Hospital Pharmacy - July/August 2018 - 222

222

Stevens-Johnson Syndrome/
Toxic Epidermal Necrolysis From
Fexofenadine4
A middle-aged woman presented to her physician with a
sore throat, eye redness, and rhinitis. She was prescribed
amoxicillin clavulanate for 5 days along with fusidic acid
eye ointment. The patient's symptoms continued to worsen
and she self-medicated with acetaminophen and ibuprofen.
Six days after visiting her physician, she started fexofenadine with pseudoephedrine twice daily. After 2 doses of
fexofenadine/pseudoephedrine, the patient noticed lip
swelling. Her other symptoms persisted, and her ear, nose
and throat specialist changed her antibiotic to clarithromycin and she was advised to continue taking her fexofenadine/pseudoephedrine.
The patient took 2 more doses of fexofenadine/pseudoephedrine, and on day 8, she developed more swelling and
blisters on her lips and presented to the emergency department. She was treated with intravenous hydrocortisone,
oral promethazine, and cetirizine/pseudoephedrine. The
next day the patient was admitted to the hospital with a
high fever of 39.5°C (103.1°F) and erythematous nonblanchable, dusky target lesions over her face, trunk, and
limbs which affected 20% of her body surface area. She
also had blistering with a positive Nikolsky sign (this sign
is present when slight rubbing of the skin results in exfoliation of the outermost layer) over less than 1% of her skin
and bilateral conjunctivitis, hemorrhagic cheilitis, and
buccal mucosal erosions.
The patient was treated for Stevens-Johnson syndrome/
Toxic Epidermal Necrolysis (SJS/TEN) overlap with topical
corticosteroids, cetirizine, and cyclosporin 1.5 mg/kg twice
daily. The patient had a skin biopsy, which revealed fullthickness epidermal necrolysis. In addition, all tests for
Epstein-Barr virus, cytomegalovirus, HIV, hepatitis, human
herpesvirus, and Mycoplasma pneumoniae as well as others
were negative. The patient recovered and had full reepithelization of her skin after 50 days.
Ten weeks after her reaction, the patient underwent
skin tests for all of the medications she had received prior
to her episode of SJS/TEN. A patch test was clearly positive for fexofenadine/pseudoephedrine while all other
medications were negative. Additional testing of fexofenadine alone versus fexofenadine/pseudoephedrine revealed
a positive patch test for both test patches. The patient was
advised to not consume products containing fexofenadine
in the future.

Hospital Pharmacy 53(4)

Memantine-Related Drug Eruption5
An 89-year-old man was treated for the past 2 months with
memantine and donepezil for his Alzheimer disease. The
patient noticed erythematous eruptions on his trunk and
extremities and sought medical attention. The patient's physical exam revealed palpable scaly erythema and papules
located on his extremities and trunk. His skin eruptions were
mainly concentrated on bent or curved areas of his trunk and
extremities. A medication history revealed the patient was
receiving no additional medications and was only receiving
donepezil and memantine. The patient also did not have a
history of allergic skin disease.
The patient's physician performed a lymphocyte stimulation test (LST) to identify the causative drug. The results of the
LST revealed a significant stimulation index for memantine,
which indicated that this was the causative agent for the
patient's skin eruptions. The patient denied further cutaneous
testing. Treatment was initiated with betamethasone ointment,
and memantine therapy was discontinued immediately. The
patient's skin eruptions began to improve with this treatment
and the continuation of donepezil. The patient's skin eruptions
did not reappear after the discontinuation of betamethasone.
The authors examined the chemical structure of memantine
and noted that it is an adamantane derivative with 3 connected
cyclohexane rings. There are several adamantane derivative
medications on the market worldwide and they are amantadine
and vildagliptin. The possible cross-reactivity between drugs,
which are adamantane derivatives, can be a clinical concern
for future pharmacotherapy in this patient. The authors conducted an LST with the patient's lymphocytes, which reacted
to amantadine, and vildagliptin with an elevated LST index.
This indicates that the patient might experience cutaneous
adverse reactions with these adamantane derivatives because
of cross-reactivity to the adamantane chemical structure.
References
1.
2.

Li X, Zhai Z, Liu X, et al. Encephalopathy associated with propofol infusion syndrome: a case report. Medicine. 2018;97:1-3.
Vollmer JP, Haen S, Wolburg H, et al. Propofol related infusion syndrome: ultrastructural evidence for a mitochondrial
disorder. Crit Care Med. 2018;46:e91-e94.
Aroke D, Tchouakam DN, Awungia AT, et al. Ivermectin
induced Steven-Johnsons syndrome: case report. BMC Res
Notes. 2017;10:179.
Teo AL, Santosa A, Bigliardi PL. Stevens-Johnson syndrome/
toxic epidermal necrolysis overlap induced by fexofenadine. J
Investig Allergol Clin Immunol. 2017;27(3):191-193.
Saito R, Sawada Y, Yamaguchi T, et al. Drug eruption caused
by memantine. Ann Allergy Asthma Immunol. 2017;119:89-90.

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