In this episode I’ll:
1. Discuss an article about the effectiveness of conivaptan and tolvaptan in neurocritically ill patients.
2. Answer the drug information question “Is concomitant carbamazepine and oxcarbazepine therapy always a therapeutic duplication?”
3. Share a resource that helps justify alternate dosing schedules for meropenem and cefepime.
The article for this episode recently appeared in a weekly literature digest for members of my Critical Care Pharmacy Academy. Every week I send Academy members a summary of the most important critical care pharmacy articles, including my analysis of where the article fits in practice. The literature summary is brief, relevant, and presented in audio and video format. You can find out more at pharmacyjoe.com/academy.
Article
Lead author: Caroline Der-Nigoghossian
Published in Pharmacotherapy March 2017
Background
Conivaptan and tolvaptan are arginine vasopressin (AVP) receptor antagonists. They cause excretion of free water (without loss of serum electrolytes) resulting in net fluid loss and an increase in serum sodium levels.
The authors of this retrospective cohort study sought to describe the effectiveness and tolerability of conivaptan and tolvaptan for the correction of hyponatremia in neurocritically ill patients.
Methods
The study enrolled 36 adults admitted to the neurocritical care unit at two academic medical centers. 5 patients received at least one dose of conivaptan and 31 patients received at least one dose of tolvaptan.
Results
The mean maximal increase in serum sodium level at 24 hours following the last dose compared with baseline was about 5 mEq/L for conivaptan and 8 mEq/L for tolvaptan. The mean maximal increases in serum sodium level at 48, 72, and 96 hours following the last dose of vaptan therapy compared with baseline were 5.5 mEq/L, 5.6, and 4.8, respectively.
None of the patients receiving conivaptan had overcorrection of sodium. In 20% of patients receiving tolvaptan, the serum sodium was overcorrected. Hypotension occurred in 20% of patients receiving conivaptan and 52% of patients receiving tolvaptan. Hypokalemia occurred in 40% of patients receiving conivaptan.
Conclusion
The authors concluded:
Use of vaptans in neurocritically ill patients led to a significant increase in serum sodium level at 24 hours after the last dose, which was sustained for 96 hours, with the majority of patients receiving a single dose. Risk of sodium overcorrection was high and necessitates appropriate patient selection and frequent monitoring.
Discussion
This study is the largest to date that examines the use of conivaptan and tolvaptan in neurocritically ill patients. Despite their expense, (hundreds of dollars per dose) the vaptans have a role in the management of hyponatremia in some neurocritically ill patients when fluid restriction or hypertonic saline are not appropriate. For example: Fluid restriction for hyponatremia is not always a good option (such as in patients with subarachnoid hemorrhage). Patients with pulmonary edema may not be able to tolerate hypertonic saline.
While conivaptan and tolvaptan have a predictable response on the serum sodium, the risk of overcorrection remains significant, and monitoring is critical to the safe use of these medications.
Drug information question
Q: Is concomitant carbamazepine and oxcarbazepine therapy always a therapeutic duplication?
A: No.
Oxcarbazepine was developed through structural variation of carbamazepine in an attempt to avoid metabolites causing side effects. However, there are significant differences between the two drugs. In addition to blocking sodium channels, oxcarbazepine also modulates calcium and other channels in the brain.
In controlled trials, add-on or substitution treatment with oxcarbazepine was effective even when carbamazepine did not achieve control of seizures. For this reason, it is reasonable to consider carbamazepine and oxcarbazepine as distinctly different medications.
Resource
Nebraska Medicine provides dosing protocols from their antimicrobial stewardship program online. Included in these protocols is a slide presentation justifying the use of alternate dosing for meropenem and cefepime. The dosing schedules advocated are the same ones used at my institution:
Meropenem 500 mg IV q6h instead of 1g IV q8h
Cefepime 1g IV q6h instead of 2g IV q8h
These alternate dosing schedules achieve superior time above MIC target attainment while using less drug.
If you like this post, check out my book – A Pharmacist’s Guide to Inpatient Medical Emergencies: How to respond to code blue, rapid response calls, and other medical emergencies.
Leave a Reply