Included as part of the PRECAUTIONS section.
Alterations in Endocrine Function
Hypothalamic-pituitary-adrenal (HPA) axis suppression, Cushing's syndrome,
and hyperglycemia. Monitor patients for these conditions with chronic use.
Corticosteroids can produce reversible HPA axis suppression with the potential
for glucocorticosteroid insufficiency after withdrawal of treatment. 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.
Since mineralocorticoid secretion may be impaired, salt and/or a mineralocorticoid
should be administered concurrently. Mineralocorticoid supplementation is of
particular importance in infancy.
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.
Increased Risks Related to Infections
Corticosteroids may increase the risks related to infections with any pathogen,
including viral, bacterial, fungal, protozoan, or helminthic infections. The
degree to which the dose, route and duration of corticosteroid administration
correlates with the specific risks of infection is not well characterized, however,
with increasing doses of corticosteroids, the rate of occurrence of infectious
Corticosteroids may mask some signs of infection and may reduce resistance
to new infections.
Corticosteroids may exacerbate infections and increase risk of disseminated
The use of Flo-Pred in active tuberculosis should be restricted to those cases
of fulminating or disseminated tuberculosis in which the corticosteroid is used
for the management of the disease in conjunction with an appropriate antituberculous regimen.
Chickenpox and measles can have a more serious or even fatal course in non-immune
children or adults on corticosteroids. In children or adults who have not had
these diseases, particular care should be taken to avoid exposure. If a patient
is exposed to chickenpox, prophylaxis with varicella zoster immune globulin
(VZIG) may be indicated. If patient is exposed to measles, prophylaxis with
pooled intramuscular immunoglobulin (IG) may be indicated. If chickenpox develops,
treatment with antiviral agents may be considered.
Corticosteroids should be used with great care in patients with known or suspected
Strongyloides (threadworm) infestation. In such patients, corticosteroid-induced
immunosuppression may lead to Strongyloides hyperinfection and dissemination
with widespread larval migration, often accompanied by severe enterocolitis
and potentially fatal gram-negative septicemia.
Corticosteroids may exacerbate systemic fungal infections and therefore should
not be used in the presence of such infections unless they are needed to control
Corticosteroids may increase risk of reactivation or exacerbation of latent
If corticosteroids are indicated in patients with latent tuberculosis or tuberculin
reactivity, close observation is necessary as reactivation of the disease may
occur. During prolonged corticosteroid therapy, these patients should receive
Corticosteroids may activate latent amebiasis. Therefore, it is recommended
that latent or active amebiasis be ruled out before initiating corticosteroid
therapy in any patient who has spent time in the tropics or in any patient with
Corticosteroids should not be used in cerebral malaria.
Alterations in Cardiovascular/Renal Function
Corticosteroids can cause elevation of blood pressure, salt and water retention,
and increased excretion of potassium and calcium. These effects are less likely
to occur with the synthetic derivatives except when used in large doses. Dietary
salt restriction and potassium supplementation may be necessary. These agents
should be used with caution in patients with hypertension, congestive heart
failure, or renal insufficiency.
Literature reports suggest an association between use of corticosteroids and
left ventricular free wall rupture after a recent myocardial infarction; therefore,
therapy with corticosteroids should be used with caution in these patients.
Use in Patients with Gastrointestinal Disorders
There is an increased risk of gastrointestinal perforation in patients with
certain GI disorders. Signs of GI perforation, such as peritoneal irritation,
may be masked in patients receiving corticosteroids.
Corticosteroids should be used with caution if there is a probability of impending
perforation, abscess or other pyogenic infections; diverticulitis; fresh intestinal
anastomoses; and active or latent peptic ulcer.
Behavioral and Mood Disturbances
Corticosteroid use may be associated with central nervous system effects 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.
Decrease in Bone Density
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
children and adolescents 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 corticosteroid therapy and bone
density should be monitored in patients on long-term corticosteroid therapy.
Prolonged use of corticosteroids may produce posterior subcapsular cataracts, glaucoma with possible damage to the optic nerves, and may enhance the establishment
of secondary ocular infections due to fungi or viruses. The use of oral corticosteroids
is not recommended in the treatment of optic neuritis and may lead to an increase
in the risk of new episodes. Intraocular pressure may become elevated in some
individuals. If steroid therapy is continued for more than 6 weeks, intraocular
pressure should be monitored.
Patients with Ocular Herpes Simplex
Corticosteroids should be used cautiously in patients with ocular herpes simplex
because of possible corneal perforation. Corticosteroids should not be used
in active ocular herpes simplex.
Administration of live or live attenuated vaccines is contraindicated in patients
receiving immunosuppressive doses of corticosteroids. Killed or inactivated
vaccines may be administered, however, the response to such vaccines can not
be predicted. Immunization procedures may be undertaken in patients who are
receiving corticosteroids as replacement therapy, e.g., for Addison's disease.
While on corticosteroid therapy, patients should not be vaccinated against
smallpox. Other immunization procedures should not be undertaken in patients
who are on corticosteroids, especially on high dose, because of possible hazards
of neurological complications and a lack of antibody response.
Effect on Growth and Development
Long-term use of corticosteroids can have negative effects on growth and development
in children. Growth and development of pediatric patients on prolonged corticosteroid
therapy should be carefully monitored.
Use in Pregnancy
Prednisolone can cause fetal harm when administered to a pregnant woman. Human
and animal studies suggest that use of corticosteroids during the first trimester
of pregnancy is associated with an increased risk of orofacial clefts, intrauterine
growth restriction and decreased birth weight. If this drug is used during pregnancy,
or if the patient becomes pregnant while using this drug, the patient should
be apprised of the potential hazard to the fetus. [see Use In Specific Populations].
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 they 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.
Elevation of creatine kinase may occur. Clinical improvement or recovery after
stopping corticosteroids may require weeks to years.
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.
Patient Counseling Information
Patients should be warned not to discontinue the use of Flo-Pred abruptly or
without medical supervision, to advise any medical attendants that they are
taking it, and to seek medical advice at once should they develop fever or other
signs of infection. Patients should be told to take Flo-Pred exactly as prescribed,
follow the instructions on the prescription label, and not stop taking Flo-Pred
without first checking with their healthcare providers, as there may be a need
for gradual dose reduction.
Patients should discuss with their physician if they have had recent or ongoing
infections or if they have recently received a vaccine.
Patients who are on immunosuppressant doses of corticosteroids should be warned
to avoid exposure to chickenpox or measles. Patients should also be advised
that if they are exposed, medical advice should be sought without delay.
There are a number of medicines that can interact with Flo-Pred. Patients should
inform their healthcare provider of all the medicines they are taking, including
overthe-counter and prescription medicines (such as phenytoin, diuretics, digitalis
or digoxin, rifampin, amphotericin B, cyclosporine, insulin or diabetes medicines,
ketoconazole, estrogens including birth control pills and hormone replacement
therapy, blood thinners such as warfarin, aspirin or other NSAIDs, barbiturates),
dietary supplements, and herbal products. If patients are taking any of these
drugs, alternate therapy, dosage adjustment, and/or special testing may be needed
during the treatment.
For missed doses, patients should be told to take the missed dose as soon as
they remember. If it is almost time for the next dose, the missed dose should
be skipped and the medicine taken at the next regularly scheduled time. Patients
should not take an extra dose to make up for the missed dose.
Patients should be told to take Flo-Pred with food to avoid GI irritation.
Patients should be advised of common adverse reactions that could occur with
Flo-Pred use to include fluid retention, alteration in glucose tolerance, elevation
in blood pressure, behavioral and mood changes, increased appetite and weight
INSTRUCTIONS FOR FILLING SYRINGE
1. Fully depress the syringe. Fig. 1
2. Remove the cap and push the syringe tip firmly into the orifice on top of
the Flo-Pred bottle. Fig. 2
3. Turn the bottle upside down. Wait 10 seconds to allow medicine to flow into
the neck of the bottle. Fig. 3
4. Stabilize the syringe barrel with your thumb, and slowly pull the plunger
with your other fingers. Fig. 4
5. Turn the bottle right-side up. Carefully remove the syringe, holding it
by the barrel. Fig. 5
INSTRUCTIONS FOR ADMINISTERING MEDICINE WITH A SYRINGE
Place the tip of the syringe into the inside cheek of the mouth and slowly
push the plunger to release the medicine. Swallow the medicine. As with all
medications delivered with oral syringes, DO NOT forcefully push the plunger,
or squirt the medicine to the back of mouth or throat.
INSTRUCTIONS FOR CLEANING SYRINGE:
Pull the plunger all the way out of the barrel. Wash the plunger and barrel
in running warm water. Rinse thoroughly and dry. To reassemble, gently push
the plunger back into barrel as far as it will go. The oral syringe should only
be used for one individual. The syringe is reusable and dishwasher safe, and
should be cleaned after each use.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Flo-Pred was not formally evaluated in carcinogenicity studies. Review of the
published literature identified carcinogenicity studies of prednisolone at doses
which were less than the typical clinical doses. In a 2-year study, male Sprague-Dawley
rats administered prednisolone in drinking water at a dose of 368 mcg/kg/day
(equivalent to 3.5 mg/day in a 60 kg individual based on a mg/m² body surface
area comparison) developed increased incidences of hepatic adenomas. Lower doses
were not studied and therefore a no effect level could not be identified. In
an 18-month study, intermittent oral gavage administration of prednisolone did
not induce tumors in female Sprague-Dawley rats when given 1, 2, 4.5 or 9 times
per month at 3 mg/kg prednisolone (equivalent to 29 mg in a 60 kg individual
based on a mg/m² body surface area comparison).
Flo-Pred was not formally evaluated for genotoxicity. However, in published
studies prednisolone was not mutagenic with or without metabolic activation
in the Ames bacterial reverse mutation assay using Salmonella typhimurium
and Escherichia coli, or in a mammalian cell gene mutation assay using
mouse lymphoma L5178Y cells, according to current evaluation standards. In a
published chromosomal aberration study in Chinese Hamster Lung (CHL) cells,
a slight increase was seen in the incidence of structural chromosomal aberrations
with metabolic activation at the highest concentration tested, however, the
effect appears to be equivocal. Prednisolone was not genotoxic in an in vivo
micronucleaus assay in the mouse though the study design did not meet current
Flo-Pred was not formally evaluated in fertility studies. However, menstrual
irregularities have been described with clinical use [see ADVERSE REACTIONS].
Use In Specific Populations
Pregnancy Category D [see WARNINGS AND PRECAUTIONS]
Multiple cohort and case controlled studies in humans suggest that maternal
corticosteroid use during the first trimester increases the rate of cleft lip
with or without cleft palate from about 1/1000 infants to 3-5/1000 infants.
Two prospective case control studies showed decreased birth weight in infants
exposed to maternal corticosteroids in utero.
Flo-Pred was not formally evaluated for effects on reproduction. Published
literature indicates prednisolone has been shown to be teratogenic in rats,
rabbits, hamsters, and mice with increased incidence of cleft palate in offspring.
In teratogenicity studies, cleft palate along with an elevation of fetal lethality
(or increase in resorptions) and reductions in fetal body weight was seen in
rats at maternal doses of 30 mg/kg (equivalent to 290 mg in a 60 kg individual
based on mg/m² body surface comparison) and higher. Cleft palate was observed
in mice at a maternal dose of 20 mg/kg (equivalent to 100 mg in a 60 kg individual
based on a mg/m² comparison). Additionally, constriction of the ductus arteriosus
has been observed in fetuses of pregnant rats exposed to prednisolone.
In humans, the risk of decreased birth weight appears to be dose-related and
may be minimized by administering lower corticosteroid doses. It is likely that
underlying maternal conditions contribute to intrauterine growth restriction
and decreased birth weight, but it is unclear to what extent these maternal
conditions contribute to the increased risk of orofacial clefts.
Prednisolone can cause fetal harm when used during pregnancy. Flo-Pred should
be used during pregnancy only if the potential benefit justifies the potential
risk to the fetus. If this drug is used during pregnancy, or if the patient
becomes pregnant while using this drug, the patient should be apprised of the
potential hazard to the fetus. Infants born to mothers who have received corticosteroids
during pregnancy should be carefully observed for signs of hypoadrenalism.
Prednisolone is secreted in human milk. Reports suggest that prednisolone concentrations
in human milk are 5 to 25% of maternal serum levels, and that total infant daily
doses are small, about 0.14% of the maternal daily dose. The risk of infant
exposure to prednisolone through breast milk should be weighed against the known
benefits of breastfeeding for both the mother and baby.
Caution should be exercised when prednisolone is administered to a nursing
woman. If prednisolone must be prescribed to a breastfeeding mother, the lowest
dose should be prescribed to achieve the desired clinical effect. High doses
of corticosteroids for long periods could potentially produce problems in infant
growth and development and interfere with endogenous corticosteroid production.
Breastfeeding women using corticosteroids should be encouraged to take their
dose immediately after breastfeeding at the time of day when the baby usually
has the longest interval between feeds. This will minimize infant exposure to
The efficacy and safety of prednisolone 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).
However, some of these conclusions and other indications for pediatric use of
corticosteroid, 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 prednisolone 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.
Children 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 children than some commonly used tests of HPA axis function. The
linear growth of children treated with corticosteroids by any route should be
monitored, and the potential growth effects of prolonged treatment should be
weighed against clinical benefits obtained and the availability of other treatment
alternatives. In order to minimize the potential growth effects of corticosteroids,
children should be titrated to the lowest effective dose.
No overall differences in safety or effectiveness were observed between elderly
subjects and younger subjects, and other reported clinical experience with prednisolone
has not identified differences in responses between the elderly and younger
patients. However, the incidence of corticosteroid-induced side effects may
be increased in geriatric patients and are dose-related. Osteoporosis is the
most frequently encountered complication, which occurs at a higher incidence
rate in corticosteroid-treated geriatric patients as compared to younger populations
and in age-matched controls. Losses of bone mineral density appear to be greatest
early on in the course of treatment and may recover over time after steroid
withdrawal or use of lower doses (i.e., ≤ 5 mg/day). Prednisolone doses of
7.5 mg/day or higher have been associated with an increased relative risk of
both vertebral and nonvertebral fractures, even in the presence of higher bone
density compared to patients with involution osteoporosis.
Routine screening of geriatric patients, including regular assessments of bone
mineral density and institution of fracture prevention strategies, along with
regular review of prednisolone indication should be undertaken to minimize complications
and keep the prednisolone dose at the lowest acceptable level. Co-administration
of certain bisphosphonates have been shown to retard the rate of bone loss in
corticosteroid-treated males and postmenopausal females, and these agents are
recommended in the prevention and treatment of corticosteroid-induced osteoporosis.
It has been reported that equivalent weight-based doses yield higher total
and unbound prednisolone plasma concentrations and reduced renal and non-renal
clearance in elderly patients compared to younger populations. 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 therapy.
This drug is known to be substantially excreted by the kidney, and the risk
of toxic reactions to this drug may be greater in patients with impaired renal
function. Because elderly patients are more likely to have decreased renal function,
care should be taken in dose selection, and it may be useful to monitor renal