This product, like many other steroid formulations, is
sensitive to heat. Therefore, it should not be autoclaved when it is desirable
to sterilize the exterior of the vial.
The lowest possible dose of corticosteroid should be used
to control the condition under treatment. When reduction in dosage is possible,
the reduction should be gradual.
Since complications of treatment with glucocorticoids are
dependent on the size of the dose and the duration of treatment, a risk/benefit
decision must be made in each individual case as to dose and duration of
treatment and as to whether daily or intermittent therapy should be used.
Kaposi's sarcoma has been reported to occur in patients
receiving corticosteroid therapy, most often for chronic conditions.
Discontinuation of corticosteroids may result in clinical improvement.
As sodium retention with resultant edema and potassium
loss may occur in patients receiving corticosteroids, these agents should be
used with caution in patients with congestive heart failure, hypertension, or
Drug-induced secondary adrenocortical insufficiency may
be minimized by gradual reduction of dosage. This type of relative
insufficiency may persist for months after discontinuation of therapy;
therefore, in any situation of stress occurring during that period, hormone
therapy should be reinstituted.
Metabolic clearance of corticosteroids is decreased in
hypothyroid patients and increased in hyperthyroid patients. Changes in thyroid
status of the patient may necessitate adjustment in dosage.
Steroids should be used with caution in active or latent
peptic ulcers, diverticulitis, fresh intestinal anastomoses, and nonspecific
ulcerative colitis, since they may increase the risk of a perforation. Signs of
peritoneal irritation following gastrointestinal perforation in patients
receiving corticosteroids may be minimal or absent.
There is an enhanced effect due to decreased metabolism
of corticosteroids in patients with cirrhosis.
Corticosteroids decrease bone formation and increase bone
resorption both through their effect on calcium regulation (i.e., decreasing
absorption and increasing excretion) and inhibition of osteoblast function.
This, together with a decrease in the protein matrix of the bone secondary to
an increase in protein catabolism, and reduced sex hormone production, may lead
to inhibition of bone growth in pediatric patients and the development of
osteoporosis at any age. Special consideration should be given to patients at
increased risk of osteoporosis (i.e., postmenopausal women) before initiating
Local injection of a steroid into a previously infected
site is not usually recommended.
Although controlled clinical trials have shown
corticosteroids to be effective in speeding the resolution of acute
exacerbations of multiple sclerosis, they do not show that corticosteroids
affect the ultimate outcome or natural history of the disease. The studies do
show that relatively high doses of corticosteroids are necessary to demonstrate
a significant effect. (See DOSAGE AND ADMINISTRATION.)
An acute myopathy has been observed with the use of high
doses of corticosteroids, most often occurring in patients with disorders of
neuromuscular transmission (e.g., myasthenia gravis), or in patients receiving
concomitant therapy with neuromuscular blocking drugs (e.g., pancuronium). This
acute myopathy is generalized, may involve ocular and respiratory muscles, and
may result in quadriparesis. Elevations of creatine kinase may occur. Clinical
improvement or recovery after stopping corticosteroids may require weeks to
Psychic derangements may appear when corticosteroids are
used, ranging from euphoria, insomnia, mood swings, personality changes, and
severe depression, to frank psychotic manifestations. Also, existing emotional
instability or psychotic tendencies may be aggravated by corticosteroids.
Intraocular pressure may become elevated in some
individuals. If steroid therapy is continued for more than 6 weeks, intraocular
pressure should be monitored.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
No adequate studies have been conducted in animals to
determine whether corticosteroids have a potential for carcinogenesis or
Steroids may increase or decrease motility and number of
spermatozoa in some patients.
Corticosteroids have been shown to impair fertility in
Pregnancy Category C.
Corticosteroids have been shown to be teratogenic in many
species when given in doses equivalent to the human dose. Animal studies in
which corticosteroids have been given to pregnant mice, rats, and rabbits have
yielded an increased incidence of cleft palate in the offspring. There are no
adequate and well-controlled studies in pregnant women. Corticosteroids should
be used during pregnancy only if the potential benefit justifies the potential
risk to the fetus. Infants born to mothers who have received corticosteroids
during pregnancy should be carefully observed for signs of hypoadrenalism.
This product contains benzyl alcohol as a preservative.
Benzyl alcohol can cross the placenta. See PRECAUTIONS: Pediatric use.
Systemically administered corticosteroids appear in human
milk and could suppress growth, interfere with endogenous corticosteroid
production, or cause other untoward effects. Because of the potential for
serious adverse reactions in nursing infants from corticosteroids, a decision
should be made whether to continue nursing, or discontinue the drug, taking
into account the importance of the drug to the mother.
Some formulations of this product contain benzyl alcohol
as a preservative (see DESCRIPTION). Carefully examine vials to
determine formulation that is being used.
Benzyl alcohol, a component of this product, has been
associated with serious adverse events and death, particularly in pediatric
patients. The “gasping syndrome” (characterized by central nervous system
depression, metabolic acidosis, gasping respirations, and high levels of benzyl
alcohol and its metabolites found in the blood and urine) has been associated
with benzyl alcohol dosages > 99 mg/kg/day in neonates and low-birth-weight
neonates. Additional symptoms may include gradual neurological deterioration,
seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown,
hepatic and renal failure, hypotension, bradycardia, and cardiovascular
collapse. Although normal therapeutic doses of this product ordinarily delivers
amounts of benzyl alcohol that are substantially lower than those reported in
association with the “gasping syndrome”, the minimum amount of benzyl alcohol
at which toxicity may occur is not known. The risk of benzyl alcohol toxicity
depends on the quantity administered and the hepatic capacity to detoxify the
chemical. Premature and low-birth-weight infants, as well as patients receiving
high dosages, may be more likely to develop toxicity. Practitioners
administering this and other medications containing benzyl alcohol should
consider the combined daily metabolic load of benzyl alcohol from all sources.
The efficacy and safety of corticosteroids in the
pediatric population are based on the well-established course of effect of
corticosteroids which is similar in pediatric and adult populations. Published
studies provide evidence of efficacy and safety in pediatric patients for the
treatment of nephrotic syndrome ( > 2 years of age), and aggressive lymphomas
and leukemias ( > 1 month of age). Other indications for pediatric use of
corticosteroids, e.g., severe asthma and wheezing, are based on adequate and
well-controlled trials conducted in adults, on the premises that the course of
the diseases and their pathophysiology are considered to be substantially
similar in both populations.
The adverse effects of corticosteroids in pediatric
patients are similar to those in adults (see ADVERSE REACTIONS). Like
adults, pediatric patients should be carefully observed with frequent
measurements of blood pressure, weight, height, intraocular pressure, and
clinical evaluation for the presence of infection, psychosocial disturbances,
thromboembolism, peptic ulcers, cataracts, and osteoporosis. Pediatric patients
who are treated with corticosteroids by any route, including systemically
administered corticosteroids, may experience a decrease in their growth
velocity. This negative impact of corticosteroids on growth has been observed
at low systemic doses and in the absence of laboratory evidence of HPA axis
suppression (i.e., cosyntropin stimulation and basal cortisol plasma levels).
Growth velocity may therefore be a more sensitive indicator of systemic
corticosteroid exposure in pediatric patients than some commonly used tests of
HPA axis function. The linear growth of pediatric patients treated with
corticosteroids should be monitored, and the potential growth effects of
prolonged treatment should be weighed against clinical benefits obtained and
the availability of treatment alternatives. In order to minimize the potential
growth effects of corticosteroids, pediatric patients should be titrated to the
lowest effective dose.
Clinical studies did not include sufficient numbers of
subjects aged 65 and over to determine whether they respond differently from
younger subjects. Other reported clinical experience has not identified
differences in responses between the elderly and younger patients. In general,
dose selection for an elderly patient should be cautious, usually starting at
the low end of the dosing range, reflecting the greater frequency of decreased
hepatic, renal, or cardiac function, and of concomitant disease or other drug