reconstitution of the infusion or improper storage conditions and the resulting unnecessary waste and disposal expenses, the nurse needs to be fully aware of the factors affecting the stability and compatibility of the infusion and to interact with other health professionals and the literature for the critical information related to maintaining the integrity of the cancer chemotherapy infusion. "Good intentions without good communication equals potential disaster."
- [Show abstract] [Hide abstract]
ABSTRACT: The physical/chemical stability and potential interactions after diluting two immunoglobulin G1 monoclonal antibodies (mAb), pertuzumab (Perjeta®) and trastuzumab (Herceptin®), in a single intravenous (i.v.) infusion bag containing 0.9% saline (NaCl) solution was evaluated. As commercial products, pertuzumab and trastuzumab are administered through i.v. infusion to patients sequentially, that is, one drug after the other. To increase convenience and minimize the in-clinic time for patients, the compatibility of coadministering pertuzumab (420 and 840 mg) mixed with either 420 or 720 mg trastuzumab, respectively, in a single 250 mL polyolefin or polyvinyl chloride i.v. bag stored for up to 24 h at 5°C or 30°C was determined. The controls (i.e., pertuzumab alone in an i.v. bag, trastuzumab alone in an i.v. bag) and the mAb mixture were assessed using color, appearance, and clarity, concentration, and turbidity by ultraviolet spectroscopy, particulate analysis by light obscuration, size-exclusion chromatography, capillary electrophoresis-sodium dodecyl sulfate, analytical ultracentrifugation, and ion-exchange chromatography. Additionally, capillary zone electrophoresis, imaged capillary isoelectric focusing, and potency were utilized to measure the stability of the admixtures containing 1:1 mixtures of pertuzumab/trastuzumab and their respective controls (420 mg pertuzumab alone and 420 mg trastuzumab alone). No observable differences were detected by the above methods in the pertuzumab/trastuzumab mixtures stored up to 24 h at either 5°C or 30°C. The physicochemical methods as listed above were able to detect both molecules as well as the minor variants in the drug mixture, even though some overlap of mAb species were seen in the chromatograms and electropherograms. Furthermore, biophysical analysis also did not show any interactions between the two mAbs or any physical instability under these conditions. Additionally, the drug mixture tested by the pertuzumab-specific inhibition of cell proliferation bioassay showed comparable potency before and after storage. On the basis of these results, pertuzumab and trastuzumab admixture in a single i.v. bag is physically and chemically stable for up to 24 h at 5°C or 30°C and can be used for clinical administration. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci.Journal of Pharmaceutical Sciences 12/2012; · 3.13 Impact Factor