BETAMETHASONE
DESCRIPTION:
The formula for betamethasone sodium phosphate is C22H28FNa2O8P with a molecular
weight of 516.41. Chemically it is 9-Fluoro- 11(beta),17,21-trihydroxy-16(beta)-
methylpregna- 1,4-diene-3,20-dione 21-(disodium phosphate).
The formula for betamethasone acetate is C24H31FO6 with a molecular weight of
434.50. Chemically it is 9-Fluoro- 11(beta),17,21-trihydroxy-16(beta)-
methylpregna- 1,4-diene-3,20-dione 21-acetate.
Betamethasone sodium phosphate is a white to practically white, odorless powder,
and is hygroscopic. It is freely soluble in water and in methanol, but is
practically insoluble in acetone and in chloroform.
Betamethasone acetate is a white to creamy white, odorless powder that sinters
and resolidifies at about 165degC, and remelts at about 200degC- 220degC with
decomposition. It is practically insoluble in water, but freely soluble in
acetone, and is soluble in alcohol and in chloroform.
ACTIONS/CLINICAL PHARMACOLOGY:
Naturally occurring glucocorticoids (hydrocortisone), which also have salt-
retaining properties, are used as replacement therapy in adrenocortical
deficiency states. Their synthetic analogs are primarily used for their potent
anti- inflammatory effects in disorders of many organ systems.
Betamethasone sodium phosphate, a soluble ester, provides prompt activity, while
betamethasone acetate is only slightly soluble and affords sustained activity.
Glucocorticoids cause profound and varied metabolic effects. In addition, they
modify the body's immune responses to diverse stimuli.
INDICATIONS AND USAGE:
When oral therapy is not feasible and the strength, dosage form, and route of
administration of the drug reasonably lend the preparation to the treatment of
the condition, CELESTONE Injectable Suspension for intramuscular use is
indicated as follows:
ENDOCRINE DISORDERS:
Primary or secondary adrenocortical insufficiency (hydrocortisone or cortisone
is the drug of choice; synthetic analogs may be used in conjunction with
mineralocorticoids where applicable; in infancy mineralocorticoid
supplementation is of particular importance).
Acute adrenocortical insufficiency (hydrocortisone or cortisone is the drug of
choice; mineralocorticoid supplementation may be necessary, particularly when
synthetic analogs are used); preoperatively and in the event of serious trauma
or illness, in patients with known adrenal insufficiency or when adrenocortical
reserve is doubtful; shock unresponsive to conventional therapy if
adrenocortical insufficiency exists or is suspected; congenital adrenal
hyperplasia; nonsuppurative thyroiditis; hypercalcemia associated with cancer.
RHEUMATIC DISORDERS:
As adjunctive therapy for short-term administration (to tide the patient over an
acute episode or exacerbation) in: post-traumatic osteoarthritis; synovitis of
osteoarthritis; rheumatoid arthritis, including juvenile rheumatoid arthritis
(selected cases may require low-dose maintenance therapy); acute and subacute
bursitis; epicondylitis; acute nonspecific tenosynovitis; acute gouty arthritis;
psoriatic arthritis; ankylosing spondylitis.
COLLAGEN DISEASES:
During an exacerbation or as maintenance therapy in selected cases of systemic
lupus erythematosus, acute rheumatic carditis.
DERMATOLOGIC DISEASES:
Pemphigus, severe erythema multiforme (Stevens- Johnson syndrome), exfoliative
dermatitis, bullous dermatitis herpetiformis, severe seborrheic dermatitis,
severe psoriasis, mycosis fungoides.
ALLERGIC STATES:
Control of severe or incapacitating allergic conditions intractable to adequate
trials of conventional treatment in: bronchial asthma, contact dermatitis,
atopic dermatitis, serum sickness, seasonal or perennial allergic rhinitis, drug
hypersensitivity reactions, urticarial transfusion reactions, acute
noninfectious laryngeal edema (epinephrine is the drug of first choice).
OPHTHALMIC DISEASES:
Severe acute and chronic allergic and inflammatory processes involving the eye,
such as: herpes zoster ophthalmicus, iritis and iridocyclitis, chorioretinitis,
diffuse posterior uveitis and choroiditis, optic neuritis, sympathetic
ophthalmia, anterior segment inflammation, allergic conjunctivitis, allergic
corneal marginal ulcers, keratitis.
GASTROINTESTINAL DISEASES:
To tide the patient over a critical period of disease in: ulcerative colitis-
(systemic therapy), regional enteritis-(systemic therapy).
RESPIRATORY DISEASES:
Symptomatic sarcoidosis, berylliosis, fulminating or disseminated pulmonary
tuberculosis when used concurrently with appropriate antituberculous
chemotherapy, Loeffler's syndrome not manageable by other means, aspiration
pneumonitis.
HEMATOLOGIC DISORDERS:
Acquired (autoimmune) hemolytic anemia, secondary thrombocytopenia in adults,
erythroblastopenia (RBC anemia), congenital (erythroid) hypoplastic anemia.
NEOPLASTIC DISEASES:
For palliative management of: leukemias and lymphomas in adults, acute leukemia
of childhood.
EDEMATOUS STATES:
To induce diuresis or remission of proteinuria in the nephrotic syndrome,
without uremia, of the idiopathic type or that due to lupus erythematosus.
MISCELLANEOUS:
Tuberculous meningitis with subarachnoid block or impending block when used
concurrently with appropriate antituberculous chemotherapy, trichinosis with
neurologic or myocardial involvement.
When the strength and dosage form of the drug lend the preparation to the
treatment of the condition, the INTRA-ARTICULAR OR SOFT TISSUE ADMINISTRATION of
CELESTONE Injectable Suspension is indicated as adjunctive therapy for
short-term administration (to tide the patient over an acute episode or
exacerbation) in: synovitis of osteoarthritis, rheumatoid arthritis, acute and
subacute bursitis, acute gouty arthritis, epicondylitis, acute nonspecific
tenosynovitis, post-traumatic osteoarthritis.
When the strength and dosage form of the drug lend the preparation to the
treatment of the condition, the INTRALESIONAL ADMINISTRATION of CELESTONE
SOLUSPAN Injectable Suspension is indicated for: keloids; localized
hypertrophic, infiltrated, inflammatory lesions of: lichen planus, psoriatic
plaques, granuloma annulare, and lichen simplex chronicus (neurodermatitis);
discoid lupus erythematosus; necrobiosis lipoidica diabeticorum; alopecia
areata.
CELESTONE Injectable Suspension may also be useful in cystic tumors of
an aponeurosis or tendon (ganglia).
CONTRAINDICATIONS:
CELESTONE Injectable Suspension is contraindicated in systemic fungal
infections.
WARNINGS:
CELESTONE Injectable Suspension should not be administered
intravenously.
In patients on corticosteroid therapy subjected to any unusual stress, increased
dosage of rapidly acting corticosteroids before, during, and after the stressful
situation is indicated.
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.
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.
CELESTONE Injectable Suspension contains two betamethasone esters one
of which, betamethasone sodium phosphate, disappears rapidly from the injection
site. The potential for systemic effect produced by the soluble portion of
CELESTONE Injectable Suspension should therefore be taken into account
by the physician when using the drug.
Average and large doses of cortisone or hydrocortisone 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.
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 IN HIGH DOSES, BECAUSE OF POSSIBLE HAZARDS OF
NEUROLOGICAL COMPLICATIONS AND LACK OF ANTIBODY RESPONSE.
Persons 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 children or adults on
corticosteroids. In such children, or adults who have not had these diseases,
particular care should be taken to avoid exposure. How the dose, route, and
duration of corticosteroid administration affects the risk of developing a
disseminated infection is not known. The contribution of the underlying disease
and/or prior corticosteroid treatment to the risk is also not known. If exposed
to chickenpox, prophylaxis with varicella-zoster immune globulin (VZIG) may be
indicated. If exposed to measles, prophylaxis with pooled intramuscular
immunoglobulin (IG) may be indicated. (See the respective package inserts for
complete VZIG and IG prescribing information.) If chickenpox develops, treatment
with antiviral agents may be considered.
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 CELESTONE Injectable Suspension 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 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.
Because rare instances of anaphylactoid reactions have occurred in patients
receiving parenteral corticosteroid therapy, appropriate precautionary measures
should be taken prior to administration, especially when the patient has a
history of allergy to any drug.
USAGE IN PREGNANCY:
Since adequate human reproduction studies have not been done with
corticosteroids, the use of these drugs in pregnancy, nursing mothers, or women
of childbearing potential requires that the possible benefits of the drug be
weighed against the potential 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.
PRECAUTIONS:
INFORMATION FOR PATIENTS
Persons 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.
GENERAL:
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.
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
for fear of corneal perforation.
The lowest possible dose of corticosteroid should be used to control the
condition under treatment, and when reduction in dosage is possible, the
reduction must 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;
also in diverticulitis, fresh intestinal anastomoses, active or latent peptic
ulcer, renal insufficiency, hypertension, osteoporosis, and myasthenia gravis.
Growth and development of infants and children on prolonged corticosteroid
therapy should be carefully followed.
THE FOLLOWING ADDITIONAL PRECAUTIONS ALSO APPLY FOR PARENTERAL CORTICOSTEROIDS.
INTRA-ARTICULAR INJECTION OF A CORTICOSTEROID MAY PRODUCE SYSTEMIC AS WELL AS
LOCAL EFFECTS.
Appropriate examination of any joint fluid present is necessary to exclude a
septic process.
A marked increase in pain accompanied by local swelling, further restriction of
joint motion, fever, and malaise are suggestive of septic arthritis. If this
complication occurs and the diagnosis of sepsis is confirmed, appropriate
antimicrobial therapy should be instituted.
Local injection of a steroid into a previously infected joint is to be avoided.
Corticosteroids should not be injected into unstable joints.
The slower rate of absorption by intramuscular administration should be
recognized.
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.
GASTROINTESTINAL:
peptic ulcer with possible subsequent perforation and hemorrhage, pancreatitis,
abdominal distention, ulcerative esophagitis.
DERMATOLOGIC:
impaired wound healing, thin fragile skin, petechiae and ecchymoses, facial
erythema, increased sweating, may suppress reactions to skin tests.
NEUROLOGICAL:
convulsions, increased intracranial pressure with papilledema (pseudotumor
cerebri) usually after treatment, vertigo, headache.
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.
OPHTHALMIC:
posterior subcapsular cataracts, increased intraocular pressure, glaucoma,
exophthalmos.
METABOLIC:
negative nitrogen balance due to protein catabolism.
The following ADDITIONAL adverse reactions are related to parenteral
corticosteroid therapy: rare instances of blindness associated with
intralesional therapy around the face and head, hyperpigmentation or
hypopigmentation, subcutaneous and cutaneous atrophy, sterile abscess, post-
injection flare (following intra- articular use), charcot-like arthropathy.
DOSAGE AND ADMINISTRATION:
The initial dosage of CELESTONE Injectable Suspension may vary from 0.5
to 9.0 mg per day depending on the specific disease entity being treated. In
situations of less severity, lower doses will generally suffice while in
selected patients higher initial doses may be required. Usually the parenteral
dosage ranges are one-third to one-half the oral dose given every 12 hours.
However, in certain overwhelming, acute, life-threatening situations,
administration in dosages exceeding the usual dosages may be justified and may
be in multiples of the oral dosages.
The initial dosage should be maintained or adjusted until a satisfactory
response is noted. If after a reasonable period of time there is a lack of
satisfactory clinical response, CELESTONE Injectable Suspension should
be discontinued and the patient transferred to other appropriate therapy. IT
SHOULD BE EMPHASIZED THAT DOSAGE REQUIREMENTS ARE VARIABLE AND MUST BE
INDIVIDUALIZED ON THE BASIS OF THE DISEASE UNDER TREATMENT AND THE RESPONSE OF
THE PATIENT. After a favorable response is noted, the proper maintenance dosage
should be determined by decreasing the initial drug dosage in small decrements
at appropriate time intervals until the lowest dosage which will maintain an
adequate clinical response is reached. It should be kept in mind that constant
monitoring is needed in regard to drug dosage. Included in the situations which
may make dosage adjustments necessary are changes in clinical status secondary
to remissions or exacerbations in the disease process, the patient's individual
drug responsiveness, and the effect of patient exposure to stressful situations
not directly related to the disease entity under treatment; in this latter
situation it may be necessary to increase the dosage of CELESTONE
Injectable Suspension for a period of time consistent with the patient's
condition. If after long-term therapy the drug is to be stopped, it is
recommended that it be withdrawn gradually rather than abruptly.
If coadministration of a local anesthetic is desired, CELESTONE
Injectable Suspension may be mixed with 1% or 2% lidocaine hydrochloride, using
the formulations which do not contain parabens. Similar local anesthetics may
also be used. Diluents containing methylparaben, propylparaben, phenol, etc.,
should be avoided since these compounds may cause flocculation of the steroid.
The required dose of CELESTONE Injectable Suspension is first withdrawn
from the vial into the syringe. The local anesthetic is then drawn in, and the
syringe shaken briefly. DO NOT INJECT LOCAL ANESTHETICS INTO THE VIAL OF
CELESTONE INJECTABLE SUSPENSION.
BURSITIS, TENOSYNOVITIS, PERITENDINITIS.
In acute subdeltoid, subacromial, olecranon, and prepatellar bursitis, one
intrabursal injection of 1.0 mL CELESTONE Injectable Suspension can
relieve pain and restore full range of movement. Several intrabursal injections
of corticosteroids are usually required in recurrent acute bursitis and in acute
exacerbations of chronic bursitis. Partial relief of pain and some increase in
mobility can be expected in both conditions after one or two injections. Chronic
bursitis may be treated with reduced dosage once the acute condition is
controlled. In tenosynovitis and tendinitis, three or four local injections at
intervals of 1 to 2 weeks between injections are given in most cases. Injections
should be made into the affected tendon sheaths rather than into the tendons
themselves. In ganglions of joint capsules and tendon sheaths, injection of 0.5
mL directly into the ganglion cysts has produced marked reduction in the size of
the lesions.
RHEUMATOID ARTHRITIS AND OSTEOARTHRITIS.
Following intra-articular administration of 0.5 to 2.0 mL of CELESTONE
Injectable Suspension, relief of pain, soreness, and stiffness may be
experienced. Duration of relief varies widely in both diseases. Intra-articular
Injection-CELESTONE Injectable Suspension is well tolerated in joints
and periarticular tissues. There is virtually no pain on injection, and the
"secondary flare" that sometimes occurs a few hours after intra- articular
injection of corticosteroids has not been reported with CELESTONE
Injectable Suspension. Using sterile technique, a 20- to 24-gauge needle on an
empty syringe is inserted into the synovial cavity, and a few drops of synovial
fluid are withdrawn to confirm that the needle is in the joint. The aspirating
syringe is replaced by a syringe containing CELESTONE Injectable
Suspension and injection is then made into the joint.
Recommended Doses for Intra-articular Injection
Size of joint Location Dose (mL)
Very Large Hip 1.0-2.0
Large Knee, Ankle, Shoulder 1.0
Medium Elbow, Wrist 0.5-1.0
Small
(Metacarpophalangeal,
interphalangeal) Hand 0.25-0.5
(Sternoclavicular) Chest
A portion of the administered dose of CELESTONE Injectable Suspension
is absorbed systemically following intra-articular injection. In patients being
treated concomitantly with oral or parenteral corticosteroids, especially those
receiving large doses, the systemic absorption of the drug should be considered
in determining intra-articular dosage.
DERMATOLOGIC CONDITIONS.
In intralesional treatment, 0.2 mL/sq cm of CELESTONE Injectable
Suspension is injected intradermally (not subcutaneously) using a tuberculin
syringe with a 25-gauge, 1/2-inch needle. Care should be taken to deposit a
uniform depot of medication intradermally. A total of no more than 1.0 mL at
weekly intervals is recommended.
DISORDERS OF THE FOOT.
A tuberculin syringe with a 25-gauge, 3/4-inch needle is suitable for most
injections into the foot. The following doses are recommended at intervals of 3
days to a week.
CELESTONE
Diagnosis INJECTABLE SUSPENSION DOSE (ML)
Bursitis
under heloma durum or
heloma molle 0.25-0.5
under calcaneal spur 0.5
over hallux rigidus or
digiti quinti varus 0.5
Tenosynovitis,
periostitis of cuboid 0.5
Acute gouty arthritis 0.5-1.0
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