Tina Harrach Denetclaw

An active-learning strategies primer for achieving ability-based educational outcomes

Active learning is an important component of pharmacy education. By engaging students in the learning process, they are better able to apply the knowledge they gain. This paper describes evidence supporting the use of active-learning strategies in pharmacy education and also offers strategies for implementing active learning in pharmacy curricula in the classroom and during pharmacy practice experiences.

Dofetilide Dose Calculation Errors in Elderly Associated with Use of the Modification of Diet in Renal Disease Equation

Objective: To report 2 cases of drug dosage calculation errors that occurred when the Modification of Diet in Renal Disease (MDRD) equation was used for initiating drug therapy with dofetilide in eiderly patients with chronic kidney disease. Case Summary: An 83-year-old woman and a 92-year-old man were admitted for dofetilide treatment initiation and cardioversion for atrial fibrillation. The estimated glomerular filtration rate (eGFR) determined with use of the MDRD equation was significantly higher than the estimated creatinine clearance (eCrCl) determined with use of the Cockcroft-Gault equation for both cases (85 vs 43 mL/min for the man and 40 vs 24 mL/min for the woman). Initial dofetilide dosages calculated by the MDRD equation were 2-fold higher than those calculated by eCrCl in both cases. Initiation of dose based on the MDRD in the first patient ted to a 32% increase in the QTc interval from baseline. Dofetilide therapy was adjusted for QTc interval prolongation based on eCrCl and reinitiated at a lower dose, and the patient did not develop further significant increases in the QTc interval. In the second patient, the lower dose based on eCrCl was initiated and the QTc interval remained within an acceptable range. Discussion: The initial dosing of dofetilide is based on eCrCl as specified by the drug manufacturer. Recent widespread use and automated reporting of the eGFR by clinical laboratories has tempted some clinicians to consider using eGFR for calculating drug doses. However, recent data suggest that the eGFR, calculated by the MDRD equation, consistently overestimates eCrCl, leading to dose discrepancies, particularly in the elderly. The cases reported here illustrate the drug dose calculation errors that may occur when using the MDRD equation for initiating doses of dofetilide. Conclusions: Use of the eGFR or MDRD equation for calculation of doses in renal dysfunction has not been validated, and significant drug dose errors have been reported. The use of eGFR to calculate doses of dofetilide should be avoided.

Successful Treatment of Ventriculostomy-Associated Meningitis Caused by Multidrug Resistant Coagulase-Negative Staphylococcus epidermidis Using Low-Volume Intrathecal Daptomycin and Loading Strategy

Objective: To report successful use of low-volume intrathecal (IT) daptomycin and loading strategy for the treatment of ventriculostomy-associated meningitis. Case Summary: A 23-year-old man with a history of multiple ventriculoperitoneal shunt revisions resulting from multidrug-resistant Staphylococcus epidermidis shunt infection presented with meningitis despite suppressive antibiotic therapy. After source control surgery, the patient improved with intravenous daptomycin plus IT vancomycin. Then, 4 days later, significant ventriculostomy output occurred, and the S epidermidis was confirmed to be intermediately sensitive to vancomycin (MIC = 8 µg/mL) and susceptible to daptomycin (MIC = 2 µg/mL). IT vancomycin was changed to IT daptomycin 5 mg in 3 mL normal saline (NS) every 24 hours for 3 days, then every 72 hours for 18 days. The cerebrospinal fluid (CSF) was sterile after 1 day of IT daptomycin and remained so. Creatine kinase remained normal throughout the course of treatment. The patient was discharged on hospital day 50 without antibiotics. Discussion: IT daptomycin has been reported for adult doses ranging from 5 to 10 mg once every 24 to 72 hours in volumes ranging from 5 to 10 mL; drug accumulation has been seen after the third dose of once every 24 hours dosing, and delayed improvement has been seen with once every 72 hours dosing. We planned for rapid load and CSF sterilization and extended the dosing interval once drug accumulation was expected to have occurred. Conclusions: IT daptomycin 5 mg diluted to 3 mL in NS and dosed in a loading strategy was effective and without adverse sequelae.

Performance of a Divided-Load Intravenous Vancomycin Dosing Strategy for Critically Ill Patients:

Background: Current guidelines recommend vancomycin trough concentrations 15 to 20 µg/mL in complicated infections and all trough concentrations above 10 µg/mL. Objective: We assessed the performance of a novel divided-load protocol designed to attain target trough concentrations within 24 hours of initiation and prevent doses given at concentrations above the target range, in critically ill patients. Methods: The protocol was evaluated in 79 critically ill patients through retrospective medical record review. Vancomycin serum concentrations were drawn before the third dose after initiation and after any dosing change. Steady-state concentrations were drawn before the fifth or sixth doses. Vancomycin concentrations before the second dose were predicted using a nonparametric expectation maximization algorithm. Results: Sixty-nine of 79 patients received scheduled doses, and 62 (90%) of the scheduled-dose patients attained therapeutic target concentrations 12 to 24 hours after therapy initiation. Eight scheduled-dose patients weighed > 150% of ideal body weight (IBW) and were significantly more likely to exhibit supratherapeutic trough concentrations before the fifth or sixth doses (P = .0004) compared with patients weighing ≤150% of IBW. Ten of 79 patients (8 dialysis dependent and 2 experiencing acute kidney injury) were dosed in response to measured serum drug concentrations drawn according to the divided-load protocol. All the 8 dialysis-dependent patients (100%) attained therapeutic concentrations 12 hours after therapy initiation. Conclusion: The divided-load vancomycin dosing strategy achieved measured trough concentrations 15 to 20 µg/mL for most critically ill patients within 24 hours of initial dosing, without allowing doses given during supratherapeutic concentrations.

Performance of a Divided-Load Intravenous Vancomycin Dosing Strategy for Obese Patients

Background: Current guidelines recommend vancomycin trough concentrations of 15 to 20 µg/mL in complicated infections and all trough concentrations >10 µg/mL to avoid developing microbial resistance. To date, no published protocol reliably meets these recommendations for obese patients. Objective: We assessed the performance of a novel, obese-specific, divided-load vancomycin protocol for attaining target trough concentrations within 12 to 24 hours of dosing initiation, and during maintenance dosing, in obese patients. Methods: The protocol was evaluated through prospective medical record review in 54 consecutive obese patients. Vancomycin serum concentrations were drawn before the third and fifth dose after initiation. Steady-state concentrations were drawn after the third dose once maintenance dosing was achieved and periodically thereafter. Results: Within 12 hours after dosing initiation, 48 (89%) study patients exhibited trough concentrations of 10 to 20 µg/mL averaging 14.5 ± 3.2 µg/mL; 51 (94%) study patients exhibited trough concentrations >10 µg/mL within 12 hours after dosing initiation, and 3 (6%) had trough concentrations >20 µg/mL. Thirty-one participants had second trough concentrations drawn within 24 hours of dosing initiation, averaging 15.0 ± 3.1 µg/mL; 24 patients had a total of 32 trough concentrations drawn during maintenance dosing, averaging 15.1 ± 2.5 µg/mL. Conclusion: Obese-specific, divided-load dosing achieved trough concentrations of 10 to 20 µg/mL for 89% of obese patients within 12 hours of initial dosing and 97% of obese patients within 24 hours of initial dosing while preventing doses given during supratherapeutic trough levels; 97% of troughs measured during steady state were within target range.

Managing Subdural Bleeding Associated With Rivaroxaban A Series of 3 Cases

Objective: To report 3 cases of subdural bleeding associated with rivaroxaban managed by 3-factor prothrombin complex concentrate (PCC3). Case Summaries: Case 1 presented with a 1-cm thick subdural hematoma (SDH) 12 hours after her last dose of rivaroxaban. Case 2 presented with a right 1-cm acute right SDH with 2 to 3 mm of midline shift 24 hours after his last dose of rivaroxaban. Case 3 presented with a 1.8-cm thick right cerebral convexity hematoma 12 hours after her last dose of rivaroxaban. All patients received 23 to 35 units/kg PCC3 with 1 to 3 units of fresh frozen plasm (FFP) and demonstrated no progression in lesions measured by repeat computed tomography (CT). Two patients were discharged to rehabilitation facilities and 1 patient ultimately died due to the location of the lesion. Discussion: Rivaroxaban has no specific antidote. Current bleeding management strategies are based on expert opinion. The risks and benefits for differing strategies are unclear, and no clinical experience has been reported to date. These cases begin to illuminate differences among choices for managing bleeding associated with Xa inhibitors. Conclusion: In this case series, 25 to 35 units/kilogram PCC3 and FFP 1 to 3 units ceased rivaroxaban-associated bleeding without thrombogenic complications.

Case Report: Apixaban-Associated Gluteal Artery Extravasation Reversed With PCC3 Without FFP

Apixaban, an oral factor Xa inhibitor, has no commercially available assay to measure its activity and no specific antidote. To date, recommendations for managing bleeding associated with apixaban are based on studies with animal models and healthy volunteers (who do not have identified thrombogenic risk factors) and expert opinion. No clinical experience has been published in the literature. Ideally, apixaban would be reversed sufficiently to stop a perilous bleed without producing more thrombogenic risk than the patients’ underlying risk factors. Three-factor prothrombin complex concentrate (PCC3) is the least thrombogenic among the suggested reversal agents. Fresh frozen plasma (FFP) is sometimes recommended to add to PCC3, but it adds considerable volume. We describe successful management of an active left gluteal arterial extravasation due to trauma and associated apixaban, in a patient with aortic stenosis and atrial fibrillation, by administration of PCC3 alone, without the added volume of FFP.

Needs Analysis for Educating Community Pharmacists to Interface with Prehospital Stroke Chain of Survival

BACKGROUND Awareness of the American Heart Associations Stroke Chain of Survival, and willingness to learn and share this information with the public, was assessed for community pharmacists practicing near a primary stroke center. METHODS Twenty-three community pharmacies local to a primary stroke center were identified and surveyed. The surveyor showed each pharmacist a flier with a mnemonic for assessing stroke symptoms, briefly explained steps in the Stroke Chain of Survival, and noted if the pharmacist was available, listened to the entire presentation, read the information on the flier, agreed to post the flier, and if the pharmacist made any comments. The surveyor also assessed whether the Stroke Chain of Survival was new information to each pharmacist. RESULTS All subjects read the information on the flier. Twenty-two (95.7%) listened to the entire presentation, and 23 (100%) were willing to post the flier. Two (11%) indicated that the parent company does not allow public posting of noncorporate information but agreed to post the flier internally. Twenty-one (91%) expressed appreciation for receiving the information. Seventeen (74%) indicated that the Stroke Chain of Survival was new information to them, 14 (61%) spontaneously remarked on the importance of the information, and 4 (17%) asked for additional information. CONCLUSIONS Community pharmacists surveyed were willing to interface with the prehospital phase of the Stroke Chain of Survival; nearly 75% of them required education to do so. Community pharmacies are potentially a venue for educating the public on the Stroke Chain of Survival. It may be necessary to approach community pharmacy corporate leadership to partner with such efforts.

Managing Nonoperable Intracranial Bleeding Associated With Apixaban: A Series of 2 Cases:

Objective: To report 2 cases of nonoperable intracranial bleeding associated with apixaban managed by 3-factor prothrombin complex concentrate (PCC3). Case Summaries: Case 1 presented with a 1.3-cm left parieto-occipital hemorrhage and a thin subdural hematoma (SDH) on the left tentorium of the brain about 6 hours after his last dose of apixaban. Case 2 presented with a 4-mm left parafalcine SDH with time of most recent apixaban dose unknown. The patients received 24.9 to 25.5 U/kg of PCC3 with none to 1 U fresh frozen plasma (FFP) and demonstrated minimal or no progression in lesions measured by repeat computed tomography (CT) after treatment. One patient was discharged to a skilled nursing facility after 8 days; the other patient was discharged to home after 18 days. Discussion: Apixaban has no specific antidote. Current bleeding management strategies are based on expert opinion. The risks and benefits for differing strategies are unclear, and little clinical experience for managing apixaban-associated intracranial bleeding has been reported to date. These cases describe the clinical use of PCC3 to manage parieto-occipital and subdural hemorrhage associated with apixaban in events not requiring surgical intervention. Conclusion: In these 2 cases, 25 U/kg PCC3, with none to one unit FFP, ceased apixaban-associated intracranial bleeding without apparent thrombogenic complications.

Reply: Pulmonary Embolism After Early Change From Rivaroxaban to Aspirin Following Total Knee Replacement in an Obese Patient

American Society of Cataract and Refractive Surgery members, and some surgeons preferred more targeted refraction. Although mini-monovision (target refraction of 0.25 D and 0.75 D)was applied in this study, it is a little low and not adequate for near reading. If the monovision group with a little more targeted refraction showed significant statistical difference compared with the accommodating IOL group, the conclusion would be more solid. Finally, the sample number was not large enough, which decreased the significance of the study.We thank Dr Miyares for the discussion on our recent publication. Our concern about possible low dosing of rivaroxaban in obese patients after knee or hip arthoplasty is a combination of 2 factors: decreased pharmacodynamic effect in conjunction with increased underlying risk for deep venous thrombosis. The combined factors may present increased risk for obese patients with preserved renal function. Body mass index (BMI) greater than 30 kg/m is associated with more than a 2-fold increased risk of deep-vein thrombosis when compared with nonobese individuals, in general. Kubitza et al found that the maximal effect of rivaroxaban on protime prolongation was decreased by about 6% in 12 individuals with body weights >120 kg when compared with 12 individuals with body weights of 70 to 80 kg (P < 0.002) and found that measured area under the curve (AUC) was not different for those with body weights >120 kg although a fixed dose was given even for increased body mass. Paradoxically, several clinical studies found an increased risk of bleeding for obese patients. We attribute the increased bleeding risk despite unchanged measured AUC in obese patients to the method of using total body weight (TBW) to estimate renal clearance for dose determination and note that the experience of obese patients who have preserved renal function, as a subgroup, is not described in the literature. Although the original Cockroft-Gault equation for estimating creatinine clearance used TBW, this equation was developed based on data from men with normal weights. Recently, Adane et al found that the Cockroft-Gault equation using ideal body weight (IBW) more closely approximated measured creatinine clearance in severely obese patients compared with the use of TBW. Therefore, use of TBW in the Cockroft-Gault equation as was done in rivaroxaban clinical trials would overestimate renal function in obese individuals, possibly resulting in an increased bleeding signal from patients with poor renal function masked by large TBW and obscure which individuals truly have preserved renal function. Furthermore, studies such as those by Kubitza et al and Turpie et al and the EINSTEIN trial that report subgroups according to weights do not adequately define obese groups because BMI depends on height as well. For example, a 6′2′′ 100-kg man would not be obese, whereas a 5′0′′ 100-kg woman would be severely obese. Also, studies that define subgroups according to BMI but use TBW to estimate creatinine clearance, such as that by Turpie et al and the ROCKET AF trial, do not differentiate between individuals who experience increased drug exposure as a result of low renal clearance and individuals who experience decreased drug exposure as a result of preserved renal function. Using IBW to estimate creatinine clearance, even for reporting purposes, and using %IBW to define subgroups, would parse out questions that remain regarding the safety and efficacy of rivaroxaban in obese patients with preserved renal function. Similar to enoxaparin, we believe that the safety and efficacy of prophylactic doses of rivaroxaban in obese patients (BMI >30 kg/m) has not been fully determined, and we hope that the currently available data will be revisited to provide clearer information regarding the use of rivaroxaban in obese individuals.