Adherence to national recommendations for safe methotrexate dispensing in community pharmacies.

BACKGROUND: The number of patients using methotrexate (MTX) has increased during the last decade. Because of the narrow therapeutic range and potential risks of incorrect use, vigilance is required when dispensing MTX. In 2009, the Royal Dutch Pharmacists Society, in accordance with the Dutch Health Care Inspectorate, published safe MTX dispensing recommendations for community pharmacies. OBJECTIVE: To examine adherence to recommendations aimed at safe MTX dispensing. METHODS: This study was conducted within a convenience sample of 78 community pharmacies belonging to the Utrecht Pharmacy Practice Network for Education and Research (UPPER). Data were collected in May 2011. RESULTS: 95 pharmacists and 337 pharmacy technicians were interviewed to assess self-reported adherence with dispensing recommendations. In addition, medication records for patients using MTX were extracted in 52 pharmacies in order to objectively assess adoption of recommendations. More than 75% of the pharmacists and pharmacy technicians reported to be adherent to 6 of the 11 recommendations. There are variations in reported adherence between team members working in 1 pharmacy; higher adherence rates ( greater than 75%) for the pharmacy team as a whole were only shown for 2 recommendations (recording of day of intake on the label and moment of authorization by the pharmacist). The medication records showed that adherence with working procedures significantly increased: The number of dispensed records with notification of the day of intake on the medication label increased from 9.9% of the records per pharmacy in 2008 to 77.1% in 2010 (P less than 0.001). CONCLUSIONS: Dutch community pharmacies seem to be adherent to most safe dispensing recommendations. However, inconsistencies exist between team members that emphasize the importance of addressing this issue and discussing recommendations within the team, as there is still room for improvement to ensure safe dispensing.

Topotecan and doxorubicin combination to treat recurrent ovarian cancer: the influence of drug exposure time and delivery systems to achieve optimum therapeutic activity.

PURPOSE: To provide proof-of-concept data to support use of Doxil-liposomal topotecan (Topophore C) combinations to treat ovarian cancer. EXPERIMENTAL DESIGN: ES-2, OVCAR-3, and SKOV-3 ovarian cancer cell lines were treated with doxorubicin-topotecan combinations by exposing the cells to drugs from 1 to 72 hours. Pharmacokinetic analysis was conducted following administration of liposomal formulations of these drugs alone and in combination. Efficacy assessments were completed in ES-2 and SKOV-3 ovarian cancer models. RESULTS: On the basis of drug doses capable of achieving 50% reduction in cell viability over 72 hours, doxorubicin-topotecan combinations were additive in SKOV-3 but highly synergistic in ES-2 and OVCAR-3 cells. Favorable drug-drug interactions increased with increased drug exposure time. Topophore C pharmacokinetic remained unaffected when co-administered with Doxil. In the ES-2 model, Doxil at maximum tolerated dose (MTD 7.5 mg/kg) in combination with free topotecan (MTD 15 mg/kg) did not enhance median survival time (MST) over that achieved with topotecan alone. In contrast, MST was increased to 52 days with combination of Topophore C (MTD 2.5 mg/kg) and Doxil (7.5 mg/kg) compared with untreated animals (MST 18 days) or those treated with Topophore C alone (MTD 5 mg/kg, MST 40 days). In the SKOV-3 model, combination treatments showed better therapeutic efficacy than the individual drugs. CONCLUSIONS: Topotecan-doxorubicin combinations produced additive or synergistic effects which were best achieved when the tumor cells were exposed to drugs over extended time. Doxil-Topophore C combinations are therapeutically superior as judged in two ovarian cancer models. Clin Cancer Res; 19(4); 865-77. ©2012 AACR.