FDA Drug Safety Communication: Updated Information about the Drug Interaction between Methylene Blue (methylthioninium chloride) and Serotonergic Psychiatric Medications

This update is in follow-up to the FDA Drug Safety Communication posted on 7/26/2011: Serious CNS reactions possible when methylene blue is given to patients taking certain psychiatric medications¹.

Safety Announcement

[10-20-2011]

The U.S. Food and Drug Administration (FDA) is updating the public on the potential drug interaction between methylene blue and serotonergic psychiatric medications.

FDA is providing additional information about the reports of serotonin syndrome. Most cases from the FDA's Adverse Event Reporting System (AERS) of serotonin syndrome in patients given serotonergic psychiatric medications and methylene blue occurred in the context of parathyroid surgery, which involved the intravenous administration of methylene blue as a visualizing agent. Methylene blue doses ranged from 1 mg/kg to 8 mg/kg.

Because methylene blue is not an FDA-approved drug at this time, and limited data exist regarding its use in various settings, it is not known whether there is a risk of serotonin syndrome in patients taking serotonergic psychiatric medications who are given methylene blue by other routes (e.g., orally or by local tissue injection) or at intravenous doses lower than 1 mg/kg.

In addition, not all serotonergic psychiatric drugs have an equal capacity to cause serotonin syndrome with methylene blue. The cases of serotonin syndrome with methylene blue occurred in patients taking specific serotonergic psychiatric drugs, namely a selective serotonin reuptake inhibitor (SSRI), a serotonin norepinephrine reuptake inhibitor (SNRI), or clomipramine (see section I). It is unclear at this time whether intravenous methylene blue administration in patients receiving other psychiatric drugs with lesser degrees of serotonergic activity poses a comparable risk (see section II).

FDA will update the public when new information is available.

I. Serotonergic psychiatric drugs implicated in the AERS cases of serotonin syndrome with methylene blue

Selective Serotonin Reuptake Inhibitors

¹ Although the FDA has not received cases of serotonin syndrome to date involving vilazodone, the pharmacology of this drug places it in the SSRI category and suggests that it possesses a risk comparable to that of the SSRIs.

Serotonin Norepinephrine Reuptake Inhibitors (SNRIs)

Tricyclic Antidepressants (TCAs)

^{Other psychiatric drugs with varying degrees of serotonergic activity for which the risk of serotonin syndrome with methylene blue is unclear}

^{Tricyclic Antidepressants (TCAs)}

^{Monoamine Oxidase Inhibitors (MAOIs)}

^{Other Psychiatric Medications}

Posted: October 2011

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