HYDROCORTISONE SOD SUCCINATE
DESCRIPTION:
Hydrocortisone sodium succinate, a synthetic adrenocortical steroid, is a white
to light yellow, odorless or practically odorless powder. It is freely soluble
in water and is exceedingly hygroscopic.
Hydrocortisone Sodium succinate injection is a sterile solution (pH 7.5 to 8.5), sealed under nitrogen, for intravenous, intramuscular,and subcutaneous administration.
ACTIONS/CLINICAL PHARMACOLOGY:
Hydrocortisone sod succinate injection has a rapid onset but short duration of action when compared with less soluble preparations. Because of this, it is suitable for the treatment of acute disorders responsive to adrenocortical steroid therapy.
Naturally occurring glucocorticoids (hydrocortisone and cortisone), which also
have salt-retaining properties, are used as replacement therapy in
adrenocortical deficiency states. They are also 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.
INDICATIONS AND USAGE:
When oral therapy is not feasible:
1. 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
2. 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
3. Collagen Diseases
During an exacerbation or as maintenance therapy in selected cases of:
Systemic lupus erythematosus
Acute rheumatic carditis
Systemic dermatomyositis (polymyositis)
4. Dermatologic Diseases
Pemphigus
Severe erythema multiforme (Stevens-Johnson syndrome)
Exfoliative dermatitis
Bullous dermatitis herpetiformis
Severe seborrheic dermatitis
Severe psoriasis
Mycosis fungoides
5. 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)
6. Ophthalmic Diseases
Severe acute and chronic allergic and inflammatory processes involving the eye,
such as:
Herpes zoster ophthalmicus
Iritis, iridocyclitis
Chorioretinitis
Diffuse posterior uveitis and choroiditis
Optic neuritis
Sympathetic ophthalmia
Anterior segment inflammation
Allergic conjunctivitis
Keratitis
Allergic corneal marginal ulcers
7. Gastrointestinal Diseases
To tide the patient over a critical period of the disease in:
Ulcerative colitis (Systemic therapy)
Regional enteritis (Systemic therapy)
8. 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
9. Hematologic Disorders
Acquired (autoimmune) hemolytic anemia
Idiopathic thrombocytopenic purpura in adults (I.V. only; I.M. administration is
contraindicated)
Secondary thrombocytopenia in adults
Erythroblastopenia (RBC anemia)
Congenital (erythroid) hypoplastic anemia
10. Neoplastic Diseases
For palliative management of:
Leukemias and lymphomas in adults
Acute leukemia of childhood
11. 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
12. Miscellaneous
Tuberculous meningitis with subarachnoid block or impending block when used
concurrently with appropriate antituberculous chemotherapy
Trichinosis with neurologic or myocardial involvement
CONTRAINDICATIONS:
Systemic fungal infections (see WARNINGS regarding amphotericin B)
Hypersensitivity to any component of this product, including sulfites (see
WARNINGS).
WARNINGS:
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. Anaphylactoid and hypersensitivity reactions
have been reported for Injection Hydrocortisone sod succinate (see ADVERSE REACTIONS).
Injection Hydrocortisone sod succinate contains sodium bisulfite, a sulfite that may
cause allergic-type reactions including anaphylactic symptoms and life-
threatening or less severe asthmatic episodes in certain susceptible people. The
overall prevalence of sulfite sensitivity in the general population is unknown
and probably low. Sulfite sensitivity is seen more frequently in asthmatic than
in nonasthmatic people.
Corticosteroids may exacerbate systemic fungal infections and therefore should
not be used in the presence of such infections unless they are needed to control
drug reactions due to amphotericin B. Moreover, there have been cases reported
in which concomitant use of amphotericin B and hydrocortisone was followed by
cardiac enlargement and congestive failure.
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.
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 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.
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 corticosteroids, 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 Hydrocortisone sod succinate injection 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:
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.
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
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.
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 antacids be
administered 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.
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.
Injection of a steroid into an infected site is to be avoided.
The slower rate of absorption by intramuscular administration should be
recognized.
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:
Aspirin should be used cautiously in conjunction with corticosteroids in
hypoprothrombinemia.
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.
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.
(See Also 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 subsequent 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
Burning or tingling, especially in the perineal area (after I.V. injection)
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
Anaphylactoid or hypersensitivity reactions
Thromboembolism
Weight gain
Increased appetite
Nausea
Malaise
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
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 intraperitoneal LD50 of hydrocortisone in female mice was 1740 mg/kg.
DOSAGE AND ADMINISTRATION:
For Intravenous, Intramuscular, And Subcutaneous Injection.
For single dose use only. Maintenance of sterility cannot be assured when used
as a multiple dose vial.
Hydrocortisone sod succinate injection can be given directly from the vial, or it can
be added to Sodium Chloride Injection or Dextrose Injection and administered by
intravenous drip.
Benzyl alcohol as a preservative has been associated with toxicity in premature
infants. Solutions used for intravenous administration or further dilution of
this product should be preservative-free when used in the neonate, especially
the premature infant.
When it is mixed with an infusion solution, sterile precautions should be
observed. Since infusion solutions generally do not contain preservatives,
mixtures should be used within 24 hours.
DOSAGE REQUIREMENTS ARE VARIABLE AND MUST BE INDIVIDUALIZED ON THE BASIS OF THE
DISEASE AND THE RESPONSE OF THE PATIENT.
The initial dosage varies from 15 to 240 mg a day depending on the disease being
treated. In less severe diseases doses lower than 15 mg may suffice, while in
severe diseases doses higher than 240 mg 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 the patient's response
is satisfactory. If a satisfactory clinical response does not occur after a
reasonable period of time, discontinue Hydrocortisone sod succinate injection and
transfer the patient to other therapy.
After a favorable initial response, the proper maintenance dosage should be
determined by decreasing the initial dosage in small amounts to the lowest
dosage that maintains an adequate clinical response.
Patients should be observed closely for signs that might require dosage
adjustment, including changes in clinical status resulting from remissions or
exacerbations of the disease, individual drug responsiveness, and the effect of
stress (e.g., surgery, infection, trauma). During stress it may be necessary to
increase dosage temporarily.
If the drug is to be stopped after more than a few days of treatment, it usually
should be withdrawn gradually.
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