Neutropenia in kidney and liver transplant recipients: Risk factors and outcomes.

No studies have directly compared the key characteristics and outcomes of kidney (KTx) and liver transplantation (LTx) recipients with neutropenia. In this single-center, retrospective, cohort study, we enrolled all adult patients who received a KTx or LTx between 2000 and 2011. Neutropenia was defined as 2 consecutive absolute neutrophil count (ANC) values <1500/mm3 in patients without preexisting neutropenia. The first neutropenia episode occurring during the first year post-transplantation was analyzed. A total of 663 patients with KTx and 354 patients with LTx met the inclusion criteria. Incidence of neutropenia was 20% in KTx and 38% in LTx, respectively. High-risk CMV status and valganciclovir (VGCV) use were significant predictors of neutropenia for KTx recipients, but only VGCV use vs nonuse in LTx recipients. Neutropenia was associated with worse survival in KTx recipients (adjusted HR 1.95, 95% CI 1.18-3.22, P<.01), but not in LTx recipients (adjusted HR 0.75, 95% CI 0.52-1.10, P=.15). Sixteen acute rejection episodes were associated with preceding neutropenia in KTx recipients (HR 1.77, 95% CI 1.16-2.68, P=.007) and 24 acute rejection episodes in LTx recipients (HR 1.41, 95% CI 0.97-2.04, P=.07). Incidence of infection was similar in patients with and without neutropenia among KTx and LTx recipients.

Generic immunosuppression in solid organ transplantation: a Canadian perspective.

The introduction of generic immunosuppressant medications may present an opportunity for cost savings in solid organ transplantation if equivalent clinical outcomes to the branded counterparts can be achieved. An interprofessional working group of the Canadian Society of Transplantation was established to develop recommendations on the use of generic immunosuppression in solid organ transplant recipients (SOTR) based on a review of the available data. Under current Health Canada licensing requirements, a demonstration of bioequivalence with the branded formulation in healthy volunteers allows for bridging of clinical data. Cyclosporine, tacrolimus, and sirolimus are designated as "critical dose drugs" and are held to stricter criteria. However, whether this provides sufficient guarantee of therapeutic equivalence in SOTR remains controversial, and failure to maintain an appropriate balance of immunosuppression may have serious consequences, including rejection, graft loss, and death. Published evidence supporting therapeutic equivalence of generic formulations in SOTR is lacking. Moreover, in the setting of multiple generic formulations the potential for uncontrolled product switching is a major concern, since generic preparations are not required to demonstrate bioequivalence with each other. Although close monitoring is recommended with any change in formulation, drug product switches are likely to occur without prescriber knowledge and may pose a significant patient safety risk. The advent of generic immunosuppression will require new practices including more frequent therapeutic drug and clinical monitoring, and increased patient education. The additional workload placed on transplant centers without additional funding will create challenges and could ultimately jeopardize patient outcomes. Until more robust clinical data are available and adequate regulatory safeguards are instituted, caution in the use of generic immunosuppressive drugs in solid organ transplantation is warranted.

Stability of cyclosporine solutions stored in polypropylene-polyolefin bags and polypropylene syringes.

PURPOSE: The stability of cyclosporine diluted to 0.2 or 2.5 mg/mL with 0.9% sodium chloride injection or 5% dextrose injection and stored in polypropylene-polyolefin containers or polypropylene syringes was evaluated. METHODS: Intravenous cyclosporine solutions (0.2 and 2.5 mg/mL) were aseptically prepared and transferred to 250-mL polypropylene-polyolefin bags or 60-mL polypropylene syringes. Chemical stability was measured using a stability-indicating high-performance liquid chromatography (HPLC) assay. Physical stability was assessed by visual inspection and a dynamic light scattering (DLS) method. RESULTS: After 14 days, HPLC assay showed that the samples of i.v. cyclosporine stored in polypropylene-polyolefin bags remained chemically stable (>98% of initial amount remaining); the physical stability of the samples was confirmed by DLS and visual inspection. The samples stored in polypropylene syringes were found to contain an impurity (attributed to leaching of a syringe component by the solution) that could be detected by HPLC after 1 day; on further investigation, no leaching was detected when the syringes were exposed to undiluted i.v. cyclosporine 50 mg/mL for 10 minutes. CONCLUSION: Samples of i.v. cyclosporine solutions of 0.2 and 2.5 mg/mL diluted in 0.9% sodium chloride injection or 5% dextrose injection and stored at 25 °C in polypropylene-polyolefin bags were physically and chemically stable for at least 14 days. When stored in polypropylene syringes, the samples were contaminated by an impurity within 1 day; however, the short-term (i.e., ≤10 minutes) use of the syringes for the preparation and transfer of i.v. cyclosporine solution is considered safe.

Impact of stress ulcer prophylaxis algorithm study.

BACKGROUND: In the intensive care unit at Royal Victoria Hospital, we noted that drugs prescribed for stress ulcer prophylaxis were not always indicated or optimal. Accordingly, we implemented an algorithm for stress ulcer prophylaxis to guide the medical team in their decisions. The agents selected for the algorithm were intravenous famotidine and omeprazole suspension or tablets, depending on the available administration route. OBJECTIVE: To evaluate the impact of a treatment algorithm on the appropriateness of prescriptions for stress ulcer prophylaxis. METHODS: A quasi-experimental-type evaluative study was conducted based on a pre-/post-intervention design without a concurrent control group. A total of 555 complete admissions met the selection criteria; 303 patients formed the pre-intervention group, and 252 made up the post-intervention group (exposed to the treatment algorithm). RESULTS: After implementation of the algorithm, the proportion of inappropriate prophylaxis was decreased (95.7% vs 88.2%; p = 0.033). The number of days of inappropriate prophylaxis was also reduced significantly (p = 0.013), as was the cost per patient (p = 0.003) for all admissions. However, no difference was observed when the subgroup of patients who received prophylaxis alone was studied (p = 0.098 and p = 0.918). The presence of bleeding was similar in both groups. CONCLUSIONS: Introduction by pharmacists of a treatment algorithm for stress ulcer prophylaxis in intensive care units allows a reduction of inappropriate prescriptions and thus a reduction in the cost of drugs. The use of omeprazole suspension seems to be an alternative to intravenous histamine2-inhibitors; however, a large-scale study is necessary to confirm the efficacy and safety of proton-pump inhibitors administered by an enteral tube.