Pharmacokinetic Characteristics of Long-Acting Injectable Antipsychotics for Schizophrenia: An Overview.

The availability of long-acting injectable (LAI) antipsychotics for the treatment of schizophrenia provides clinicians with options that deliver continuous drug exposure and may improve adherence compared with daily oral antipsychotics. However, all LAI antipsychotics have unique formulations and pharmacokinetic characteristics that have implications for medication selection, administration interval, and injection site. This review outlines key differences in drug formulations and pharmacokinetics among LAI antipsychotics. A systematic search of the PubMed database was conducted to identify physical and formulation properties and pharmacokinetic data of commercially available LAI antipsychotics, including flupentixol decanoate, fluphenazine decanoate, haloperidol decanoate, zuclopenthixol decanoate, aripiprazole monohydrate, aripiprazole lauroxil, olanzapine pamoate, paliperidone palmitate, risperidone microspheres, and risperidone polymeric microspheres. Additional information was obtained from package inserts and product monographs. Relevant data on drug properties, administration details, pharmacokinetic parameters, and oral dose equivalencies of LAI antipsychotics are summarized. Based on our analysis, formulation characteristics (e.g., vehicle medium) and administration characteristics (e.g., injection site) can affect rate of absorption and adverse effects and may factor into whether oral supplementation or an additional injection is needed. Dose adjustments may be necessary based on potential drug-drug interactions, and approximate dose equivalence with oral formulations can help inform titration when switching from oral to LAI formulations. Clinicians administering LAI antipsychotics should consider these formulation and pharmacokinetic factors to maximize clinical impact and to adjust to an individual patient's needs and treatment goals.

Analysis of adherence to national nosocomial pneumonia treatment guidelines.

BACKGROUND: Guidelines for the management of adults with hospital-acquired (HAP), ventilator-associated (VAP), and healthcare-associated (HCAP) pneumonia were recently updated. These evidence-based guidelines emphasize early, appropriate antimicrobials, as well as, de-escalation of initial therapy based upon microbiologic cultures and clinical response of the patient, and to shorten duration of therapy to a minimum effective period. OBJECTIVE: To evaluate adherence to the nosocomial pneumonia guidelines before and after a multifaceted educational intervention in conjunction with the implementation of an adult pneumonia order set. METHODS: A three phase, retrospective, observational analysis was performed among patients with nosocomial pneumonia in a tertiary care facility. The phases consisted of an analysis of medical charts to identify empiric antimicrobial therapy for patients with nosocomial pneumonia; education of physicians on the guidelines; and repeat review of medical charts of patients with nosocomial pneumonia to observe for guideline adherence. An adult pneumonia order set was introduced to the medical staff prior to the initiation of the observational analysis and provided a modality for prescribers to be most compliant with the current recommendations for treating pneumonia. Order set utilization was tracked throughout the observational analysis to determine if various educational interventions increased compliance. RESULTS: Thirty-three patients were evaluated pre-education: 5 transferred, 16 discharged, and 12 died. Thirty-one patients were evaluated post-education: 6 transferred, 21 discharged, and 4 died. The combined sixty-seven patients received two hundred forty-eight orders for forty-four unique antimicrobial agents from five different services. Appropriateness of antimicrobial prescribing, designated by adherence to the clinical practice guidelines, did not improve following an educational intervention. However, the adult pneumonia order set was utilized in forty-eight percent of the post-education group while only being implemented in nine percent of the pre-education group. The prescribing of single or additional antimicrobials, while utilizing the adult pneumonia order set, commonly resulted in overall noncompliance with the consensus guidelines. CONCLUSION: This analysis showed that educational efforts alone were not effective in improving the appropriateness of prescribing empiric antimicrobial therapy in accordance with the guidelines. Prescribing compliance with pre-printed orders, in addition to periodic interactive educational interventions, should be addressed when introducing and maintaining adherence to new clinical practice guidelines.

Comparison of the modification of diet in renal disease and Cockcroft-Gault equations for antimicrobial dosage adjustments.

BACKGROUND: Direct measurement of glomerular filtration rate (GFR) is considered to be the most accurate method of assessing kidney function, albeit difficult and costly. With the derivation of the Modification of Diet in Renal Disease (MDRD) equation to estimate GFR in patients with chronic kidney disease, questions exist as to whether this method should be preferred over the Cockcroft-Gault (CG) equation when making dosage adjustments for renally eliminated antimicrobials. OBJECTIVE: To determine whether a difference exists when making antimicrobial dosage adjustments in patients with chronic kidney disease based on estimation of GFR using the MDRD and CG equations. METHODS: We conducted an observational analysis of 409 patients with chronic kidney disease who were admitted to a tertiary care facility with an inpatient dialysis center and nephrology unit. GFR was calculated using both the 4- or 6-variable MDRD equation and the CG equation and compared using correlation and Bland-Altman methodology. Dosage discordance rates of the selected antimicrobials were determined on the basis of manufacturer renal dose recommendations. RESULTS: Average +/- SD GFR for all patients using the CG equation was 34.8 +/- 12 mL/min and, using the MDRD equation, was 40.2 +/- 12 mL/min (absolute mean difference 5.40; 95% CI 4.66 to 6.15; p < 0.001). The correlation coefficient between the 2 estimations, among all patients, was excellent (r = 0.80). The Bland-Altman plot yielded limits of agreement of -9.8 and 20.6; thus, the MDRD estimation may range from 9.8 mL/min below to 20.6 mL/min above the CG estimation for 95% of the cases. A discordance rate of 21-37% (p < 0.001) existed among the recommended dosing adjustments of the selected antimicrobials. CONCLUSIONS: This analysis demonstrated statistically significant differences between the CG and MDRD equations, resulting in different dosing recommendations in 21-37% of patients. The clinical significance of these differences is uncertain in the absence of data regarding clinical outcomes that would result from the use of the discordant doses.