Compatibility of commonly used bone marrow transplant drugs during Y-site delivery.

The Y-site compatibility of medications routinely used in bone marrow transplant patients was studied. Two methods were used to evaluate the compatibility of pairs of various i.v. drugs and nutrient fluids. In the first, the drugs were combined in a 1:1 ratio in test tubes, which were visually evaluated immediately and at 1, 4, and 24 hours under normal light and against a white background. The second method involved simulated infusion through a Y-site and a membrane filter. Filter disks were examined under 51 x magnification for precipitates. "Administration" time ranged from one minute to five hours. Most of the combinations were compatible. Exceptions (incompatibilities or inconclusive findings) were amikacin plus a total parenteral nutrient (TPN) admixture; cyclosporine plus dopamine hydrochloride, magnesium sulfate, ondansetron, a parenteral nutrient solution, the TPN admixture, or the TPN admixture with phytonadione; and heparin sodium in either 5% dextrose injection or 0.9% sodium chloride injection plus the TPN admixture or vancomycin. The two study methods were in agreement for all drug combinations except those involving cyclosporine. Cyclosporine in 0.9% sodium chloride injection yielded many fine particles on the filter disk. The combination of cyclosporine with other drugs did not appear to increase the number of particles on the disk, but the results must still be considered inconclusive. Two methods used to determine the compatibility of bone marrow transplant agents when mixed in a Y injection site yielded the same results, except for combinations involving cyclosporine. Most of the combinations were compatible.

Compatibility of cefmetazole sodium with commonly used drugs during Y-site delivery.

The compatibility of cefmetazole sodium and selected other drugs during Y-site delivery was evaluated. Cefmetazole 100 mg/mL (as the sodium salt) in sterile water for injection and each of 34 drugs or solutions commonly used with it were mixed together by Y-site injection. Secondary drugs were administered at selected concentrations and rates and delivered by the method (i.v. push, i.v. infusion, or syringe pump) commonly used for the drug at the institution where the study was done. Each injection set included a filter system with a 0.8-micron filter disk. Tests were done in triplicate. After each test, the Y injection site and the tubing after it were visually inspected for precipitate and color change. If no particles or color change was detected, the filter disk was observed under a microscope. Drugs were deemed compatible with cefmetazole if unaided observation detected no color change or particles and the number of particles detected by microscopic examination was below that specified in USP guidelines. A precipitate formed when cefmetazole sodium mixed with diphenhydramine hydrochloride, droperidol, erythromycin (50 mg/mL, as the lactobionate), haloperidol lactate, prochlorperazine edisylate, promethazine hydrochloride, or vancomycin (50 mg/mL, as the hydrochloride salt). No particles or color change was detected by unaided observation of mixtures containing dobutamine or erythromycin 10 mg/mL, but the number of particles detected by microscopic examination exceeded USP limits. All other drugs tested were compatible with cefmetazole. Cefmetazole 100 mg/mL (as the sodium salt) in sterile water for injection was shown to be compatible with 25 of 34 tested drug solutions during Y-site delivery.

Effect of filtration on complications of postoperative intravenous therapy.

The incidence of intravenous complications (phlebitis) and the length of hospital stay in postoperative patients whose infusions were filtered through inline final filters were compared with those in patients whose infusions were not filtered. Identical i.v. solutions were administered to 150 postoperative orthopedic patients randomly assigned to three study groups: control (no filter), 5-micrometers membrane filter and 0.45-micrometers membrane filter. An i.v. therapy team of seven nurses inspected patients for phlebitis. The phlebitis rate of the control group (27%) was significantly greater (p less than 0.05) than that of the 0.45-micrometers filter group (6%) but not significantly different (p less than 0.9) from that of the 5-micrometers filter group (22%). In a subgroup of 104 patients undergoing total hip replacement, the mean reduction in length of postoperative hospital stay compared with the control group (13.6 days) was: 5-micrometers filter group--3.4 days (p less than 0.01); and 0.45-micrometer filter group--3.3 days (p less than 0.01). The results suggest that final filters can be used to reduce the incidence of phlebitis-related i.v. complications and thereby reduce the length of hospital stay.

Compatibility of common respiratory therapy drug combinations.

Respiratory therapists are being asked to take care of sicker patients and in many cases this requires the administration of multiple inhalation drugs. In an effort to reduce the workload, therapists are combining drugs in the same nebulizer. Pharmacists also are being asked to prepare unit dose preparations of combined inhalation drugs without physical compatibility data. It is theorized that some drug combinations precipitate and that these particulates are ultimately inhaled into the patient's lungs. These particulates can cause locally high concentrations of drug resulting in tissue irritation or actual occlusion of the airway. This study tested the physical compatibility of 22 common combinations used in our hospital and found 19 of these combinations incompatible. Due to the potential of precipitaion, we recommend that inhalation drugs not be routinely combined without specific compatibiltiy data.

Calcium and phosphorus compatibility in parental nutrition solutions for neonates.

Factors affecting calcium-phosphate solubility in parenteral nutrition solutions used in neonates were studied. Six neonatal parenteral nutrition solutions were prepared using either Aminosyn or FreAmine III and various amino acid and dextrose concentrations. Phosphorus (as mono- and dibasic potassium phosphate) and calcium (as 10% calcium gluconate) were added in concentrations of calcium 2.5-100 meq/liter and phosphorus 2.5-100 mmol/liter. Duplicate samples were prepared and analyzed either after they were heated in a water bath (37 degrees C) for 20 minutes or after 18 hours at 25 degrees C followed by 30 minutes in a water bath (37 degrees C). Precipitation was detected visually and spectrophotometrically, and pH was measured. Lipid emulsion was added to two Fre-Amine III solutions in a ratio of 7.5:1 (parenteral nutrition solution:lipid) and the resulting pH was measured. Time and temperature affected calcium-phosphate solubility in all solutions tested. Precipitation curves of amount of calcium versus amount of phosphate added were prepared for each solution. Amino acid and dextrose concentrations affected the pH of the solutions, and when a lipid emulsion was added, the pH rose more in the 1% than in the 2% FreAmine III solution. In selected solutions, as much as 120 mg/kg/day calcium and 55 mg/kg/day phosphate can be administered, approximating daily third-trimester accumulation of these minerals. Use of the precipitation curves in this paper, with attention to their limitations, should aid in the safe delivery of calcium and phosphorus intravenously to neonates.

Phase I study of ftorafur, an analog of 5-fluorouracil.

Ftorafur, a furanyl analog of 5-fluorouracil (5-FU), is reported to be five to six times less toxic and possibly more effective in cancer of the breast and colon than 5-FU. The drug was synthesized, formulated, and utilized in toxicologic studies, and then in 24 patients with advanced incurable malignancies. When Ftorafur is given by intravenous push, it results in immediate flushing, dizziness, nausea, retching, and in some cases transient hypotension. These immediate side effects are largely eliminated by administering the drug slowly by infusion. In patients, 60 mg/kg of Ftorafur given i.v. daily for up to 10 days resulted in mild toxicity. However, 80 mg/kg given i.v. daily for 7 days resulted in severe toxicity, with nausea, vomiting, stomatitis, leukopenia, and thrombocytopenia. These studies confirm those of the Russian investigators as to toxicity and dosage, even with a different method of administration more convenient for therapy. Phase II studies are presently being carried out to compare the effectiveness of Ftorafur and 5-FU.