Included as part of the PRECAUTIONS section.
Alterations In Endocrine
Corticosteroids, such as
HEMADY, can cause serious and life-threatening alterations in endocrine
function, especially with chronic use. Monitor patients receiving HEMADY for
adrenal insufficiency after corticosteroid withdrawal and CushingÃ¢â¬™s syndrome
and hyperglycemia while receiving corticosteroids. In addition, patients with
hypopituitarism, primary adrenal insufficiency, or congenital adrenal
hyperplasia, altered thyroid function, or pheochromocytoma may be at risk for
adverse endocrine events.
Risk Of Adrenal Insufficiency
Following Corticosteroid Withdrawal
Corticosteroids can produce
reversible hypothalamic-pituitary adrenal (HPA) axis suppression, with the
potential for the development of secondary adrenal insufficiency after
withdrawal of corticosteroid treatment. Acute adrenal insufficiency can occur
if glucocorticoids are withdrawn abruptly and can be fatal. The degree and
duration of adrenocortical insufficiently produced is variable among patients
and depends on the dose, frequency, and duration of glucocorticoid therapy. The
risk may be reduced by gradually tapering the corticosteroid dose when
withdrawing treatment. This insufficiency may persist for months after
discontinuation of therapy; therefore, in any situation of stress occurring
during that period, corticosteroid therapy should be reinstituted. For patients
already taking corticosteroids during times of stress, the dosage may have to
A steroid “withdrawal syndrome”, seemingly unrelated to
adrenocortical insufficiency, may also occur following abrupt discontinuance of
corticosteroids. This syndrome includes symptoms such as: anorexia, nausea,
vomiting, lethargy, headache, fever, joint pain, desquamation, myalgia, and/or
weight loss. These effects are thought to be due to the sudden change in
glucocorticoid concentration rather than to low corticosteroid levels.
CushingÃ¢â¬™s syndrome (hypercortisolism) may occur with
prolonged exposure to exogenous corticosteroids, including HEMADY. Symptoms
include hypertension, truncal obesity and thinning of the limbs, purple striae,
facial rounding, facial plethora, muscle weakness, easy and frequent bruising
with thin fragile skin, posterior neck fat deposition, osteopenia, acne,
amenorrhea, hirsutism and psychiatric abnormalities. Using the lowest dose of
corticosteroid for the shortest duration possible may reduce the risk.
Corticosteroids can increase blood glucose, worsen
pre-existing diabetes, and predispose those on long-term therapy to diabetes
mellitus, and may reduce the effect of the antidiabetic drugs. Monitor blood
glucose at regular intervals. For patients with hyperglycemia, anti-diabetic
treatment should be initiated or adjusted accordingly.
Considerations For Use In Patients With Altered Thyroid
Metabolic clearance of corticosteroids is decreased in
hypothyroid patients and increased in hyperthyroid patients. Changes in thyroid
status of the patient may necessitate a dose adjustment of the corticosteroid.
When concomitant administration of corticosteroids and levothyroxine is
required, administration of corticosteroid should precede the initiation of
levothyroxine therapy to avoid adrenal crisis.
There have been reports of pheochromocytoma crisis, which
can be fatal, after administration of systemic corticosteroids. In patients
with suspected or identified pheochromocytoma, consider the risk of
pheochromocytoma crisis prior to administering HEMADY.
Immunosuppression And Increased Risk Of Infections
Corticosteroids, including HEMADY, suppress the immune
system and increase the risk of infection with any pathogen, including viral,
bacterial, fungal, protozoan, or helminthic.
Corticosteroids reduce resistance to new infections,
exacerbate existing infections, increase the risk of disseminated infections,
increase the risk of reactivation or exacerbation of latent infections, and
mask some signs of infection. These infections can be severe, and at times
fatal. The degree to which the dose, route, and duration of corticosteroid
administration correlates with the specific risks of infection is not well
characterized; however, the rate of occurrence of infectious complications
increases with increasing doses of corticosteroids.
Monitor for the development of infection and consider
withdrawal of HEMADY or reduction of the dose of corticosteroids as needed.
Varicella Zoster And Measles Viral Infections
Chickenpox caused by Varicella Zoster virus and measles
can have a serious or even fatal course in non-immune children or adult on
corticosteroids, including HEMADY. In patients 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 a patient is exposed to measles, prophylaxis with immune globulin
(IG) may be indicated. If chickenpox develops, treatment with antiviral agents
may be considered.
Hepatitis B Virus Reactivation
Hepatitis B virus reactivation can occur in patients who
are hepatitis B carriers undergoing treatment with immunosuppressive drugs
including corticosteroids. Reactivation can also occur in patients who appear
to have resolved hepatitis B infection.
HEMADY is contraindicated in patients with systemic
fungal infections. Corticosteroids may exacerbate systemic fungal infections.
For patients on chronic corticosteroids who have developed systemic fungal
infections, withdrawal of corticosteroids or reduction of the dose of
corticosteroids is recommended.
The following infections have been reported during the
use of corticosteroids to treat other conditions that HEMADY is not indicated
Corticosteroids may activate latent amebiasis. Rule out
latent amebiasis or active amebiasis before initiating corticosteroid therapy
in any patient who has spent time in the tropics or any patient with
In patients with known or suspected Strongyloides
(threadworm) infestation, 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. For patients on HEMADY who develop known or suspected
Strongyloides (threadworm) infection, withdrawal of corticosteroids or
reduction of the dose of corticosteroids is recommended.
The use of corticosteroids in active tuberculosis should
generally be limited to cases of fulminating or disseminated tuberculosis in
which the corticosteroid is used for the management of the disease in
conjunction with an appropriate anti-tuberculous regimen.
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 chemoprophylaxis.
Corticosteroids should not be used in cerebral malaria.
Alterations In Cardiovascular/Renal Function
Corticosteroids, including HEMADY, can cause elevation of
blood pressure, salt, and water retention, and increased excretion of potassium
and calcium. Monitor blood pressure and assess for signs and symptoms of volume
overload. Monitor serum potassium levels. Dietary salt restriction and
potassium supplementation may be necessary. HEMADY should be used with caution
in patients with congestive heart failure.
Literature reports suggest an association between use of
corticosteroids and left ventricular free wall rupture after a recent
myocardial infarction; therefore, therapy with HEMADY should be used with great
caution in these patients.
Venous And Arterial Thromboembolism
Thromboembolism is a known adverse reaction of
dexamethasone, including HEMADY. The risk for venous and arterial
thromboembolism increases significantly when dexamethasone is administered with
anti-myeloma products (e.g., thalidomide, lenalidomide, pomalidomide, and
carfilzomib). Refer to the Prescribing Information of these anti-myeloma
products for information about the risk of venous and arterial thromboembolism.
Consider thromboprophylaxis based on an assessment of individual
patientsÃ¢â¬™ underlying risk factors and the anti-myeloma drugs. Agents that also
may increase the risk of thromboembolism should be used with caution in
patients with multiple myeloma receiving combination regimens of HEMADY and
Avoid administration of live or live attenuated vaccines
in patients receiving immunosuppressive doses of corticosteroids for the
treatment of multiple myeloma. Killed or inactivated vaccines may be
administered. However, the response to such vaccines cannot be predicted.
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 bacteria, fungi, or
viruses. Consider referral to an ophthalmologist for patients who develop
ocular symptoms or use corticosteroid-containing products for more than 6
weeks. 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.
Corticosteroids should not be used in patients with active ocular herpes
Intraocular pressure may become elevated in some
individuals. If steroid therapy is continued for more than 6 weeks, intraocular
pressure should be monitored.
There is an increased risk of gastrointestinal
perforation during corticosteroid use in patients with certain gastrointestinal
disorders such as active or latent peptic ulcers, diverticulitis, fresh
intestinal anastomoses, and nonspecific ulcerative colitis.
Signs of gastrointestinal perforation, such as peritoneal
irritation, may be masked in patients receiving corticosteroids. Avoid
corticosteroids if there is a possibility of impending perforation, abscess, or
other pyrogenic infections; diverticulitis; fresh intestinal anastomoses; or
active or latent peptic ulcer.
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 (e.g., postmenopausal women) before initiating HEMADY
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
Behavioral And Mood Disturbances
Potentially severe psychiatric adverse reactions may
occur with systemic corticosteroids, including HEMADY. Symptoms typically
emerge within a few days or weeks of starting treatment and may be
dose-related. These reactions may improve after either dose reduction or
withdrawal, although pharmacologic treatment may be necessary. Psychiatric
adverse reactions usually involve hypomanic or manic symptoms (e.g., euphoria,
insomnia, mood swings) during treatment and depressive episodes after
discontinuation of treatment. Inform patients and caregivers of the potential
for behavioral and mood changes and encourage them to seek medical attention if
psychiatric symptoms develop, especially if depressed mood or suicidal ideation
KaposiÃ¢â¬™s sarcoma has been reported to occur in patients
receiving corticosteroid therapy to treat other chronic conditions for which
HEMADY is not indicated. Discontinuation of corticosteroids may result in
HEMADY In Combination With Anti-Myeloma Products
HEMADY is administered in combination regimens with anti-myeloma
products; please refer to the Prescribing Information of these products for
Based on findings from clinical and animal reproduction
studies, corticosteroids, including HEMADY, can cause fetal harm when
administered to a pregnant woman. Dexamethasone administration to pregnant
women has resulted in adverse effects on fetal growth, skeletal
development/osteogenesis and low birth weight with prolonged use. Dexamethasone
administration to pregnant animals during organogenesis resulted in structural
abnormalities, embryo-fetal mortality, functional impairment, and alterations
to growth at doses equivalent to or below the recommended doses.
Advise pregnant women of the potential risk to a fetus.
Advise females of reproductive potential to use effective contraception during
treatment with HEMADY and for at least one month after the last dose [see Use
In Specific Populations].
Carcinogenesis, Mutagenesis, Impairment Of Fertility
No adequate studies have been conducted in animals to
determine whether corticosteroids have a potential for carcinogenesis.
Dexamethasone was tested for in vitro and in vivo
genotoxic potential and was positive in the following assays: chromosomal
aberrations and sister-chromatid exchanges in human lymphocytes, and
micronuclei and sisterchromatid exchanges in mouse bone marrow. The
Ames/Salmonella assay, with and without S9 mix, did not show an increase in
Published literature identified reduced testicular
spermatozoids and reduced spermatogenesis in male mice dosed intraperitoneally
for 7 days at doses equivalent to the human dose based on a mg/m² body surface
Use In Specific Populations
Corticosteroids, including HEMADY, readily cross the
placenta. Adverse developmental outcomes including orofacial clefts (cleft lip
with or without cleft palate), intrauterine growth restriction, and decreased
birth weight have been reported with maternal use of corticosteroids, including
HEMADY, during pregnancy. In animal developmental and reproductive toxicology
studies administration of corticosteroids to pregnant animals during
organogenesis resulted in structural abnormalities, embryo-fetal mortality,
functional impairment, and alterations to growth at doses equivalent to or
below the recommended doses (see Data).
Advise pregnant women of the potential risk to a fetus.
HEMADY is administered in combination with anti-myeloma
products that can cause embryo-fetal harm and are contraindicated for use in
pregnancy. Refer to the Prescribing Information of the other anti-myeloma
products used in combination with HEMADY for additional information.
The estimated background risk of major birth defects and
miscarriage for the indicated population is unknown. All pregnancies have a
background risk of birth defect, loss, or other adverse outcomes. The
background risk in the U.S. general population of major birth defects is 2% to
4% and of miscarriage is 15% to 20% of clinically recognized pregnancies.
HEMADY should be used during pregnancy only if the
potential benefit justifies the potential risk to the fetus. Multiple courses
of antenatal dexamethasone had been associated with reduced birth weight,
susceptibility to infections, and increase blood glucose level in the newborns.
Neonatal hypoglycemia was also reported. Infants born to mothers who have
received substantial doses of corticosteroids during pregnancy should be
carefully observed for signs of hypoadrenalism.
In pregnant animals administered dexamethasone during
organogenesis, doses equivalent to or below the recommended human dose have
caused adverse developmental outcomes including structural abnormalities (cleft
palate), alterations to growth (growth restrictions including reduced bone
lengths and fetal weights), functional impairment (neurodevelopmental and
metabolic effects), and embryo-fetal mortality (reduced number of embryonic
implantations and fewer live fetuses).
Systemically administered corticosteroids appear in human
milk and could suppress growth, interfere with endogenous corticosteroid
production, or cause other untoward effects. Advise women not to breastfeed
during treatment and for 2 weeks after the last dose.
Females And Males Of Reproductive Potential
Pregnancy testing is recommended for females of
reproductive potential prior to initiating HEMADY [see Use In Specific
HEMADY is used in combination with other anti-myeloma products
that require pregnancy testing in females of reproductive potential. Refer to
the Prescribing Information for the products used in combination with HEMADY.
Advise patients of reproductive potential to use
effective contraception during treatment with HEMADY and for at least one month
following the final dose of HEMADY.
HEMADY is used in combination with other anti-myeloma
products that require contraception in females and males of reproductive
potential. Refer to the Prescribing Information for the products used in
combination with HEMADY.
Steroids may increase or decrease motility and number of
spermatozoa in some patients. In animals, dexamethasone affects male
spermatogenesis [see Nonclinical Toxicology].
Safety and effectiveness in pediatric patients have not
No overall differences in safety or effectiveness were
observed between elderly subjects and younger subjects, and other reported
clinical experience with dexamethasone has not identified differences in
responses between the elderly and younger patients. However, the incidence of
corticosteroid-induced adverse reactions 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. Higher doses increase the relative risk of both vertebral and
nonvertebral fractures, even in the presence of higher bone density compared to
patients with involution osteoporosis. Perform routine screening of geriatric
patients, including regular assessments of bone mineral density and institution
of fracture prevention strategies, along with regular review of the dose of and
need for continued dexamethasone therapy [see WARNINGS AND PRECAUTIONS].
HEMADY is used in combination with other anti-myeloma
products. Refer to the Prescribing Information of the other anti-myeloma
products used as part of a combination regimen with HEMADY, for information on
the use of those products in elderly patients.