Clinical utility of treprostinil in the treatment of pulmonary arterial hypertension: an evidence-based review.

Pulmonary arterial hypertension (PAH) remains a progressive disease without a cure, despite the development of several treatment options over the past several decades. Its management strategy consists of the endothelin receptor antagonists (ambrisentan, bosentan, macitentan), phosphodiesterase-5 inhibitors (sildenafil, tadalafil, vardenafil), and prostacyclin analogs (epoprostenol, treprostinil, iloprost). Treprostinil, a stable prostacyclin analog, displays vasodilatory effects in the pulmonary vasculature, as well as antiplatelet aggregation properties. Clinical practice guidelines recommend oral endothelin receptor antagonist or phosphodiesterase inhibitor therapy in mild to moderate PAH. Epoprostenol is specifically suggested as first-line therapy in moderate to severe PAH patients (ie, World Health Organization/New York Heart Association functional class III-IV). However, treprostinil may be an alternative option in these severe PAH patients. The longer half-life and stability at room temperature with treprostinil may be associated with lower risk of pulmonary hemodynamic worsening as a result of abrupt infusion discontinuation and less frequent drug preparation. These characteristics make treprostinil an attractive alternative to continuous infusion of epoprostenol, due to convenience and patient safety. The purpose of this review is to evaluate the safety and efficacy of continuous infusion of treprostinil as well as the inhaled and oral routes of administration in PAH.

Conivaptan for treatment of hyponatremia in neurologic and neurosurgical adults.

OBJECTIVE: To review the literature evaluating the clinical safety and efficacy of conivaptan in the management of hyponatremia in a neurologic and neuro-surgical adult patient population. DATA SOURCES: A literature search was conducted using MEDLINE, EMBASE, PubMed, and the Cochrane Central Register of Controlled Trials (1966-May 2013). Search limits were English, human, and adult using the terms vasopressin receptor antagonist, conivaptan, tolvaptan, lixivaptan, neurology, neurological disorder, neurosurgery, neurointensive care, and neurocritical care. STUDY SELECTION AND DATA EXTRACTION: All case reports, case series, and clinical trials investigating the use of conivaptan in neurosurgical patients were included. DATA SYNTHESIS: Seven reports were identified using conivaptan as monotherapy or adjunctive treatment for hyponatremia in a neurosurgical patient population. One study was a prospective, randomized, controlled trial, while 6 reports were case reports or case series. The prospective randomized trial found a significant increase in serum sodium concentration over baseline with a conivaptan 20-mg intravenous bolus dose followed by a 20-mg/day continuous infusion for 24 hours compared to "usual care" at 6 hours (7.0 ± 1.7 vs -0.6 ± 2.1 mEq/L, respectively; p = 0.008) and 36 hours (8.0 ± 5.6 vs -1.7 ± 2.1 mEq/L, respectively; p = 0.05) after treatment. One case series found that the mean serum sodium remained significantly increased from baseline up to 72 hours (5.12 ± 4.0 mEq/L; p < 0.001) after a single conivaptan 20-mg intravenous bolus dose. All reports demonstrated clinical effectiveness of conivaptan in significantly increasing serum sodium concentrations following administration compared to baseline. However, the clinical significance of this finding remains debatable since some of these patients remained hyponatremic. CONCLUSIONS: Overall, conivaptan is a promising and well-tolerated agent for the management of hyponatremia in neurologic and neurosurgical patients. However, its use should be limited to patients in whom conventional therapies fail or as adjunctive therapy.

Apparent lack of cross-reactivity for infusion-related reactions between two forms of lipid-based amphotericin B.

PURPOSE: The case of a patient who experienced probable infusion-related reactions to amphotericin B lipid complex (ABLC) but tolerated continued amphotericin B therapy after a switch to an alternative lipid-based formulation is reported. SUMMARY: A 28-year-old immunocompromised man with pneumonia, respiratory failure, and neutropenic fever was initiated on ABLC and other antibiotics for suspected invasive aspergillosis. Due to the patient's deteriorating renal function, the use of amphotericin B was deemed preferable to the standard therapy for invasive aspergillosis (voriconazole) even though he had experienced likely infusion-related reactions to ABLC on two prior occasions. During the infusion of ABLC, significant increases in the man's temperature, respiratory rate, systolic blood pressure, and heart rate were observed. Although those symptoms were suspected to be infusion related, it was decided that continuing amphotericin B therapy with an alternative lipid-based form of the drug was the best course of action. After the patient was switched to liposomal amphotericin B one day later, no further infusion-related adverse reactions were noted for the duration of therapy. While this case suggests that adverse reactions to one type of amphotericin B might not occur with the use of an alternative formulation, further research is needed to better define the potential for cross-reactivity among various forms of amphotericin B and related safe-infusion practices. CONCLUSION: A patient with invasive aspergillosis who experienced likely infusion- related reactions to ABLC was able to tolerate continued amphotericin B therapy after a switch to the liposomal formulation.

Clinical and economic evaluation of an evidence-based institutional epoetin-utilization management program.

BACKGROUND: Anemia is common in several patient populations, including those with chronic kidney disease, cancer, and HIV/AIDS, and may require treatment with erythropoietin-stimulating agents (ESAs). Given the potential risks of the ESA, epoetin, and the significant costs associated with this agent, a large teaching medical institution developed a the drug-utilization management program using evidence-based guidelines on appropriate use. OBJECTIVE: This study was designed to determine the clinical and financial impact of the drug-utilization management program. METHODS: This retrospective cohort study was conducted at the medical institution that implemented the program using clinical pharmacists. Patients were included if epoetin was administered during their hospital stay (evaluation period, December 1, 2010, to December 31, 2011). The rate of inappropriate epoetin prescribing and the economic impact of guideline implementation were evaluated using comparisons of data from cohorts prescribed epoetin before and after guideline implementation. RESULTS: Data from 796 patients were included in the analyses (pre-implementation, 496; post-implementation, 300). The proportion of patients prescribed epoetin was significantly smaller after guideline implementation (2.4% vs 1.6%; P < 0.001). The reduction in the total number of epoetin units administered was 45%. The significant reduction (25%) in inappropriate prescribing after guideline implementation was primarily attributed to a 17% decrease in epoetin use in nonspecific anemia. The reduction in inappropriate epoetin prescribing translated into a 23.8% reduction in costs (P < 0.001) associated with inappropriate epoetin use. The estimated annual cost-savings of this program was $198,352 ($16,529/mo). CONCLUSION: The implementation of a drug-utilization management program using clinical pharmacists who evaluated epoetin was associated with a decrease in inappropriate epoetin prescribing and with significant cost-savings.