Stefano Loiacono

Experience of compounding total parenteral nutrition admixtures for preterm infants in a hospital pharmacy: evidence of calcium and phosphate compatibility problem

Objective Parenterally fed preterm newborn infants require large amounts of calcium and phosphate in a low volume of solution. The lower the volume of solution, the higher is the possibility of precipitation of calcium hydrogen phosphate (CaHPO4). Precipitation could cause respiratory distress and pulmonary embolism, and the use of organic salts of calcium and phosphorus may reduce the likelihood of this problem. To date, no previous work on the stability of solutions with organic salts has been published in the literature. This study aims to evaluate the visible precipitation of calcium and phosphorus in total parenteral nutrition solutions. Methods 20 parenteral nutrition solutions were aseptically prepared in a laminar airflow hood in a clean room. The solutions are intended to facilitate precipitation, with the amino acid ratio below the standard concentration and other parameters also modulated to promote the precipitation of CaHPO4. The solutions contained dextrose, amino acids, calcium gluconate and fructose 1,6-bisphosphate. We did not use lipid emulsion so that we could see all precipitations. Results No visible precipitation was observed during 4 weeks of observation at 25°C. The only observed event was the change in colour of the solution, which became yellow, maybe because of a Maillard reaction. Conclusions This study evaluated the compatibility of organic calcium and phosphorus in order to prevent the precipitation of CaHPO4 when preparing total parenteral nutrition solutions. The fact that no precipitation was observed is very significant as it indicates the compatibility of the ions, even though no instrumental analysis was performed.

Complete Remission of a Refractory Acute Myeloid Leukemia with Myelodysplastic- and Monosomy 7-Related Changes after a Combined Conditioning Regimen of Plerixafor, Cytarabine and Melphalan in a 4-Year-Old Boy: A Case Report and Review of Literature

Acute myeloid leukemia with myelodysplastic changes and monosomy 7 is a rare form of pediatric leukemia associated with very poor disease-free survival. The refractoriness of the disease is due to the protection offered by the bone marrow niche, making leukemic stem cells impervious to whatever chemotherapy or myeloablative regimen is chosen. Using a mobilizing agent for haematopoietic stem cells, Plerixafor, could sensitise leukemic cells to the myeloablative therapy. This approach was not previously used in a pediatric population, and in adult populations, was used in combination with busulphan with no difference in overall survival. We describe the case of a 4-year-old boy affected by refractory acute myeloid leukemia with myelodysplastic changes and monosomy 7. The child had never achieved a remission. We proposed a combined time-scheduled scheme of therapy with plerixafor and melphalan. Combining pharmacokinetics of plerixafor with pharmacokinetics and rapid and elevated myeloablative potential of melphalan in high dosage (200 mg/m2), we succeeded in mobilizing more than 85% of stem blasts immediately before infusion of Melphalan. The count of residual blasts after 8 h from melphalan infusion was only 1.3 cells/μL. The child achieved an engraftment at day +32 with full donor chimerism. Sixteen months after haematopoietic stem cell transplantation (HSCT), he is well and in complete remission. Our case suggests that the use of plerixafor before a conditioning therapy with melphalan could induce remission in acute myeloid leukemia refractory to the usual conditioning therapy in pediatric patients. This work adds strength to the body of knowledge regarding the “personalized” conditioning regimen for high-risk leukemic patients.

PKP-016 Pharmacokinetic interactions: An analysis from the prescriptions for elderly people

Background The elderly are a high risk population, especially because they are often receiving polytherapy. The use of two or more drugs increases the risk of drug-drug interactions that can easily cause an adverse drug reaction. Pharmacokinetic interactions concern absorption, distribution, metabolism and elimination of drugs: the most common site of interaction is hepatic metabolism and the various subtypes of cytochrome P450. Purpose To analyse the number of prescriptions containing possible pharmacokinetic interactions. The prescriptions were verified for both hepatic metabolism and P-glycoprotein (PgP, or MDR1) interactions. Material and methods We evaluated discharge prescriptions from the medical area (cardiology, rehabilitation, neurology and medicine) from 1 January 2014 to 30 June 2014. We used two websites to check the cytochrome P450 isozymes responsible for drug metabolism and its possible induction/inhibition. The same websites gave us information about possible interactions mediated by the PgP. Results We analysed 833 discharge prescriptions, 176 of which contained theoretical drug-drug interactions (21.13%). 55.68% of these prescriptions came from the cardiology unit (98 of 176). This unit prescribed 45 times (15.05% of 299 cardiology prescriptions) clopidogrel with pantoprazole: this proton pump inhibitor reduces the concentration of the active metabolite of clopidogrel by 20% through inhibition of CYP2C19. Digoxin and warfarin are drugs with a low therapeutic index. Physicians showed good prescribing behaviour: 11.93% (21) of 176 prescriptions contained possible interactions, respectively, 14 and 7. A risky interaction occurred between warfarin and prednisone that enhanced CYP3A4 action, reducing warfarin blood levels. 29 prescriptions (3.48%) included possible interactions at the PgP level with various active principles, such as spironolactone, atorvastatin, prednisone and amiodarone. 19 (65.52%, 19 of 29) interactions concerned atorvastatin. Analysing the prescriptions of the medicine unit (20), 11 (55%) contained quinolones and glucocorticosteroids: co-administration of these two drugs may increase the risk of tendon rupture. Conclusion This study focused on the pharmacokinetic interactions evaluable at discharge of patients. It intended to check if physicians are aware of the pharmacokinetic interactions by analysing their discharge prescriptions, and by evaluating the most common interactions. References and/or Acknowledgements http://reference.medscape.com/drug-interactionchecker http://www.codifa.it/cont/codifa-interazioni-multiple/74/trova-interazioni-multiple.asp No conflict of interest.