DEXAMETHASONE TRIMETHYL ACETATE
It is used in topical preparations and has same properties as dexamethasone sod
phosphate except that it is not readily absorbed from the unbroken skin. So see
below at dexamethasone sodium phosphate record for details.
DEXAMETHASONE SODIUM PHOSPHATE
DESCRIPTION:
Glucocorticoids are adrenocortical steroids, both naturally occurring and
synthetic, which are readily absorbed from the gastrointestinal tract.
Dexamethasone, a synthetic adrenocortical steroid, is a white to practically
white, odorless, crystalline powder. It is stable in air. It is practically
insoluble in water. The molecular weight is 392.47. It is designated chemically
as 9-fluoro-11beta, 17, 21-trihydroxy- 16alpha-methylpregna-1, 4-diene-3,20-
dione.The empirical formula is C22H29FO5.
ACTIONS/CLINICAL PHARMACOLOGY:
Naturally occurring glucocorticoids (hydrocortisone and cortisone), which also
have salt-retaining properties, are used as replacement therapy in
adrenocortical deficiency states. Their synthetic analogs including
dexamethasone are primarily used for their potent anti-inflammatory effects in
disorders of many organ systems.
Glucocorticoids cause profound and varied metabolic effects. In addition, they
modify the body's immune responses to diverse stimuli.
At equipotent anti-inflammatory doses, dexamethasone almost completely lacks the
sodium- retaining property of hydrocortisone and closely related derivatives of
hydrocortisone.
INDICATIONS AND USAGE:
1. Endocrine Disorders
Primary or secondary adrenocortical insufficiency (hydrocortisone or cortisone
is the first choice; synthetic analogs may be used in conjunction with
mineralocorticoids where applicable; in infancy mineralocorticoid
supplementation is of particular importance)
Congenital adrenal hyperplasia
Nonsuppurative thyroiditis
Hypercalcemia associated with cancer
2. Rheumatic Disorders
As adjunctive therapy for short-term administration (to tide the patient over an
acute episode or exacerbation) in:
Psoriatic arthritis
Rheumatoid arthritis, including juvenile rheumatoid arthritis (selected cases
may require low-dose maintenance therapy)
Ankylosing spondylitis
Acute and subacute bursitis
Acute nonspecific tenosynovitis
Acute gouty arthritis
Post-traumatic osteoarthritis
Synovitis of osteoarthritis
Epicondylitis
3. Collagen Diseases
During an exacerbation or as maintenance therapy in selected cases of--
Systemic lupus erythematosus
Acute rheumatic carditis
4. Dermatologic Diseases
Pemphigus
Bullous dermatitis herpetiformis
Severe erythema multiforme (Stevens-Johnson syndrome)
Exfoliative dermatitis
Mycosis fungoides
Severe psoriasis
Severe seborrheic dermatitis
5. Allergic States
Control of severe or incapacitating allergic conditions intractable to adequate
trials of conventional treatment:
Seasonal or perennial allergic rhinitis
Bronchial asthma
Contact dermatitis
Atopic dermatitis
Serum sickness
Drug hypersensitivity reactions
6. Ophthalmic Diseases
Severe acute and chronic allergic and inflammatory processes involving the eye
and its adnexa, such as--
Allergic conjunctivitis
Keratitis
Allergic corneal marginal ulcers
Herpes zoster ophthalmicus
Iritis and iridocyclitis
Chorioretinitis
Anterior segment inflammation
Diffuse posterior uveitis and choroiditis
Optic neuritis
Sympathetic ophthalmia
7. Respiratory Diseases
Symptomatic sarcoidosis
Loeffler's syndrome not manageable by other means
Berylliosis
Fulminating or disseminated pulmonary tuberculosis when used concurrently with
appropriate antituberculous chemotherapy
Aspiration pneumonitis
8. Hematologic Disorders
Idiopathic thrombocytopenic purpura in adults
Secondary thrombocytopenia in adults
Acquired (autoimmune) hemolytic anemia
Erythroblastopenia (RBC anemia)
Congenital (erythroid) hypoplastic anemia
9. Neoplastic Diseases
For palliative management of:
Leukemias and lymphomas in adults
Acute leukemia of childhood
10. Edematous States
To induce a diuresis or remission of proteinuria in the nephrotic syndrome,
without uremia, of the idiopathic type or that due to lupus erythematosus
11. Gastrointestinal Diseases
To tide the patient over a critical period of the disease in:
Ulcerative colitis
Regional enteritis
12. Cerebral Edema associated with primary or metastatic brain tumor,
craniotomy, or head injury. Use in cerebral edema is not a substitute for
careful neurosurgical evaluation and definitive management such as neurosurgery
or other specific therapy.
13. Miscellaneous
Tuberculous meningitis with subarachnoid block or impending block when used
concurrently with appropriate antituberculous chemotherapy
Trichinosis with neurologic or myocardial involvement
14. Diagnostic Testing Of Adrenocortical Hyperfunction.
CONTRAINDICATIONS:
Systemic fungal infections
Hypersensitivity to this drug
WARNINGS:
In patients on corticosteroid therapy subjected to unusual stress, increased
dosage of rapidly acting corticosteroids before, during, and after the stressful
situation is indicated.
Drug-induced secondary adrenocortical insufficiency may result from too rapid
withdrawal of corticosteroids and 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. If the patient is
receiving steroids already, dosage may have to be increased. Since
mineralocorticoid secretion may be impaired, salt and/or a mineralocorticoid
should be administered concurrently.
Corticosteroids may mask some signs of infection, and new infections may appear
during their use. There may be decreased resistance and inability to localize
infection when corticosteroids are used. Moreover, corticosteroids may affect
the nitroblue-tetrazolium test for bacterial infection and produce false
negative results.
In cerebral malaria, a double-blind trial has shown that the use of
corticosteroids is associated with prolongation of coma and a higher incidence
of pneumonia and gastrointestinal bleeding.
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 any patient with unexplained
diarrhea.
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.
Usage In Pregnancy: Since adequate human reproduction studies have not been done
with corticosteroids, use of these drugs in pregnancy or in women of
childbearing potential requires that the anticipated benefits be weighed against
the possible hazards to the mother and embryo or fetus. Infants born of mothers
who have received substantial doses of corticosteroids during pregnancy should
be carefully observed for signs of hypoadrenalism.
Corticosteroids appear in breast milk and could suppress growth, interfere with
endogenous corticosteroid production, or cause other unwanted effects. Mothers
taking pharmacologic doses of corticosteroids should be advised not to nurse.
Average and large doses of hydrocortisone or cortisone can cause elevation of
blood pressure, salt and water retention, and increased excretion of potassium.
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. All corticosteroids increase calcium excretion.
Administration of live virus vaccines, including smallpox, is contraindicated in
individuals receiving immunosuppressive doses of corticosteroids. If inactivated
viral or bacterial vaccines are administered to individuals receiving
immunosuppressive doses of corticosteroid the expected serum antibody response
may not be obtained. However, immunization procedures may be undertaken in
patients who are receiving corticosteroids as replacement therapy, e.g., for
Addison's disease.
Patients who are on drugs which suppress the immune system are more susceptible
to infections than healthy individuals. Chickenpox and measles, for example, can
have a more serious or even fatal course in non-immune patients on
corticosteroids. In such patients who have not had these diseases, particular
care should be taken to avoid exposure. The risk of developing a disseminated
infection varies among individuals and can be related to the dose, route and
duration of corticosteroid administration as well as to the underlying disease.
If exposed to chickenpox, prophylaxis with varicella zoster immune globulin
(VZIG) may be indicated. If chickenpox develops, treatment with antiviral agents
may be considered. If exposed to measles, prophylaxis with immune globulin (IG)
may be indicated. (See the respective package inserts for VZIG and IG for
complete prescribing information.)
Similarly, 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.
The use of DECADRON tablets 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.
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.
Literature reports suggest an apparent association between use of
corticosteroids and left ventricular free wall rupture after a recent myocardial
infarction; therefore, therapy with corticosteroids should be used with great
caution in these patients.
PRECAUTIONS:
Following prolonged therapy, withdrawal of corticosteroids may result in
symptoms of the corticosteroid withdrawal syndrome including fever, myalgia,
arthralgia, and malaise. This may occur in patients even without evidence of
adrenal insufficiency.
There is an enhanced effect of corticosteroids in patients with hypothyroidism
and in those with cirrhosis.
Corticosteroids should be used cautiously in patients with ocular herpes simplex
because of possible corneal perforation.
The lowest possible dose of corticosteroids should be used to control the
condition under treatment, and when reduction in dosage is possible, the
reduction should be gradual.
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.
Aspirin should be used cautiously in conjunction with corticosteroids in
hypoprothrombinemia.
Steroids should be used with caution in nonspecific ulcerative colitis, if there
is a probability of impending perforation, abscess, or other pyogenic infection,
diverticulitis, fresh intestinal anastomoses, active or latent peptic ulcer,
renal insufficiency, hypertension, osteoporosis, and myasthenia gravis. Signs of
peritoneal irritation following gastrointestinal perforation in patients
receiving large doses of corticosteroids may be minimal or absent. Fat embolism
has been reported as a possible complication of hypercortisonism.
When large doses are given, some authorities advise that corticosteroids be
taken with meals and antacids taken between meals to help to prevent peptic
ulcer.
Steroids may increase or decrease motility and number of spermatozoa in some
patients.
Phenytoin, phenobarbital, ephedrine, and rifampin may enhance the metabolic
clearance of corticosteroids, resulting in decreased blood levels and lessened
physiologic activity, thus requiring adjustment in corticosteroid dosage. These
interactions may interfere with dexamethasone suppression tests which should be
interpreted with caution during administration of these drugs.
False-negative results in the dexamethasone suppression test (DST) in patients
being treated with indomethacin have been reported. Thus, results of the DST
should be interpreted with caution in these patients.
The prothrombin time should be checked frequently in patients who are receiving
corticosteroids and coumarin anticoagulants at the same time because of reports
that corticosteroids have altered the response to these anticoagulants. Studies
have shown that the usual effect produced by adding corticosteroids is
inhibition of response to coumarins, although there have been some conflicting
reports of potentiation not substantiated by studies.
When corticosteroids are administered concomitantly with potassium-depleting
diuretics, patients should be observed closely for development of hypokalemia.
Information For Patients
Susceptible 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.
Pediatric Use
Growth and development of pediatric patients on prolonged corticosteroid therapy
should be carefully followed.
DRUG INTERACTIONS:
SEE PRECAUTIONS
ADVERSE REACTIONS:
Fluid And Electrolyte Disturbances
Sodium retention
Fluid retention
Congestive heart failure in susceptible patients
Potassium loss
Hypokalemic alkalosis
Hypertension
Musculoskeletal
Muscle weakness
Steroid myopathy
Loss of muscle mass
Osteoporosis
Vertebral compression fractures
Aseptic necrosis of femoral and humeral heads
Pathologic fracture of long bones
Tendon rupture
Gastrointestinal
Peptic ulcer with possible perforation and hemorrhage
Perforation of the small and large bowel, particularly in patients with
inflammatory bowel disease
Pancreatitis
Abdominal distention
Ulcerative esophagitis
Dermatologic
Impaired wound healing
Thin fragile skin
Petechiae and ecchymoses
Erythema
Increased sweating
May suppress reactions to skin tests
Other cutaneous reactions, such as allergic dermatitis, urticaria, angioneurotic
edema
Neurologic
Convulsions
Increased intracranial pressure with papilledema (pseudotumor cerebri) usually
after treatment
Vertigo
Headache
Psychic disturbances
Endocrine
Menstrual irregularities
Development of cushingoid state
Suppression of growth in children
Secondary adrenocortical and pituitary unresponsiveness, particularly in times
of stress, as in trauma, surgery, or illness
Decreased carbohydrate tolerance
Manifestations of latent diabetes mellitus
Increased requirements for insulin or oral hypoglycemic agents in diabetics
Hirsutism
Ophthalmic
Posterior subcapsular cataracts
Increased intraocular pressure
Glaucoma
Exophthalmos
Metabolic
Negative nitrogen balance due to protein catabolism
Cardiovascular
Myocardial rupture following recent myocardial infarction (see WARNINGS).
Other
Hypersensitivity
Thromboembolism
Weight gain
Increased appetite
Nausea
Malaise
Hiccups
OVERDOSAGE:
Reports of acute toxicity and/or death following overdosage of glucocorticoids
are rare. In the event of overdosage, no specific antidote is available;
treatment is supportive and symptomatic.
The oral LD50 of dexamethasone in female mice was 6.5 g/kg.