Cholestyramine Ointment to Treat Buttocks Rash and Anal

plaquettes jusqu' 11 <20 x J()l/mm3, et I'hemoglobine jusqu' 11 3.7 g/dL.
Plusieurs culots de globules rouges furent transfuses et du sargramostim
fut ajoute au jour 3 de I'hospitalisation, afin d' accelerer la recuperation
de la moelle osseuse. Le patient ~ut son conge de I'h6pital apres 8
jours et I'azathioprine, dont I'administration avait ete suspendue 11
I'admission, fut redebutee et ajusiee 11 200 mg/jour au cours des 2
semaines suivant Ie conge. Le cout du sejour hospitalier de ce patient
s'ele \ve 11 $13 042 (US).
DISCUSStON: L'impact qu'a produit cette interaction sur la qualite de vie
du patient n'est pas inclu dans ce prix. Meme apres son depart de
l'h6pital, on a estime que Ie patient necessiterajusqu'1I 3 mois pour
recuperer sa force et sa capacite fonctionnelle d'antan. Cette interaction
entre I'allopurinol et I'azathioprine aurait aisement pu etre eviiee. Le
medecin et Ie pharmacien du patient ont manque cette interaction bien
documentee et potentiellement mortelle. De plus, Ie patient a neglige
d'aviser I'equipe de transplantation de la prescription d'allopurinol par
son medecin de famille. On doit insister sur I'importance de la
responsabilire du patient envers sa therapie medicamenteuse, afin
d'aider 11 eviter des interactions medicamenteuses inutiles.
CONCLUSIONS: Les interactions medicamenteuses non-detectees peuvent
presenter un risque pour la vie du patient, de meme que des couts
importants pour Ie systeme de sante. Les interactions medicamenteuses
peuvent aussi exhiber un effet negatif considerable sur la qualite de vie
du patient, effet dont Ie prix ne peut etre mesure uniquement en terme de
dollars. II est vital que Ie medecin, Ie pharmacien, et Ie patient travaillent
ensemble afin d'optimiser les resultats therapeutiques et d'eviter
d'inutiles interactions medicamenteuses.
PIERRE MARTINEAU
CHOLESTYRAMINE OINTMENT TO TREAT
BUTTOCKS RASH AND ANAL EXCORIATION IN AN INFANT
C Michael White, Ronald A Gailey, and Scott Lippe
OBJECfIVE: To describe a novel treatment for perianal excoriation in
an infant receiving a promotility agent.
CASE SUMMARY: A 2-month-old boy with reflux and regurgitation
was treated with cisapride. Shortly after cisapride therapy he
developed a ra~h on his buttocks and anal irritation that progressed
in severity despite the use of numerous topical products and
extended diaper-free periods. A topical cholestyramine ointment
compound wa~ prepared and administered, resulting in complete
resolution within 3 days.
DISCUSSION: Cisapride can decrease the gastrointestinal transit time,
which can lead to less time for bile acid reabsorption in the distal
ileum. If high concentrations of bile acids are contained in the stool,
they can irritate the anus and buttocks in a manner similar to the skin
irritation experienced by patients with ostomies. Cholestyramine, a
bile acid sequestrant, can irreversibly bind the bile when applied
topically and bring relief to the patient.
CONCLUSIONS: Topical cholestyramine ointment may be a safe and
efficacious treatment option for perianal irritation due to bile acids.
Ann Phamulcother 1996;30:954-6.
is a prokinetic agent that elicits the release of
acetylcholine from the postganglionic nerve endings of the
CISAPRIDE
C Michael White BSPharm. PharmD Student. Albany College of Pharmacy. New
Scotland Ave, Albany, NY 12208. FAX 518/445-7202
Ronald A Gailey PharmD, Clinical Pharmacist, Department of Pharmacy. Albany
Medical Center Hospital, Albany, NY
Scott Lippe MD. Intensive Care Unit Medical Resident, Albany Medical Center Hospital
Reprints: C Michael White BSPharm
954 •
The Annals of Plzannacotherapy
•
myenteric plexus. l ,2 Its activty on the small and large intestine can lead to a reduction in bile acid reabsorption. l -6 This
effect may increase the anal excretion of bile acids, and
can result in anal excoriation. The use of cholestyramine
ointment in patients who have undergone an ostomy has
been efficacious in decreasing excoriation of the ostomy
site. However, no literature exists on its use in infants or to
treat cisapride-induced anal excoriation. We describe a
possible case of cisapride-induced anal excoriation in an
infant who was successfully treated with cholestyramine
ointment.
CASE REPORT
A 2-month-old boy was born after normal gestation and vaginal
delivery. At 2 weeks of age he developed significant regurgitation after feedings. A confirmatory barium swallow for reflux
was performed and the child was started on cimetidine therapy,
which did not fully ameliorate the regurgitation and associated
discomfort. Cisapride 0.2 mg/kg three times per day with feedings was started and successfully treated the regurgitation. However, he then developed irritation around the anus and a rash on
his buttocks that progressed in severity to an extremely painful
erythematous rash with fissures. From 3 to 10 weeks of age the
infant was treated with numerous topical products including
petrolatum, nystatin, vitamin A and D ointment, Mylanta, Balmex, and Desitin. These therapies were used for at least I week at a
time and were usually applied concurrently with extended diaperfree periods.
At 10 weeks of age a cholestyramine 5% ointment in Aquaphor wa~ prepared. The infant had the ointment applied to erythematous areas after each bowel movement. Although no changes
1996 September, Volume 30
Case Reports
in diet or stool frequency were noted, significant rash improvement was noted within 2 days and all areas of erythema were
clear by day 3. No rash or discomfort was noted 2 weeks after the
initiation of therapy.
Discussion
Cisapride is a unique prokinetic agent as it does not
?ave d?pamine~gic a~tivity.l,2 Cisapride exerts its effect by
mcreasmg phYSIOlogic release of acetylcholine specifically
from the postganglionic nerve ending of the myenteric
plexus. l This stimulation induces increased motility in the
esophagus, stomach, and the small and large intestine that
could result in less bile acid reabsorption in the distal
I'1eum. 1-6 Thi s suggests that decreased gastrointestinal transit time could be responsible for the increased excretion of
bile acids in this infant and thus, be the source of the erythematous rash. This assertion seems plausible especially
considering that the other common causes would have
been treated by the wide range of topical products used
previously.
The dosage of cisapride, 0.2 mglkg three times per day
with feedings, is not approved by the Food and Drug Ad~nistration.7 However, dosages of 0.2 mglkg three to four
urnes per day have been used in infants and dosages of 0.3
mglkg three to four times per day were used in children
ranging from 75 weeks to 47 months old, to relieve gastro~s?phageal reflux.l,s Furthermore, a study of constipation
m mfants also de.scribed a similar dosage of 0.3 mglkg given three to four hmes per day.9
Cholestyramine is a quarternary ammonium chloride
anion-exchange resin that exchanges chloride ions for bile
ac~ds,.f~r~ng a nonreabsorbable complex. Cholestyra~me IS mdl~ated as an antihyperlipidemic agent. When
gIVen ?rally It sequesters cholesterol-containing bile acids,
removmg them from the gut, which leads to the manufacture of new bile acids and effectively lowers serum cholesterol. Cholestyramine is not systemically absorbed when
in?ested. The ~os~ common adverse effects of cholestyramme are consupauon and cramping, both of which are not
seen when the agent is applied topically.IO
Since the 1970s, topical cholestyramine has been used
to treat skin breakdown associated with ostomy sites. n .13
The theoretical skin pathology associated with skin breakdown at ostomy sites centers around the excretion of bile
acids due to the decreased transit time in the shortened
gut. 4,5 Two small trials were performed showing positive
results of cholestyramine ointment for this indication.n,ll A
trial by ~~~uez ~t al. n treated six children experiencing
?stomy tmtauon. With a topical ointment of cholestyramine
m Aquaphor while treating two other children with Aquaphor alone. All but one child, who was lost to follow-up,
had a complete remission of ostomy irritation when treated
with cholestyramine, while neither of the children treated
with Aquaphor alone showed clinical improvement. In an
open, non'pla~ebo-~ontrol~ed trial, topical cholestyramine
was used m SIX pauents With severe perineal skin irritation
~er the closu~e of temporary ileostomies. None of the pauents showed Improvement after treatment with zinc oxide
an~ dimethicone for a median of 18 days before receiving
top~cal cholestyramine. This trial was stopped because all
pauents had complete resolution of irritation after a median
of 7 days of therapy with cholestyramine. ll Bell and Vari-
gosl3 described a 57-year-old woman with severe skin excoriation around a T-tube draining the common bile duct.
After no alleviation from Stomahesive, the patient received
topical cholestyramine and had complete remission of inflammation within 48 hours. 13
The cholestyramine concentration used in our formula~ion was
which is lower than concentrations reported
m ~e pr~vIOus cases (20%). We have been using cholestyramme omtment for the treatment of adult ostomy sites for
many years in the oncology department for ostomy treatment and found that the 5% formulation gives a much
smoother end-product that is easier to prepare and apply.
5:0'
Formulation Procedure
To prepare a cholestyramine 5% ointment, use the folprocedure: (1) disperse three packets of cholestyramme powder (12 g total) in 120 mL of sterile water for
irrigation. (2) Place 120 g of Aquaphor in a 240-mL ointmentjar and. microwave on medium power for approximately 15 mmutes, stirring at 5-minute intervals. (3) Add
the cholestyramine suspension obtained in step 1 to the
~el~ed Aquaphor while stirring continuously with a glass
strrnng rod. (4) Allow to cool and dispense with an "external use only" label.
This procedure leads to a smooth, non-gritty final consistency that is not irritating to spread. No scientific deterrninati~n of product expiration has been done but personal expenence has shown physical stability for over 6 months.
lo~ing
Summary
This case shows that topical cholestyramine ointment
may be a successful therapy for infants and children with
rash and excoriation of the anus and buttocks due to a hyperdynamic gastrointestinal tract or when many other treatment modalities have failed. Based on cholestyramine's
proven safety as an oral agent and the literature on
cho~es~raminefor ostomy, it appears that topical cholestyrarrnne IS a safe treatment option for this indication. ~
References
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McC~lu~ RW,
Pr.ekash C, Campoli-Richards DM, Goa KL. Cisapride:
a preliminary revIew of its pharmacodynamic and pharmacokinetic
properties, and therapeutic use as a prokinetic agent in gastrointestinal
motility disorders. Drugs 1988;36:652-81.
McCallum RW, TheACG Committee on FDA-Related Matters. Cisapride: a new class of prokinetic agent. Am J Gastroenterol 1991'86:
135-49.
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McHugh S, Lico S, Diamant NE. Cisapride vs. metoclopramide: an
acute study in diabetic gastroparesis. Dig Dis Sci 1992;37:997-1001.
Gaze H, Murphy GM, Nelson R, Corkery JJ, Anderson CM. Bile acid
excretion after pull through operation for Hirschprung' s disease. Arch
Dis Child 1975;50:243-5.
Pa~mer RH, c,;lie~an ~B, .Kappas A. Pyrogenic and inflammatory propertIes of certain bIle aCids In man. J Clin Invest 1%2;41: 1573-7.
Guyton AC. Textbook of medical physiology. 7th ed. Philadelphia: WB
Saunders Co, 1986:753-806.
Product information. Propulsid (cisapride). Titusville, NJ: Janssen Pharmaceutica Inc, 1995.
Cucchiara S, Minella R, Riezzo G, Vallone G, Vallone F, Castellone F,
et al. Reversal of gastric electrical dysrhythmia~ by cisapride in children
with functional dyspepsia: report of three cases. Dig Dis Sci 1992'37:
1136-40.
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Murray RD, Li BUK, McClung HJ, Heitlinger L, Rehm D. Cisapride for
The Annals ofPharmacotherapy •
1996 September, Volume 30 •
955
10.
II.
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intractable constipation in children: observations from an open trial. J Pediatr Gastroenterol Nutr 1990: II :503-8.
Antilipidemic agents. In: McEvoy GK, Litvak K, Welsh OH, eds. AHFS
Drug Information. Bethesda, MD: American Society of Hospital Pharmacists Inc, 1995: 1011-5.
Rodriguez IT, Huang TL, Ferry GD, Kilsh WJ, Harberg FJ, Nichols BL.
Treatment of skin irritation around enterostomies with cholestyramine
ointment. J Pediatr 1976:88:659-61.
Moller P, Lohmann M, Brynity S. Cholestyramine ointment in the treatment of perianal skin irritation following ileoanal anastomosis. Dis
Colon Rectum 1987:30:106-7.
Bell SN, Varigos GA. Treatment of skin irritations around biliary fistula~
with cholestyramine. Br J Surg 1980;67:785.
EXTRACTO
OBJEllVO: Describir un nuevo tratamiento pam la excoriaci6n perianal
causada pol' un medicamento utilizado para aumentar la motilidad
intestinal en un nino.
RJ<:SUMEN DEL CASO: Un nino de 2 meses de edad con reflujo y
regurgitaci6n fue tratado con cisaprida. Dfas despues de comenzada la
terapia desarro1l6 erupci6n en las nalgas e irritaci6n anal que se convirti6
en sevem a pesar de ser tratado con numerosos productos t6picos y
mantenerlo sin paiial. La erupci6n se resolvi6 en 3 dfa~ con la aplicaci6n
t6pica de un ungtiento de colestiramina.
DlSCUStON: Cisaprida puede disminuir el tninsito ga~trointestinal
acortando el tiempo para la reabsorci6n de acidos biliares en el ileo
distal. Concentraciones altas de acidos biliares en la~ heces pueden
causar irritaci6n del ano y la~ nalgas, similar a la irritaci6n de piel que
experimentan los pacientes con ostomfas. Colestimmina, un secuestrante
del acido biliar, puede unirse irreversiblemente a la bilis cuando se
administra t6picamente y aliviar la irritaci6n.
956 •
The Annals (~f Pharmacotherapy
•
CONCLUSIONES: El ungtiento de colestiramina puede ser un tratamiento
seguro y efectivo pam la irritaci6n perianal causada pol' los acidos
biliares.
RAFAELA MENA
RESUME
OBJECrw: Decrire un nouveau traitement pour l'irritation perianale chez
un enfant recevant du cisapride.
RF.sUME DU CAS: Un jeune gar~on de 2 mois avec Ie reflux et de
regurgitation a ete traite avec du cisapride. Peu apres que Ie traitement
au cisapride ait ete debute, I' enfant a developpe un rash au niveau des
fesses ainsi que de l'irritation anale, lesquels se sont aggraves malgre
l'utilisation de plusieurs produits topiques et des periodes prolongees
sans couche. Un onguent topique de cholestyramine a ete prepare et son
utilisation a permis une guerison complete en moins de 3 jours.
DISCUSSION: Le cisapride peut accelerer Ie transit gastro-intestinal et, par
consequent, peut diminuer la reabsorption des acides biliaires au niveau
de l'ileon terminal. Si les selles renferment de fortes concentrations
d'acides biliaires, elles peuvent alors provoquer une irritation de l'anus
et des fesses semblable 11 l'irritation cutanee ressentie par les patients
stomises. La cholestyramine, une resine liant les acides biliaires, peut
soulager les patient~ en liant la bile de fa~on irreversible lorsqu'elle est
appliquee par voie topique.
CONCLUSIONS: L'onguent topique de cholestyramine peut constituer un
traitement securitaire et efficace pour l'irritation anale causee par les
acides biliaires.
1996 September, Volume 30
ALAIN MARCOlTE