|
MEMORANDUM |
DEPARTMENT OF HEALTH AND HUMAN SERVICES PUBLIC HEALTH SERVICE FOOD AND DRUG ADMINISTRATION CENTER FOR DRUG EVALUATION AND RESEARCH |
DATE: September
26, 2003
FROM: Claudia B. Karwoski, Pharm.D.,
Safety Evaluator Team Leader
Division
of Drug Risk Evaluation, HFD-430
THROUGH: Mark Avigan, M.D., C.M., Acting Director
Division
of Drug Risk Evaluation, HFD-430
TO: Jonathan
Wilkin, M.D., Director
Division
of Dermatologic and Dental Drug Products, HFD-540
Division of Pediatric Drug
Development, HFD-960
SUBJECT: Postmarketing Safety Review—PID D030565
Drugs:
Topical Corticosteroids
EXECUTIVE SUMMARY
This consult is
written in preparation of a Pediatric Advisory Subcommittee meeting to discuss
the effects of topical corticosteroids on HP axis suppression in children. As
requested by the Division
of Dermatologic and Dental Drug Products (DDDDP) and the Division of Pediatric Drug Development (DPDD) we reviewed cases of adrenal hypo- and hyperfunction and
growth retardation with the topical corticosteroids in children. A previous review of all
adverse events in children in July 2001 by Joyce Weaver, PharmD, summarized 11
cases of adrenal insufficiency (2), Cushing’s syndrome (7), and/or growth
retardation (5).1
We
reviewed 22 cases of adrenal suppression/insufficiency, Cushing’s syndrome, and
growth retardation in children aged 6 weeks to 15 years. Some cases resulted in
serious outcomes, including hospitalization and death. Long-term application of
topical corticosteroids in high-risk settings (for example, application to the
genital and groin area in very young children) resulted in numerous adverse
events. It is important to keep in mind
that the degree of HP suppression is unknown. Most adverse event reports do not
contain complete laboratory data and if present, interpretation is difficult
because standard laboratory measurements to determine the degree of HP suppression
are often lacking. It is unknown whether the sequential use of different
corticosteroid formulations resulted in possible subsequent additive
suppressive effects on the HP axis. For example, some patients treated with a
topical corticosteroid may have been treated earlier with a systemic steroid.
SELECTION OF CASE SERIES
Adverse Event Reporting
System
We searched AERS on September
11, 2003 for adverse adrenal events and growth retardation in children 0 to 18
years of age using the following terms and active ingredients:
MedDRA
terms:
Adrenal gland disorders (HLGT)
Hypothalamus and pituitary gland
disorders (HLGT)
Growth retardation (PT)
Blood growth hormone decreased (PT)
Blood growth hormone abnormal (PT)
|
Active Ingredients |
|
|
Alclometasone
dipropionate Amcinonide Betamethasone
dipropionate Betamethasone
valerate Clobetasol
propionate Clocortolone
pivalate Desonide Desoximetasone Dexamethasone Diflorasone
diacetate Fluocinolone
acetonide Fluocinonide |
Flurandrenolide Fluticasone
propionate Halcinonide Halobetasol
propionate Hydrocortisone Hydrocortisone
butyrate Hydrocortisone
probutate Hydrocortisone
valerate Methylprednisolone
acetate Mometasone
furoate monohydrate Prednicarbate Triamcinolone
acetonide |
We
retrieved 21 unique reports from AERS using the criteria above. Two cases were
excluded. One was excluded because the consumer reported an event unrelated to
adrenal suppression or growth retardation. A second case was excluded because
it involved the use of topical corticosteroid drops used either for an otic or
ophthalmic indication. One report contained two cases.
Medical
Literature
We searched the medical literature for published articles
of adrenal suppression and growth retardation in children following exposure to
topical corticosteroids. Are search was limited to published case reports. This
search resulted in two additional cases found in the literature not already in
AERS.6, 7
We
included a total of 22 cases from AERS and/or the medical literature2-7 in this review.
SUMMARY OF CASE SERIES
Twenty-two pediatric patients
experienced adrenal insufficiency (7), Cushing’s syndrome (13), and/or growth
retardation (10) after receiving topical corticosteroids. Six of the cases are
published in English-language or foreign medical literature. The
characteristics of the 22 cases in the series are presented below. Narrative
summaries of all cases are provided in attachment 1 and a listing of all cases
is presented in attachment 2.
|
Table 1. Characteristics of
Case Series |
||
|
Age: (n=21) |
Mean 5.3 yrs, median 3 yrs
(range, 44 days to 15 years) |
|
|
Gender: |
Male-14, female-6, not reported-2 |
|
|
Mean 21 months, median 6
months (range, 22 days to 7 years) |
||
|
Location: |
US-10, Foreign-12
|
|
|
*Outcome: |
Death-2
Disability-1
Hospitalization-10 |
Medically significant-5 None reported-6
|
|
*Indication: |
Atopic dermatitis-4 Eczema-3 Diaper rash-6 Alopecia areata/Hair loss-2 Not
reported-2
|
Icthyosis-1 Leiner’s disease-1 Patches of red skin-1 Psoriasis-1 Scar
from laceration-1 Second-degree
burn-1 |
|
*Site of application: |
Diaper area-7
Scalp-4 Entire body-2 |
Inner thigh-1 Neck, pectoral, upper arm-1 Not reported-9 |
*more than one possible per case
Drugs and dosage forms implicated:
Betamethasone
dipropionate ointment—1
dipropionate/clotrimazole cream—1
dipropionate/neomycin
cream—1
valerate/gentamicin
ointment—1
valerate/gentamicin/tolnaftate/iodochlorhydroxyquin
cream—1
valerate cream—2
valerate ointment—1
Clobetasol propionate
cream—4
unknown—3
Mometasone furoate
monohydrate
cream—4
ointment—2
lotion—1
Flurandrenolide tape—2
Fluocinonide—1
Triamcinolone—1
Hydrocortisone butyrate—1
(More than one product was implicated in some cases)
The patients ranged from 6
weeks to 15 years of age. Nine (41%) of the adverse events occurred in
pediatric patients younger than 3 years of age, and five (24%) occurred in
infants. The patients in the case series received topical corticosteroids for 22
days to 7 years. Eleven were receiving the product for 3 months or longer, and
in seven cases application of topical corticosteroids continued for over a
year.
Seven
children were being treated with topical corticosteroids for atopic dermatitis
(4) or eczema (3). In six cases the children received topical corticosteroids
to treat diaper rash, and two were being treated for hair loss or alopecia. Betamethasone-containing, mometasone, and
clobetasol products were the most frequently implicated in reports of adverse
reactions.
In four
cases the patient was treated with more than one topical corticosteroid product,
one of which was also being treated with oral prednisolone for asthma. An
additional case mentioned the use of oral betamethasone, however the dates of
administration in relation to the onset of the event was unknown. One case of
growth retardation was possibly due to underlying endocrinopathy or pituitary
failure however an endocrine workup had not performed at the time of reporting
and follow-up was not provided.
In eight
cases, there was indication that the topical corticosteroid was misused. In six
cases, parents applied large amounts of potent topical corticosteroids to treat
diaper rash (5) or second-degree burns (1). In 4 of the 6, treatment occurred
without medical supervision because the product was obtained over-the-counter
and continued for prolonged periods of time. Two adolescent males appeared to
be misusing topical corticosteroids. The cases described the application of the
topical steroid to the entire body or self-medicating with large quantities of
the topical corticosteroid product. It is unknown whether misuse occurred
because the treatment was ineffective. The treatment course of therapy of the eight
cases is described below.
Ten
patients were hospitalized, and two patients with Cushing’s syndrome died. One
death was secondary to a respiratory infection. The circumstances in the other
case were not provided.
The
most profound case was published over 20 years ago and involves an infant who
was treated with topical betamethasone for six months in the diaper area and
scalp. Several days prior to admission, she developed vomiting, anorexia, and a
cough. She was hospitalized in the infant intensive care unit with a
temperature of 104OF, in shock and comatose. Her immediate care in the ICU lasted 14 days and
she eventually recovered however she was followed and maintained on oral
hydrocortisone for 14 months and suffered residual mental retardation.2
Clinical laboratory evidence
of adrenal suppression was provided in some cases (attachment 1 cases 1, 2, 3, 9,
and 20). In several other cases, there
was mention that the diagnosis of adrenal suppression or growth retardation was
supported by laboratory or other objective evidence, however the actual data was
not provided (attachment 1, cases 12, 13, 21, and 22).
DISCUSSION
The
factors affecting penetration or absorption of topical corticosteroids into the
skin are multifactorial and include (but may not be limited to) the potency of
the corticosteroid, the size of the area being treated, the duration of
treatment, the use of occlusive dressing, and the skin site. Penetration of the steroid is related to
thickness of the stratum corneum and the vascular supply to the area. Additionally,
infants may be at increased risk for systemic events of topical corticosteroids
because they have a higher ratio of skin surface area to weight.8
One
or more of these factors were present the cases we reviewed. Five of the 22 patients were infants. Fifteen
of the 22 cases reported the use of “very high” or “high” potency
corticosteroids (attachment 3 includes the relative potency of topical
corticosteroids). Two reported the use of the topical corticosteroid on the
entire body and three reported the use in more than one location. The duration of use was for 3 months or longer in 11 cases, and over a year in seven
cases. Although the use of occlusive dressings was not specifically stated in
the cases, application of the topical corticosteroid to the diaper area in
seven cases resulted in occlusion of the steroid by the diaper. The site of
application may have been a factor in some cases. It is unknown if the specific
sites of application in some of the cases such as the diaper area are associated
with greater absorption of the topical corticosteroids. However, there was one
case where the product was applied to second degree burns which were devoid of
epidermis.
CONCLUSION
We
reviewed 22 cases of adrenal suppression/insufficiency, Cushing’s syndrome, and
growth retardation in children aged 6 weeks to 15 years. Some cases resulted in
serious outcomes, including hospitalization and death. Long-term application of
topical corticosteroids in high-risk settings (for example, application to the
genital and groin area in very young children) resulted in numerous adverse
events. It is important to keep in mind
that the degree of HP suppression is unknown. Most adverse event reports do not
contain complete laboratory data and if present, interpretation is difficult
because standard laboratory measurements to determine the degree of HP
suppression are often lacking. It is unknown whether the sequential use of
different corticosteroid formulations resulted in possible subsequent additive
suppressive effects on the HP axis. For example, some patients treated with a
topical corticosteroid may have been treated earlier with a systemic steroid.
References
1. Joyce Weaver, PharmD, Safety Evaluator. Summary of Adverse Events in Pediatric Patients (PID-D010141), July 9, 2001.
2. Dandine M, Lavaud J, Besson-Leaud M, Limal JM. Adrenal insufficiency and iatrogenic Cushing’s syndrome due to percutaneous absorption of corticosteroids in an 8-month-old infant. Ann Dermatol Venereol 1980; 107: 191-5. (translation from French)
3. Cherian MP, Jabbar MA. Cushing’s syndrome and adrenal suppression from percutaneous absorption of clobetasol propionate in infants. Saudi Med J 2001; 22(12):1139-41.
4. Tang PS, Low LCK. Childhood Cushing’s Syndrome due to topical clobetasol proprionate. Journal of the Hong Kong Medical Association 1989; 41(3):275-6.
5. Fook LW, Labuan FT. Correspondence: use steroids sparingly especially in children. Medical Journal of Malaysia 1985; 107:142.
6. Ermis B, Ors R, Tastekin A, Ozkan B. Cushing’s syndrome secondary to topical corticosteroid abuse. Clinical Endrocrinology 2003; 58:795-7.
7. Ruiz-Maldonado R, Zapata G, Tamayo L, et al. Cushing’s syndrome after topical application of corticosteroids. Am J Dis Child 1982; 138: 274-5.
8.
Valencia IC, Kerdel FA. Topical Glucocorticoids; in
Fitzpatrick’s Dermatology in General Medicine, vol II, p2324-7.
|
Claudia
B. Karwoski, Pharm.D. |
Attachment 1—Narrative Summaries of all Cases
1.
Literature
Case, Foreign, 2003
A 4-month-old boy
was hospitalized with a one month history of accelerated weight gain, obesity,
and diaper dermatitis which was unresponsive to topical corticosteroid therapy.
At about 2 months of age, he developed skin lesions on his bottom. He was
prescribed hydrocortisone 0.1% cream 3 to 4 times per day for a week. In
addition the mother also used clobetasol propionate due to persisting lesions.
A total of 8 tubes of hydrocortisone and 6 tubes of clobetasol were used in a
two-month time frame. On physicial exam, he appeared cushingoid with mild
hypertricosis. He had a weight gain of 2.2 kg in the prior month. Laboratory
evaluation included the following: ACTH < 5pg/ml (normal 10-42pg/ml), cortisol
1µg/dL (normal 8-25µg/dL), and 24 hour urinary free cortisol 15µg/day (normal
< 90 µg/day). A low-dose (1µg) corticotrophin test showed no increase in
cortisol level which confirmed a clinical suspicion of adrenal suppression. The
parents were instructed to reduce the frequency of the applications to prevent
adrenal crisis. After 1 month the child appeared less cushingoid and his ACTH
level was still below 5pg/ml but his cortisol was within normal limits. Two
months later, a low dose ACTH test was repeated and showed a significant
cortisol response.6
2.
MFR B0133418A,
AERS 3906438-0, Foreign, 2002 (Case 1)
A 4 ˝ month old male infant presented with a
history of sudden increase in weight and body fat since 2 months of age. It was
discovered that the mother had been applying clobetasol propionate 0.05%
(available OTC in country of origin) for diaper rash for over 2 months,
(approximately 8 to 10 25g tubes). The infant had cushingoid features with
unequal distribution of body fat, ‘buffalo hump’, double chin, and thick
subcutaneous collection of fat on the scalp. He also had hypertrichosis mainly
on the forehead. The skin in the diaper area was hypopigmented and atrophied.
His morning serum cortisol was 0.5 mcg/dL (normal being 5-18mcg/dL) and in the
evening was 0.8mcg/dL (normal being 2-13mcg/dL). He also had biochemical
evidence of vitamin D deficiency. The infant was discharged on physiological
oral replacement with hydrocortisone and vitamin D drops. On two subsequent
physician visits 2 months apart the child had evidence of adrenal suppression.
A normal response was seen after 6 months of observation at which time his
hydrocortisone was tapered and eventually discontinued. During the 6 months,
his weight also reduced and there was an increase in linear growth.3
|
|
Serum Cortisol
Level (mcg/dL) |
||
|
Pre ACTH |
30 min post ACTH |
60 min post ACTH |
|
|
2mos after hosp
dc |
5.4 |
4.3 |
2.8 |
|
4 mos after hosp
dc |
NR |
NR |
NR |
|
6 mos after hosp
dc |
14.6 |
18.4 |
19.4 |
3.
MFR B0133418A,
AERS 3906438-0, Foreign, 2002 (Case 2)
A 1 year old male
infant was brought in to the baby clinic with a history of sudden increase in
weight (2.2kg in 10 weeks) and increasing fat deposits all over his body. It
was discovered that the mother used approximately 7 tubes of clobetasol
propionate 0.05% (available OTC in country of origin) for diaper rash for over
2 months. He exhibited cushingoid features with ‘moon face’ and extensive fat
deposits in the abdominal wall and thighs. He also had hypertrichosis of the
forehead, upper lip and extremities as well as hyperpigmentation of the skin.
The skin in the diaper area was hypopigmented and atrophied. His serum cortisol
was 0.5 mcg/dL. The infant was placed on physiological oral replacement with
hydrocortisone. Adrenocorticotrophic hormone stimulation tests 2 months later
showed a serum cortisol of 2.8mcg/dL, 20mcg/dL, and 23mcg/dL before, and 30 and
60 minutes after ACTH injection. Hydrocortisone was tapered and stopped. On
subsequent visits, his cushingoid features gradually improved and his weight
decreased to a normal range.3
4.
MFR
2002-07-2888, AERS 3970267-2, US, 2002
A 4-year-old boy
was treated with mometasone furoate cream 0.01% for atopic dermatitis. He had
been prescribed the therapy as an infant by a dermatologist and it was
continued on and off by the pediatrician for about 3 ˝ years. The boy
experienced growth suppression which was being treated with growth hormone
injections.
5.
MFR
2001-05-1933, AERS 3860727-7, US, 2001
A 4-year-old
female initiated betamethasone dipropionate ointment for eczema. Treatment was
continued for approximately five years. During this time frame “serious medical
problems and metabolic dysfunctions” were noted. The patient began to show
signs of growth retardation, hypertension, and Cushing’s syndrome. The patient
had a history of eczema since the age of 2 months, mild atopic dermatitis,
multiple food allergies, reactive airway disease, and multiple hospital
admission during early childhood. In addition to being treated with
betamethasone ointment she was concomitantly treated with flurandrenolide
topical for an unknown period of time.
6.
MFR B0104663A,
AERS 375083-1, Foreign, 2001
A 15-year-old was
receiving clobetasol proprionate cream for psoriasis. It was noted that he
self-medicated and had used 1 to 2 tubes of clobetasol per day for 1 to 2
months. He developed severe depigmentation on his face, arm, and trunk with
skin striae. Clobetasol was discontinued and he was hospitalized for possible
adrenal insufficiency. No additional information provided.
7.
MFR
2000-10-0055, AERS 3592691-2, US, 2000
A 9-year-old child
was treated with mometasone furoate cream for an unknown indication and
duration and developed Cushing’s syndrome “symptoms”. No additional information
provided.
8.
MFR
1999-03-0240, AERS 3219210-4, US, 1999
A 2-year-old child
was treated with mometasone furoate lotion for alopecia areata on the scalp. A
flattened growth curve was reported. The reporting dermatologist did not
believe the mometasone was related to the patient’s condition. He felt the
patient had multiple organ endocrinopathy/pituitary failure and that the growth
suppression preceded the use to mometasone. The endocrinologist wanted to rule
out other causes prior to a full endocrine workup. It is unknown if the
mometasone was discontinued.
9.
MFR
1999-12-0738, AERS 3434995-X, Foreign, 1999
An 11-year-old
male with a history of atopic dermatitis (8 years) developed Cushing’s syndrome
secondary to long term use of topical betamethasone valerate/gentamicin
sulfate. He presented with amnesia and somnolence and with hospitalized with
moon face, “low height”, and obesity (42kg).
His ACTH was 9.6pg/dL and serum cortisol level was noted to be 0.9mcg/dL
(ref 5-15 mcg/dL). He was diagnosed with Cushing’s syndrome. Betamethasone
ointment was discontinued Decreased adrenal cortical was noted. A rapid ACTH test was 1.1 pre-test, 4.3 at
30 minutes, and 2.8 at 60 minutes. He had concomitantly receive betamethasone
tablets and betamethasone/dexchlorphenirame maleate tablets at some point in
his treatment, however the actual date of administration and duration were not
reported.
10.
MFR
1998-07-1081, AERS 3113532-3, US, 1998
A 3-year-old male
was treated with mometasone furoate cream for an atopic dermatitis. A few
months later, linear growth retardation was noted. The boy had not responded to
ACTH stimulation at the time of the report. No additional information provided.
11.
MFR B0058504,
AERS 3112510-8, Foreign, 1998
A physician reported
that a female child (age unknown) died from Cushing’s syndrome while receiving
clobetasol propionate. No additional information provided.
12.
MFR 97-10-8020,
AERS 3000375-4, Foreign, 1997
A 14-year-old male
receiving prednisolone for asthma, applied 30g of vetamethasone valerate 0.02%
every 7-10 days and 15g of mometasone furoate ointment every 2 to 3 days for
eczema. Adrenal suppression and delay in puberty was noted. A bone scan
indicated that there was a 2-3 year growth delay and a syncthen stimulation
test showed a flat plasma cortisol curve. It was suspected that the patient was
self-medicating and applied both products over his whole body.
13.
MFR B0042474,
AERS 1872624, Foreign, 1996
A 10 year old girl
with a history of atopic dermatitis since infancy received clobetasol
propionate scalp lotion for loss of hair. After one month of treatment she
developed Cushing’s syndrome with obesity, hypertrichosis on her back and legs,
red cutaneous striae on her thighs, moon face, erythema on her cheeks, and facial
acne. The clobestasol was discontinued after three months of treatment and she
was hospitalized three weeks later for adrenocortical suppression. Blood and
urine cortisol and ACTH were below the limit of detection. A dexamethasone
suppression test revealed complete suppression of cortisols. Cortisol function
recovered after three weeks. The patient had previously been receiving
flumetasone pivalate for 5 months for the same condition with no effect.
(foreign literature report, citation not provided)
14.
MFR 95-08-0174,
AERS 1733286, US, 1995
A 3-year-old boy who was
being treated with mometasone furoate cream for about 15 months for “patches of
red skin”, experienced growth retardation (height and weight) and leukoderma.
He was also on two other corticosteroid creams, triamcinolone and fluocinolnide
on the head and for diaper rash. An MRI
of the brain, bone and many blood tests were performed which the reporter
states were normal.
15.
MFR 9409043,
AERS 5231157, US, 1994
A 6-year-old girl who was
being treated with mometasone furoate ointment for four years experienced
growth retardation. No additional information provided.
16.
MFR 94-10-0184,
AERS 1652362, US, 1994
A 15 month old boy was
treated with betamethasone/clotrimazole for approximately six months for a monilial
diaper rash. Growth retardation was noted by the infants parents, however the
reporting physician considered this event to be unrelated to the mometasone
therapy.
17.
AERS 4918014,
MFR 9207239, Foreign, 1992
A 6-week-old infant with
icthyosis was treated intermittently with betamethasone cream for 4 weeks. The
product used was not specified. The baby was hospitalized with severe dyspnea,
generalized edema, Cushingoid features, and heart failure. The infant initially
responded to unspecified treatment, but eventually died of a respiratory system
infection.5
18.
MFR 92-09-024
AERS 1443792, US, 1992
A 9-year-old girl who was
being treated with betamethasone valerate cream for five years for eczema
experienced growth retardation. No additional information provided.
19. MFR US91070727A, AERS 840618, US, 1991
A 14-year-old female was
involved in a bicycle accident and lacerated her right inner thigh. The
laceration was closed surgically and plastically reconstructed about 11 days
after the accident. About 6 weeks later she was placed on flurandreonolide tape
for 22 days at which time she was noted to have Cushing’s syndrome. No
additional information provided.
20. MFR G0003711, AERS 687092, Foreign, 1990
A 15-month-old boy was
admitted to the hospital because of suspected Cushing’s syndrome. He developed
a napkin rash at the age of 5 months and was prescribed clobetasol propionate
cream. Treatment was continued without medical supervision for the next 10
months. The product was available without prescription and one 25g tube was
applied every 2 weeks. The parents noticed an increase in weight and
hypertrichosis for 3 months before admission. On exam he was found to be
cushingoid with plethoric moon facies, generalized obesity, hypertrichosis and
buffalo hump. He had an erythematous napkin rash with raised patches and
satellite lesion suggestive of candidiasis. The morning cortisol was 15 nmol/L
and the evening cortisol was 13 nmol/L. A diagnosis of Cushing’s syndrome
resulting from the prolonged use of a potent topical steroid was made.
Following discontinuation of clobetasol, the morning cortisol rose to 79 nmol/L
after 12 days and 394 nmol/L after 17 days. A synacthen test was performed 3
weeks after his presentation. The morning cortisol was 177, rising to 778nmol/L
and 501 nmol/L at 30 and 60 minutes after 250mcg synacthen IM. Two months after
initial presentation, he was well with a decrease in body weight and
examination was unremarkable except for very mild cushingoid features.4
21. MFR 92-05-178, AERS 869652, Foreign, 1992
An 8-month-old girl was
hospitalized with coma, adrenal insufficiency, and Cushing’s syndrome. She had
been treated with betamethasone propionate/neomycin ointment twice daily for 6
months for nonpruriginous diaper rash with scalp involvement. The rate of
application was 3 tubes every 2 weeks or 1.5mg/day of betamethasone. Three days
prior to admission, she developed vomiting, anorexia and a cough. She was
admitted to the intensive care unit comatose, with temperature of 104F, and was
in a preagonal state. She was cushingoid with a puffy and erythrotic face,
pilosity of the forehead and interscapular area, adiposity of the neck and
trunk and atrophic muscle mass. She was intubated, rehydrated, and administered
hydrocortisone IV. She eventually improved over the next 3 weeks. After
transfer from the ICU, she underwent a metopirone test with confirmed adrenal
insufficiency. Hormone replacement therapy was continued for additional 6
months at 10mg/day. Another metopirone
test performed 9 months after hospitalization confirmed the persistence of
corticotropic deficiency with low blood levels of cortisol (3mcg/dL).
Eventually all hormone therapy was discontinued after 14 months.2
22. Literature Case, Foreign, 1982
A 2-year-old boy was
hospitalized with Cushing’s syndrome following prolonged topical corticosteroid
treatment. At the age of 11 months, he suffered accidental second-degree burns
caused by boiling water, on the neck, pectoral area, and right upper arm. The
burned areas were treated with topical application of a cream containing a
mixture of 0.06% betamethasone valerate, 1% tolnaftate, 1%iodochlorhydroxyquin,
and 1% gentamicin. The mother applied 30g of the cream to the burned areas
every week for 17 months. After six months she noticed physical changes
suggestive of Cushing’s syndrome. At the time of examination, he was 50th
percentile for weight and less than 3rd percentile for height. He
had a moon face, facial and body hypertrichosis, and atrophic striae on the
abdomen and thighs. There were deep ulcerations with exposed muscles and fat
tissue on upper half of the anterior thoracic wall. Bone roentgenogram showed
generalized osteoporosis and retarded bone growth. On admission the topical
corticosteroid was discontinued. The ulcers were gently cleaned and proteolytic
enzyme ointment was applied twice a day. Twenty-five units of corticotropin was
given every other day during the first four weeks and once a week during the
next two months. The ulcers healed after 83 days and the Cushing’s syndrome regressed.
*Reported outcomes (OT): DE=death; HO=hospitalization; DS=disability; MS=medically significant; None=none reported
Attachment 3—Potency Ranking of Some Topical
Corticosteroids
The relative potency of a product depends on several factors including the characteristics and concentration of the drug and the vehicle used. Vasoconstrictor assays are used to measure the relative potency of the commercially available products. Ranking is based on vasoconstrictor assays of brand name products.
|
Estimated Relative Potency of Selected Topical
Corticosteroid Products |
|||
|
|
CORTICOSTEROID INGREDIENT |
DOSAGE FORM |
STRENGTH |
|
I Very High Potency |
Augmented betamethasone dipropionate |
Ointment |
0.05% |
|
Clobetasol propionate |
Cream, Ointment |
0.05% |
|
|
II High Potency |
Augmented betametasone dipropionate |
Cream |
0.05% |
|
Betamethasone dipropionate |
Cream, Ointment |
0.05% |
|
|
Betamethasone valerate |
Ointment |
0.1% |
|
|
Desoximetasone |
Cream, Ointment, Gel |
0.25% 0.05% |
|
|
Fluocinolone acetonide |
Cream |
0.2% |
|
|
Fluocinonide |
Cream, Ointment, Gel |
0.05% |
|
|
Triamcinolone acetonide |
Cream, Ointment |
0.5% |
|
|
III Medium Potency |
Betamethasone dipropionate |
Lotion |
0.05% |
|
Betamethasone valerate |
Cream |
0.1% |
|
|
Desoximetasone |
Cream |
0.05% |
|
|
Fluocinolone acetonide |
Cream, Ointment |
0.025% |
|
|
Hydrocortisone valerate |
Cream, Ointment |
0.2% |
|
|
Mometasone furoate |
Cream, Ointment, Lotion |
0.1% |
|
|
Triamcinolone acetonide |
Cream, Lotion, Ointment |
0.025%, 0.1% |
|
|
IV Low Potency |
Aclometasone dipropionate |
Cream, Ointment |
0.05% |
|
Desonide |
Cream |
0.05% |
|
|
Dexamethasone |
Aerosol |
0.01%, 0.04% |
|
|
Dexamethasone sodium phosphate |
Cream |
0.1% |
|
|
Fluocinolone acetonide |
Cream, Solution |
0.01% |
|
|
Hydrocortisone |
Lotion Cream, Ointment, Lotion, Aerosol Cream, Ointment, Lotion, Solution Cream, Lotion, Ointment |
0.01% 0.5% 1% 2.5% |
|
|
Hydrocortisone acetate |
Cream, Lotion |
0.5% |
|