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Milnacipran-Associated Morbilliform Rash and Serotonin Toxicity

  [ 1 vote ]   [ Discuss This Article ] • July 19, 2013

Editor's comment: Although rare, a morbilliform rash and/or serotonin toxicity can be serious side effects of milnacipran (Savella).  A morbilliform rash is one that has a flat reddish base with a raised eruption in the center, resembling measles.  Serotonin toxicity (also called Serotonin Syndrome) is a potentially life-threatening condition resulting from elevated levels of serotonin, usually due to ingestion of two or more drugs (for example, MAOIs, SSRIs) that interfere with serotonin metabolism at different points.  The following abstract is a case study of a patient who developed a morbilliform rash and serotonin toxicity after adding milnacipran to the medications she was already taking. 

Occurrence of milnacipran-associated morbilliform rash and serotonin toxicity.

By Amanda M. Huskey, Cassandra C. Thomas, and James Aubrey Waddell


OBJECTIVE: To report the development of morbilliform rash and serotonin toxicity after the addition of milnacipran to a patient's medication therapy.

CASE SUMMARY: A 57-year-old white female presented to the emergency department because of a full-body morbilliform rash, which appeared 9 days after initiation of milnacipran 50 mg twice daily. In the emergency department the patient's vital signs were: heart rate 121 beats/min, blood pressure 180/100 mm Hg, and temperature 38.9 °C. The patient reported diarrhea, nausea, dizziness, restlessness, and increased muscle pain.

Her history included recurrent breast cancer first diagnosed in 1999, hypertension, fibromyalgia, depression, osteopenia, gastroesophageal reflux disease, insomnia, and endometriosis. Her home medications included milnacipran, fluoxetine, alprazolam, zolpidem, zoledronic acid, anastrozole, doxepin, ranitidine, levocetirizine, doxazosin, tramadol, vitamin D, and ferrous gluconate.  The patient's increased heart rate, blood pressure, and temperature, as well as restlessness, self-reported diarrhea and nausea, and self-reported increase in muscle pain, indicated serotonin toxicity.

Milnacipran, fluoxetine, and tramadol were discontinued, while doxepin was continued. Treatment consisted of acetaminophen, diphenhydramine, methylprednisolone, promethazine, and hydralazine 10 mg intravenously. The following morning all vital signs were within normal limits and the patient's diarrhea, nausea, dizziness, restlessness, and muscle pain resolved. She was discharged the following morning. The rash had resolved after day 2 of hospital discharge, which was the fourth day after discontinuation of milnacipran.

DISCUSSION: Given the patient's symptoms, the timing of symptom onset, the patient's history, and findings on physical examination, as well as use of the Naranjo probability scale, milnacipran was deemed the probable cause of the morbilliform reaction and serotonin toxicity. Only 1 case report of rash and 2 case reports of serotonin syndrome associated with milnacipran have been reported.

CONCLUSIONS: It is important to increase awareness of the possibility of developing morbilliform rash and serotonin toxicity with milnacipran therapy, as both conditions can be associated with poor outcomes if not detected early and treated appropriately.

Source: The Annals of Pharmacotherapy, July 2013. By Amanda M. Huskey, Cassandra C. Thomas, and James Aubrey Waddell. PharmD Student, College of Pharmacy, University of Tennessee, Knoxville, TN.

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