Subtherapeutic concentrations of posaconazole tablet: determining risk factors and effectiveness of a standardized dose adjustment in hematology inpatients.

Posaconazole is indicated for antifungal prophylaxis in hematology patients at high-risk of invasive fungal infections (IFI). Consensus guidelines recommend maintaining steady-state trough concentrations above 0.7 mg/L; however, upto one-third of patients return subtherapeutic concentrations which is associated with breakthrough IFI. This retrospective observational study of 496 concentrations from 90 hematology inpatients prescribed posaconazole tablet (PCZ-tab) between May 2017 and May 2019 identified 24% (n = 121) of posaconazole concentrations were subtherapeutic after the dosage of 300 mg daily. On multivariable analyses, diarrhea (p = 0.002), male gender (p = 0.018), and concurrent regular metoclopramide (p = 0.002) were significantly associated with subtherapeutic posaconazole concentrations. Eighty-nine percent of patients (n = 16) who underwent dose adjustment to 200 mg twice daily successfully achieved target posaconazole concentrations at first steady-state measurement. This study confirms that therapeutic drug monitoring of posaconazole remains necessary as subtherapeutic posaconazole concentrations are relatively common, and that dose adjustment of 200 mg twice daily, safely enabled achievement of therapeutic concentrations.

Pharmacist review of high-risk haematology outpatients to improve appropriateness of antifungal prophylaxis.

Background Patients with haematological malignancies are at high risk of invasive fungal infections. However, there is a lack of information about the utilisation of the recommended Australian antifungal prophylaxis guidelines in haematology outpatients. Objective To assess the impact of a weekly pharmacist review of high-risk adult haematology outpatients on the utilisation of appropriate antifungal prophylaxis. Setting Outpatient cancer centre, tertiary referral hospital in Sydney, Australia. Method A 3-month pre-and post-interventional study was conducted. A retrospective audit was conducted to obtain baseline utilisation of antifungal guidelines in adult haematology outpatients with acute myeloid leukemia, acute lymphoblastic leukemia and myelodysplastic syndrome receiving chemotherapy. This was followed by a weekly pharmacist review over a 3-month period of all eligible outpatients assessing the appropriateness of antifungal agent, dose, use of therapeutic drug monitoring and presence of drug-interactions/contraindications. Recommendations to physicians were conveyed weekly and outcomes recorded. Main outcome measure Appropriate utilisation of antifungal prophylaxis guidelines in outpatient haematology patients before and after implementation of a 3-month weekly pharmacist review service. Results Forty patients were included in the retrospective group, equating to 348 reviews, while 42 patients equating to 269 reviews were included in the prospective group. Appropriate utilisation of antifungal prophylaxis guidelines increased from 31 to 54% post implementation of a pharmacist review (Odds Ratio = 2.44, 95% Confidence Interval: 1.07-5.58, p = 0.0344). The most common reason for nonadherence to guidelines in both groups was lack of therapeutic drug monitoring and failure to prescribe antifungal prophylaxis where indicated. The percentage of appropriate use of antifungal prophylaxis in patients with acute myeloid leukemia increased from 13 to 46% (p value < 0.01) after pharmacist intervention. The pharmacist made 153 recommendations from 269 reviews, with a percentage uptake of 40%. Moderate to severe drug interactions were identified in 19 reviews from 10 patients. One major azole antifungal-chemotherapy interaction was avoided. Conclusions Appropriate utilisation of antifungal prophylaxis guidelines can be improved through a regular pharmacist review. Future studies should identify whether improving adherence to antifungal guidelines leads to improved patient outcomes.

Adherence to Antifungal Guidelines in Malignant Hematology Patients: A Review of the Literature.

Objective: To review the published literature assessing adherence rates to antifungal guidelines and reasons for nonadherence in the adult malignant hematology inpatient setting. Data sources: The databases Embase, MEDLINE, and PubMed (from data inception to May 2019) were searched using the terms hematology, oncology, antifungal, guidelines, adherence, and stewardship with the search limited to adult human subjects and published in English. This yielded 123 articles. From this list, studies that were published in peer-reviewed journals were extracted, leaving 10 citations that met the final inclusion criteria. Study Selection and Data Extraction: Ten studies were selected assessing adherence to consensus antifungal guidelines in the malignant hematology setting. These included studies investigating the introduction of antifungal stewardship programs in tertiary hospitals. Data Synthesis: Although the studies were heterogeneous, all focused on appropriateness of antifungal therapy in the inpatient setting. Adherence to antifungal guidelines for optimal antifungal prophylaxis and treatment was low in most studies, with rates of inappropriate antifungal therapy ranging from 25% to 70% of fungal prescriptions. Relevance to Patient Care and Clinical Practice: Adherence rates with guidelines for antifungal therapy are low in the hematology inpatient setting. This may affect infection rates influencing morbidity and mortality in this high-risk population. Conclusion: Given the prevalence of invasive fungal infections in malignant hematology inpatients, suboptimal adherence with antifungal guidelines is concerning. This demands a focus on education, antifungal stewardship, and updating guidelines to meet real-world scenarios. Adherence with antifungal guidelines in the outpatient hematology setting is unknown and requires further research.

Intravenous warfarin as an alternative for anticoagulation.

Oral warfarin is the standard of care for patients requiring long-term anticoagulation due to venous thromboembolic disease. Patients with Crohn's disease may have reduced absorption in the small bowel due to loss of effective surface area secondary to chronic inflammation, ulcerative lesions, or resection. A 27-year-old Caucasian woman with end-stage Crohn's disease was hospitalized with an upper extremity thrombosis. In this complicated patient, who was resistant to oral warfarin and unable to receive subcutaneous low-molecular-weight heparin, therapeutic anticoagulation was achieved with intravenous warfarin. Intravenous warfarin provides an alternative administration route for patients who cannot receive the oral formulation and cannot be administered subcutaneous low-molecular-weight heparins due to adverse effects.