In this episode I’ll:
1. Discuss an article about the safety of high-dose IV labetalol
2. Answer the drug information question “Why is oral ketorolac restricted to patients that are continuing a 5-day course that started as parenteral therapy?”
Article
Safety of high-dose intravenous labetalol in hypertensive crisis
Lead author: Jason P. Hecht
Published in American Journal of Health System Pharmacy March 2019
Background
Prescribing information for IV labetalol lists a maximum dose of 300 mg, without any explanation of how or why this maximum dose was set. In most patients, hypertension should be controlled after this dose is reached and the patient can be transitioned to another antihypertensive.
However, some patients have refractory hypertension where continued administration of labetalol may be the only option. In this case, when no better options exist, labetalol has been continued.
Labetalol has a half-life of 6 hours, which is long for an IV antihypertensive. Use of labetalol beyond 300 mg carries a risk of prolonged hypotension and/or bradycardia.
The authors of this study sought to assess the safety of high-dose IV labetalol in adults.
Methods
The study was a retrospective analysis of 188 patients. Five years of records from 28 hospitals in the same system were reviewed in order to find 188 patients who received more than 300 mg of IV labetalol within a 24 hour period. The authors defined adverse events as any systolic blood pressure measurement less than 90 mmHg or heart rate less than 60 beats per minute.
Results
The mean dose of labetalol was just under 1000 mg with a range of 300 to 4465 mg. Analysis did not find that the cumulative dose of labetalol was associated with the adverse events of hypotension or bradycardia. A total of 66 patients experienced bradycardia and 34 patients experienced hypotension. There was some overlap with 12 patients experiencing both hypotension and bradycardia. Despite this very high rate of 44% of patients experiencing an adverse event, only 5 patients required a rescue agent for refractory adverse events.
Conclusion
The authors concluded:
A retrospective review of high-dose i.v. labetalol hydrochloride with doses greater than 300 mg in 24 hours observed a high rate of bradycardia and hypotension, but the study found that these events rarely caused clinically significant hemodynamic compromise and was not statistically associated with adverse events.
Discussion
Despite the small number of refractory adverse events, I would still only consider high doses of labetalol infusion if there are no better alternatives available. If I do use labetalol past 300 mg, I am vigilant for hypotension and bradycardia, and ensure that treatment such as glucagon or high dose insulin therapy can be initiated immediately if necessary.
Drug information question
Q: Why is oral ketorolac restricted to patients that are continuing a 5-day course that started as parenteral therapy?
A: Not long after the introduction of oral ketorolac in the early 1990s, world-wide post marketing reports of adverse effects, primarily bleeding, caused regulators in many countries to alter the prescribing information. In the UK, the recommended duration was shortened to 2 days and Germany withdrew the drug from the market. In the US in 1995 the labeling for oral ketorolac was changed to require initial doses be given via IV or IM route, and oral therapy continue for a total of no more than 5 days. The background behind this change is described in this article.
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