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

Generic Name

Found in Brand Names

paroxetine

Paxil, Paxil CR

fluvoxamine

Luvox, Luvox CR

fluoxetine

Prozac, Symbyax

sertraline

Zolort

citalopram

Celexa

escitalopram

Lexapro

vilazodone1

Viibryd

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)

Generic Name

Found in Brand Names

venlafaxine

Effexor, Effexor XR

desvenlafaxine

Pristiq

duloxetine

Cymbalta


Tricyclic Antidepressants (TCAs)

Generic Name

Found in Brand Names

clomipramine

Anafranil


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


Tricyclic Antidepressants (TCAs)

Generic Name

Found in Brand Names

amitriptyline

Amitid, Amitril, Elavil, Endep, Etrafon, Limbitrol, Triavil

desipramine

Norpramin, Pertofrane

imipramine

Tofranil, Tofranil PM, Janimine, Pramine, Presamine

nortriptyline

Pamelor, Aventyl hydrochloride

protriptyline

Vivactil

doxepin

Sinequan, Zonalon, Silenor

trimipramine

Surmontil

Monoamine Oxidase Inhibitors (MAOIs)

Generic Name

Found in Brand Names

isocarboxazid

Marplan

phenelzine

Nardil

transdermal selegiline

Emsam

tranylcypromine

Parnate


Other Psychiatric Medications

Generic Name

Found in Brand Names

amoxapine

Asendin

maprotiline

Ludiomil

nefazodone

Serzone

trazodone

Desyrel, Oleptro, Trialodine

bupropion

Wellbutrin, Wellbutrin SR, Wellbutrin XL, Aplenzin

buspirone

Buspar

mirtazapine

Remeron, Remeron Soltab

II.

Posted: October 2011


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