4- Thursday Pharmacotherapy News – 22th July

1 – Risk of Intracranial Hemorrhage With Concomitant Use of Antidepressants and Nonsteroidal Anti-inflammatory Drugs: A Nested Case-Control Study

• Whereas previous studies found that concomitant antidepressant and nonsteroidal anti-inflammatory drug (NSAIDs) use may increase the risk of gastrointestinal bleeding, either drug alone increases the risk of intracranial hemorrhage (ICH).
• This study aims to assess the risk for ICH in patients on concomitant treatment with antidepressants and NSAIDs.
• The results suggested that the concomitant use of antidepressants and NSAIDs was associated with an increased odds of developing ICH. NSAIDs, especially nonselective NSAIDs, and serotonergic antidepressants played an important role in this risk. Given the prevalent use of these 2 classes of drugs, this potential drug interaction deserves more attention.

Source: SAGE Journal

2 – Safety of High-Dose Unfractionated Heparin for Prophylaxis of Venous Thromboembolism in Hospitalized Obese Patients

• Optimal dosing of unfractionated heparin (UFH) for thromboprophylaxis in the obese patient population is uncertain because of their high-risk, prothrombotic state and a complexity of pharmacokinetic considerations.
• Literature on the appropriateness of the use of a higher dose UFH regimen remains unclear and inconsistent.
• This study aims to evaluate the safety of the use of 7500 units every 8 hours (high-dose) of subcutaneous UFH compared with the use of 5000 units every 8 hours (standard-dose) of subcutaneous UFH for thromboprophylaxis in obese patients.
• High-dose UFH was associated with an increased bleeding event rate compared with standard-dose UFH in patients with a BMI ≥30 kg/m2.
• This raises safety concerns about the appropriateness of utilizing this regimen in this population.

Source: SAGE Journal

3 – Comparison of Vasopressor Duration in Septic Shock Patients With and Without Cirrhosis

• Patients with cirrhosis have immune dysfunction, altered inflammatory response, and hemodynamic changes which increase risk of septic shock and potentially prolong management with fluids, vasopressors, and other therapies.
• Due to limited available guidance, this study aimed to characterize vasopressor use in patients with cirrhosis in relation to patients without cirrhosis in septic shock.
• Patients with cirrhosis in septic shock have increased vasopressor durations and overall requirements compared with patients without cirrhosis.
• Increased durations and requirements is associated with poorer outcomes independent of presence of cirrhosis.
• Future studies are needed to improve vasopressor treatment strategies and end points utilized in cirrhosis.

Source: SAGE Journal

4- 23.4% Sodium Chloride Versus Mannitol for the Reduction of Intracranial Pressure in Patients With Traumatic Brain Injury: A Single-Center Retrospective Cohort Study

• Intermittent doses of mannitol or hypertonic saline are recommended to treat elevated intracranial pressure (ICP).
• However, it is unclear if one agent is more effective than the other.
• Previous studies have compared mannitol and hypertonic saline in reduction of ICP, with conflicting results.
• However, no study thus far has compared 23.4% sodium chloride with mannitol.
• The objective of this study was to determine the difference in absolute reduction of ICP 60 minutes after infusion of 23.4% sodium chloride versus mannitol.
• No difference was found for absolute reduction of ICP at 30, 60, and 120 minutes, respectively, after infusion of hyperosmolar agent or time to next elevated ICP.
• Patient-specific parameters should be used to guide the choice of hyperosmolar agent to be administered.

Source: SAGE Journal

5 – A Review of β-Lactam–Associated Neutropenia and Implications for Cross-reactivity

• Drug-induced neutropenia is a well-documented adverse reaction of β-lactam antibiotics, with an incidence of approximately 10% following at least 2 weeks of intravenous therapy.
• However, multiple gaps in knowledge remain in the mechanism of pathophysiology and optimal management of this reaction.
• This study aims to review the incidence, management, and current understanding of the pathophysiology of β-lactam–induced neutropenia and to critically evaluate the practicality and safety of direct substitution to an alternative β-lactam in the setting of this reaction.
• Future use of β-lactams with differing R1 side chains, particularly those from a separate class, should not be deemed contraindicated following β-lactam–induced neutropenia and may be considered when indicated, with close laboratory monitoring.

Source: SAGE Journal

6 – Osilodrostat: A Novel Steroidogenesis Inhibitor to Treat Cushing’s Disease

• This study aims to review data on efficacy and safety of osilodrostat (Isturisa), a novel oral steroidogenesis inhibitor for treatment of Cushing’s disease (CD), a life-threatening endocrine disorder.
• Osilodrostat provides a potent and consistent effect in reducing life-threatening supraphysiological levels of cortisol in patients with CD.
• Osilodrostat was efficacious in decreasing cortisol levels and safe in treating patients who have failed or are ineligible for pituitary surgery.
• Although risks exist, a pivotal clinical trial revealed efficacy in 86% of participants.

Source: SAGE Journal

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