Pharmacotherapy
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Our aim was to review the efficacy, safety, and pharmacology of brexanolone (Zulresso), a new antidepressant with a novel mechanism of action, in the treatment of postpartum depression (PPD). Pertinent data and information were obtained via PubMed (1993 to August 2018). Articles published in English that evaluated the safety and efficacy of brexanolone and other off-label PPD treatments were included. ⋯ Brexanolone is a novel antidepressant indicated for the treatment of PPD. Clinical trials demonstrated that brexanolone significantly reduces depression scores in women with moderate to severe PPD. Due to risk of oversedation and loss of consciousness, a REMS program will be put in place to mitigate the risk of adverse events.
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Review
Potential Role of Direct Oral Anticoagulants in the Management of Heparin-induced Thrombocytopenia.
Heparin-induced thrombocytopenia (HIT) is a rare, potentially life-threatening condition secondary to unfractionated heparin or low molecular weight heparin exposure. This immune-mediated drug reaction manifests as thrombocytopenia with a paradoxical hypercoagulable state that can result in life-threatening thrombosis. It is imperative to ensure cessation of heparin-based products as soon as HIT is identified. ⋯ Twenty-seven articles met inclusion criteria for review: 1 prospective trial, 5 retrospective cohort studies, and 21 case reports totaling 104 patients treated with a DOAC for HIT. The DOACs prevented new and recurrent thrombosis in 98% (n=102) of cases, and bleeding complications occurred in 3% (n=3). While current literature remains limited, it is suggestive of a potential role of DOACs for HIT, which has led to their integration into the 2018 American Society Hematology Guidelines with a conditional recommendation.
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The impact of vasopressin and norepinephrine discontinuation order in the recovery phase of septic shock remains controversial. This systematic review and patient-level meta-analysis were performed to determine the impact of vasopressin and norepinephrine discontinuation order on clinically significant outcomes in the recovery phase of septic shock. ⋯ Discontinuation of norepinephrine prior to vasopressin during the recovery phase of septic shock resulted in less clinically significant hypotension but no difference in mortality or lengths of stay. Larger, prospective studies evaluating the impact of relative vasopressin deficiency and norepinephrine and vasopressin discontinuation order and timing on patient-centered outcomes are needed.
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Four-factor prothrombin complex concentrate (4F-PCC) has emerged as the preferred option for emergent reversal of vitamin K antagonists (VKAs); however, the optimal dosing strategy is unknown. Although several studies have attempted to determine the optimal dose of 4F-PCC using a variety of dosing regimens, no dosing strategy has been found to be superior. Many of these studies have evaluated a low, fixed dose of 4F-PCC rather than individualized dosing as recommended in product labeling. ⋯ However, many of these studies consistently identified a trend toward international normalized ratio (INR) reversal failure in patients presenting with high baseline INR values or intracranial hemorrhage, suggesting that higher 4F-PCC doses are needed in these patients. Available studies are underpowered to determine whether a dose-dependent association with thrombotic risk exists. Additional large, randomized studies are needed to determine the optimal dosing strategy and ascertain the role for fixed-dose 4F-PCC.
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The antiretroviral combination of emtricitabine-tenofovir disoproxil fumarate (FTC/TDF) was approved by the U. S. Food and Drug Administration for use as pre-exposure prophylaxis (PrEP) in individuals at high risk for acquiring human immunodeficiency virus (HIV) in July 2012. ⋯ The cost-effectiveness of PrEP continues to be assessed with the greatest cost-effectiveness remaining in those at highest risk of acquiring HIV. Additionally, cases of HIV acquisition in individuals who are adherent to PrEP highlight scenarios in which PrEP is not 100% effective including against the transmission of drug-resistant HIV strains. This review examines data on the implementation of PrEP outside the setting of clinical trials with the aim of providing clinicians with a summary of the current barriers and opportunities for PrEP use with a specific focus on the role of pharmacists in the optimization of PrEP implementation.