Piperacillin/Tazobactam and Risk of Acute Kidney Injury with Vancomycin

There are a few reasons why piperacillin/tazobactam (Zosyn) is not usually my first choice for a broad-spectrum gram-negative agent in the ED. First, at my institution, the Pseudomonas aeruginosa susceptibilities to pip-tazo are lower than that for cefepime. Second, pip-tazo does not have great CNS penetration, especially compared to ceftriaxone, cefepime, or even meropenem. Third, do we really need the anaerobic coverage that pip-tazo provides for every sick patient? Pip-tazo is great for empiric treatment of intra-abdominal and severe diabetic foot infections, but may not be needed for a hospital-acquired pneumonia. Fourth, with its frequent dosing (every 6 hours), too often the second dose is missed if the patient is still boarding in the ED.

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By Bryan D. Hayes, PharmD, DABAT, FAACT, FASHP|2019-02-12T06:02:25-08:00May 20, 2014|Renal, Tox & Medications|

New Antibiotic Dalbavancin: Should we use this in the ED?

A new antibiotic will soon be approved for skin and soft tissue infections (SSTIs): dalbavancin. The company behind the drug will likely begin marketing heavily to emergency physicians as many patients with SSTIs seek care in the Emergency Department (ED). However, should we seriously consider dalbavancin as an addition to an ED’s arsenal against SSTIs and should it change our practice?

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By Zlatan Coralic, PharmD|2019-02-19T18:22:22-08:00May 12, 2014|Tox & Medications|

Atypical Antipsychotic Medication Re-initiation in the ED

Pills antipsychotic medication The acute episode of intoxication and agitation has subsided and your patient is calm. She has been medically cleared and is ready to be moved to a less acute, less monitored portion of the ED to await further assessment and treatment for her underlying psychiatric conditions. As a well-intentioned emergency medicine practitioner, you wish to give your patient the tools she needs to maintain this calm status by restarting her home atypical antipsychotic medication. What is the best way to go about doing this?

While the atypical antipsychotics have generally been considered safer than the first generation agents due to the decreased risk of extrapyramidal side effects at therapeutic doses, this class is not without adverse effects. All of the medications in this class are capable of causing sedation due to their antihistaminergic effects and some of these agents also have an alpha-blockade effect possibly leading to orthostatic hypotension.¹

Re-Initiation Strategy: Atypical Antipsychotic Medication

When faced with the prospect of re-initiation of atypical antipsychotics, it is necessary to determine how long the patient has been without medication if possible. While there is a lack of literature regarding this topic, select medications make reference to re-initiation in their package inserts.^2–4 These recommendations range from “an interval off” to “more than one week”, possibly indicating that a few missed doses may not have an impact on the re-initiation dose. However, when it is determined that a patient has been without their atypical antipsychotic for a few days to a week or the period of nonadherence is unknown, caution with re-initiation is justified and some package inserts call for restarting the initial dosing titration.

Medication	Package insert: Day 1 dosing	Re-initiation recommendation
Aripiprazole (Abilify)	Schizophrenia: 10-15 mg PO Q 24 hours Bipolar mania: 15 mg PO Q 24 hours Bipolar mania (adjunctive therapy): 10-15 mg PO Q 24 hours	No recommendations
Asenapine (Saphris)	Schizophrenia: 5 mg PO Q 12 hours Bipolar mania (monotherapy): 10 mg PO Q 12 hours Bipolar mania (adjunctive therapy): 5 mg PO Q 12 hours	No recommendations
Iloperidone (Fanapt)	Schizophrenia: 1 mg PO Q 12 hours	When off > 3 days, the initial dosing titration schedule should be followed
Lurasidone (Latuda)	Schizophrenia: 40 mg PO Q 24 hours Bipolar depression: 20 mg PO Q 24 hours	No recommendations
Olanzapine (Zyprexa)	Schizophrenia: 5-10 mg PO Q 24 hours Bipolar disorder: 10-15 mg PO Q 24 hours	No recommendations
Paliperidone (Invega)	Schizophrenia: 6 mg PO Q 24 hours Schizoaffective disorder: 6 mg PO Q 24 hours	No recommendations
Quetiapine (Seroquel)	Schizophrenia: 25 mg PO Q 12 hours Bipolar mania: 50 mg PO Q 12 hours Bipolar depression: 50 mg PO Q HS	When off ≥ 1 week, the initial dosing titration schedule should be followed
Risperidone (Risperdal)	Schizophrenia: 2 mg PO Q 24 hours Bipolar mania: 2-3 mg PO Q 24 hours	When off for an interval, the initial titration schedule should be followed
Ziprasidone (Geodon)	Schizophrenia: 20 mg PO Q 12 hours Bipolar I disorder: 40 mg PO Q12 hours	No recommendations
* Dosing above is not adjusted for renal or hepatic dysfunction or concomitantly administered interacting medications

Due to the risk of agranulocytosis for which there is a black box warning, all patients prescribed clozapine must be enrolled in a registry which monitors the patient’s white blood cell count and absolute neutrophil count. As a result, clozapine dosing must be made in collaboration with the patient’s clozapine registry. In addition, clozapine also carries a black box warning for cardiovascular and respiratory effects and states that for patients who have been without clozapine for 2 or more days, they are to start with 12.5 mg once or twice daily.⁵

Other Agents

For other agents, the course of action is less clear. Dosing decisions should ideally be made in conjunction with a psychiatric care provider; however this is not always feasible in the ED setting. For patients on atypical antipsychotics without clear re-initiation instructions in the prescribing information and doses higher than initial dosing (see table), consider a dose reduction. Anecdotally, re-initiating the dose at 50-80% of the maintenance dose seems reasonable in hemodynamically stable patients; however, there are not identified data to support this strategy. Regardless of the strategy implored, vigilance is important when re-initiating atypical antipsychotics. This is especially noteworthy in patients who will be in a less monitored area of the department.

Take Home Points

Determine how long the patient has been without their atypical antipsychotic if possible.
Use caution when re-initiating home doses of atypical antipsychotic agents and consider dosing reductions in patients who have been without their medications for more than a few doses.
Clozapine must be ordered in conjunction with the patient’s clozapine registry and when off for 2 or more days usually requires restarting initial dosing.
When the maintenance dose is above the initial dosing and re-initiation instructions are not within the package insert, consider a dose reduction (such as restarting 50-80% of the patient’s stabilized dose, depending on the clinical picture) to avoid adverse events, especially in less monitored patients

Reviewer: Clayton English, PharmD, BCPP

References

Minns A, Clark R. Toxicology and overdose of atypical antipsychotics. J Emerg Med. 2012;43(5):906-913. [PubMed]
Risperdal® [package insert]. Titusville, NJ. Janssen Pharmaceutical, Inc; 2007. Rev 11/2013.
Seroquel® [package insert]. Wilmington, DE. AstraZenica; 2013.
Fanapt® [package insert]. East Hanover, NH. Novartis Pharmaceutical Corporation; 1/2013.
Clozapine [package insert]. Morgantown, WV. Mylan Pharmaceuticals Inc. 5/2013.

By Jill Logan, PharmD BCPS|2023-07-30T23:43:01-07:00Apr 22, 2014|Psychiatry, Tox & Medications|

Understanding Phenytoin Equivalents

Sometimes, in an effort to make things simpler, we actually make them more confusing. Such is the case with phenytoin equivalents.

Fosphenytoin is a water-soluble prodrug of phenytoin. After IV administration, much of the fosphenytoin is metabolized to phenytoin within 15 minutes. Advantages over phenytoin include the option for IM administration and less cardiotoxicity allowing for faster infusion rates. Even the potential for hyperphosphatemia from the release of phosphate is generally inconsequential.

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By Bryan D. Hayes, PharmD, DABAT, FAACT, FASHP|2016-11-11T19:19:39-08:00Apr 15, 2014|Tox & Medications|

Over the last 5 years, the use of neuraminidase inhibitors for the treatment of influenza has skyrocketed. Emergency physicians have been pushed to prescribe these medications under the belief that they reduced symptoms, the risk of complications, hospitalizations, and transmission. However, the recommendation for the use of these drugs has never sat on firm evidence-based ground. So what did we know then, and what do we know now?

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By Anand Swaminathan, MD MPH|2019-01-28T23:34:05-08:00Apr 14, 2014|Infectious Disease, Tox & Medications|

Beware of fluoroquinolones: You, your patient, and the FDA

Fluoroquinolones are a widely used class of antibiotic that are effective in treating a wide variety of infections. Despite their popularity there is increasing concern regarding to the potential complications associated with these agents. In 2008, the U.S. Food and Drug Administration (FDA) issued a black box warning involving fluoroquinolone use and an increased risk of tendon rupture. More recently in 2013 the FDA released another warning regarding the risk of peripheral neuropathy and required additional warnings to be added to the drug labels [1].

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By Matthew DeLaney, MD|2017-03-05T14:18:39-08:00Apr 7, 2014|Medicolegal, Tox & Medications|

Is the Patient Sober? Clinical Sobriety versus Blood Alcohol Concentration

There is significant practice variability when providers are asked to determine if a patient is intoxicated. Some providers will evaluate a patient to determine if a patient is “clinically sober”, while other providers will rely on a patient’s blood alcohol concentration (BAC) to evaluate a patient’s level of intoxication. There is very little data to suggest that either approach is superior; however, both practice patterns have significant limitations and carry a certain degree of medicolegal risk.

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By Matthew DeLaney, MD|2016-11-11T19:19:30-08:00Mar 6, 2014|Medicolegal, Tox & Medications|